ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction （清肺渗湿汤） combined with western medicine for patients with bronchial asthma of heat wheezing syndrome， and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group， each group with 43 participants. The control group received conventional western medicine， and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group， 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness； secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， asthma control test （ACT） score， pulmonary function indices such as forced expiratory volume in 1 second （FEV₁）， forced vital capacity （FVC）， peak expiratory flow （PEF）， serum inflammatory factor levels including interleukin-4 （IL-4）， tumour necrosis factor-α （TNF-α）， and high-sensitivity C-reactive protein （hs-CRP）， and immune function indices including CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺. All outcome measures were evaluated before and after treatment. Vital signs were monitored， and electrocardiography， blood routine， urine routine， liver function， and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% （39/40）， which was significantly higher than that of the control group （85.0%， 34/40， P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， IL-4， TNF-α， hs-CRP， and CD8⁺ levels， as well as increased ACT scores， CD3⁺， CD4⁺， CD4⁺/CD8⁺， FEV₁， FVC， and PEF levels （P＜0.05 or P＜0.01）. Moreover， the improvements in these indices were more significant in the treatment group than in the control group （P＜0.05 or P＜0.01）. No significant abnormalities in safety indicators were observed in either group， and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms， pulmonary function， and clinical effectiveness， with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.

Objective To elucidate the application scope and delineate the criteria of dobutamine stress echocardiography (DSE) in assessing surgical risk associated with valvular heart diseases in patients presenting with reduced left ventricular ejection fraction (LVEF). Methods This retrospective analysis encompassed data from patients with reduced LVEF (LVEF<40%) who underwent DSE prior to valvular heart surgery at the Valvular Surgery Center of Beijing Anzhen Hospital between May 2016 and September 2024. Patients were stratified based on the terminal dose of dobutamine into two cohorts: a limited dose group [receiving a maximum dobutamine dose of <5 µg/(kg·min) due to concomitant conditions such as suspected atrial thrombus, aortic dilation, or previous myocardial infarction] and a non-limited dose group (where dosage was adjusted to either achieve the maximum positive standard or the maximal dose tolerable by the patient). Within the non-limited dose group, patients were further classified into positive and negative response groups. The positive response post DSE was defined based on the following criteria: LVEF≥55% (the maximum positive standard), LVEF<55% but with a 5% improvement (the minimum positive standard) from resting situation, aortic maximum velocity (AVmax)≥400 cm/s, or mean pressure gradient (meanPG)≥40 mm Hg, latter two applicable only to patients with aortic stenosis. Clinical indicators were compared in the three groups. Results A total of 99 patients were enrolled, aged 35 to 87 years, with an average age of (61.7±10.1) years. The number of males was significantly higher than that of females (3:1). There were 61 (61.6%) patients undergoing aortic valve surgery, 25 (25.3%) undergoing mitral valve surgery, and 13 (13.1%) undergoing combined aortic and mitral valve surgery. Nineteen (19.2%) patients experienced adverse symptoms such as palpitations, head and face numbness, dizziness, chest tightness post DSE. Additionally, new-onset or aggravated ventricular premature ventricular contractions were in 40 (40.4%) patients. All above symptoms and signs resolved minutes after cessation of the test. No severe adverse events necessitating oxygen therapy or emergency intervention occurred. Among the 93 patients in the non-limited dose group, 86 were classified in the positive response group and 7 in the negative response group. The left ventricular end diastolic diameter, left ventricular end systolic diameter, and LVEF in the positive group all showed significant improvement compared to preoperative values, and were also significantly better than those in the negative group (P<0.05). All 7 patients with negative DSE results underwent interventional surgery, which was significantly different from the positive group (36 patients, 41.9%). In the limited dose group (n=6), 4 patients with a positive result or a positive trend on DSE underwent median sternotomy, 2 received interventional treatment due to a negative response. No significant differences in mortality were observed among the groups (P>0.05). Conclusion Dobutamine stress echocardiography significantly contributes to risk stratification in surgical interventions for patients with valvular heart disease complicated by reduced LVEF. It aids in determining optimal timing and methods for surgery. With comprehensive patient evaluation and controlled dobutamine dosing, the application of DSE can be safely expanded.

Objective:To explore the clinical characteristics and gene variant of a fetus with Farber lipogranulomatosis caused by ASAH1 gene variant. Methods:A fetus with Farber lipogranulomatosis caused by ASAH1 gene variant diagnosed at Women and Children′s Hospital of Ningbo University in August 2024 was selected as the subject. Clinical data and abortion tissue samples of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Sanger sequencing validation and bioinformatics analysis were performed on candidate variants. This study was approved by Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048). Results:Generalized skin oedema, pericardial effusion, right pleural effusion and increased bowel echogenicity of the fetus were founded by prenatal ultrasound. WES revealed that the fetus has harbored a homozygous c. 101C>A(p.Ser34Ter) variation in exon 2 of the ASAH1 gene. Sanger sequencing confirmed that both parents carry the heterozygous nonsense variation c. 101C>A (p.Ser34Ter) in ASAH1 gene, which has not been included in databases such as HGMD, ClinVar, 1000 Genomes, ExAC, dbSNP, and gnomAD. Based on the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PM2_Supporting+ PVS1+ PM3_Supporting). The AlphaFold3 model protein structure prediction reveals that the c. 101C>A variant caused the premature appearance of a termination codon, resulting in only a small partial α-helix structure in the N-terminal of the encoded ASAH1 protein, with the complete loss of the α-helix structure in the core domain, which might lead to the loss of function of this protein. Conclusion:The c. 101C>A(p.Ser34Ter) variant of the ASAH1 gene probably underlay the Farber lipogranulomatosis with hydrops fetalis in this fetus. The newly discovered c. 101C>A(p.Ser34Ter) variant has enriched the mutational spectrum of Farber lipogranulomatosis.

Objective:To explore the genetic etiology of a child with brain small vessel disease 1 with ocular anomalies.Methods:A child who was adwstted to Ningbo Women and Children′s Hospital on May 28, 2022, was selected for the study. Clinical data were collected, and peripheral blood samples from the child and her parents were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed to screen for pathogenic variants. Candidate variants were validated via Sanger sequencing and subjected to bioinformatic analysis. This study was approved by the Medical Ethics Committee of Ningbo Women and Children′s Hospital (Ethics No. EC2020-048).Results:① The child was a 7-year-old female with a diagnosis of epilepsy. ② WES revealed that she has carried a heterozygous missense variant in the COL4A1 gene: c. 1792G>A (p.Gly598Ser). Sanger sequencing confirmed that her parents both had the wild-type genotype for this variant. Based on American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, the variant were predicted to be a likely pathogenic (PS2+ PM1+ PM2_Supporting+ PP3). ③ Bioinformatics predicted that amino acid 598 was highly conserved in different species, formed hydrogen bond with Asp599 after becoming Ser598. Conclusion:The heterozygous missense variant of the COL4A1 gene c. 1792G>A (p.G598S) could be the pathogenic cause of this child with Brain small vessel disease 1 with ocular anomalies.

Objective:To explore the genetic characteristics of a fetus affected with Structural heart defects and renal anomalies syndrome (SHDRA).Methods:A pedigree with SHDRA (fetus and the parents) who had visited the Affiliated Women and Children′s Hospital of Ningbo University in April 2023 was selected as the study subject. Clinical data of the family were collected. A total of 10 mL of amniotic fluid cells from the fetus and 5 mL of peripheral blood samples from the parents were collected for genomic DNA extraction. Trio whole-exome sequencing (Trio-WES) was performed, and Sanger sequencing was used to validate candidate variants in the family. The identified variants were classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines). Relevant research literature on SHDRA in domestic and international databases were searched for literature review. This study was approved by the Affiliated Women and Children′s Hospital of Ningbo University (Ethics No. EC2023-094).Results:①In this family, prenatal ultrasound at 18 weeks of gestation revealed left renal multicystic dysplasia in the fetus. After birth, the infant exhibited an ostium secundum atrial septal defect, patent ductus arteriosus, and left renal multicystic dysplasia. Trio-WES revealed that the fetus had carried c. 344dup(p.L116Afs*32) and c. 90_104dup(p.Ala31_Ala35dup) compound heterozygous variants in the TMEM260 gene, which were respectively inherited from its father and mother. According to the ACMG guidelines, the c. 344dup(p.L116Afs*32) and c. 90_104dup (p.Ala31_Ala35dup) variants were classified as pathogenic (PM2_Supporting+ PVS1+ PP4) and likely pathogenic (PM2_Supporting+ PM4+ PM3+ PP4), respectively. ②According to the literature search strategy set for this study, a total of 6 literature was retrieved, involving 25 SHDRA patients from 20 families. Together with the patients in this study, there were 14 TMEM260 gene variants, most of which were frameshift variants (7 types) and had located in exons 3, 11 and 13. The main clinical features of SHDRA were congenital heart malformation, renal abnormality and neurodevelopmental abnormality, and there was a lack of genotype-phenotype correlation. Conclusion:The c. 344dup(p.L116Afs*32) and c. 90_104dup(p.Ala31_Ala35dup) variants of the TMEM260 gene probably underlay the SHDRA in this family. Above finding has provided a basis for clinical diagnosis and genetic counseling for the family.

Objective:To evaluate the safety and feasibility of radical hepatectomy after conversion therapy in patients with initially unresectable advanced hepatocellular carcinoma (HCC).Methods:Clinical data of 72 patients with initially unresectable advanced HCC admitted to the Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University and the Department of Hepatobi-liary and Pancreatic Surgery, Henan Provincial People's Hospital from January 2020 to July 2024 were retrospectively collected, including 61 males and 11 females, aged (58.4±9.1) years. The clinicopathological data of the patients, such as tumor characteristics, conversion treatment regimens, perioperative data, and follow-up situations were analyzed to evaluate the therapeutic effect and safety.Results:Among the patients, there were five cases of China liver cancer staging Ⅰb, six cases of Ⅱa, 22 cases of Ⅱb, 32 cases of Ⅲa and sevene cases of Ⅲb. There were 53 patients scored as Child-Pugh A and 19 as Child-Pugh B. Conversion treatment fashion included immunotherapy combined with targeted therapy and immunotherapy plus targeted therapy combined with hepatic arterial chemoembolization or hepatic arteryinfusion chemotherapy. Liver resection after conversion therapy was as follows: 16 cases of right hemihepatectomy, 20 cases of left hemihepatectomy, 11 cases of mesohepatectomy, seven cases of right posterior hepatectomy, 1 case of caudate lobectomy, 17 cases of local resection. Postoperative pathology showed that there were 17 cases of pathologic complete response and 55 cases of pathologic partial response. One patient died of liver failure after surgery, while the rest had no major complications. The postoperative hospital stay was (13.1±5.1) d. The follow-up time was 21.5(10.2, 32.1) months. The multivariate Cox analysis demonstrated that pathologic partial response and adjuvant therapy duration shorter than 5 cycles were identified as independent risk factors-affecting both recurrence-free survival and overall survival in patients with HCC undergoing sequential surgery after conversion therapy (all P<0.05). Conclusion:Sequential surgical resection provides survival benefits for patients with initially unresectable and advanced HCC after conversion therapy, which is a safe and effective therapeutic strategy.

OBJECTIVE: To explore the clinical characteristics and gene variant of a fetus with Farber lipogranulomatosis caused by ASAH1 gene variant. METHODS: A fetus with Farber lipogranulomatosis caused by ASAH1 gene variant diagnosed at Women and Children's Hospital of Ningbo University in August 2024 was selected as the subject. Clinical data and abortion tissue samples of the fetus and peripheral blood samples of its parents were collected for whole exome sequencing (WES). Sanger sequencing validation and bioinformatics analysis were performed on candidate variants. This study was approved by Women and Children's Hospital of Ningbo University (Ethics No. EC2020-048). RESULTS: Generalized skin oedema, pericardial effusion, right pleural effusion and increased bowel echogenicity of the fetus were founded by prenatal ultrasound. WES revealed that the fetus has harbored a homozygous c.101C>A (p.Ser34Ter) variation in exon 2 of the ASAH1 gene. Sanger sequencing confirmed that both parents carry the heterozygous nonsense variation c.101C>A (p.Ser34Ter) in ASAH1 gene, which has not been included in databases such as HGMD, ClinVar, 1000 Genomes, ExAC, dbSNP, and gnomAD. Based on the Standards and Guidelines for the Interpretation of Sequence Variants of the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic (PM2_Supporting+PVS1+PM3_Supporting). The AlphaFold3 model protein structure prediction reveals that the c.101C>A variant caused the premature appearance of a termination codon, resulting in only a small partial α-helix structure in the N-terminal of the encoded ASAH1 protein, with the complete loss of the α-helix structure in the core domain, which might lead to the loss of function of this protein. CONCLUSION The c.101C>A (p.Ser34Ter) variant of the ASAH1 gene probably underlay the Farber lipogranulomatosis with hydrops fetalis in this fetus. The newly discovered c.101C>A (p.Ser34Ter) variant has enriched the mutational spectrum of Farber lipogranulomatosis.
Humans ; Female ; Pregnancy ; Acid Ceramidase/chemistry* ; Farber Lipogranulomatosis/diagnostic imaging* ; Fetus ; Exome Sequencing ; Adult

OBJECTIVE: To explore the genetic characteristics of a fetus affected with Structural heart defects and renal anomalies syndrome (SHDRA). METHODS: A pedigree with SHDRA (fetus and the parents) who had visited the Affiliated Women and Children's Hospital of Ningbo University in April 2023 was selected as the study subject. Clinical data of the family were collected. A total of 10 mL of amniotic fluid cells from the fetus and 5 mL of peripheral blood samples from the parents were collected for genomic DNA extraction. Trio whole-exome sequencing (Trio-WES) was performed, and Sanger sequencing was used to validate candidate variants in the family. The identified variants were classified according to the Standards and Guidelines for the Interpretation of Sequence Variants established by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the "ACMG Guidelines). Relevant research literature on SHDRA in domestic and international databases were searched for literature review. This study was approved by the Affiliated Women and Children's Hospital of Ningbo University (Ethics No. EC2023-094). RESULTS: In this family, prenatal ultrasound at 18 weeks of gestation revealed left renal multicystic dysplasia in the fetus. After birth, the infant exhibited an ostium secundum atrial septal defect, patent ductus arteriosus, and left renal multicystic dysplasia. Trio-WES revealed that the fetus had carried c.344dup (p.L116Afs*32) and c.90_104dup (p.Ala31_Ala35dup) compound heterozygous variants in the TMEM260 gene, which were respectively inherited from its father and mother. According to the ACMG guidelines, the c.344dup (p.L116Afs*32) and c.90_104dup (p.Ala31_Ala35dup) variants were classified as pathogenic (PM2_Supporting+PVS1+PP4) and likely pathogenic (PM2_Supporting+PM4+PM3+PP4), respectively. According to the literature search strategy set for this study, a total of 6 literature was retrieved, involving 25 SHDRA patients from 20 families. Together with the patients in this study, there were 14 TMEM260 gene variants, most of which were frameshift variants (7 types) and had located in exons 3, 11 and 13. The main clinical features of SHDRA were congenital heart malformation, renal abnormality and neurodevelopmental abnormality, and there was a lack of genotype-phenotype correlation. CONCLUSION The c.344dup (p.L116Afs*32) and c.90_104dup (p.Ala31_Ala35dup) variants of the TMEM260 gene probably underlay the SHDRA in this family. Above finding has provided a basis for clinical diagnosis and genetic counseling for the family.
Humans ; Female ; Pedigree ; Membrane Proteins/genetics* ; Male ; Heart Defects, Congenital/genetics* ; Kidney/abnormalities* ; Pregnancy ; Adult ; Kidney Diseases/congenital* ; Exome Sequencing ; Mutation ; Genetic Testing

OBJECTIVE: To explore the genetic etiology of a child with Brain small vessel disease 1 with ocular anomalies. METHODS: A child who was admitted to Ningbo Women and Children's Hospital on May 28, 2022 was selected for the study. Clinical data were collected, and peripheral blood samples from the child and her parents were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed to screen for pathogenic variants. Candidate variants were validated via Sanger sequencing and subjected to bioinformatic analysis. This study was approved by the Medical Ethics Committee of Ningbo Women and Children's Hospital (Ethics No. EC2020-014). RESULTS: The child was a 7-year-old female with a diagnosis of epilepsy. WES revealed that she has carried a heterozygous missense variant in the COL4A1 gene: c.1792G>A (p.Gly598Ser). Sanger sequencing confirmed that her parents both had the wild-type genotype for this variant. Based on American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants, the variant were predicted to be a likely pathogenic (PS2+PM1+PM2_Supporting+PP3). Bioinformatics predicted that amino acid 598 was highly conserved in different species, formed hydrogen bond with Asp599 after becoming Ser598. CONCLUSION The heterozygous missense variant of the COL4A1 gene c.1792T>C (p.G598S) could be the pathogenic cause of this child with Brain small vessel disease 1 with ocular anomalies.
Humans ; Female ; Child ; Collagen Type IV/genetics* ; Eye Abnormalities/genetics* ; Exome Sequencing ; Mutation, Missense ; Cerebral Small Vessel Diseases/genetics*

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with Fliedner-Zweier syndrome (FZS). METHODS: A pregnant woman who was diagnosed with FZS at the Affiliated Women and Children's Hospital of Ningbo University in November 2023 for "intellectual disability, epilepsy, delayed language development and facial abnormalities" was selected as the study subject. Peripheral blood samples were collected from the woman and her husband, whilst amniotic fluid sample was obtained from the fetus. Following extraction of genomic DNA, whole-exome sequencing (WES) and chromosomal karyotyping analysis were performed. Candidate variant was validated by Sanger sequencing. Pathogenicity of the variant was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: EC2023-094). RESULTS: The proband, a 23-year-old woman, was at 19⁺² weeks of gestation and had a history of epilepsy, mild intellectual disability, delayed language development, and subtle facial dysmorphism. Chromosomal analysis showed the she has a normal karyotype. WES revealed that the woman and her fetus both harbored a heterozygous c.1489C>T (p.Gln497Ter) nonsense variant of the SCAF4 gene, which was verified by Sanger sequencing as de novo. Based on the ACMG guidelines, the variant was classified as pathogenic (PVS1+PM2_supporting+PS2_supporting). According to pre-set search strategy, five articles were retrieved. Together with the patient in this study, a total of 69 FZS patients were involved (including 7 from China). The main clinical features have included intellectual disability, epilepsy, behavioral abnormalities, and facial dysmorphism. CONCLUSION The heterozygous c.1489C>T (p.Gln497Ter) variant of the SCAF4 gene probably underlyay the FZS in this patient. Above finding has expanded the mutational spectrum of the SCAF4 gene.
Humans ; Female ; Intellectual Disability/genetics* ; Pregnancy ; Young Adult ; Exome Sequencing ; Epilepsy/genetics* ; Abnormalities, Multiple/genetics* ; Mutation ; Karyotyping