Objective:To explore the genetic characteristics of a Chinese pedigree with rare mosaic 11q partial duplication and its pathogenetic mechanisms.Methods:A pedigree which underwent prenatal diagnosis at Wenzhou Central Hospital between September 25, 2015 and November 30, 2023 was selected for the study. Clinical data were collected from the pedigree. Peripheral blood samples from the parents, amniotic fluid from the fetus, and peripheral blood sample from the neonate were obtained. Genetic testing was carried out by using G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) technology. Relevant literature was searched in the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases to summarize the clinical phenotypes of patients with 11q partial duplication. This study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethics No. L2024-07-080).Results:The pregnant woman (G 3) had a history of adverse pregnancy outcomes. During her first pregnancy (G 1), prenatal ultrasound indicated intrauterine growth restriction and a Dandy-Walker variant. Follow-up at 8 years of age showed developmental delays and mild intellectual disability. During her second pregnancy (G 2), prenatal ultrasound revealed nasal bone hypoplasia, and the pregnancy was terminated at 23rd gestational week. During her third pregnancy (G 3), all prenatal tests were normal, and the neonate showed normal growth and development at 4 months of age. The karyotype of amniotic fluid of her first pregnancy was 46, X? , and the SNP-array analysis of neonatal peripheral blood showed arr[GRCh37/hg19]11q13.4q25(70432450_134607121)×2~3, with a mosaicism rate being approximately 40%. The karyotype for her second pregnancy was 46, X? , rec(11)dup(11q)inv(11)(p15q13)dmat[6]/46, X? [27], and the SNP-array result was arr[GRCh38]11q13.4q25(71406636_135067522)×2~3, with a mosaicism rate being approximately 75%. The karyotype for her third pregnancy was 46, X? , inv(11)(p15q13)mat, and the SNP-array result was arr(XN)×1, (1~22)×2. The karyotype of the woman was 46, XX, inv(11)(p15q13), and that of her husband was 46, XY. A review of 12 similar cases (including G 1) from the literature revealed that the common clinical phenotypes of 11q partial duplication included intellectual disability (12/12), developmental delay (12/12), ear abnormalities (12/12), microcephaly (10/12), seizures (8/12), hypotonia (8/12), and congenital heart malformations (7/12). Conclusion:Mosaic partial duplication of 11q may underlie the genetic etiology of this pedigree. The pregnant woman is a carrier of an inversion on chromosome 11, which might have formed the mosaic 11q partial duplication through meiotic errors and mitotic trisomy rescue mechanisms during reproduction.

Objective:To investigate the factors influencing the prescribing habits of general practitioners (GPs) in relation to single-pill combination (SPC) antihypertensive drugs.Methods:This was a qualitative study. Using the purposive sampling method, 2 general hospitals (designated as HAZ1-2) and 4 community health service centers (designated as HAS1-4) in Huai′an city, Jiangsu province were selected from April to May 2023. In addition, 4 general practitioners (designated as A-D) were selected as interviewees from each general hospital and center. The selected individuals were interviewed using on-site thematic group interviews. The interview mainly included the principles of clinical selection of SPC antihypertensive drugs; the degree of acceptance of SPC antihypertensive drugs by patients after prescription; the evaluation of SPC antihypertensive drugs and the difficulties existing in their clinical use. The data of the interview were analyzed according to the thematic framework.Results:Twenty-four GPs were interviewed. Four themes and 9 sub-themes were extracted regarding factors influencing GP prescribing of SPC antihypertensive drugs. The study showed that: (1) the prescribing of SPC antihypertensive drugs by GPs according to patients′ specific conditions; (2) the prescribing of SPC antihypertensive drugs by GPs was influenced by factors such as price and drug adjustment; (3) the different evaluations of SPC antihypertensive drugs among GPs; (4) GPs in community health service centers faced many difficulties in prescribing SPC antihypertensive drugs (relatively fewer varieties of SPC drugs in the community, lower patient trust in community GPs, and lower standardization of prescribing by community GPs).Conclusion:The factors influencing GPs′ prescribing of SPC antihypertensive drugs mainly include the patients′ specific situation, price, medication adjustment, attitude of GPs, and some clinical practice problems.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

OBJECTIVE: To explore the genetic characteristics of a Chinese pedigree with rare mosaic 11q partial duplication and its pathogenetic mechanisms. METHODS: A pedigree which underwent prenatal diagnosis at Wenzhou Central Hospital between September 25, 2015 and November 30, 2023 was selected for the study. Clinical data were collected from the pedigree. Peripheral blood samples from the parents, amniotic fluid from the fetus, and peripheral blood sample from the neonate were obtained. Genetic testing was carried out by using G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) technology. Relevant literature was searched in the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases to summarize the clinical phenotypes of patients with 11q partial duplication. This study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethics No. L2024-07-080). RESULTS: The pregnant woman (G₃) had a history of adverse pregnancy outcomes. During her first pregnancy (G₁), prenatal ultrasound indicated intrauterine growth restriction and a Dandy-Walker variant. Follow-up at 8 years of age showed developmental delays and mild intellectual disability. During her second pregnancy (G₂), prenatal ultrasound revealed nasal bone hypoplasia, and the pregnancy was terminated at 23rd gestational week. During her third pregnancy (G₃), all prenatal tests were normal, and the neonate showed normal growth and development at 4 months of age. The karyotype of amniotic fluid of her first pregnancy was 46,X?, and the SNP-array analysis of neonatal peripheral blood showed arr[GRCh37/hg19]11q13.4q25(70432450_134607121)×2~3, with a mosaicism rate being approximately 40%. The karyotype for her second pregnancy was 46,X?,rec(11)dup(11q)inv(11)(p15q13)dmat[6]/46,X?[27], and the SNP-array result was arr[GRCh38]11q13.4q25(71406636_135067522)×2~3, with a mosaicism rate being approximately 75%. The karyotype for her third pregnancy was 46,X?,inv(11)(p15q13)mat, and the SNP-array result was arr(XN)×1,(1~22)×2. The karyotype of the woman was 46,XX,inv(11)(p15q13), and that of her husband was 46,XY. A review of 12 similar cases (including G₁) from the literature revealed that the common clinical phenotypes of 11q partial duplication included intellectual disability (12/12), developmental delay (12/12), ear abnormalities (12/12), microcephaly (10/12), seizures (8/12), hypotonia (8/12), and congenital heart malformations (7/12). CONCLUSION Mosaic partial duplication of 11q may underlie the genetic etiology of this pedigree. The pregnant woman is a carrier of an inversion on chromosome 11, which might have formed the mosaic 11q partial duplication through meiotic errors and mitotic trisomy rescue mechanisms during reproduction.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Chromosome Duplication ; Chromosomes, Human, Pair 11/genetics* ; East Asian People/genetics* ; Karyotyping ; Mosaicism ; Pedigree ; Polymorphism, Single Nucleotide ; Prenatal Diagnosis

Objective:To explore the genetic characteristics of a Chinese pedigree with rare mosaic 11q partial duplication and its pathogenetic mechanisms.Methods:A pedigree which underwent prenatal diagnosis at Wenzhou Central Hospital between September 25, 2015 and November 30, 2023 was selected for the study. Clinical data were collected from the pedigree. Peripheral blood samples from the parents, amniotic fluid from the fetus, and peripheral blood sample from the neonate were obtained. Genetic testing was carried out by using G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) technology. Relevant literature was searched in the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases to summarize the clinical phenotypes of patients with 11q partial duplication. This study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethics No. L2024-07-080).Results:The pregnant woman (G 3) had a history of adverse pregnancy outcomes. During her first pregnancy (G 1), prenatal ultrasound indicated intrauterine growth restriction and a Dandy-Walker variant. Follow-up at 8 years of age showed developmental delays and mild intellectual disability. During her second pregnancy (G 2), prenatal ultrasound revealed nasal bone hypoplasia, and the pregnancy was terminated at 23rd gestational week. During her third pregnancy (G 3), all prenatal tests were normal, and the neonate showed normal growth and development at 4 months of age. The karyotype of amniotic fluid of her first pregnancy was 46, X? , and the SNP-array analysis of neonatal peripheral blood showed arr[GRCh37/hg19]11q13.4q25(70432450_134607121)×2~3, with a mosaicism rate being approximately 40%. The karyotype for her second pregnancy was 46, X? , rec(11)dup(11q)inv(11)(p15q13)dmat[6]/46, X? [27], and the SNP-array result was arr[GRCh38]11q13.4q25(71406636_135067522)×2~3, with a mosaicism rate being approximately 75%. The karyotype for her third pregnancy was 46, X? , inv(11)(p15q13)mat, and the SNP-array result was arr(XN)×1, (1~22)×2. The karyotype of the woman was 46, XX, inv(11)(p15q13), and that of her husband was 46, XY. A review of 12 similar cases (including G 1) from the literature revealed that the common clinical phenotypes of 11q partial duplication included intellectual disability (12/12), developmental delay (12/12), ear abnormalities (12/12), microcephaly (10/12), seizures (8/12), hypotonia (8/12), and congenital heart malformations (7/12). Conclusion:Mosaic partial duplication of 11q may underlie the genetic etiology of this pedigree. The pregnant woman is a carrier of an inversion on chromosome 11, which might have formed the mosaic 11q partial duplication through meiotic errors and mitotic trisomy rescue mechanisms during reproduction.

Objective:To investigate the factors influencing the prescribing habits of general practitioners (GPs) in relation to single-pill combination (SPC) antihypertensive drugs.Methods:This was a qualitative study. Using the purposive sampling method, 2 general hospitals (designated as HAZ1-2) and 4 community health service centers (designated as HAS1-4) in Huai′an city, Jiangsu province were selected from April to May 2023. In addition, 4 general practitioners (designated as A-D) were selected as interviewees from each general hospital and center. The selected individuals were interviewed using on-site thematic group interviews. The interview mainly included the principles of clinical selection of SPC antihypertensive drugs; the degree of acceptance of SPC antihypertensive drugs by patients after prescription; the evaluation of SPC antihypertensive drugs and the difficulties existing in their clinical use. The data of the interview were analyzed according to the thematic framework.Results:Twenty-four GPs were interviewed. Four themes and 9 sub-themes were extracted regarding factors influencing GP prescribing of SPC antihypertensive drugs. The study showed that: (1) the prescribing of SPC antihypertensive drugs by GPs according to patients′ specific conditions; (2) the prescribing of SPC antihypertensive drugs by GPs was influenced by factors such as price and drug adjustment; (3) the different evaluations of SPC antihypertensive drugs among GPs; (4) GPs in community health service centers faced many difficulties in prescribing SPC antihypertensive drugs (relatively fewer varieties of SPC drugs in the community, lower patient trust in community GPs, and lower standardization of prescribing by community GPs).Conclusion:The factors influencing GPs′ prescribing of SPC antihypertensive drugs mainly include the patients′ specific situation, price, medication adjustment, attitude of GPs, and some clinical practice problems.

Objective:To analyze the clinicopathological features of prostate cancers with BRCA2 pathogenic mutations, and the association between BRCA2 pathogenic mutation and clinicopathological characteristics. Patient survivals were also examined.Methods:Clinicopathological data of 249 prostate cancer patients who underwent genetic testing in West China Hospital of Sichuan University, Chengdu, China from June 2014 to August 2021 were collected. A retrospective analysis of histopathological morphology, clinicopathological characteristics, and patient survivals was conducted.Results:The genetic testing in the 249 prostate cancer patients showed a pathogenic mutation of DNA damage repair gene (DRG) in 73 cases (73/249, 29.3%), including 22 cases (8.8%) with BRCA2 pathogenic mutation and 51 cases with pathogenic mutations of other DRG. Among the 22 patients with BRCA2 pathogenic mutation, 14 patients (5.6%) harbored germline mutations and 8 patients (3.2%) somatic mutations. Their ages ranged from 48 to 91 years, with a median of 67 years. Seventeen patients (77.3%) had distant metastasis, including 16 cases with bone metastasis and 1 case with multiple metastases. Thirteen patients (59.1%) were castration-resistant prostate cancer. The histological type was mainly classical prostatic acinar adenocarcinoma, including 16 cases (72.7%) with intraductal carcinoma of the prostate (IDC-P). Six cases (27.3%) showed focal neuroendocrine differentiation. Perineural/vascular invasion and extraprostatic extension were seen in 11 cases (50.0%) and 8 cases (36.4%), respectively. The Gleason scores of 19 patients (86.4%) were≥8. IDC-P was more commonly found in patients with BRCA2 germline pathogenic mutation than those with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P=0.002). With a total follow-up time of 189 months, the median overall survival (OS) was 132.3 months. Patients with DRG pathogenic mutation had shorter OS than those with no-DRG pathogenic mutation ( P=0.040). The OS of patients with BRCA2 germline pathogenic mutation did not significantly differ from that of patients with BRCA2 somatic pathogenic mutation, other DRG pathogenic mutation or no-DRG pathogenic mutation ( P=0.216). Conclusions:The presence of BRCA2 gene pathogenic mutation is common in the prostate cancers with high Gleason grade, advanced clinical stage, and castration resistance. IDC-P is more commonly noted in cases with BRCA2 germline pathogenic mutation than those without. Patients with DRG pathogenic mutation have shorter OS than those with no-DRG pathogenic mutation, but there is no significant association between BRCA2 pathogenic mutations and OS.

Objective To explore the clinical characteristics and genetic mechanisms of patients with Mucolipidosis Ⅲα/β caused by GNPTAB gene mutations.Methods A retrospective analysis was conducted on the clinical data and genetic tests of a confirmed case of Mucolipidosis Ⅲα/β.Various protein prediction tools were used to generate protein models of the wild type and mutant GNPTAB proteins,and computational biology tools were employed to elucidate the differences in protein structure and function between the wild type and mutant variants.Results The patient in this case mainly presented with joint deformities and short stature.Genetic sequencing revealed compound heterozygous mutations in the GNPTAB gene,c.2715+1G＞A and c.1582T＞C;the missense mutation c.1582T＞C has not been reported in the literature.By constructing and analyzing three-dimensional models of the mutants,it was found that the c.2715+1G＞A mutation alters the overall structure of the protein,leading to the loss of protein function,while the c.1582T＞C mutation affects the interaction between the subunit of N-acetylglucosamine-1-phosphate transferase and its ligand.Conclusions This case of MLⅢα/β results from a mutation in the GNPTAB gene,including a missense mutation c.1582T＞C that has not been previ-ously reported,which expands the spectrum of pathogenic mutations of this gene.Through computational analysis of the protein variants resulting from the GNPTAB gene mutation,the understanding of their structure-function relationship has been elaborated,revealing the molecular mechanisms behind the onset of ML Ⅲα/β disease.

The patient was diagnosed with "motor retardation for 3 years" in the neurology department of our hospital,accompanied by static tremors and ataxia. Physical examination showed that there was a tendency to decrease for amplitude of repetitive finger movements of the left hand and the left hand clenched fist and toe tapping movements were slightly slower. The left heel knee tibia test and rotation test were not accurate,and the father and elder sister had similar symptoms. After admission,laboratory tests such as urinary tract ultrasound and residual urine in the bladder were completed,and the tests did not reveal any significant abnormalities. Brain MRI shows scattered non-specific white matter changes in the left parietal lobe. Levodopa challenge test was positive. The patient was then suspected to have Parkinsonism. considering that the patient has a family history. Genetic testing was ordered and the results showed abnormal amplification of the ATXN2 gene CAG sequence. Therefore,the final diagnosis was spinocerebellar ataxia type 2. The patient's symptoms are stable and there is no progression during the follow-up. SCA2 should be considered in the case of Parkinsonism accompanied by ataxia and a family history to avoid misdiagnosis and missed diagnosis.