[Update on B cell depletion therapy for demyelinating optic neuritis with disease-specific antibody].

Demyelinating optic neuritis coexisting with seropositive aquaporin-4 antibody or myelin oligodendrocyte glycoprotein antibody is different from the typical optic neuritis in immunopathological, clinical and radiological features, as well as therapeutic response. Due to the high recurrence rate and the potential risk of blindness, immunosuppressive therapy is warranted in most cases. The current review tracks and summarizes both the update and the potential controversies of B cell depletion therapy with a special focus on rituximab for demyelinating optic neuritis to optimize clinical decision-making.

[Normocalcemic with elevated post-operative parathormone in primary hyperpara-thyroidism: 9 case reports and literature review].

OBJECTIVE: To summarize and analyze the clinical characteristics of primary hyperpara-thyroidism (PHPT) with normocalcemic parathormone elevation (NPE) after surgical treatment, so as to improve the therapeutic ability and standardized post-operative follow-up of PHPT patients. METHODS: Nine patients who were diagnosed with PHPT in the Department of Endocrinology of China-Japan Friendship Hospital from August 2017 to November 2019 were selected as the subjects. They all developed NPE within 6 months after surgical treatment. The clinical features and outcomes were collected and analyzed retrospectively, in addition, the related literature was reviewed. RESULTS: Clinical features: among the 9 patients, 6 were middle-aged and elderly females and 3 were male. The main clinical manifestations were bone pain, kidney stones, nausea and fatigue except for one case of asymptomatic PHPT. Pre-operative examination showed high serum calcium [(3.33±0.48) mmol/L], low serum phosphorus [0.76 (0.74, 0.78) mmol/L], high 24-hour urinary calcium [8.1(7.8, 12.0) mmol/24 h], obviously elevated intact PTH [(546.1±257.7) ng/L], vitamin D deficiency [25-hydroxyvitamin D3 (21.0±5.7) nmol/L]. Serum levels of bone alkaline phosphatase [7 patients 41.3(38.6, 68.4) µg/L, 2 patients >90 µg/L] and N-terminal midcourse osteocalcin (>71.4 µg/L) were significantly elevated. The estimated glomerular filtration rate decreased in 2 patients. Imaging examination: 7 patients had osteoporosis. Renal calculi were found in 3 patients by renal ultrasound. Imaging examination of parathyroid glands found definite lesions in all the patients, including 2 cases of multiple lesions and 7 cases of single lesions. TREATMENT AND OUTCOME: two patients underwent parathyroidectomy, while other patients were treated with microwave thermal ablation. PTH increased 1 month after therapy [(255.0±101.4) ng/L], and no recurrent lesions were found by parathyroid ultrasound. After combined treatment with cal-cium and vitamin D for six months, PTH decreased significantly and the level of serum calcium remained normal at anytime during the follow-up period. CONCLUSION: The occurrence of postoperative NPE may be related to the higher pre-operative PTH, vitamin D deficiency and lower creatinine clearance. However, NPE may not predict recurrent hyperthyroidism or incomplete parathyroidectomy. Adequate calcium and vitamin D supplementation after surgery seems to be beneficial for patients with NPE. Post-operative follow-up of PHPT patients should be standardized to prevent and treat post-operative NPE.

Distribution of immunoglobulin G subclasses of anti-thyroid peroxidase antibody in sera from patients with Hashimoto's thyroiditis with different thyroid functional status.

The mechanism of disease progression in Hashimoto's thyroiditis (HT) is still unclear. Anti-thyroid peroxidase antibody (TPOAb), a diagnostic hallmark of HT, is principally of the immunoglobulin G (IgG) isotype, and it appears to be a response to thyroid injury. The aim of our study was to evaluate the distribution of IgG subclasses of TPOAb in sera from patients with HT with different thyroid functional status. Sera from 168 patients with newly diagnosed HT were collected and divided into three groups according to thyroid function: patients with hypothyroidism (n = 66), subclinical hypothyroidism (n = 60) and euthyroidism (n = 42). Antigen-specific enzyme-linked immunosorbent assay was used to detect the distribution of TPOAb IgG subclasses. The prevalence of TPOAb IgG subclasses in all patients' sera with HT was IgG1 70.2%, IgG2 35.1%, IgG3 19.6% and IgG4 66.1% respectively. The prevalence of IgG2 in sera from patients with hypothyroidism (51.5%) was significantly higher than that of subclinical hypothyroidism (33.3%) (P < 0.05), and the latter was also significantly higher than that of euthyroidism (11.9%) (P < 0.05). The positive percentage of IgG2 subclass in sera from patients with hypothyroidism and subclinical hypothyroidism was significantly higher than that of euthyroidism (P < 0.05), the prevalence and positive percentage of IgG4 subclass in sera from patients with hypothyroidism and subclinical hypothyroidism was significantly higher than that of euthyroidism respectively (P < 0.05). The predominant TPOAb IgG subclasses in sera from patients with HT were IgG1 and IgG4. Patients with high levels of TPOAb IgG2, IgG4 subclasses might be at high risk of developing overt hypothyroidism.

Changes of biophysical behavior of k562 cells for p16 gene transfer.

p16 gene was transferred into human erythroleukemia cell line K562 that had been subjected to p16 deletion. The changes of biophysical behavior of K562 cells after gene transfer were studied with the micropipette technique. The micropipette data were analyzed with a standard solid viscoelastic model. In comparison to untransfected control K562 cells and the cells transfected with an empty vector, the p16-transfected K562 cells showed an increase in the elastic element K(1), which is inversely proportional to the maximum deformation over a long period of time, whereas the viscous element mu and the other elastic element K(2) showed no significant difference. The results indicate that K562 cells became more rigid after p16 transfer. The p16-transfected K562 cells also had a higher surface charge density. This study contributes to our knowledge about the suppression effect of p16 gene on tumor cell migration and about its use in gene therapy.

Effects of fluvastatin on structure and function of resistant vessels in spontaneously hypertensive rats.

AIM: To evaluate the effects of fluvastatin, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor, on the alterations of structure and function of resistant vessels in spontaneously hypertensive rats (SHR). METHODS: Eight-week-old male SHR were given fluvastatin 20 mg.kg-1.d-1 by gavage. Rats were decapitated at 16 wk. Wall-to-lumen area ratios (W/L) of thoracic aorta and mesenteric arteries (3rd grade branch) were assessed by morphometric assay. The effects of fluvastatin on vascular reactivity to sodium nitroprusside (SNP) and norepinephrine (NE), were studied with rings of thoracic aorta and mesenteric arteries isolated from rats. RESULTS: After 8 wk of treatment, histological examination showed that the wall-to-lumen area ratio was lower in SHRflu than that in SHR (0.44 +/- 0.09 vs 0.79 +/- 0.09, P < 0.05). EC50 of vasodilation response was much lower in SHRflu than that in SHR [(4.9 vs 190) pmol.L-1, P < 0.05], while EC50 of mesenteric artery rings from SHRflu was somewhat lower than that of SHR [(0.02 vs 0.04) nmol.L-1, P > 0.05]. In both aortic and mesenteric artery rings, EC50 of vasoconstriction in response to NE from SHRflu was higher than that of SHR [thoracic aorta: (0.20 vs 0.02) nmol.L-1, P < 0.05; mesentric arteries: (1.46 vs 0.72) nmol.L-1, P < 0.05]. CONCLUSION: Short-term treatment with fluvastatin ameliorated the vasomotoricity of resistant vessels, enhanced the sensitivity to vasodilator and depressed the sensitivity to vasoconstrictor; fluvastatin also attenuated the resistant vascular hypertrophy during the development of hypertension in SHR.

Sympatholytic effect of captopril in regression of cardiovascular remodeling in spontaneously hypertensive rats.

Fifty-eight spontaneously hypertensive rats (SHR) at 12 wk of age were divided into 3 groups: A) captopril (Cap) 20 mg.kg-1.d-1; B) clonidine (Clo) 30 micrograms.kg-1.d-1; C) Clo 30 micrograms.kg-1.d-1 + Cap 20 mg.kg-1.d-1 orally for 24 wk. Concomitant administration of Cap and Clo did not result in more lowering of the systolic blood pressure (SBP) than that by Cap alone. Regression of left ventricular hypertrophy (LVH) were remarkable in Groups A and C, but not to the extent in that of WKY. No significant difference between these two groups was found. Cap alone resulted in a greater decrease of myocardial norepinephrine (NE) than that of Groups B and C. The wall/lumen ratio and the number of smooth muscle cell (SMC) layers of renal artery decreased in Groups A and C, but little difference was found between them. It seemed that combined blockade of renin-angiotensin-aldosterone (RAA) system and sympathetic nervous system (SNS) did not produce more significant BP reduction and reversal of cardiovascular remodeling than Cap alone did. The sympathetic inhibitory effect of angiotensin converting enzyme inhibitor (ACEI) was not enhanced by sympatholytic treatment.