Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Objective:To investigate the incidence rate and gene variation of methylmalonic academia (MMA) in Ji′nan city by analyzing biochemical and genetic screening results, and to explore the carrier frequency of MMA-related pathogenic genes in the population in Ji′nan.Methods:The children diagnosed with MMA by tandem mass spectrometry screening in Ji′nan Neonatal Disease Screening Centre from May 2011 to May 2022 were enrolled in this study.Their genetic test results were retrospectively analyzed and summarized.The dried heel blood tablets collected from 6 800 newborns were tested for neonatal gene screening. MMAA, MMAB, MMACHC and MMUT genes in 4 800 cases were detected by high-throughput sequencing+ target area capture technology.Ultra-multiplex polymerase chain reaction+ target gene locus capture technology was used to detect 174 target loci of 8 genes related to MMA in 2 000 cases.The hotspot mutation and related gene carrier rate of MMA were analyzed. Results:A total of 367 452 newborns were screened by tandem mass spectrometry, and 103 cases (56 males and 47 females) were diagnosed with MMA by screening.The estimated incidence of MMA was 1∶3 567.Among the 103 MMA cases, 76 were genetically diagnosed, and 4 gene variants of MMA ( MMAHC, MMUT, MMAA, MMADHC) were identified.A total of 6 800 neonates underwent neonatal genetic screening.Three of them were diagnosed with MMA.About 318 infants carried pathogenic variants of MMA, with a total carrier rate of 4.68%.Specifically, the carrier rates of MMACHC and MMUT gene variants were 3.09%(210/6 800) and 1.43% (97/6 800), respectively. Conclusions:MMA is the most common organic acid metabolism disorder in our country.The incidence and carrier rate of this disease are high in Jinan city.Neonatal genetic screening is an important supplement to neonatal biochemical screening.Carrier screening for MMA-related pathogenic genes is recommended for couples of childbearing age in Jinan.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Mental retardation autosomal dominant 51 (MRD51). METHODS: A child with MRD51 who was hospitalized at Guangzhou Women and Children's Medical Center on March 4, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-and-3-month-old girl, had manifested autism spectrum disorder (ASD), mental retardation (MR), recurrent febrile convulsions and facial dysmorphism. WES revealed that she has harbored a novel heterozygous variant of c.142G>T (p.Glu48Ter) in the KMT5B gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. The variant has not been recorded in the ClinVar, OMIM and HGMD, ESP, ExAC and 1000 Genomes databases. Analysis with online software including Mutation Taster, GERP++ and CADD indicated it to be pathogenic. Prediction with SWISS-MODEL online software suggested that the variant may have a significant impact on the structure of KMT5B protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic. CONCLUSION The c.142G>T (p.Glu48Ter) variant of the KMT5B gene probably underlay the MRD51 in this child. Above finding has expanded the spectrum of KMT5B gene mutations and provided a reference for clinical diagnosis and genetic counseling for this family.
Humans ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; Autism Spectrum Disorder/genetics* ; Mutation

Objective:The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.
Adult ; Humans ; Cross-Sectional Studies ; Nasal Cavity/surgery* ; Allergens ; Pollen ; Artemisia ; Hydrodynamics

Objective:To analyze the distribution and drug sensitivity of pathogens in bronchoalveolar lavage fluid(BALF)of children with severe community acquired pneumonia(CAP)in Qingdao from 2018 to 2020.Methods:The clinical data of 482 children with severe CAP in Qingdao admitted to Women and Children′s Hospital of Qingdao University were collected.BALF was collected by bronchoscopy for detection of bacteria and mycoplasma.Results:(1)Bacterial infection was detected in 139 cases(27.84%), mycoplasma infection in 119 cases(24.69%), and virus infection in 141 cases(29.25%). (2)The detection rates of bacteria and virus infection in the 1-12 months old group were higher.The detection rate of mycoplasma pneumoniae was the highest in the group over 5 years old.(3)A total of 139 strains were positive in bacterial culture of lavage fluid under bronchoscope: 55 strains(39.57%) of gram-negative bacilli and 84 strains(60.43%) of gram-positive cocci.Streptococcus pneumoniae was the most common gram-positive bacteria.Haemophilus influenzae was the most common gram-negative strain.(4)Streptococcus pneumoniae and Staphylococcus aureus were highly sensitive to amoxicillin clavulanate potassium, vancomycin and linezolid.The resistance rate to erythromycin was high(100%). (5)Haemophilus influenzae, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were highly sensitive to meropenem and cefoperazone sulbactam.They were highly resistant to amoxicillin, ampicillin and cefuroxime(>80%).Conclusion:Severe CAP in Qingdao area is mainly caused by virus and bacteria within 1 year old.Mycoplasma pneumoniae infection is the main cause of children over 5 years old.Respiratory syncytial virus, adenovirus and parainfluenza virus are main causes of virus infection.Streptococcus pneumoniae and haemophilus influenzae are the main pathogens, which are more sensitive to vancomycin, linezolid, meropenem and cefoperazone sulbactam, but resistant to erythromycin and amoxicillin.

Objective To analyze the infection situation and risk factors of Helicobacter pylori (Hp) in children in Yulin, Shaanxi province. Methods A total of 374 preschool children with digestive tract symptoms in Yulin area from December 2019 to December 2020 were selected. All the research object of personal data by using self-designed questionnaire (gender, age), personal experiences and health habits (common tableware, common koubei brushing your teeth, wash your hands before the rice then empress), the life habits (whether diet, koubei utilities, brushing your teeth regularly to suck finger), socioeconomic status, place of residence, with the number of living, family economic income), caregivers has a history of stomach problems (parents, nanny) And so on. The investigation method is the combination of telephone inquiry and on-site investigation. 3ml fasting venous blood was collected, and the supernatant was centrifuged. Serum IL-17 and IL-10 levels were determined by ENZYme-linked immunosorbent assay, and Treg and Th17 cell levels were determined by flow cytometry. Hp infection was detected by 14C urea breath test. Univariate analysis and logistic regression were used to analyze the independent risk factors of Hp infection in children. Results Eighty-three of the 374 children were infected with Hp, and the infection rate was 22.19%. The levels of Treg and IL-10 in peripheral blood of Hp infected children were significantly lower than those of non-hp infected children (P<0.05). The levels of Th17 and IL-17 in peripheral blood of children with Hp infection were significantly higher than those without Hp infection (P<0.05). In univariate analysis, there were statistically significant differences between the two groups in age, parental education level, per capita monthly income, sharing tableware, sharing toothbrushing cups, washing hands before and after meals, sucking fingers, parents' knowledge of Hp, and caregivers' history of stomach disease (P<0.05). Logistic regression analysis showed that sharing tableware, sharing toothbrushing cups, sucking fingers, parents' lack of knowledge about Hp, and caregivers' history of gastric diseases were independent risk factors for Hp infection in children (P<0.05). Conclusion The infection rate of Hp in children is high, and Hp infection can cause immune system dysfunction in children. It is necessary to take targeted and effective clinical measures to prevent Hp infection.

Objective:To explore the feasibility and clinical value of artificial intelligence-assisted breast ultrasound in screening breast cancer in Tibet.Methods:Two hundred and eighty-six women who participated in breast cancer screening in Shigatse People′s Hospital from August to September in 2021 were selected. The study included four groups. Group 1, ultrasound screening by senior breast ultrasound doctors from Shanghai; Group 2: local ultrasound doctors used intelligent-assisted ultrasound equipment for screening; Group 3: local ultrasound technicians used intelligent-assisted ultrasound equipment for screening; Group 4: ultrasound screening by local ultrasound doctors. The pathological results of screening positive cases and six-month ultrasound follow-up results of negative cases were set as the gold standard.Results:Twenty-seven lesions of 21 persons were screened positive. Pathology showed that 1 case of invasive ductal carcinoma, 1 case of severe atypical hyperplasia, 6 cases of fibroadenoma, 5 cases of breast disease, 14 cases of breast hyperplasia. Two hundred and sixty-five persons were screened negative, and the results of the six-month ultrasound follow-up were still negative. The accuracy, sensitivity, and specificity of group 2 were 0.966, 1, and 0.964 respectively; The accuracy, sensitivity, and specificity of group 3 were 0.935, 0.769, and 0.943 respectively; The accuracy, sensitivity, and specificity of group 4 were 0.860, 0.308 and 0.885 respectively. The accuracy and area under the curve of groups 2 and 3 were significantly different from that of group 4 (all P<0.001), and there was no significant difference from that of group 1 ( P=0.063, P=0.055). Conclusions:Artificial intelligence-assisted breast ultrasound screening technology can effectively improve the screening efficiency of non-breast ultrasound specialists and technicians. It is very suitable to solve the problems faced by grass-roots screening in Tibet and has great social significance and clinical value.

Objective:To explore the application value of real-time three-dimensional echocardiography (RT-3DE) in evaluating the characteristics and regularities of left atrial volume and function changes in patients with hyperthyroidism and hyperthyroid heart disease.Methods:Fifty-six patients who were diagnosed with hyperthyroidism and hyperthyroid heart disease without treatments in Henan Provincial People′s Hospital from March 2020 to September 2020 were selected. They were divided into hyperthyroidism group(30 patients) and hyperthyroid heart disease group (26 patients). Another 30 healthy volunteers were selected as the control group. The following parameters were obtained by RT-3DE left atrial automatic quantification technology, left atrial minimum, maximum, presystolic volume index(LAVImin, LAVImax, LAVIpreA), left atrial passive, active emptying volume index and stroke volume index (LAVIp, LAVIa, LAVIEV), left atrial passive, active, total ejection fraction(LApEF, LAaEF, LAEF), during left ventricular systole, early diastole, late diastole left atrial longitudinal strain (LASr, LAScd, LASct) and circumferential strain (LASr-c, LAScd-c, LASct-c). The differences of the above parameters between the two groups were compared.Results:Compared with the control group, LAVImax, LAVIpreA, LAaEF, LAVIEV, LAVIa, LASr, LASct-c increased and LApEF decreased in the hyperthyroidism group (all P<0.05). While, LAVImin, LAVImax, LAVIpreA and LAVIEV increased, and LAaEF, LApEF, LAEF, LASct, LAScd-c and LASr-c decreased in hyperthyroid heart disease group(all P<0.05). Compared with the hyperthyroidism group, LAVImin, LAVImax and LAVIpreA in hyperthyroid heart disease group were further increased, while LAEF, LAaEF, LASr, LASr-c, LASct, LASct-c and LAScd-c were decreased (all P<0.05). LAEF were positively correlated with LASr and LASr-c ( r=0.617, 0.837; all P<0.01), LApEF were positively correlated with LAScd and LAScd-c ( r=0.620, 0.800, all P<0.01), LAaEF were positively correlated with LASct and LASct-c ( r=0.680, 0.727; all P<0.01). Conclusions:In the patients with hyperthyroidism, the left atrial reserve and systolic function are increased, which are still in the compensation stage, and the pipeline function is decreased. The left atrial reserve, pipeline and systolic function in the hyperthyroid heart disease patients are all decreased, and the pipeline function may be impaired earlier than the systolic and reserve function.

Objective:To explore genetic counseling and prenatal diagnosis strategies for women who have androgen insensitivity syndrome (AIS) family history or pregnancy history of AIS proband.Methods:Three families of complete AIS (CAIS) were retrospectively reported and summarized. The subsequent pregnancies and processes of prenatal diagnosis were followed up.Results:Among three CAIS families, one family had androgen receptors (AR) gene mutation diagnosis; the other two families were diagnosed clinically without gene diagnosis. All three mothers of CAIS probands were in pregnant again when they sought counseling, with gestational weeks between 7－13 weeks. They underwent chorionic villi sampling or amniocentesis in their second trimester (at 12, 16, 17 weeks respectively). Chromosome gender of all three fetuses were 46,XY, which was inconsistent with the ultrasonographic phenotype of external genitalia. All patients chose selective abortion in their second trimester. The external genitalia of all aborted fetuses were female phenotype, which supported the diagnosis of CAIS.Conclusion:Genetic counseling and prenatal diagnosis should be provided to high-risk patients with family history of AIS or proband pregnancy history, so as to achieve the goal of good childbearing and sound childrearing.

A 44-year-old pregnant woman (G5P3) who had delivered two children with DMD was admitted and underwent prenatal diagnosis at Peking Union Medical College Hospital in 2019. (1) The karyotype of the fetus in 2019 was 47,XXY. The fluorescence in situ hybridization (FISH) result showed a nucish(CSPX×2, CSPY×1)[100] and multiplex ligation-dependent probe amplification (MLPA) suggested sex chromosome abnormality. Based on the above results, the fetus was diagnosed with Klinefelter syndrome. Fetal short tandem repeat (STR) linkage analysis and Sanger sequencing indicated a heterozygous mutation of c.9543delG(p.Trp3181CysfsTer2). (2) Sanger sequencing of the proband found a novel frameshift mutation of c.9543delG(p.Trp3181CysfsTer2 ) in exon 65 of the DMD gene. (3) The male fetus performing prenatal diagnosis in 2008 was found to have the same maternal gene markers as the proband with the same genotype. While the genotype of the fetus in 2009 obtained a different maternal gene marker from the proband and did not detect the same DMD gene mutation. This fetus was delivered at full term and was good during follow-up. (4) The elder brother and cousin of the proband had the same frameshift mutation in exon 65 of the DMD gene as the proband. The mother of the proband was a heterozygous carrier of the mutation.