Humans ; Stroke Volume ; Valsartan/therapeutic use* ; Heart Failure/drug therapy* ; Hypotension/drug therapy* ; Aminobutyrates/therapeutic use* ; Drug Combinations ; Angiotensin Receptor Antagonists/therapeutic use* ; Tetrazoles/therapeutic use* ; Treatment Outcome ; Ventricular Function, Left

Humans ; Stroke Volume ; Valsartan/therapeutic use* ; Heart Failure/drug therapy* ; Hypotension/drug therapy* ; Aminobutyrates/therapeutic use* ; Drug Combinations ; Angiotensin Receptor Antagonists/therapeutic use* ; Tetrazoles/therapeutic use* ; Treatment Outcome ; Ventricular Function, Left

OBJECTIVE: To explore the genetic etiology of a small-for-date infant with gastrointestinal bleeding, developmental delay and thrombocytopenia (Zhu-Tokita-Takenouchi-Kim syndrome). METHODS: Clinical and laboratory examinations were carried out for the patient. Next-generation sequencing (NGS) was used to detect potential variant associated with the disease. Candidate variant was verified by Sanger sequencing of the child and her parents. RESULTS: NGS revealed that the child has carried a heterozygous c.5751_5754del variant of the SON gene, which resulted in a frameshift p.V1918Efs*87. The same variant was detected in neither parent. CONCLUSION The heterozygous variant of SON gene probably underlay the ZTTK syndrome in this child. Above finding has enriched the mutational spectrum of the SON gene and provides a basis for genetic counseling and clinical decision-making.
Child ; Family ; Female ; Genetic Testing ; Heterozygote ; Humans ; Infant ; Intellectual Disability/genetics* ; Mutation

Objective: To examine the outcomes of Slide tracheoplasty for the children with severe congenital tracheal stenosis received previous repeated balloon dilatation or metal stent placement under endoscopy. Methods: A retrospective study was conducted in 9 children with congenital tracheal stenosis undergoing previous interventional therapy under tracheoscopy and later received Slide tracheoplasty due to obvious respiratory symptoms at Department of Cardiac Surgery, Qilu Children's Hospital of Shandong University between February 2017 and July 2021. There were 7 males and 2 females with a median age at operation of 72.4 months (range: 13.3 to 98.9 months), and the median weight was 19.0 kg (range: 9.0 to 33.0 kg). Among the 9 patients, 2 patients began to receive repeated balloon dilatation (more than 3 times) 17.8 and 51.8 months ago respectively. One patient received metal stents placement into the trachea for 4 days and the other 6 children for median 56.8 months (range: 21.6 to 74.2 months). Complete tracheal cartilage rings and long segmental stenosis were present. in all 9 children. Operative details and outcome measures, including the need for endoscopic airway intervention and mortality, were collected. Results: Slide tracheoplasty was performed in all cases. Two patients with repeated balloon dilatation had different thickness of tracheal wall, local scar hyperplasia and irregular lumen. Among them, 1 case had obvious local calcification of tracheal wall, which was difficult to suture. The metal stent in one patient with short time of placement was completely removed. However, only part of the metal stents could be removed due to the long placement time in the other 6 cases. There was no operative death in the 9 children. The median postoperative tracheal intubation time was 25.3 hours (range: 17.4 to 74.5 hours). A silicone stent was placed in the trachea of 1 child due to obvious respiratory symptoms. Follow-up of median 11 months (range: 1 to 23 months) showed that no death occurred after discharge and all children had basically normal activity tolerance with no obvious respiratory symptoms. Conclusions: Slide tracheoplasty is feasible for children undergoing prior balloon dilatation or metal stents placement. Previously repeated balloon dilatation or metal stent placement under endoscopy increased the difficulty of slide tracheoplasty, the metal stent could not be completely removed after a long time.
Child ; Constriction, Pathologic ; Dilatation ; Endoscopy ; Female ; Humans ; Infant ; Male ; Reconstructive Surgical Procedures ; Retrospective Studies ; Stents ; Trachea/surgery* ; Tracheal Stenosis/surgery* ; Treatment Outcome

OBJECTIVE: To analyze the clinical and genetic characteristics of a boy featuring unexplained developmental delay, malnutrition and distinct facial appearance. METHODS: Physical examination was carried out for the child. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA and trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The patient had facial dysmorphism including nasal alae aplasia, scalp defect and teeth deformities, in addition with recurrent diarrhea due to pancreatic exocrine insufficiency. DNA sequencing revealed that he has harbored compound heterozygous variants of the UBR1 gene, namely c.3167C>G (p.S1056X) and c.1911+14C>G, which were inherited from his father and mother, respectively. Database search has suggested the c.3167C>G to be a novel nonsense variant and c.1911+14C>G a known splicing variant. Based on the guidelines of the American College of Medical Genetics and Genomics, the two variants were predicted to be pathogenic and likely pathogenic, respectively. CONCLUSION The child was diagnosed with Johanson-Blizzard syndrome due to the compound heterozygous variants of the UBR1 gene. Above finding has enriched the mutational spectrum of the UBR1 gene and provided a basis for genetic counseling for this family.
Child ; Humans ; Male ; Ectodermal Dysplasia/genetics* ; Pancreatic Diseases/genetics* ; Ubiquitin-Protein Ligases/genetics*

Objective: To understand the study method and the baseline characteristics of the survey subjects of Shandong hilly rural natural population cohort study, and provide reference for the research of the prevalence and risk factors of common chronic and non-communicable diseases. Methods: Baseline survey, including questionnaire survey, physical examination, biochemical index examination and blood and saliva collection, was conducted in local residents aged 20-79 years in Kongcun and Xiaozhi townships of Pingyin county, Shandong province, from 2017 to 2019. Shandong hilly rural natural population cohort was established and main baseline characteristics of the study subjects were statistically analyzed. Results: A total of 10 296 study subjects aged 54.45 years were included in the study, in whom 40.6% were males. Among the study subjects, 88.3% had education level of junior high school or below, 62.1% were famers, and 90.7% were married. Smokers accounted for 45.6% of men and 0.9% of women, and drinkers accounted for 65.8% of men and 3.0% of women, respectively. The self-reported rates of hypertension, diabetes, coronary heart disease, stroke and tumors were 19.8%, 3.2%, 2.8%, 2.7% and 1.2%, respectively. Conclusion: The Shandong hilly rural cohort natural population study provided important evidence for assessing the risk for common chronic and non-communicable diseases and disease prevention and control in hilly rural areas.
Male ; Female ; Humans ; Cohort Studies ; Noncommunicable Diseases ; Rural Population ; Surveys and Questionnaires ; Self Report

【Objective】 To explore the polymorphism of HPA-1-6w, HPA-15 and 32bw-35bw in platelet donors in Deyang, Sichuan, and estimate whether to include the detection of 32bw-35bw in the platelet bank. 【Methods】 Polymerase chain reaction with sequenced based typing (PCR-SBT) was used to sequence the HPA-1-6w, HPA-15 and 32bw-35bw loci of 205 platelet donors in Deyang. Allele frequencies were calculated by the direct counting method. The frequencies of HPA-1-6 and 15 alleles in northern and southern Chinese, Japanese and Australian population were compared, and those HPA loci and HPA-32bw-35bw were searched in the Chinese Millionome Database (CMDB) and genomAD to obtain the polymorphism data. Then the Chi-square test was performed with the data of this study through GraphPad Prism 9 software. 【Results】 The allele frequencies of HPA-1b, 2b, 3b, 5b, 6bw and HPA-15b were 0.005(2/410), 0.037(15/410), 0.471(193/410), 0.020(8/410), 0.010(4/410) and 0.461(189/410), respectively, b allele of HPA-32bw-35bw and HPA-4 was not detected. Statistical significance was observed between the HPA-1b allele frequency of this study and northern Chinese, Australian population and genomAD global population sample (P< 0.05, 0.005 vs 0.014 vs 0.145 vs 0.122). The frequency of HPA-2b alleles in this study, Japanese population and genomAD global population samples was 0.037 vs 0.120 vs 0.100, with statistical difference(P<0.05). Comparison of HPA-5b and HPA-6bw allele frequencies with those of genomAD global population showed a statistical difference (P<0.05, 0.020 vs 0.089 and 0.010 vs 0.000 008, respectively). 【Conclusion】 The polymorphisms of HPA-1-6w and HPA-15 of donors in Deyang has characteristics of the southern Chinese. The frequencies of HPA-32bw-35bw were extremely low, which could be excluded from the platelet bank in Deyang.

[Abstract] Objective: To investigate whether AP1903, a small-molecule chemical inducer, can terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vivo and in vitro. Methods: CD19CAR-T cells over-expressing iCasp9 (iCasp9-CD19CAR-T) were constructed and co-incubated with AP1903. Then, the cell phenotype and apoptosis were detected by Flow cytometry, and the iCasp9/CID suicide gene system was verified on K562 and T cells, respectively. The cytotoxicity of iCasp9-CD19CAR-T cells was detected in vivo (survival rate of NCG mice bearing Raji cell transplanted xenograft) and in vitro (cell killing function was detected by Flow cytometry) under the administration of AP1903. Results: Compared with CD19CAR-T cells, iCasp9-CD19CAR-T cells showed in significant difference in proliferation, phenotype and cytotoxicity both in vitro and in vivo (all P>0.05). At 2 h after AP1903 administration, the apoptosis rates of K562 and T cells co-expressing iCasp9 and CD19CAR were (33.8±0.9)% and (27.95±0.35)%, respectively; and at 24 h after AP1903 administration, the apoptosis rates reached 100% in both cell lines. The in vitro cytotoxicity of iCasp9-CD19CAR-T cells induced by AP1903 was significantly lower than that without AP1903 treatment (P<0.01); the 60-day survival rate of mice bearing Raji cell transplanted tumor treated with AP1903-induced iCasp9-CD19CAR-T cells was also significantly lower than those treated with iCasp9-CD19CAR-T cells alone (P<0.01). Conclusion: AP1903 can effectively terminate the cytotoxicity of CD19CAR-T cells over-expressing iCasp9 suicide gene in vitro and in vivo.

China/epidemiology* ; Coronary Angiography ; Coronary Artery Disease/diagnosis* ; Humans ; Registries ; Risk Assessment ; Risk Factors

BACKGROUND: Reduced application of percutaneous coronary intervention (PCI) is associated with higher mortality rates after ST-segment elevation myocardial infarction (STEMI). We aimed to evaluate potential factors contributing to the refusal of PCI in STEMI patients in China. METHODS: We studied 957 patients diagnosed with STEMI in the emergency departments (EDs) of six public hospitals in China. The differences in baseline characteristics and 30-day outcome were investigated between patients who refused PCI and those who underwent PCI. Multivariable logistic regression was used to evaluate the potential factors associated with refusing PCI. RESULTS: The potential factors contributing to refusing PCI were older than 65 years (odds ratio [OR] 2.66, 95% confidence interval [CI] 1.56-4.52, P < 0.001), low body mass index (BMI) (OR 0.91, 95% CI 0.84-0.98, P = 0.013), not being married (OR 0.29, 95% CI 0.17-0.49, P < 0.001), history of myocardial infarction (MI) (OR 2.59, 95% CI 1.33-5.04, P = 0.005), higher heart rate (HR) (OR 1.02, 95% CI 1.01-1.03, P = 0.002), cardiac shock in the ED (OR 5.03, 95% CI 1.48-17.08, P = 0.010), pre-hospital delay (>12 h) (OR 3.31, 95% CI 1.83-6.02, P < 0.001) and not being hospitalized in a tertiary hospital (OR 0.45, 95% CI 0.27-0.75, P = 0.002). Compared to men, women were older, were less often married, had a lower BMI and were less often hospitalized in tertiary hospitals. CONCLUSIONS Patients who were older, had lower economic or social status, and had poorer health status were more likely to refuse PCI after STEMI. There was a sex difference in the potential predictors of refusing PCI. Targeted efforts should be made to improve the acceptance of PCI among patients with STEMI in China.
China ; Female ; Humans ; Male ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Risk Factors ; ST Elevation Myocardial Infarction/surgery* ; Time Factors ; Treatment Outcome