[Clinical analysis of 10 cases of multi-center tumor necrosis factor receptor-associated periodic syndrome].

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.

Long non-coding RNA CARLo-5 upregulation associates with poor prognosis in patients suffering gastric cancer.

OBJECTIVE: Accumulating evidence has demonstrated that microRNAs (miRNAs) play critical roles in cancer initiation and development. The present study aims to explore the clinical significance of long noncoding RNA CARLo-5 (CARLo-5) in gastric cancer. PATIENTS AND METHODS: CARLo-5 expression in normal gastric tissue, gastric cancer were quantified by Quantitative reverse transcription PCR. The relationship between CARLo-5 expression and the clinical features of gastric cancer was assessed. Kaplan-Meier method with log-rank test was applied to compare survival curves. The univariate and multivariate Cox regression models were employed to evaluate the prognostic value of the CARLo-5 expression in overall survival (OS) and relapse-free survival (RFS). RESULTS: We observed that the relative expression of CARLo-5 in gastric cancer tissues was significantly higher than that of their matched adjacent normal tissues (p < 0.001). High CARLo-5 expression was found to be closely correlated with advanced T stage (p = 0.003), positive distant metastasis (p = 0.009), lymph node involvement (p = 0.001), and poor differentiation (p = 0.001). Furthermore, Kaplan-Meier analysis demonstrated that gastric cancer patients with high CARLo-5 expression had poorer OS (p < 0.001) and RFS (p < 0.001). Finally, univariate and multivariate Cox analysis indicated that high CARLo-5 expression were independent predictors for both OS and RFS. CONCLUSIONS: Our findings implicated that CARLo-5 could be considered promising biomarkers for prognosis of gastric cancer.

Diabetic autonomic neuropathy: evidence for apoptosis in situ in the rat.

We examined the hypothesis that activation of the apoptosis cascade occurs relatively early in diabetes mellitus affecting three distinct neuronal populations that are involved in regulating gut function: (i) dorsal root ganglion (DRG), (ii) vagus nodose ganglion and (iii) colon myenteric plexus. A validated streptozotocin-induced diabetic rat model and age-matched healthy controls were studied. After 4-8 weeks of diabetes the animals were anaesthetized, fixed in situ and the relevant tissues removed. After 1 month of diabetes some animals were treated with insulin for 2 weeks to restore euglycaemia. Apoptosis was measured using immunohistochemical detection of activated caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL)-positive cells in adjacent sections in neurones (PGP 9.5-positive cells). The level of apoptosis was confirmed using double-label assessment of caspase-3 and TUNEL in DRG preparations. Caspase-3 immunoreactive neurones demonstrated a range in staining intensity. When all grades of staining were included, 6-8% of the DRG, nodose ganglia and myenteric neurones were immunoreactive in the preparations from diabetic rats compared with 0.2-0.5% in controls. Neurones staining positive for both caspase-3 and TUNEL accounted for 1-2% of the total neuronal population in all three preparations in diabetic rats compared with 0.1-0.2% in controls (P < 0.05). Insulin treatment reversed the percentage of TUNEL-positive neurones in diabetic rats to control levels. Activation of the apoptosis cascade occurs relatively early in diabetic autonomic neuropathy and may contribute to the pathophysiology of this disorder.

Cholecystokinin octapeptide reverses the kappa-opioid-receptor-mediated depression of calcium current in rat dorsal root ganglion neurons.

Although the cholecystokinin octapeptide (CCK-8) is reported to antagonize the kappa-opioid-receptor-mediated analgesic effect in spinal cord, its mechanism and sites of action remain obscure. In the present study, the whole-cell patch-clamp recording technique was employed to examine the effect of kappa-opioid agonist U50488H on voltage-gated calcium channels and the interaction between the CCK-8 and U50488H in acutely isolated rat dorsal root ganglion neurons. The results indicate that the calcium currents elicited in dorsal root ganglion neurons can be depressed by U50488H, an effect readily reversed by the kappa-opioid receptor antagonist Nor-BNI or by the antiopioid peptide CCK-8. The effect of the CCK-8 can be abolished by the CCK-B receptor antagonist, L365,260. While CCK-8 showed a potent opioid-reversal effect, it by itself exerted a slight inhibitory effect on calcium current. This novel observation in the dorsal root ganglion neurons indicates that CCK-8 can antagonize the kappa-opioid-receptor-mediated depressant effect on voltage-gated calcium current, and this antagonizing effect appears to be mediated via CCK-B receptor.

[The cardiovascular reactions mediated by TPA and tamoxifen in spinal cord of conscious rats].

Intrathecal administration (ith) of phorbol 12-myristate (TPA), an activator of protein kinase C, (31.24, 26.5, 125 and 250 ng/10 micrograms) to conscious rats produced a marked dose-dependent pressor effect without significant change in heart rate (HR). Intrathecal administration of tamoxifen (3.125, 6.5 and 100 micrograms/10 microliters), one of the inhibitors of protein kinase C, produced a marked dose-dependent hypotensive effect. Intrathecal injection of exogenous DBcAMP (12.5, 25, 50 and 100 micrograms/10 microliters) also increased the mean arterial blood pressure (mABP) and markedly lowered HR. It was further observed that, based on the effect of DBcAMP (25 micrograms/10 microliters), the pressor effect of four doses of TPA can be augmented. The results indicate that TPA in spinal cord may exert hypertensive effect via activation of PKC and tamoxifen may exert a hypotensive effect via inhibition of PKC. In addition, the pressor effect of TPA could be augmented by preadministration of DBcAMP.