Optical coherence tomography in patients with Wilson's disease.

BACKGROUND: Morphological changes of retina in patients with Wilson's disease (WD) can be found by optical coherence tomography (OCT), and such changes had significant differences between neurological forms (NWD) and hepatic forms (HWD) of WD. The aim of this study was to evaluate the relationship between morphological parameters of retina and brain magnetic resonance imaging (MRI) lesions, course of disease, type of disease, and sexuality in WD. METHODS: A total of 46 WD patients and 40 health controls (HC) were recruited in this study. A total of 42 WD patients were divided into different groups according to clinical manifestations, course of disease, sexuality, and brain MRI lesions. We employed the Global Assessment Scale to assess neurological severity of WD patients. All WD patients and HC underwent retinal OCT to assess the thickness of inner limiting membrane (ILM) layer to retinal pigment epithelium layer and inner retina layer (ILM to inner plexiform layer, ILM-IPL). RESULTS: Compared to HWD, NWD had thinner superior parafovea zone (108.07 ± 6.89 vs. 114.40 ± 5.54 µm, p < .01), temporal parafovea zone (97.17 ± 6.65 vs. 103.60 ± 4.53 µm, p < .01), inferior parafovea zone (108.114 ± 7.65 vs. 114.93 ± 5.84 µm, p < .01), and nasal parafovea zone (105.53 ± 8.01 vs. 112.10 ± 5.44 µm, p < .01) in inner retina layer. Course of disease influenced the retina thickness. Male patients had thinner inner retina layer compared to female patients. CONCLUSION: Our results demonstrated that WD had thinner inner retina layer compared to HC, and NWD had thinner inner retina layer compared to HWD. We speculated the thickness of inner retina layer may be a potential useful biomarker for NWD.

Analysis of risk factors for neurological symptoms in patients with purely hepatic Wilson's disease at diagnosis.

OBJECTIVE: To analyze and explore the risk factors for neurological symptoms in patients with purely hepatic Wilson's disease (WD) at diagnosis. METHODS: This retrospective study was conducted at the First Affiliated Hospital of the Guangdong Pharmaceutical University on 68 patients with purely hepatic WD aged 20.6 ± 7.2 years. The physical examinations, laboratory tests, color Doppler ultrasound of the liver and spleen, and magnetic resonance imaging (MRI) of the brain were performed. RESULTS: The elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels and 24-h urinary copper level were higher in the purely hepatic WD who developed neurological symptoms (NH-WD) group than those in the purely hepatic WD (H-WD) group. Adherence to low-copper diet, and daily oral doses of penicillamine (PCA) and zinc gluconate (ZG) were lower in the NH-WD group than those in the H-WD group. Logistic regression analysis showed that insufficient doses of PCA and ZG were associated with the development of neurological symptoms in patients with purely hepatic WD at diagnosis. CONCLUSION: The development of neurological symptoms in patients with purely hepatic WD was closely associated with insufficient doses of PCA and ZG, and the inferior efficacy of copper-chelating agents. During the course of anti-copper treatment, the patient's medical status and the efficacy of copper excretion should be closely monitored.

Linear structural features of Wilson's disease and its correlation with neurological symptoms.

To measure the linear structure of the brain in patients with Wilson's disease (WD) and analyze its correlation with neurological symptoms. A total of 174 patients diagnosed with WD were enrolled. According to the type of clinical presentation, the patients with WD were divided into two groups: neurological (NWD) and hepatic (HWD). Sixty healthy volunteers were assigned to a control group. All patients with WD and healthy controls underwent brain magnetic resonance imaging (MRI). The severity of the neurological symptoms was assessed using the Burke Fahn Marsden Movement subscale (BFM-M). Linear brain measurements were performed using T1-weighted MRI scans of all the patients, and the correlation between these linear indices and BFM-M score was investigated. The Huckman index, third ventricle width, and sulcus width of the NWD group were significantly higher than those of the HWD and control groups (P < .05). The frontal horn index, ventricular index, and lateral ventricular body width index of the NWD group were significantly lower than those of the HWD and control groups (P < .05). The Huckman index and third ventricle width of the HWD group were higher than those of the control group (P < .05), whereas the body width index of the lateral ventricle was lower than that of the control group (P < .05). The BFM-M score correlated with the Huckman index (r = 0.29, P < .05), third ventricle width (r = 0.426, P < .001), and lateral ventricular body width index (r = -0.19, P < .05). This study demonstrated significant changes in the linear structure of patients with WD. Linear brain measurement analysis could be used as a potential method to assess the severity of neurological symptoms in WD.

Maternal Ureaplasma exposure during pregnancy and the risk of preterm birth and BPD: a meta-analysis.

PURPOSE: Perinatal Ureaplasma infection is associated with a variety of adverse outcomes and neonatal diseases. This meta-analysis is to evaluate current evidence evaluating the association between Ureaplasma and adverse pregnancy outcomes and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: We searched for published articles on Ureaplasma, preterm and BPD in PubMed, the Cochrane Library, and Embase databases posted before August 28, 2021. In addition, the references of these articles were screened. A random/fixed-effect model was used to synthesize predefined outcomes. RESULTS: A total of 19 cohort studies involving 11,990 pregnancy women met our inclusion criteria. Pregnancy Ureaplasma positive increased the risk of preterm birth [odds ratios (OR) 2.76, 95% confidence intervals (CI) 1.63-4.68], BPD (OR 2.39 95% CI 1.73-3.30), chorioamnionitis (OR 2.71, 95% CI 2.02-3.64) and premature rupture of membranes (PROM, OR 2.19, 95% CI 1.34-3.58). CONCLUSIONS: Pregnancy Ureaplasma positive may increase the risk of developing preterm birth, chorioamnionitis, PROM and BPD in the preterm infant. The evidence base is, however, of low quality and well-designed studies are needed.

[Stem cells for the treatment of Peyronie's disease].

Peyronie's disease (PD) is a connective tissue disorder characterized as fibrotic plaque localized in the tunica albuginea (TA), and its pathomechanism remains obscure. Endeavors are being made to explore effective and minimally invasive therapeutic strategies for PD, and some experimental studies have verified the preventative and therapeutic effects of stem cells (SC), especially adipose tissue-derived SCs (ADSC), on this disease and excavated some of their action mechanisms. Some scholars attempted the integration of SCs with graft tissues, aiming at the improvement of TA grafting and reconstruction. The only publicly available clinical trial of SC therapy for PD was encouraging, and further on-coming relevant researches are expected with simultaneous optimization of the scheme. In a word, the application of SCs in the prevention and treatment of PD is a promising topic for clinical research, and there remain quite a lot of unknowns to be explored. This article summarizes the existing researches in this field.

Ureteral polyps protruding from the urethra.

BACKGROUND: Ureteral fibro-epithelial polyp (UFP) is a rare benign ureteral tumor, and surgical removal of the polyps is still the preferred solution. Although many cases have reported polyps extending to the bladder, our case was the first to report a huge UFP that underwent endoscopic laser resection to highlight the urethra and cause severe end hematuria permanently. CASE PRESENTATION: In 2019, a 37-year-old woman came to the hospital because of hematuria and a dark red extraurethral mass. CTU inspection showed: filling defect between the right ureter and the bladder at the entrance of the bladder. After ureteroscopy, it was found that the ureteral mass came out of the urethral orifice. Then, under the direct view of the ureteroscope, a Ho:YAG laser was used to remove the tumor by cutting off along the its base, and the patient was discharged 3 days after the operation. CONCLUSION: Urethral polyps from the ureter should be considered in the differential diagnosis of urethral neoplasms. Ho:YAG laser resection under ureteroscopy is an effective option for treating UFP, but be careful of ureteral stricture after surgery.

[Predictive factors for clinically significant elevation of post-prostatectomy Gleason score in patients with biopsy Gleason score ≤7].

OBJECTIVE: To investigate the prognostic factors for clinically significant increase in post-prostatectomy Gleason score (pGS) in patients with biopsy Gleason score (bGS) ≤7. METHODS: This retrospective study included 170 cases of prostate cancer treated by radical prostatectomy in our hospital from January 2010 to December 2017. We analyzed the clinical and pathological data on the patients, including the age, preoperative serum tPSA, fPSA, fPSA / tPSA, prostate volume, PSA density (PSAD), and positive puncture rate of the patients with clinically significant elevation of pGS, as well as the possible factors for clinically significant pGS increase in patients with bGS = 7 and those with bGS ≤ 6. RESULTS: The pGS was found consistent with the bGS in 95 (55.9%) of the 170 patients, decreased in 11 (6.5%) and increased in 64 (37.6%). Among those with elevated pGS, 55 (32.4%) were shown with and the other 9 (5.3%) without clinical significance. Clinically significant escalation of pGS was markedly correlated with the positive puncture rate in the patients with bGS = 7 (P = 0.021) and with the age (P = 0.018) and PSAD (P = 0.033) of those with bGS ≤ 6. ROC curve analysis further showed the positive puncture rate > 0.528 in the patients with bGS = 7 and a higher risk of clinically significant pGS increase in those aged > 64.5 years with bGS ≤ 6 and PSAD > 0.267 µg/(L·g). CONCLUSIONS: Clinically significant elevation of pGS is correlated with the rate of positive punctures in prostate cancer patients with bGS = 7 and with age and PSAD in those with bGS ≤ 6.

Quality control of Lycium chinense and Lycium barbarum cortex (Digupi) by HPLC using kukoamines as markers.

BACKGROUND: Lycii Cortex (LyC), composed of Lycium chinense and Lycium barbarum cortex and having the Chinese name Digupi, is used to treat chronic diseases like cough, hypertension, and diabetes in Eastern Asia. However, chromatographic methods, such as TLC and HPLC, to determine the phytochemical composition of LyC have not been included in any official compendiums. This study aims to establish a validated HPLC method for quality control of LyC. METHODS: Kukoamines A and B (KA and KB, respectively) were selected as markers for the HPLC method. An acetic acid solution was adopted for sample extraction because it facilitated the release of kukoamines and effectively prevented their degradation. Optimal separation of the kukoamine isomers was achieved on hydrophilic ligand-coated C18 columns with a gradient elution of acetonitrile and 0.1% (v/v) trifluoroacetic acid. The average contents and proposed contents for LyC were calculated with a t test and an uncertainty test based on 16 batches of authentic samples. RESULTS: The method was validated with linearity (r2 = 0.9999 for both KA and KB), precision (RSD = 1.29% for KA and 0.57% for KB), repeatability (RSD = 1.81% for KA and 0.92% for KB), and accuracy (recovery of 90.03-102.30% for KA, and 98.49-101.67% for KB), indicating that the method could offer reliable results for quality control analysis of LyC. At the 95% confidence level, the calculated content limits were 1.45 mg/g for KA and 4.72 mg/g for KB. CONCLUSION: Compared with conventional morphological identification, the HPLC method involving KA and KB contents offers precise, objective, and quantitative results for quality control of LyC.

miRNA-30a functions as a tumor suppressor by downregulating cyclin E2 expression in castration-resistant prostate cancer.

MicroRNAs (miRNAs) act as tumor promoters or tumor suppressors in different human malignancies. In the current study, using an Agilent miRNA microarray, miR­30a was found to be a significantly downregulated miRNA in castration­resistant prostate cancer (CRPC) tissues, compared with androgen­dependent prostate cancer tissues. Aberrant expression of cyclin E2 (CCNE2) has been reported in a variety of types of cancer including prostate cancer, and correlates with clinical outcome. The purpose of the current study was to determine the functions of miR­30a in CRPC cell lines and identify whether CCNE2 was regulated by miR­30a. To analyze the associations between miR­30a and CCNE2 expression levels, pathological specimens were collected, and reverse transcription­quantitative polymerase chain reaction and immunohistochemical staining were conducted. The effect of miR­30a overexpression on CRPC cell lines and the predicted target gene, CCNE2, were evaluated by MTT assay, flow cytometry, tumor formation, luciferase reporter assay and western blotting. miR­30a overexpression resulted in a significant suppression of cell growth in vitro, and reduced tumorigenicity in vivo. miR­30a repressed the expression of CCNE2 through binding to its 3'­untranslated region. CCNE2 was observed to be overexpressed in patients with CRCP and had an approximately inverse correlation with the level of miR­30a. The results suggest that miR­30a may function as a novel tumor suppressor in CRPC. Its anti­oncogenic activity may occur by the reduced expression of a distinct cell cycle protein, CCNE2.

Identification and Characterization of Kukoamine Metabolites by Multiple Ion Monitoring Triggered Enhanced Product Ion Scan Method with a Triple-Quadruple Linear Ion Trap Mass Spectrometer.

Kukoamines are a series of bioactive phytochemicals conjugated by a polyamine backbone and phenolic moieties. Understanding the structural diversity of kukoamine metabolites in plants is meaningful for drug discovery. In this study, an LC-MS/MS method was established for kukoamine profiling and characterization from lycii cortex (LyC) via a triple-quadrupole linear ion trap mass spectrometry (Q-TRAP). On the basis of the typical fragmentation of kukoamine, a diagnostic ion, which represents the features of the backbone and phenolic substitute, was chosen as the product ion for precursor ion scan, and then the screened precursor ions were applied to a successive multiple ion monitoring triggered enhanced product ion scan (MIM-EPI) to simultaneously present the profile survey and MS/MS acquisition. Because the MIM narrowed the ion scan range in Q1 and the ion trap enhanced the ion fragments passing through Q2, the qualitative capability of quadrupole MS can be greatly improved, especially for capture of the uncommon metabolites. There are 12 kukoamine metabolites identified from LyC, with either spermine or spermidine backbone and with conjugation of one to three dihydrocaffeoyls or other kinds of phenolic moieties. Except for kukoamines A and B, other metabolites were identified in LyC for the first time. This approach can be utilized for metabolite identification in other substrates.

Sensitivity improvement of kukoamine determination by complexation with dihydrogen phosphate anions in capillary zone electrophoresis.

A novel complexation between kukoamines and dihydrogen phosphate ions (DPI) during CZE was discovered to improve the UV signal of kukoamine by around 30-fold. This complexation formed by electric current was attributed to the hydrogen bonding of hydroxyl and amino (or amide) groups between the analyte and electrolyte anions. The established CZE method is low-cost, easy to operate, and eco-friendly, and it was shown to be superior to HPLC in terms of separation capability, efficiency, specificity, and sensitivity. We believe that our CZE method can be applied as an alternative to HPLC for kukoamine assay. The approach described here can be also extended for analyzing other compounds with similar functional groups.

Phytochemical profiles, antioxidant activities of functional herb Abrus cantoniensis and Abrus mollis.

It has been claimed that consumptions of Abrus cantoniensis (AC) and Abrus mollis (AM) as folk beverages and soups are good to cleanse liver toxicants and prevent liver diseases. There is scant information on the phytochemical profiles and antioxidant activities of these two varieties. Five major phytochemicals in these two cultivars were qualitatively and quantitatively compared using UPLC-PDA. A high level of total phenolic content (TPC) and total flavonoid content (TFC) was found in AC and AM. AC, in general, showed some antioxidant activities comparable to that of BHT, and stronger radical scavenging activities and higher reducing power than that of AM (p<0.05). When principal component analysis (PCA) was applied, high correlation between TPC, TFC and their antioxidant activities was found. Hence, this study proved that, both AC and AM could serve as antioxidant-rich component in foods or beverages to promote health function.

Identification and characterization of a novel splice-site mutation in the Wilson disease gene.

This study aimed to identify aberrant transcripts of the new splice-site mutation c.3244-2A>C in the Wilson disease (WD) gene (ATPase, Cu++ transporting, beta polypeptide, ATP7B) and discuss its genotype and clinical phenotype. DNA and RNA were extracted from peripheral blood lymphocytes, amplified by polymerase chain reaction (PCR) and nested reverse transcription PCR (RT-nested PCR) to characterize the aberrant transcripts. RT-nested PCR product sequencing comparison showed that c.3244-2A>C splice-site mutation caused aberrant transcripts and formatted a new splice acceptor. Patient carrying the splice-site mutation c.3244-2A>C presented early onset age, severe clinical manifestations, and poor prognosis. WD patients with the splice-site mutation show severe clinical manifestations, indicating that aberrant transcripts have important implications for WD phenotype.

Mutation analysis of 73 southern Chinese Wilson's disease patients: identification of 10 novel mutations and its clinical correlation.

This study was designed to investigate the molecular basis and the correlation between genotype and phenotype in the southern Chinese patients with Wilson's disease (WD). Genotypes of the ATP7B gene in 73 WD patients were examined by denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing. A total of 38 different disease-causing mutations were identified, including 10 novel mutations: missense mutations (p.Gln707Arg, p.Cys1079Phe, p.Gly1149Glu, p.Ser855Tyr, p.Ala874Pro and p.Ser921Arg), nonsense mutation (p.Arg1228Stop), splice-site mutations (2121+3A>T and 3244-2A>G) and frameshift mutation (1875_1876insAATT). We found that a pair of siblings carried the same genotype but different clinical type, and two patients were found to have three mutations. In addition, we compared the clinical data for p.Arg778Leu homozygotes and compound heterozygotes. Our research has enriched the mutation spectrum of the ATP7B gene in the Chinese population and can serve as the basis for genetic counseling and clinical/prenatal diagnosis to prevent WD in China.

Super-high-dose methylprednisolone does not improve efficacy or induce glucocorticoid resistance in experimental allergic encephalomyelitis.

OBJECTIVE: To investigate whether a super-high dose (SHD) of methylprednisolone (MP) improves its efficacy or induces glucocorticoid (GC) resistance, and to explore the potential mechanisms of GC resistance in experimental allergic encephalomyelitis (EAE). METHODS: The therapeutic effects of SHD and low-dose MP were evaluated in EAE by analyzing clinical scores, pathological changes and cytokine production. Immunohistochemistry and RT-PCR were used to investigate the expression of GC receptor (GR) isoforms and splicing factor SRp30c. RESULTS: Both MP doses had similar therapeutic effects. The ratio of GRα to GRß was positively correlated with clinical score changes. However, there was no difference in the GRα/GRß ratio between SHD and low-dose MP groups. SRp30c mRNA was correlated with GRß expression. CONCLUSION: This study indicates that the GRα/GRß ratio is associated with GC sensitivity, and SRp30c may play an important role in promoting alternative splicing of GR pre-mRNA to generate GRß in EAE rats. Compared with low-dose MP, SHD MP does not improve efficacy or induce GC resistance.