Adult ; Enchondromatosis ; diagnosis ; diagnostic imaging ; Femur ; diagnostic imaging ; Humans ; Male ; Radiography

Objective:To investigate the pathogenic gene locus and prenatal genetic diagnosis of 54 families with oculocutaneous albinism (OCA).Methods:This retrospective study enrolled 54 OCA probands and their families from Gansu Province Maternal and Child Health Care Hospital from May 2014 to May 2020. TYR gene variation screening was performed on the probands by Sanger sequencing. Those with negative results were analyzed by high-throughput sequencing, and further verification was performed on their parents by Sanger sequencing. Among the 54 families, 15 ml amniotic fluid were collected from 16 women at 18-21 gestational weeks in their subsequent pregnancy. Sanger sequencing combined with short tandem repeats sequence for linkage analysis were performed for genetic analysis. All data were analyzed using descriptive statistical analysis. Results:Out of the 54 OCA probands, 48 were diagnosed as OCA1, five were OCA2 and one was OCA4 based on the Sanger sequencing and high-throughput sequencing detection. A total of 26 different variation sites were involved in the 48 OCA1 probands, including 15 missense mutations, five nonsense mutations, three splicing mutations, and three frame-shift mutations, among which, c.929insC (29%, 28/96) was the most frequent mutation, followed by c.896G>A (11%, 11/96), c.832C>T (8%, 8/96) and c.703T>C (5%, 5/96). The diagnosis was confirmed in all 16 fetuses in the 16 families that underwent prenatal diagnosis. Five of them were affected and their mothers chose to terminate the pregnancies, the other 11 pregnancies continued to delivery, including seven heterozygous carriers and four fetuses without the same pathogenic allele as the proband. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. All 11 children were in good health during telephone follow-up one month after birth. Postnatal validations were consistent with the prenatal tests.Conclusions:Genetic diagnosis could accurately identify various types of OCA and help to provide prenatal diagnosis and fertility consultation for subsequent pregnancies.

OBJECTIVETo compare the long-term effect and safety of tacrolimus (FK506) and cyclosporine (CsA) in kidney transplant (KT) recipients carrying hepatitis B Virus(HBV).

METHODSA total of 109 patients with HBV were randomized into FK506 group (52 cases) and CsA group (57 cases) after KT, and a 2-year-long follow-up of the patients was conducted to record the patient and graft survival, incidence of acute graft rejection and postoperative liver function.

RESULTSThe 2-year patient/graft survival was 86.0%/73.7% and 94.2%/90.3% in CsA and FK506 groups, respectively (P<0.05), with incidence of acute rejection of 10.5% and 9.6% (P>0.05), and rate of abnormal liver function of 26.3% and 15.4% (P<0.05), respectively. Eight patients (14.4%) in CsA group required a drug conversion but none in FK506 group. The drug conversion resulted in significant reduction of ALT/AST level from 255.13+/-31.38/201.88+/-21.25 U/L to 31.25+/-11.50/25.13+/-9.68 U/L (P<0.01).

CONCLUSIONFor HBV-carrying renal transplant recipients, FK506 as the primary choice of immunosuppressant can be more effective and safer than CsA.

Adolescent ; Adult ; Carrier State ; physiopathology ; Cyclosporine ; administration & dosage ; adverse effects ; pharmacology ; Drug-Related Side Effects and Adverse Reactions ; Female ; Graft Rejection ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B virus ; Humans ; Kidney Transplantation ; adverse effects ; Liver ; drug effects ; physiology ; Male ; Middle Aged ; Tacrolimus ; administration & dosage ; adverse effects ; pharmacology ; Young Adult

OBJECTIVE To detect potential mutation of SOX10 gene in a pedigree affected with Warrdenburg syndrome type II. METHODS Genomic DNA was extracted from peripheral blood samples of the proband and his family members. Exons and flanking sequences of MITF, PAX3, SOX10, SNAI2, END3 and ENDRB genes were analyzed by chip capturing and high throughput sequencing. Suspected mutations were verified with Sanger sequencing. RESULTS A c.127C>T (p.R43X) mutation of the SOX10 gene was detected in the proband, for which both parents showed a wild-type genotype. CONCLUSION The c.127C>T (p.R43X) mutation of SOX10 gene probably underlies the ocular symptoms and hearing loss of the proband.

OBJECTIVETo evaluate the type V phosphodiesterase (PDE-5) inhibitor erection-provoking test with audio-visual sexual stimulation in the diagnosis of erectile dysfunction.

METHODSA total of 853 out-patients diagnosed with erectile dysfunction were divided into an injury and a non-injury group. After scored on IIEF-5 questionnaires, all the patients received oral administration of PDE-5 inhibitors and, 30 minutes later, audio-visual sexual stimulation. The data on penile erection were recorded with Rigiscan Plus.

RESULTSThe patients with mild, moderate and severe ED accounted for 18.8, 31.9 and 49.3% in the injury group, and 50.6, 39.8 and 9.6% in the non-injury group, with statistic differences between the two groups in the mild and severe parts (P < 0.05). The rates of conspicuous effectiveness, effectiveness, ineffectiveness and total effectiveness of the combined method were 13.0, 14.5, 72.5 and 27.5% in the injury group, but 55.7, 20.7, 23.6 and 76.4% in the non-injury group, with significant differences (P < 0.05).

CONCLUSIONThe PDE-5 inhibitor erection-provoking test with audio-visual sexual stimulation is a simple, practical, safe and effective method for the differentiation of organic from psychological erectile dysfunction.

Adult ; Aged ; Erectile Dysfunction ; diagnosis ; physiopathology ; Humans ; Male ; Middle Aged ; Penile Erection ; physiology ; psychology ; Phosphodiesterase 5 Inhibitors ; Phosphodiesterase Inhibitors ; administration & dosage ; Photic Stimulation ; methods ; Sensitivity and Specificity ; Sexual Behavior ; Surveys and Questionnaires ; Television ; Young Adult

The occurrence and progression of hepatic fibrosis are regulated by multicytokines and multiple molecular signal trans-duction pathways in cells. Currently,the molecular signaling pathway is the target for drugs to treat diseases. The study of the active ingredients of Chinese medicine to interfere with the sig-naling pathways of liver fibrosis is a hot topic. In the past ten years,it has been reported that hydroxysafflor yellow A,total flavonoids from litchi seed,ursolic acid,curcumin can interfere the signaling pathway of p38MAPK,TGF-β/ Smad,Wnt,Ras/ERK and Hedgehog liver fibrosis. The research on the active in-gredients of Chinese traditional medicine,which is targeted at signaling pathways,is expected to open new areas for Chinese and western medicine in the treatment of liver fibrosis.

OBJECTIVE: To explore the clinical features and genetic basis for a child with 3-methylglutaconic aciduria type VII. METHODS: A child who was diagnosed at the Gansu Provincial Maternity and Child Health Care Hospital on August 9, 2019 was selected as the study subject. Clinical data of the child, including urine gas chromatography and mass spectrometry, were collected. The child and her parents were subjected to whole exome sequencing. RESULTS: The child, a female neonate, had presented mainly with intermittent skin cyanosis, convulsions, hypomagnesemia, apnea, neutropenia after birth. Her urine 3-methylpentenedioic acid has increased to 17.53 μmol/L. DNA sequencing revealed that she has harbored compound heterozygous variants of the CLPB gene, namely c.1016delT (p.L339Rfs*5) and c.1087A>G (p.R363G), which were respectively inherited from her mother and father. Both variants were unreported previously. Based on the standards from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively predicted to be pathogenic and likely pathogenic. CONCLUSION The child was diagnosed with 3-methylglutenedioic aciduria type VII. Discovery of the c.1016delT and c.1087A>G variants has enriched the mutational spectrum of the CLPB gene.
Female ; Humans ; Infant, Newborn ; Pregnancy ; Base Sequence ; Metabolism, Inborn Errors/diagnosis* ; Mutation ; Neutropenia/genetics* ; Sequence Analysis, DNA

OBJECTIVE: To carry out pedigree analysis for a rare child with comorbid X-linked ichthyosis (XLI) and Duchenne muscular dystrophy (DMD). METHODS: Whole exome sequencing (WES) and multiple ligation-dependent probe amplification (MLPA) were used to detect potential deletions in the STS and DMD genes. RESULTS: The proband was found to harbor hemizygous deletion of the STS gene and exons 48 to 54 of the DMD gene. CONCLUSION The child has comorbid XLI and DMD, which is extremely rare.
Child ; Dystrophin/genetics* ; Exons ; Gene Deletion ; Genetic Testing ; Humans ; Ichthyosis/genetics* ; Muscular Dystrophy, Duchenne/genetics* ; Mutation

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I (TYRSN1). METHODS: A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject. The child was subjected to tandem mass spectrometry (MS-MS) and urine gas chromatography-mass spectrometry (GC-MS) for the detection of inherited metabolic disorders, in addition with whole exome sequencing (WES). Candidate variants were validated by Sanger sequencing. RESULTS: The child's clinical features included abdominal distension, hepatomegaly, anemia and tendency of bleeding. By mass spectrometry analysis, her serum and urine tyrosine and succinylacetone levels have both exceeded the normal ranges. WES and Sanger sequencing revealed that she has harbored c.1062+5G>A and c.943T>C (p.Cys315Arg) compound heterozygous variants of the FAH gene, which were inherited from her father and mother, respectively. Among these, the c.943T>C was unreported previously. CONCLUSION Considering her clinical phenotype and result of genetic testing, the child was diagnosed with TYRSN1 (acute type). The compound heterozygous variants of the FAH gene probably underlay the disease in this child. Above finding has further expanded the spectrum of FAH gene variants, and provided a basis for accurate treatment, genetic counseling and prenatal diagnosis for her family.
Female ; Humans ; Gas Chromatography-Mass Spectrometry ; Genetic Testing ; Mutation ; Phenotype ; Prenatal Diagnosis ; Tyrosinemias/genetics* ; Child

BACKGROUNDElectroconvulsive therapy (ECT) can alleviate the symptoms of treatment-resistant depression (TRD). Functional network connectivity (FNC) is a newly developed method to investigate the brain's functional connectivity patterns. The first aim of this study was to investigate FNC alterations between TRD patients and healthy controls. The second aim was to explore the relationship between the ECT treatment response and pre-ECT treatment FNC alterations in individual TRD patients.

METHODSThis study included 82 TRD patients and 41 controls. Patients were screened at baseline and after 2 weeks of treatment with a combination of ECT and antidepressants. Group information guided-independent component analysis (GIG-ICA) was used to compute subject-specific functional networks (FNs). Grassmann manifold and step-wise forward component selection using support vector machines were adopted to perform the FNC measure and extract the functional networks' connectivity patterns (FCP). Pearson's correlation analysis was used to calculate the correlations between the FCP and ECT response.

RESULTSA total of 82 TRD patients in the ECT group were successfully treated. On an average, 8.50 ± 2.00 ECT sessions were conducted. After ECT treatment, only 42 TRD patients had an improved response to ECT (the Hamilton scores reduction rate was more than 50%), response rate 51%. 8 FNs (anterior and posterior default mode network, bilateral frontoparietal network, audio network, visual network, dorsal attention network, and sensorimotor network) were obtained using GIG-ICA. We did not found that FCPs were significantly different between TRD patients and healthy controls. Moreover, the baseline FCP was unrelated to the ECT treatment response.

CONCLUSIONSThe FNC was not significantly different between the TRD patients and healthy controls, and the baseline FCP was unrelated to the ECT treatment response. These findings will necessitate that we modify the experimental scheme to explore the mechanisms underlying ECT's effects on depression and explore the specific predictors of the effects of ECT based on the pre-ECT treatment magnetic resonance imaging.

Adult ; Brain ; pathology ; physiopathology ; Depression ; physiopathology ; therapy ; Depressive Disorder, Treatment-Resistant ; physiopathology ; therapy ; Electroconvulsive Therapy ; methods ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged