Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ² test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.
Ceruloplasmin/metabolism* ; Child ; Child, Preschool ; Copper/metabolism* ; Copper-Transporting ATPases/genetics* ; Female ; Hepatolenticular Degeneration/genetics* ; Humans ; Male ; Mutation ; Phenotype ; Retrospective Studies

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

BACKGROUND: Catheter ablation is effective in restoring sinus rhythm and left atrial appendage closure (LAAC) is increasingly used for stroke prevention in patients with atrial fibrillation (AF). We aimed to observe the feasibility and safety of performing AF ablation and LAAC in a single (one-stop) procedure. METHODS: Consecutive AF patients who underwent the combined procedure of AF ablation and LAAC with WATCHMAN device between March 2017 and September 2018 were prospectively enrolled. Baseline and intra-procedural parameters were evaluated. Three-month and subsequent 1-year follow-up were performed in all and earlier-enrolled subjects, respectively. RESULTS: A total of 178 AF patients (94 males, 68.9 ± 8.1 years) underwent the one-stop procedure with CHA2DS2-VASc score 3.3 ± 1.5 and HAS-BLED score 1.6 ± 1.0, respectively. Pulmonary vein isolation was achieved in all patients while additional linear ablation was applied if the operator deemed necessary, yielding immediate ablation success rate of 98.9% (176/178). In the subsequent LAAC, satisfactory seal (residual leak <5 mm) was achieved in all patients. One stroke and four cardiac perforations occurred peri-operatively. At 3-month follow-up, sinus rhythm and satisfactory seal were maintained in 153/178 (86.0%) and 178/178 (100%) patients, respectively. One stroke and one delayed cardiac tamponade occurred, while no device-related thrombus or device migration was observed. During the 1-year follow-up for the earlier enrolled subjects, 52/72 (72.2%) of the patients maintained sinus rhythm. There was no stroke or systemic embolism observed. CONCLUSION Combining catheter ablation and LAAC in a single procedure can be successfully and safely performed in non-valvular AF patients of Chinese population.

Objective To study the clinicopathological characteristics, immunophenotype, pathologic diagnosis and differential diagnosis of diffuse pulmonary meningotheliomatosis (DPM). Methods The clinical data, histological features and immunohistochemical results of three cases of DPM collected from January 2016 to May 2018 at Guangdong Provincial People′s Hospital were analyzed, and the relevant literature reviewed. Results The three DPM patients age was 53, 69 and 74 years. The lesions consisted of multiple minute pulmonary meningothelial?like nodules profusely involving the lungs. Microscopically, they showed typical morphology, characterized by medium?sized elongated tumor cells resembling meningothelial cells with whorled/nested clusters. The cells were uniform and had abundant eosinophilic cytoplasm with oval nuclei with delicate chromatin. Immunohistochemical staining showed tumor cells were diffusely and strongly positive for EMA, vimentin and PR, but were negative for CAM5.2, CgA, Syn, CK7 and TTF1. Conclusions DPM is extremely rare, and may be confused with primary interstitial pulmonary processes and metastatic malignant tumors of lung. Recognition of this entity is essential for pathologists to avoid misdiagnosis and unnecessary treatment.

Objective: To study the clinicopathological characteristics, immunophenotype, pathologic diagnosis and differential diagnosis of diffuse pulmonary meningotheliomatosis (DPM). Methods: The clinical data, histological features and immunohistochemical results of three cases of DPM collected from January 2016 to May 2018 at Guangdong Provincial People′s Hospital were analyzed, and the relevant literature reviewed. Results: The three DPM patients age was 53, 69 and 74 years. The lesions consisted of multiple minute pulmonary meningothelial-like nodules profusely involving the lungs. Microscopically, they showed typical morphology, characterized by medium-sized elongated tumor cells resembling meningothelial cells with whorled/nested clusters. The cells were uniform and had abundant eosinophilic cytoplasm with oval nuclei with delicate chromatin. Immunohistochemical staining showed tumor cells were diffusely and strongly positive for EMA, vimentin and PR, but were negative for CAM5.2, CgA, Syn, CK7 and TTF1. Conclusions DPM is extremely rare, and may be confused with primary interstitial pulmonary processes and metastatic malignant tumors of lung. Recognition of this entity is essential for pathologists to avoid misdiagnosis and unnecessary treatment.

Objective To evaluate the significance of liver biopsy and B ultrasonograpgy in the diagnosis of fatty liver. Methods The results of 62 patients with liver steatosis diagnosed by liver puncture biopsy but not by B-ultrasonograpgy were contrastively analyzed and combined with liver function, blood lipids, blood glucose, and body mass index. Results The 62 cases which were not diagnosed as fatty liver by B-ultrasonograpgy were proved to be 5％-33％liver steatosis after liver puncture biopsy. Among the 62 cases, 23 cases were indicated by the B-ultrasonograpgy that the liver parenchyma echo did not see abnormalities, 18 cases showed the liver parenchyma echo slightly was enlarged, 17 cases showed the liver parenchyma echo density was a bit enhanced and 4 cases were diffuse liver damage,which respectively were 37.01％、29.03％、27.42％and 6.45％. Pathologically it indicated that 45 cases were 5％≤liver steatosis≤19％. Among the 45 cases, 18 cases were indicated by the B-ultrasonograpgy that the liver parenchyma echo was not seen abnormalities, 8 cases showed the liver parenchyma echo slightly was enlarged, 17 cases showed the liver parenchyma echo density was a bit enhanced, and 2 cases were diffuse liver damage, and the change of ultrasound was mainly showed by the liver parenchyma echo not seen abnormalities and the enhanced liver parenchyma echo density. Pathologically it indicated that 17 cases were 20％≤liver steatosis≤33％, 6 cases were indicated by the B-ultrasonograpgy that the liver parenchyma echo did not see abnormalities, 5 cases showed the liver parenchyma echo slightly was enlarged, 5 cases showed the liver parenchyma echo density was a bit enhanced, and 1 case was diffuse liver damage, and the change of ultrasound was mainly showed by the liver parenchyma echo not seen abnormalities, the slightly enlarged liver parenchyma echo and the enhanced liver parenchyma echo density. By analyzing the influence to the ultrasound changes by patients' liver function, body mass index, blood fat and blood sugar, and with logistic regression analysis through a disorderly classification, it was found that the larger value of the glutamine transferase, alkaline phosphatase, body mass index, triglyceride and low density lipoprotein cholesterol, the higher possibility of diffuse liver damage, and the higher level of fatty degeneration, the higher possibility of diffuse liver damage. Conclusion In the diagnosis of fatty liver, when the fatty degeneration is below 1/3, B-ultrasonic examination can't show characteristic changes of fatty liver. It should be closely observed or take liver puncture biopsy to make a definite diagnosis of fatty liver.

Cerebral Hemorrhage ; pathology ; physiopathology ; Child ; Child, Preschool ; Female ; Heart Defects, Congenital ; pathology ; physiopathology ; Hemodynamics ; physiology ; Humans ; Infant ; Male ; Risk Factors ; Stroke ; pathology ; physiopathology ; Vascular Malformations ; pathology ; physiopathology

Objective To explore the mechanism underlying a selective liver nitric oxide donor V-PYRRO/NO effects on the gene expression of LTC4 synthase(LTC4S) during hepatic ischemia reperfusion(I/R).Methods Adult male SD rats were divided into 3 groups:control group(sham),ischemic-reperfusion group(I/R) and V-PYRRO/NO group. Liver subjected to 1 hour of partial hepatic ischemia followed by 5 hours of reperfusion, saline or V-PYRRO/NO[1.06 mmol/(kg·h)] administered intravenously. The mRNA expression of LTC4S in rat liver was examined by RT-PCR method,the protein expressions of NF-κB p65,p50 and IκB in liver cell lysates and nu-clear extracts were detected by Western blot analysis. Results Hepatic mRNA expression of LTC4S in I/R group was higher than that in sham group(P<0.05), whereas it was lower in V-PYRRO/NO group than that in I/R group(P<0.05). Moreover,compared with sham group,the protein expressions of NF-κB p65 and p50 in nucleus extract were markedly increased(P<0.01) but significantly decreased in cytoplasm(P<0.01) in I/R group. V-PYRRO/NO reversed completely the increase of these protein expressions in nucleus extract (P<0.05) and the decrease of them in cytoplasm(P<0.01,P<0.05) during hepatic I/R injury.However,IκB protein in three groups did not change. Immunohistochemistry staining revealed that no marked positive staining for NF-κB p65 was found in sham liver,I/R liver exhibited strong cytoplasmic and nuclear positive staining for NF-κB p65,but V-PYRRO/NO I/R group liver presented slight cytoplasmic and nuclear staining. Conclusions V-PYRRO/NO may down-regulate LTC4S mRNA expression by inhibiting NF-κB activation independent of IκB during hepatic I/R injury.

Objective To investigate the distribution of insulin resistance (HOMA-IR) index and its influencing factorsamong middle and old aged people with normal glucose and to provide the basis for early screening and prevention of type 2diabetes. Methods A total of 229 residents were selected with health records showed normal blood glucose (fasting bloodglucose < 7.0mmol/L, postprandial 2h blood glucose<11.1 mmol/L) and more than 40 years old from July, 2012 to June,2015. Height, weight, waist and hip circumference, and the fasting plasma glucose (FPG), insulin (FINS), lowdensity lipoprotein (LDL), uric acid, tumor necrosis factor (TNF) and interleukin -6 (IL-6) were recorded to analyzethe distribution of HOMA-IR and its influencing factors. Results Totally 229 people were included, of which 113 were male(49.34%), 116 female(50.66%) . The average age was(63.58 + 8.85) years old. The average HOMA-IR index was 0.94(1.08) and there were 21 people that HOMA-IR exceed the standard (HOMA-IR≥2.68), accounting for 9.17%.TheHOMA-IR index of different gender, age, waist circumference, hip circumference, uric acid in the elderly had significantdifference (P < 0.05) .Multiple linear regression analysis showed that HOMA-IR index was positively correlated withfemale, waist circumference and IL-6 and was negatively correlated with age. Conclusion The possibility of IR was higherin women with relatively low age, female, central obesity and high IL-6 levels among the middle and old aged people withnormal blood glucose.

A large number of bacteria were carried by mites parasitizing on animals and human,which including symbiotic and pathogenic bacteria.Mites were an important transmission media and could spread pathogenic bacteria.A total of 184 literatures were collected from database to analye diversity of bacteria carried by mites.There were about 105 species bacteria were carried by 94 mites.These bacteria belong to 9 phylums,22 orders,40 families and 55 genuses(including 17 pathogen and 20 opportunistic pathogen).In this paper,we reviewed the diversity of mites-associated bacteria,which could offer some data for investigation on the relationship between mites and mites-associate bacteria.