OBJECTIVE: To investigate the clinical characteristics and genetic etiology in a fetus with 12q14 microdeletion syndrome. METHODS: A fetus diagnosed with 12q14 microdeletion syndrome at Wenzhou People's Hospital in July 2019 was selected as the study subject. The fetus was from a twin pregnancy by in vitro fertilization-embryo transfer, with ultrasound findings including growth restriction, cleft lip/palate, ventricular septal defect, tricuspid regurgitation, and pericardial effusion. Clinical data and family history were collected. Amniotic fluid sample was collected from both twins, and peripheral blood samples were obtained from their parents. Amniocytic karyotyping analysis and chromosomal microarray analysis (CMA) were performed, and familial validation was conducted. This study was approved by the Medical Ethics Committee of Wenzhou People's Hospital (Ethics No.: KY-202408-034). RESULTS: Prenatal ultrasound showed no significant abnormality in one of the twins, whilst the other twin exhibited severe growth restriction accompanied by cleft lip/palate, ventricular septal defect, tricuspid regurgitation, and pericardial effusion. Karyotyping and CMA analyses of first twin showed no abnormalities, whilst the second twin had a chromosomal karyotype of 46,XN,t(3;12)(q26.3;q14), and CMA revealed a 4.9 Mb deletion in the 12q14.3-q15 region (arr[hg19]12q14.3q15(65,574,059_70,488,106)x1). Karyotyping and CMA analyses of both parents revealed no abnormalities, confirming that the fetus deletion was de novo in origin. Literature review suggested that prenatal diagnosis of 12q14 microdeletion syndrome has been extremely rare. CONCLUSION The fetus was diagnosed with 12q14 microdeletion syndrome. This de novo deletion may have dervied from chromosomal translocation. As a first-tier prenatal diagnostic technique, CMA can effectively detect microdeletion/microduplications missed by conventional karyotyping analysis.
Humans ; Female ; Pregnancy ; Chromosome Deletion ; Chromosomes, Human, Pair 12/genetics* ; Karyotyping ; Adult ; Prenatal Diagnosis ; Chromosome Disorders/diagnosis* ; Ultrasonography, Prenatal ; Fetus ; Male

BACKGROUND: Pulmonary arterial hypertension (PAH) presents a significant health burden in Asia and remains a critical challenge. This study aims to delineate the PAH burden in Asia from 1990 to 2021. METHODS: Using the latest data from the Global Burden of Disease 2021, we evaluated and analyzed the distributions and patterns of PAH disease burden among various age groups, sexes, regions, and countries in Asia. Additionally, we examined the associations between PAH disease burden and key health system indicators, including the socio-demographic index (SDI) and the universal health coverage (UHC) index. RESULTS: In 2021, there were 25,989 new PAH cases, 103,382 existing cases, 13,909 PAH-associated deaths, and 385,755 DALYs attributed to PAH in Asia, which accounted for approximately 60% of global PAH cases. The age-standardized rates (ASRs) for prevalence and deaths were 2.05 (95% uncertainty interval [UI]: 1.66-2.52) per 100,000 population and 0.31 (95% UI: 0.23-0.38) per 100,000 population, respectively. From 1990 to 2021, Asia reported the lowest ASRs for PAH prevalence but the highest ASRs for deaths compared to other continents. While the ASRs for prevalence increased slightly, ASRs for mortality and DALYs decreased over time. This increasing burden of PAH was primarily driven by population growth and aging. The burden was especially pronounced among individuals aged ≥60 years and <9 years, who collectively accounted for the majority of deaths and DALYs. Moreover, higher SDI and UHC levels were linked to reduced incidence, but higher prevalence rates. CONCLUSIONS Although progress has been made in reducing PAH-related mortality and DALYs, the disease continues to impose a substantial burden in Asia, particularly among older adults and young children. Region-specific health policies should focus on improving early diagnosis, expanding access to treatment, and effectively addressing the growing PAH burden in the region.
Humans ; Global Burden of Disease ; Male ; Female ; Middle Aged ; Adult ; Asia/epidemiology* ; Prevalence ; Aged ; Pulmonary Arterial Hypertension/mortality* ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Hypertension, Pulmonary/epidemiology*

BACKGROUND: The potential impact of pre-existing coronary artery stenosis (CAS) on right ventricular (RV) function during acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and RV dysfunction in patients with acute PE. METHODS: In this multicenter, case-control study, 89 cases and 176 controls matched for age were enrolled at three study centers (Peking Union Medical College Hospital, Fuwai Hospital, and the Second Affiliated Hospital of Harbin Medical University) from January 2016 to December 2020. The cases were patients with acute PE with CAS, and the controls were patients with acute PE without CAS. Coronary artery assessment was performed using coronary computed tomographic angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression analysis was used to evaluate the association between CAS and RV dysfunction. RESULTS: The percentages of RV dysfunction (19.1% [17/89] vs. 44.6% [78/176], P <0.001) and elevated systolic pulmonary artery pressure (sPAP) (19.3% [17/89] vs. 39.5% [68/176], P = 0.001) were significantly lower in the case group than those in the control group. In the multivariable logistic regression model, CAS was independently and negatively associated with RV dysfunction (adjusted odds ratio [OR]: 0.367; 95% confidence interval [CI]: 0.185-0.728; P = 0.004), and elevated sPAP (OR: 0.490; 95% CI: 0.252-0.980; P = 0.035), respectively. CONCLUSIONS Pre-existing CAS was significantly and negatively associated with RV dysfunction and elevated sPAP in patients with acute PE. This finding provides new insights into RV dysfunction in patients with acute PE with pre-existing CAS.
Humans ; Pulmonary Embolism/complications* ; Case-Control Studies ; Male ; Ventricular Dysfunction, Right/physiopathology* ; Female ; Middle Aged ; Aged ; Coronary Stenosis/complications* ; Logistic Models ; Adult

To explore the impact of an airway stepwise management strategy in the treatment of hospital acquired pneumonia (HAP) in the ultra elderly critically ill patients.

Objective:To analyze the genus, drug resistance/virulence and phylogenetic characteristics of Brucella strains isolated from brucellosis surveillance sentinels in Henan Province from 2013 to 2022, and provide baseline data for the surveillance, early warning and outbreak tracing of brucellosis. Methods:Blood samples were collected from patients with Brucella infection for strain isolation, culture and species identification, drug susceptibility test, whole genome sequencing, splicing and assembly, functional/virulence/resistance gene prediction analysis and phylogenetic tree drawing based on single nucleotide polymorphism (SNP). Results:In 36 brucellosis patients, the majority were men (86.11%, 31/36), young adults aged 18-50 (88.89%, 32/36) and farmers/herdsmen (72.22%, 26/36). A total of 36 strains of Brucella melitensis were isolated, and average 1 305 functional proteins of 21 categories were predicted by strain genome; all the strains carried four main virulence factors (pmm, VirB group, BtpA/BtpB, BvrS/BvrR). The drug sensitivity rate was 100.00% to six types of antibiotics including levofloxacin, rifampicin, doxycycline, streptomycin, tetracycline and gentamicin, they showed different resistances to three antibiotics including compound trimethoprim-sulfamethoxazole, ciprofloxacin and ampicillin. The strains carried four types of resistance genes and two clusters of resistance genes, with four combinations of genotypes, the resistance mechanisms included antibiotic degradation/modification enzymes, resistant nodular cell differentiation (RND) efflux pumps, 16S/23S ribosomal rRNA binding site mutations, etc. The number of SNP differed in the genomes of 36 Brucellamelitensis strains ranged from 0 to 454 and phylogenetic tree was divided into three major branches, with relative branch distances between 0.000 0 and 0.498 6 for each strain. Conclusions:Human Brucellamelitensis strains isolated from surveillance sentinels in Henan from 2013 to 2022 carried multiple virulence and antibiotic resistance genes and had different drug resistance phenotypes. Single nucleotide polymorphism analysis and phylogenetic tree analysis showed significant differences in phylogenetic relationships among different strains.

Objective:To explore the clinical phenotype and gene characteristics of a case of TSC2/PKD1 adjacency gene syndrome, so as to improve the clinical understanding of the disease.Methods:A case of TSC2/PKD1 adjacency gene syndrome diagnosed in the Department of Neurology of the Children′s Hospital Affiliated to Zhengzhou University was analyzed retrospectively. The clinical data, laboratory examination, imaging characteristics and gene variation characteristics of the child were summarized.Results:The patient was a 17 months old girl, with the main complaint of "intermittent convulsion with 17 months of underdevelopment". The clinical manifestations were epileptic seizures, which were in the form of a series of spastic seizures, absence seizures, focal seizures, and depigmentation spots can be seen in the trunk and neck. Cranial magnetic resonance imaging showed multiple patchy signals in the cortex and subcortical areas of the bilateral cerebral hemispheres, multiple small nodular shadows under the ependyma of the bilateral lateral ventricles, the heart color Doppler ultrasound showed patent foramen ovale and pericardial effusion, and the abdomen color Doppler ultrasound showed polycystic kidney. Ophthalmic color Doppler ultrasound showed that there were localized small swelling lesions around the optic disc of the left eye. The whole exon gene sequencing of the pedigree showed the proband had partial deletion of TSC2 gene (NM_000548) at chromosome position chr16: 2125799-2185690. The real-time quantitative detection system verified that exons 23-42 were deleted, and all exons of PKD1 gene were deleted (NM_001009944), and multiple ligation dependent probe amplification verified that exons 1-46 were deleted, and no downstream gene deletion was found. The overall deletion size was about 60 kb. Both of the girl's father and mother had normal phenotypes and were wild-type.Conclusions:TSC2/PKD1 adjacency gene syndrome is relatively rare. It can have clinical manifestations of tuberous sclerosis/autosomal dominant polycystic kidney disease. Most of the nervous system and kidney are seriously affected, and the prognosis is poor. TSC2/PKD1 gene deletion and variation is the genetic cause of the TSC2/PKD1 adjacency gene syndrome.

Objective:To explore the effects of adriamycin（Adc）combined with hyperbaric oxygen（HBO）on the apoptosis of HepG2 cells and immunomodulatory factors in transplanted hepatocellular carcinoma（HCC）tissues in nude mice.Methods:The model of transplanted HCC was established in 20 nude mice，then the mice were divided into four groups：control group，HBO group，Adc group，and HBO + Adc group，with five mice in each group. The control group was reared normally. The HBO group was treated with HBO at 0.20 MPa for 1 h；the Adc group was treated with 10 mg/kg of Adc by gavage；the HBO + Adc group was treated with HBO at 0.20 MPa for 1 h and then given 10 mg/kg of Adc by gavage. All groups were treated once every other day for 21 days. After drug withdrawal，the tumors were dissected from the sacrificed mice，of which the tumor volume and weight were measured. The apoptosis of HepG2 cells was detected by TUNEL. The changes of apoptosis-related proteins in HepG2 cells were detected by western blotting. The changes of the contents of immunomodulatory factors in transplanted tumor tissues of nude mice were detected by ELISA.Results:After 21 days，the tumor volume and weight in the HBO + Adc group were lower than those in the other three groups（ P<0.05）. The proportion of apoptotic cells in the transplanted tumor tissues of nude mice of the HBO + Adc group was the highest. In the HBO + Adc group，the protein expression levels of Bax，caspase-3，and Cytochrome C were significantly increased；the protein expression of Bcl-2 was significantly reduced（ P<0.01）；and the IL-6 was significantly reduced；while the IL-18 and IFN-γ were significantly increased（ P<0.05）. Conclusion:The Adc combined with HBO can promote apoptosis of HepG2 cells in transplanted HCC tissues in nude mice，and effectively regulate the immunomodulatory factors to promote the recovery of the body’s immune function，suggesting obvious sensitizing and detoxifying effects.

Objective:To explore the effects of adriamycin（Adc）combined with hyperbaric oxygen（HBO）on the apoptosis of HepG2 cells and immunomodulatory factors in transplanted hepatocellular carcinoma（HCC）tissues in nude mice.Methods:The model of transplanted HCC was established in 20 nude mice，then the mice were divided into four groups：control group，HBO group，Adc group，and HBO + Adc group，with five mice in each group. The control group was reared normally. The HBO group was treated with HBO at 0.20 MPa for 1 h；the Adc group was treated with 10 mg/kg of Adc by gavage；the HBO + Adc group was treated with HBO at 0.20 MPa for 1 h and then given 10 mg/kg of Adc by gavage. All groups were treated once every other day for 21 days. After drug withdrawal，the tumors were dissected from the sacrificed mice，of which the tumor volume and weight were measured. The apoptosis of HepG2 cells was detected by TUNEL. The changes of apoptosis-related proteins in HepG2 cells were detected by western blotting. The changes of the contents of immunomodulatory factors in transplanted tumor tissues of nude mice were detected by ELISA.Results:After 21 days，the tumor volume and weight in the HBO + Adc group were lower than those in the other three groups（ P<0.05）. The proportion of apoptotic cells in the transplanted tumor tissues of nude mice of the HBO + Adc group was the highest. In the HBO + Adc group，the protein expression levels of Bax，caspase-3，and Cytochrome C were significantly increased；the protein expression of Bcl-2 was significantly reduced（ P<0.01）；and the IL-6 was significantly reduced；while the IL-18 and IFN-γ were significantly increased（ P<0.05）. Conclusion:The Adc combined with HBO can promote apoptosis of HepG2 cells in transplanted HCC tissues in nude mice，and effectively regulate the immunomodulatory factors to promote the recovery of the body’s immune function，suggesting obvious sensitizing and detoxifying effects.

Objective:To correlate homocysteine (Hcy) and blood lipid levels with neurological function in patients with progressive ischemic stroke.Methods:A total of 400 patients with ischemic stroke who received treatment between June 2018 and June 2020 in Linhai Second People's Hospital were included in this study. Progressive ischemic stroke ( n = 126) and non-progressive ischemic stroke ( n = 274) groups were designated. Hcy level was determined by enzyme-linked immunosorbent assay. High-density lipoprotein cholesterol, triacylglycerol, low-density lipoprotein cholesterol and cholesterol levels were measured using a biochemical analyzer. Hcy and blood lipid levels as well as National Institute Health of Stroke Scale (NIHSS) score were determined in each group. Hcy and blood lipid levels were correlated with NIHSS score. Results:Hcy level in the progressive ischemic stroke group was significantly higher than that in the non-progressive ischemic stroke group [(28.39 ± 4.36) μmol/L vs. (20.17 ± 3.24) μmol/L, t = 18.894, P < 0.05]. Low-density lipoprotein cholesterol , triacylglycerol and TC levels in the progressive ischemic stroke group were (3.29 ± 0.45) mmol/L, (2.08 ± 0.34) mmol/L and (4.82 ± 0.79) mmol/L, respectively, which were significantly higher than those in the non-progressive ischemic stroke group [(2.48 ± 0.37) mmol/L, (1.56 ± 0.29) mmol/L and (4.08 ± 0.43) mmol/L, t = 17.644, 14.859, 9.860, P < 0.05]. High-density lipoprotein cholesterol level in the progressive ischemic stroke group was significantly lower than that in the non-progressive ischemic stroke group [(1.03 ± 0.13) mmol/L vs. (1.19 ± 0.14) mmol/L, t =11.158, P < 0.05]. NIHSS score in the progressive ischemic stroke group was significantly higher than that in the non-progressive ischemic stroke group [(21.72 ± 4.35) points vs. (15.52 ± 2.89) points, t = 14.582, P < 0.05]. Hcy, low-density lipoprotein cholesterol, cholesterol and triacylglycerol levels were linearly and positively correlated with NIHSS score ( r = 0.846, 0.724, 0.718, 0.765, all P < 0.05), while igh-density lipoprotein cholesterol level was linearly and negatively correlated with NIHSS score ( r = -0.710, P < 0.05). Conclusion:In patients with progressive ischemic stroke, Hcy level is increased and blood lipid level is obviously abnormal. Hcy and blood lipid levels are greatly correlated with neurological function.

Objective:To investigate the efficacy and the safety of intravascular therapy for cerebrovascular ischemic tandem stenosis.Methods:Clinical data of 35 patients with symptomatic anterior circulation and posterior circulation tandem stenosis who received intravascular therapy for two sites of stenosis at the same time at Department of Neurosurgery of Peking University First Hospital from January 2013 to December 2018 were analyzed retrospectively. There were 27 males and 8 females,aged (65.6±9.4)years (range:47 to 81 years).There were 14 cases of anterior circulation tandem stenosis and 21 of posterior circulation tandem stenosis.The medical records were collected with emphasis on postoperative symptoms,imaging manifestations and modified Rankin scale(mRS) scores.Results:Sixty-eight stents were implants in to 35 patients,including 49 extracranial implants and 19 intracranial implants.The surgical success rate was 100%.The perioperative death rate was 0,and 1 patient(1/35,2.9%) had cerebral hemorrhage.All patients were followed up for 18 months.During 3 to 12 months after the intervention,1 case(1/35,2.9%) had stent restenosis,and 4 cases(4/35,11.4%) had persisted symptoms such as dizziness and weakness in limbs.All patients′mRS scores were ≤2. No new stroke occurred. During 12 to 18 months after the intervention,3 cases had in-stent restenosis,increasing the rate to 11.4% (4/35). The mRS scores of 32 patients(32/35,91.4%) were ≤2.Conclusion:Intravascular therapy for patients with symptomatic tandem stenosis is a feasible and safe procedure with good short-term outcomes.