BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Clinical practice of Medical Genetics involves application of various genetic techniques for the diagnosis of genetic disorders and subsequent genetic counseling and treatment. The principles of Medical Ethics must be fully taken into account when applying genetic knowledge for medical practice. Medical Ethics education is therefore essential for the standardized training of resident doctors in medical genetics department. With a basic system of Medical Genetics Physician Training established, our hospital has made a preliminary exploration for the development of Medical Ethics teaching in resident training through various teaching practices including seminar, network teaching, case study, scene teaching and outpatient teaching, with an aim to strengthen Medical Ethnics knowledge, professionalism and communication skills, and implement Medical Ethics principles throughout clinical practice.
Curriculum ; Educational Status ; Ethics, Medical ; Genetics, Medical ; Humans

Objective:To evaluate the deformity changes in the treatment of congenital clubfoot in infants by ultrasound, and to explore its clinical application value.Methods:Seventeen infants with congenital clubfoot treated in the Department of Pediatric Orthopaedics of the Third Affiliated Hospital of Zhengzhou University from March 2020 to June 2021 and 27 normal infants in the same period were selected. The distance between medial malleolus and scaphoids (MM-N distance) of all feet was measured by ultrasound. The distance from the tangent line of the lateral edge of calcaneus to the midpoint of the lateral edge of the chondroid bone (C-C distance), medial soft tissue thickness and tibial calcaneal angle were measured by ultrasound. The data before, after treatment and during follow-up were statistically analyzed.Results:A total of 88 feet of 44 infants were evaluated. The mean number of cast was 4.7±1.1, the follow-up time was (96.9±59.3)days. The MM-N distance, C-C distance and posterior tibial calcaneal angle in the clubfoot group were improved after treatment and at the last follow-up, and the differences were statistically significant (all P<0.01). During the treatment, 1 case had false correction, and 2 cases recurred in the last follow-up. Conclusions:Ultrasound can clearly display the medial, dorsal, lateral and posterior articular structures of normal and clubfoot, and can observe the deformity changes of clubfoot during the correction process, which can provide guidance for the clinical treatment of clubfoot.

OBJECTIVE: To assess the value of copy number variation analysis based on next generation sequencing (CNV-seq) in prenatal diagnosis for women at advanced maternal age. METHODS: A prospective analysis was carried out for women who underwent amniocentesis at 18~36 weeks of gestation for fetal CNV-seq for advanced maternal age. RESULTS: For 1461 unrelated Chinese women with a singleton pregnancy, CNV-seq was performed for all samples successfully. The proportion of chromosomal abnormalities was 2.3% (34/1461), of which 44.12% were submicroscopic copy number variations (<5 Mb). CONCLUSION Pregnant women at an advanced maternal age should be informed for not only common trisomies but all pathogenic chromosomal aberrations. NGS was a sensitive and accurate approach for detecting CNVs.
Chromosome Aberrations ; Chromosome Disorders ; DNA Copy Number Variations ; Female ; Humans ; Maternal Age ; Pregnancy ; Prenatal Diagnosis ; Prospective Studies

OBJECTIVETo analyze mutations of DYSF gene in two pedigrees affected with limb-girdle muscular dystrophy 2B (LGMD-2B).

METHODSGenomic DNA was extracted from peripheral blood samples of the two probands and unaffected family members. Variant sites were screened by next-generation sequencing using gene panel as well as Sanger sequencing.

RESULTSFour pathogenic mutations of the DYSF gene were detected, which included a de novo mutation and three mutations with uncertain significance. In pedigree 1, the proband carried compound heterozygous mutations of c.1667T to C (p.Leu556Pro) and c.5567T to A (p.Val1856Glu), which were respectively inherited from her mother and father. Proband of pedigree 2 carried compound heterozygous mutations of c.4853A to G (p.Tyr1618Cys) and c.4876G to A (p.Val1612Ile), among which c.4876G to A (p.Val1626Ile) was also found in his father and grandfather, while c.4853A to G (p.Tyr1618Cys) was detected in his mother and grandmother.

CONCLUSIONThe two compound heterozygous mutations of the DYSF gene probably underlie the LGMD2B in the two pedigrees. Next generation sequencing has conferred great advantage for gene diagnosis of hereditary myopathy.

OBJECTIVETo analyze the outcome of chromosomal microarray analysis (CMA) in prenatal diagnosis for fetal abnormalities detected by ultrasonography.

METHODSAmniotic fluid samples from 477 pregnancies with abnormal ultrasound findings but without common aneuploidies were detected by CMA with Affymetrix CytoScan 750K arrays. The results were analyzed with ChAS v3.0 software.

RESULTSAmong the 477 samples, 24 (5.03%) were detected with pathogenic copy number variations (pCNVs) by CMA. Six (9.68%) among 62 cases with structural fetal abnormalities in multiple organ systems were detected with pCNVs, 11 (7.48%) among 147 cases with a single structural anomaly were detected with pCNVs, and 7 (2.61%) among 268 cases with a soft marker were detected with pCNVs.

CONCLUSIONCMA has offered a clear advantage over conventional karyotyping for the detection of fetal chromosomal abnormalities, and can provide an effective diagnostic tool for those with one or more structural abnormalities detected by ultrasound.

Adolescent ; Chromosome Aberrations ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; diagnostic imaging ; genetics ; Fetus ; diagnostic imaging ; Humans ; Karyotyping ; Male ; Microarray Analysis ; methods ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal ; methods ; Young Adult

OBJECTIVETo assess the value of chromosomal microarray analysis (CMA) for the diagnosis of children with intellectual disability/developmental delay (ID/DD) but a normal karytype.

METHODSPeripheral blood samples from 92 ID/DD patients were analyzed with CMA using Affymetrix CytoScan 750K arrays. The results were analyzed by ChAS v3.0 software.

RESULTSEighteen cases (19.57%) were detected with abnormalities by CMA, among which 10 cases were diagnosed with microdeletion/microduplication syndromes. These included 2 Williams-Beuren syndromes, 2 Angelman syndromes, 2 Russell-Silver syndromes, 1 Smith-Magenis syndromes, 1 Wolf-Hirschhorn syndromes, 1 15q26 overgrowth syndrome and 1 Xq28 (MECP2) duplication syndrome. In addition, 8 cases were diagnosed with pathogenic copy number variations (pCNV).

CONCLUSIONCMA can significantly improve the diagnostic rate for patients with ID/DD, which is of great value for the treatment of such children and guidance of reproduction for their parents. Therefore, CMA should become the first-line diagnostic test for patients with ID/DD.

Adolescent ; Adult ; Child ; Child, Preschool ; DNA Copy Number Variations ; Developmental Disabilities ; genetics ; psychology ; Female ; Humans ; Intellectual Disability ; genetics ; psychology ; Intelligence ; Karyotype ; Male ; Microarray Analysis ; Middle Aged ; Pedigree ; Young Adult

Objective To analyze the characteristics of rhabdomyolysis (RM) caused by alcohol withdrawal syndrome (AWS). Methods The clinical data of 7 patients with RM induced by AWS were analyzed retrospectively. Results All 7 patients were male;the age was 38-63 (51.3 ± 9.8) years. All of the 7 patients showed obvious myalgia and fatigue, of whom 4 patients had limb swelling, and 3 patients had epigastric pain. Creatine kinase and myoglobin levels of 7 cases were significantly increased. One case had acute renal failure. Seven patients were improved after treatment with a large amount of fluid infusion. Conclusions For patients with AWS who have generalized withdrawal seizures and epileptic seizures, muscle cells can be damaged due to prolonged muscle contraction, which can cause RM. Changes of myoglobin, creatine kinase, renal function and liver function in patients with AWS should be monitored at clinical admissions. If RM occurs, the patients should be given early fluid therapy.

Objective To analyze the features of diagnosis, treatment and prognosis of primary renal neuroendocrine tumors, and to improve the understanding of primary renal neuroendocrine tumors. Methods From January 2008 to June 2015, 5 cases of primary renal neuroendocrine tumors were hospitalized and their data was analyzed retrospectively, with 1 male 4 females, aged 40-73 years with the middle age of 48 years.Tumors were all located in the left kidney, whose diameters arranged from 4 to 9 cm, with an average of 6.5cm.One case presented with hematuria, one case was identified because of abdominal pain, and the other three cases were identified via physical examination.Four cases underwent a renal contrast-enhanced ultrasound, which indicated a medium-hypoechoic mass in three cases and a hyperechoic mass in one case.All five cases underwent CT scan, presenting irregularly shape and density. Calcification was found in three cases on plain scanning.Significantly heterogeneous enhancement was found in three cases and moderate heterogeneous enhancement was found in one case on enhanced scanning. Results All five cases underwent operations, with two cases undergoing radical nephrectomy and three cases undergoing partial nephrectomy.Pathological examination showed three cases of tumor cells arranged in a nest slug or ribbon-like infiltrative growth, with no or rare mitosis and no necrosis, which is consistent with renal carcinoids.Three out of 4 renal hilar lymph nodes containing tumor cells were identified in one case. The tumor cells in another case exhibited a ribbon-like arrangement, with some round nuclei, no significant atypia, and rare mitosis, which is consistent with renal atypical carcinoid.Two out of two renal hilar lymph nodes containing tumor cells were identified in this case. The tumor tissue of one case showed morphologically uniform, medium-sized cells arranged in nest slug form with necrosis, a high nuclear cytoplasm ratio, an obvious allotype and frequent mitosis, which is consistent with renal small cell carcinoma.The immunohistochemistry of the five cases indicated synaptophysin( Syn) and chromogranin A ( CgA) positive in varying degree.One case of renal carcinoid relapsed approximately 78 months after partial nephrectomy, following with radical surgery.The other two cases were followed up for 8 or 27 months and no recurrence or metastasis was detected.One case of renal atypical carcinoid was followed up for 4 months after radical nephrectomy and no recurrence or metastasis was detected.One case of renal small cell carcinoma died of multiple organ failure 11 months after radical nephrectomy plus hepatic metastatic carcinoma radio-frequency ablation approximately.Conclusions Primary renal neuroendocrine tumors are rare clinically. Renal neuroendocrine tumors may be expressed as carcinoid, atypical carcinoid or small cell carcinoma, and the clinical manifestations, pathological characteristics and prognosis varied.Primary renal carcinoids may be treated by surgery with a nice prognosis.Patients with primary renal small cell carcinoma require comprehensive treatment, and their prognosis is poor.

OBJECTIVETo analyze mutation of the PMP22 gene in a pedigree affected with Charcot-Marie-Tooth disease.

METHODSGenomic DNA was extracted from peripheral blood samples of the proband and members from his family, and fetal DNA was extracted from amniotic fluid sample. Multiplex ligation-dependent probe amplification (MLPA) and array-based comparative genomic hybridization (array-CGH) analyses were carried out to determine the copy number of the PMP22 gene. Sanger sequencing was carried out to detect point mutations of the PMP22 gene.

RESULTSA heterozygous duplication of the PMP22 gene was detected in the proband and his father, while no point mutation, insertion or deletion was found in them. No duplication or deletion of the PMP22 gene was found in other family members.

CONCLUSIONBased on clinical symptoms and genetic findings, the heterozygous duplication of the PMP22 gene is probably the cause of the disease in the proband. The fact that the father has carried the same duplication but with no detectable symptom may be due to irregular transmission pattern of the mutation. Genetic counseling for the family should therefore be with caution.

Adult ; Charcot-Marie-Tooth Disease ; genetics ; Comparative Genomic Hybridization ; methods ; DNA Mutational Analysis ; Family Health ; Female ; Gene Dosage ; Gene Duplication ; Genetic Predisposition to Disease ; genetics ; Heterozygote ; Humans ; Male ; Multiplex Polymerase Chain Reaction ; methods ; Myelin Proteins ; genetics ; Pedigree