A combination of risk stratification systems for thyroid nodules and cervical lymph nodes may improve the diagnosis and management of thyroid nodules.

Introduction: To assess the performance of the European Thyroid Association Thyroid Imaging and Reporting Data System (EU-TIRADS) and the Korean Thyroid Imaging Reporting and Data System (K-TIRADS), which combine risk stratification systems for thyroid nodules (TN-RSS) and cervical lymph nodes (LN-RSS) in diagnosing malignant and metastatic thyroid cancer in a single referral center. Methods: We retrospectively analyzed 2,055 consecutive patients who underwent thyroidectomy or fine-needle aspiration (FNA) from January 2021 to December 2022. TNs and LNs were categorized according to the ultrasonography (US) features of EU-TIRADS and K-TIRADS, respectively. The diagnostic performance and postponed malignancy rate (PMR) were compared with those of EU-TIRADS and K-TIRADS. PMR was defined as the number of patients with malignant nodules not recommended for biopsy among patients with cervical LN metastasis. Results: According to the EU-TIRADS and K-TIRADS, for TN-RSS alone, there were no significant differences in sensitivity, specificity, accuracy, unnecessary FNA rate (UFR), missed malignancy rate (MMR), and PMR between the two TIRADSs (29.0% vs. 28.8%, 50.5% vs. 51.1%, 32.3% vs. 32.2%, 23.6% vs. 23.5%, 88.6% vs. 88.5%, and 54.2% vs. 54.5%, P > 0.05 for all). Combining the LN-RSS increased the diagnostic accuracy (42.7% vs. 32.3% in EU-TIRADS; 38.8% vs. 32.2% in K-TIRADS) and decreased the PMR (54.2% vs. 33.9% in EU-TIRADS; 54.5% vs. 39.3% in K-TIRADS). EU-TIRADS had higher sensitivity and accuracy and lower PMR than K-TIRADS (41.3% vs. 36.7%, 42.7% vs. 38.8%,33.9% vs. 39.3%, P < 0.05 for all). Conclusions: A combination of TN-RSS and LN-RSS for the management of thyroid nodules may be associated with a reduction in PMR, with enhanced sensitivity and accuracy for thyroid cancers in EU-TIRADS and K-TIRADS. These results may offer a new direction for the detection of aggressive thyroid cancers.

Expanding the clinical spectrum of anti-DPPX encephalitis: a multicenter retrospective study.

Objective: Anti-dipeptidyl-peptidase-like protein-6 (DPPX) encephalitis is a rare autoimmune encephalitis, and clinical and experimental information regarding this disease is limited. We conducted this study to comprehensively describe the clinical characteristics, ancillary test results, neuroimaging results, and treatment response in a group of Chinese patients with anti-DPPX encephalitis for better understanding this disease. Methods: We recruited 14 patients who tested positive for anti-DPPX antibodies in the serum and/or cerebrospinal fluid from 11 medical centers between March 2021 and June 2023. This retrospective study evaluated data on symptoms, autoantibody test, auxiliary examinations, treatments, and outcomes. Results: The average age at diagnosis was 45.93 ± 4.62 years (range: 11-72 years), and 9 of the 14 patients were males. The main symptoms included cognitive impairment (50.0%, 7/14), central nervous system hyperexcitability (42.9%, 6/14), gastrointestinal dysfunction (35.7%, 5/14), and psychiatric disorders (35.7%, 5/14). Notably, we discovered specific findings on 18F-fluorodeoxyglucose positron-emission tomography (PET)/magnetic resonance imaging in two patients. Co-existing autoantibodies were identified in two patients. Parainfection was identified in four patients. One patient had other autoimmune diseases, and one had tumor. Eleven patients received immunotherapy and most patients improved at discharge. Surprisingly, three male patients but no female patients relapsed during the 6 months of follow-up. Conclusion: The development and outcome of anti-DPPX encephalitis are variable. Male patients were predominant in our cohort. The most common symptoms were the classical triad of prodromal gastrointestinal dysfunction, cognitive and mental disorders, and central nervous system hyperexcitability. Infections, immune dysregulation, and tumors may be important etiologies. Long-term monitoring of disease development should be done in male patients. Overall, our results highlight novel clinical characteristics of anti-DPPX encephalitis.

Fibroblast growth factor-21 alleviates proteasome injury via activation of autophagy flux in Parkinson's disease.

Parkinson's disease (PD) is one of the most common and complex Neurodegeneration, with an inherited metabolic disorder. Fibroblast growth factor 21 (FGF21), an endocrine hormone that belongs to the fibroblast growth factor superfamily, plays an extensive role in metabolic regulation. However, our understandings of the specific function and mechanisms of FGF21 on PD are still quite limited. Here, we aimed to elucidate the actions and the underlying mechanisms of FGF21 on dopaminergic neurodegeneration using cellular models of parkinsonism. To investigate the effects of FGF21 on dopaminergic neurodegeneration in vitro, proteasome impairment models of PD were utilized. Human dopaminergic neuroblastoma SH-SY5Y cells were treated with the proteasome inhibitor lactacystin (5 µmol/L) for 12 h, then with 50 ng/ml FGF-21 with or without 5 mmol/L of 3-methyladenine.The cells were dissected to assess alterations in autophagy using immunofluorescence, immunoblotting and electron microscopy assays. Our data indicate that FGF21 prevents dopaminergic neuron loss and shows beneficial effects against proteasome impairment induced PD syndrome, indicating it might be a potent candidate for developing novel drugs to deal with PD.

The clinical characteristics of neuronal intranuclear inclusion disease and its relation with inflammation.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a great imitator with a broad spectrum of clinical manifestations that include dementia, parkinsonism, paroxysmal symptoms, peripheral neuropathy, and autonomic dysfunction. Hence, it may also masquerade as other diseases such as Alzheimer's disease, Parkinson's disease, and Charcot-Marie-Tooth disease. Recent breakthroughs on neuroimaging, skin biopsy, and genetic testing have facilitated the diagnosis. However, early identification and effective treatment are still difficult in cases of NIID. OBJECTIVE: To further study the clinical characteristics of NIID and investigate the relationship between NIID and inflammation. METHODS: We systematically evaluated the clinical symptoms, signs, MRI and electromyographical findings, and pathological characteristics of 20 NIID patients with abnormal GGC repeats in the NOTCH2NLC gene. Some inflammatory factors in the patients were also studied. RESULTS: Paroxysmal symptoms such as paroxysmal encephalopathy, stroke-like episodes, and mitochondrial encephalomyopathy lactic acidosis and stroke (MELAS)-like episode were the most common phenotypes. Other symptoms such as cognitive dysfunction, neurogenic bladder, tremor, and vision disorders were also suggestive of NIID. Interestingly, not all patients showed apparent diffusion-weighted imaging (DWI) abnormality or intranuclear inclusions, while abnormal GGC repeats of NOTCH2NLC were seen in all patients. And fevers were noticed in some patients during encephalitic episodes, usually with increasing leukocyte counts and neutrophil ratios. Both IL-6 (p = 0.019) and TNF-α (p = 0.027) levels were significantly higher in the NIID group than in normal controls. CONCLUSION: Genetic testing of NOTCH2NLC may be the best choice in the diagnosis of NIID. Inflammation might be involved in the pathogenesis of NIID.

miR-30b protects nigrostriatal dopaminergic neurons from MPP(+)-induced neurotoxicity via SNCA.

OBJECTIVE: To explore the function of miR-30b in pathogenesis of Parkinson's disease (PD) and its underlying molecular mechanism. MATERIALS AND METHODS: We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP(+)) as a tool for constructing the PD cell model, using miR-30b mimics or inhibitors to manipulate miR-30b level for an experimental model of acquisition. The cell viability of SH-SY5Y was detected by CCK, and luciferase was used to screen the binding of target genes. The protein levels of SNCA were measured by Western blot. Then, we investigate the changes in pro- and anti-apoptotic markers with or without miR-30b treatment. RESULTS: There was a significant low expression of MiR-30b in MPP(+)-induced cells. SH-SY5Y cell viability was rescued by MiR-30b overexpression. Luciferase experiments showed that MiR-30b may bind to the 3'-UTR side of SNCA and inhibited its expression. By Western blot, the SNCA level was markedly decreased by miR-30b. miR-30b attenuated the upregulation of Bax and the depletion of Bcl-2 induced by MPP(+).

Genetic testing of FUS, HTRA2, and TENM4 genes in Chinese patients with essential tremor.

INTRODUCTION: Essential tremor (ET) is one of the most prevalent movement disorders. The genetic etiology of ET has not been well defined although a significant proportion (≥50%) are familial cases. Linkage analysis and genome-wide association studies (GWASs) have identified several risk variants. In recent years, whole-exome sequencing of ET has revealed several specific causal variants in FUS (p.Q290X), HTRA2 (p.G399S), and TENM4 (c.4324 G>A, c.4100C>A, and c.3412G>A) genes. OBJECTIVE: To investigate the genetic contribution of these three genes to ET, the protein-coding sequences of FUS, HTRA2, and TENM4 were analyzed in a total of 238 ET patients and 272 controls from eastern China using direct Sanger sequencing. RESULTS: We identified two synonymous coding single nucleotide polymorphisms (SNPs), rs741810 and rs1052352 in FUS, and three previously reported synonymous SNPs, rs11237621, rs689369, and rs2277277 in TENM4. No nonsynonymous exonic variants were identified in these subjects. We found that the frequency of the rs1052352C allele was significantly higher (P = .001) in the ET group than in the control group. CONCLUSION: Overall, our findings suggest that rs1052352 of FUS might contribute to ET risk in Chinese population.