To investigate the exon mutation of vitamin K-dependent gamma-glutamyl carboxylase (GGCX or VKDC) in patients with calcium oxalate urolithasis, renal cortex and peripheral blood samples were obtained from severe hydronephrosis patients (with or without calculi), and renal tumor patients undergoing nephrectomy. GGCX mutations in all 15 exons were examined in 44 patients with calcium oxalate urolithiasis (COU) by polymerase chain reaction (PCR) and denatured high pressure liquid chromatography (DHPLC), and confirmed by sequencing. Mutation was not found in all COU samples compared to the controls. These data demonstrated that functional GGCX mutations in all 15 exons do not occur in most COU patients. It was suggested that there may be no significant association between the low activity and mutation of GGCX in COU.

Atherosclerosis (As) is an important pathological basis of cardiovascular and cerebrovascular diseases. The pathogenesis studies of As have been a hot topic in the field of vascular biology research. The inflammation is known as a major participant in the development process of As. And monocyte-macrophage plays a central role in inflam-mation. In recent years, with the deepening research on inflammatory mechanisms, the As macrophage polarization is attracting researchers' attention. Under different environmental inductions, macrophages develop into M1 and M2 phenotypes. M1 macrophages (classical type), which can stimulate the secretion of pro-inflammatory cytokines, is generally considered as pro-inflammatory subtypes and can facilitate the progress of As. Whereas, M2 macrophages (alternative type), which can inhibit pro-inflammatory factor production, function as anti-inflammatory subtypes and likely to inhibit the progression of As. The mechanisms of As, macrophage polarization in As, and opportunities for herbal medicines will be summarized in this review.

OBJECTIVETo detect potential mutations of fibrillin-1 (FBN1) gene in a child with Marfan syndrome (MFS) and explore its molecular pathogenesis.

METHODSThe 66 exons of the FBN1 gene were analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the structural and functional changes at the protein level.

RESULTSA novel heterozygous mutation c.3998 G>A (p.Cys1333Tyr) was found in exon 32 in the child. The same mutation was not found among his unaffected family members and 683 healthy controls. Multiple sequence alignment showed that this novel mutation was located in a highly conserved region of the FBN1 protein across various species and may induce structural change to a functional domain.

CONCLUSIONThe novel c.3998G>A (p.Cys1333Tyr) mutation of the FBN1 gene probably predisposed the MFS in the child. Above finding has enriched the spectrum of FBN1 mutations.

Objective:To observe the imaging features of fundus lesions associated with COVID-19.Methods:A observational case series study. Twenty eyes of 10 patients with fundus lesions associated with COVID-19 at Xiamen Eye Center of Xiamen University from December 10, 2022 to January 20, 2023 were included in this study. There were 1 males and 9 females, aged from 17 to 49 years, with the median age of 26 years. The time of ocular symptoms after the diagnosis of COVID-19 was 0-2 days. The time from the onset of ocular symptoms to seeing a doctor was 1-14 days. All patients were examined by best-corrected visual acuity (BCVA), intraocular pressure, color fundus photography, infra-red fundus photography (IR), optical coherence tomography (OCT). Serum D-dimer examination was performed in 3 patients. The median BCVA was 0.4. There was no abnormalities in intraocular pressure and anterior segment examination. Among 20 eyes of 10 patients, there were 10 eyes of 5 patients with acute macular neuroretinopathy (AMN), 6 eyes of 3 patients with Purtscher-like retinopathy (PLR), 4 eyes of 2 patients with central retinal vein occlusion (CRVO). The imaging features of fundus were observed and analyzed.Results:Retinal lesions included AMN, paramacular central medial retinopathy (PAMM), PLR, cotton wool spots, hemorrhage, optic disc edema, macular edema. AMN was found in 10 eyes, with reddish-brown and wedge-shaped lesion in the fovea, dark area in IR and hyper reflectivity in outer nuclear layer and outer plexiform layer by OCT. The cotton wool spot showed hyper reflectivity on retinal nerve fiber layer whereas PAMM showed band-shape hyper reflectivity in inner nuclear layer by OCT. The Purtscher spot was seen at the posterior pole and/or peripapillary in 6 eyes of PLR. By OCT examination, the retinal nerve fiber layer corresponding to Purtscher flecken was significantly thickened and the reflex was enhanced. Among 6 eyes of PLR, there were 4 eyes combined with AMN, 1 eye with PAMM and macular edema. In 4 eyes of CRVO, vitreous cells, optic disc edema, retinal flame, spot hemorrhage, and atypical cotton wool spots were seen in 2 eyes.Conclusions:The manifestations of fundus lesions associated with COVID-19 are varied. The multilayer structure of retina is involved, and the microvessels of retina and choroidal capillary layer are damaged.

To investigate the exon mutation of vitamin K-dependent gamma-glutamyl carboxylase (GGCX or VKDC) in patients with calcium oxalate urolithasis, renal cortex and peripheral blood sam-ples were obtained from severe hydronephrosis patients (with or without calculi), and renal tumor pa-tients undergoing nephrectomy. GGCX mutations in all 15 exons were examined in 44 patients with calcium oxalate urolithiasis (COU) by polymerase chain reaction (PCR) and denatured high pressure liquid chromatography (DHPLC), and confirmed by sequencing. Mutation was not found in all COU samples compared to the controls. These data demonstrated that functional GGCX mutations in all 15 exons do not occur in most COU patients. It was suggested that there may be no significant association between the low activity and mutation of GGCX in COU.

ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L^-1）， Coptidis Rhizoma group（B group， 38.4 g·L^-1）， processed Euodiae Fructus group（C group， 5.88 g·L^-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L^-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC_0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（C_max） of Ber， Pal， Evo， and Rut were the highest and time to peak（t_max） were the lowest in the liver of A group. In plasma， the AUC_0-t and C_max of Evo and Rut were increased in A group compared with C group， t_max of Pea was elevated and its C_max was decreased in A group compared with D group. In the liver， compared with B-D groups， C_max values of 5 representative components except Pae were elevated， AUC_0-t of Pae was decreased and AUC_0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t_1/2） of each representative components in A group was elevated and t_max was decreased， and C_max of each representative ingredient except Pal was decreased， AUC_0-t values of Ber and Pal were increased， whereas the AUC_0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

OBJECTIVE: To detect mutations of fibrillin-1 (FBN1) gene in two pedigrees affected with Marfan syndrome (MFS). WETHODS: Peripheral blood samples were collected from MFS patients and their healthy family members for extracting genomic DNA. All of the 65 exons of the FBN1 gene were analyzed by next-generation sequencing. PolyPhen-2 and SIFT was used to predict structural and functional changes in FBN1 protein. RESULTS: Patients from both pedigrees presented ocular and skeletal manifestations suggestive of MFS. Two novel heterozygous mutations of the FBN1 gene, including c.1879C>T (p.R627C) in exon 16 and c.2584T>C (p.C862R) in exon 22, were identified. The same mutations were not found among unaffected members. By bioinformatic analysis, the mutations may affect the structure and function of the FBN1 protein. CONCLUSION The c.1879C>T and c.2584T>C mutations of the FBN1 gene probably account for the disease in the two pedigrees, respectively. Identification of the c.2584T>C has enriched the spectrum of FBN1 gene mutations.
DNA Mutational Analysis ; Exons ; Fibrillin-1 ; genetics ; Fibrillins ; Humans ; Marfan Syndrome ; genetics ; Mutation ; Pedigree

Humans ; Soft Tissue Neoplasms ; Mesenchymoma/diagnostic imaging* ; Paraneoplastic Syndromes/pathology*

Brain ; pathology ; China ; Humans ; Organ Preservation ; standards ; Tissue Banks ; ethics ; standards