[Clinical characteristics of "classical" and "non-classical" paraneoplastic neurological syndrome].

Objective: To explore the clinical features of classical and non-classical paraneoplastic neurological syndrome (PNS). Methods: From 2015 to 2020, 48 cases of definite PNS admitted to the First Affiliated Hospital of University of Science and Technology of China were retrospectively collected, and classification, clinical characteristics, onconeural antibodies and primary tumors were analyzed. The included cases were divided into classical and non-classical groups according to Graus criteria, and the differences of clinical characteristics, onconeural antibodies, combined tumors, time of diagnosis and mortality were compared between the two groups. Results: Among the 48 confirmed patients, 21 (43.8%) were positive for well-characterized onconeural antibodies. There were 28 cases (58.3%) and 20 cases (41.7%) in classic and non-classical PNS groups, respectively. No significant differences of age, sex, clinical involvement site, characteristic positive antibody type, tumor diagnosis rate and follow-up mortality were found between the two groups (all P>0.05). The time of diagnosis in the non-classical PNS group was 3.0 (2.0, 6.5) months, which was significantly longer than that in the classical PNS group 1.0(0.6, 3.0) months (P<0.05). Meanwhile, the combination rate of non-characteristic antibodies in the classical PNS group (10 cases, 35.7%) was significantly higher than that in the non-classical PNS group (1 case, 5.0%) (P=0.016). During the follow-up, 39 patients (81.3%) with tumor were confirmed, and 29 patients (60.4%) were diagnosed with PNS before the tumor was found. Conclusions: The"non-classical"PNSs are common in clinical settings. Diagnosis may be delayed due to the nonclassical symptoms of the patients. When patients have clinical symptoms related to PNS, onconeural antibodies should be detected and the relevant tumors should also be screened. Patients have positive antibodies but with no tumors should be closely followed up for more than 5 years.

Hypoxia is involved in hypoxic pulmonary hypertension through inhibiting the activation of FGF2 by miR-203.

OBJECTIVE: The aim of this study was to investigate whether hypoxia in vivo can induce hypoxic pulmonary hypertension by inhibiting the activation of FGF2 by miR-203. MATERIALS AND METHODS: We established a rat model of hypoxic pulmonary hypertension (HPH), and measured the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (right ventricular hypertrophy index). The ventricular hypertrophy index (RVHI) was calculated and HE staining of the lung tissue of HPH rats was performed. We extracted pulmonary arterial smooth muscle cells (PASMCs) from rats and identified them by immunofluorescence assay. The expression of miR-203 in hypoxic PASMCs was detected by quantitative Real time-polymerase chain reaction (qRT-PCR). The proliferation and migration of PASMCs were detected by EDU (5-Ethynyl-2'-deoxyuridine), cell counting kit-8 (CCK-8) and scratch assay, respectively. Dual Luciferase reporting assay and Western blot were used to detect the binding of miR-203 and FGF2. RESULTS: The results of qRT-PCR showed that miR-203 expression in rat PASMCs was significantly lower than that in normoxia control group at 24 h and 48 h after hypoxic treatment. EDU, CCK8 and scratch test results showed that proliferation and migration ability of PASMCs were weakened after overexpression of miR-203, and vice versa. Dual Luciferase reporter gene assays and Western blot experiments showed that miR-203 could target and combine with FGF2 to inhibit its expression. In vivo experiments showed that low expression of FGF2 could lead to decreased RVSP and RVHI, decreased FGF2 protein levels, and decreased WT% and (PM+FM)% in hypoxia-treated rats. CONCLUSIONS: Hypoxia in vivo is involved in the development of HPH by inhibiting the activation of FGF2 by miR-203. Meanwhile, specific inhibition of FGF2 can reduce hypoxia-induced pulmonary hypertension and improve pulmonary vascular remodeling.

Distribution of exogenous complement factor H in mice in vivo.

Factor H is an important regulator of complement activation in plasma and on cell surfaces in both humans and mice. If FH function is compromised, inappropriate complement activation on self-surfaces can have disastrous effects as seen in the kidney diseases atypical haemolytic uremic syndrome (aHUS) and C3 glomerulopathy. As FH constructs have been proposed to be used in treatment for these diseases, we studied the distribution of exogenous FH fragments in mice. Full-length mFH, mFH1-5 and mFH18-20 fragments were radiolabelled, and their distribution was examined in WT, FH-/- and FH-/- C3-/- mice in vivo. Whole body scintigraphy revealed accumulation of radioactivity in the abdominal part of the mice, but also to the thyroid gland and urinary bladder. At organ level in WT mice, some full-length FH accumulated in internal organs, but most of it remained in the circulation. Both of the mFH fragments accumulated in the kidneys and were excreted in urine. For mFH1-5, urinary secretion is the likely cause for the accumulation. Concentration of mFH18-20 to kidneys was slower, and at tissue level, mFH18-20 was localized at the proximal tubuli in WT and FH-/- C3-/- mice. No C3-independent binding to glomeruli was detected. In conclusion, these results show that glomerular glycosaminoglycans and sialic acids alone do not collect FH in kidneys. Deposition of C3 fragments is also needed, which implies that in aHUS, the problem is in simultaneous recognition of C3 fragments and glycosaminoglycans or sialic acids by FH, not just the inability of FH to recognize glomerular endothelium as such.

Genetic relationships analysis of olive cultivars grown in China.

The olive tree is an iconic tree of the Mediterranean, and is used extensively to produce high-quality olive oil. Although the China olive industry has just begun to be valued, there were also existed mislabeling and synonyms in introduced cultivars. The aim of this study was to analyze genetic similarities among olive cultivars in China using SSR and ISSR techniques. Thirty-two samples were collected from Xichang. Five of these cultivars were issued from a Chinese breeding program. Genomic DNA samples were extracted from young leaves and PCR was used to generate SSR and ISSR markers. A total of 107 polymorphic bands were detected on thirteen SSR loci, with an average of eight alleles per locus. The observed heterozygosity ranged from 0.785 (DCA03) to 0.990 (GAPU47), and the expected heterozygosity varied between 0.782 (DCA03) and 0.940 (GAPU103A). The discrimination power ranged from 0.57 to 0.83, while the polymorphism information content values ranged from 0.768 (DCA03) to 0.934 (GAPU103A). Nine ISSR primers generated 85 reproducible bands of which 78 (91.8%) were polymorphic. Based on our data, genetic similarity between cultivars ranged from 0.57 to 0.83. Cluster analysis revealed that 32 cultivars were clustered into six groups, which supports similar morphology such as use, oil content and fruit weight but not similar geographical origins. Our data also allow the identification of unknown cultivars and cases of synonyms.