Humans ; Infant ; Child ; Infant, Newborn ; Developmental Disabilities ; Bronchopulmonary Dysplasia

Objective: To summarize the genetic and clinical phenotypic characteristics of patients with early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD) caused by multiple epidermal growth factor 10 (MEGF10) gene defect. Methods: The clinical data of 3 infants in 1 family with EMARDD caused by MEGF10 gene defect diagnosed in the Department of Neonatology, Xiamen Children's Hospital in April 2022 were analyzed retrospectively. Using "multiple epidermal growth factor 10" "myopathy" or "MEGF10" "myopathy" as the key words, and searching the relevant literature reports of CNKI, Wanfang Database and PubMed Database from the establishment of the database to September 2022. Combined with this family, the main clinical information and genotype characteristics of EMARDD patients caused by MEGF10 gene defect were summarized. Results: The proband, male, first infant of monozygotic twins, was admitted to hospital 7 days after birth "due to intermittent cyanosis with weak sucking". The infant had dysphagia accompanied with cyanosis of lips during feeding and crying after birth. Physical examination on admission revealed reduced muscle tone of the extremities, flexion of the second to fifth fingers of both hands with limited passive extension of proximal interphalangeal joints, and limited abduction of both hips. He was diagnosed as dysphagia of newborn, congenital dactyly. After admission, he was given limb and oral rehabilitation training, breathing gradually became stable and oral feeding fully allowed, and discharged along with improvement. The younger brother of the proband was admitted to the hospital at the same time, and his clinical manifestations, diagnosis and treatment process were the same as those of the proband. The elder brother of the proband died at the age of 8 months due to the delayed growth and development, severe malnutrition, hypotonia, single palmoclal crease and weak crying. A whole exon sequencing of the family was done, and found that the 3 children were all compound heterozygous variations at the same site of MEGF10 gene, with 2 splicing variants (c.218+1G>A, c.2362+1G>A), which came from the father and mother respectively, and the new variation was consistent with the autosomal recessive inheritance model. Three children were finally diagnosed as EMARDD caused by MEGF10 gene defect. There are 0 Chinese literature and 18 English literature that met the search conditions. Totally 17 families including 28 patients were reported. There were 31 EMARDD patients including 3 infants from this family. Among them, there were 13 males and 18 females. The reported age of onset ranged from 0 to 61 years. Except for 5 patients with incomplete clinical data, 26 patients were included in the analysis of phenotypic and genotypic characteristics. The clinical features were mainly dyspnea (25 cases), scoliosis (22 cases), feeding difficulties (21 cases), myasthenia (20 cases), and other features including areflexia (16 cases) and cleft palate or high palatal arch(15 cases). Muscle biopsy showed non-specific changes, with histological characteristics ranging from slight muscle fiber size variation to minicores change which was seen in all 5 patients with at least 1 missense mutation of allele. In addition, the adult onset was found in patients with at least 1 missense variant of MEGF10 gene. Conclusions: MEGF10 gene defect related EMARDD can occur in the neonatal period, and the main clinical features are muscle weakness, breathing and feeding difficulties. Patients with myopathy who have at least 1 missense mutation and muscle biopsy indicating minicores change may be relatively mild.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Young Adult ; Cyanosis ; Deglutition Disorders ; EGF Family of Proteins ; Muscle Hypotonia ; Muscle Weakness ; Muscular Diseases/genetics* ; Retrospective Studies

Objective:To evaluate the effects of platelet-rich plasma(PRP)supernatants with different activation methods and storage time on human monocyte-derived macrophages phenotype and explore the possible mechanism.Methods:Human monocyte-derived macrophages were cultured in vitro with PRP or activated PRP supernatants activated with different activators.The expression of marker molecules on the surface of macrophages was detected by flow cytometry,and the concentration of growth factors in PRP supernatants was detected by ELISA.Results:After 24 h of coculture,the expression level of CD86 in macrophages stimulated by PRP supernatant(thrombin and CaCl2 activated)was significantly higher than that by PRP group(P＜0.05),and the expression of CD163 in macrophages was increased by CaCl2 activated PRP supernatant.Compared with different activator groups,the expression of CD163 in macrophages of CaCl2 activated group was significantly higher than that of thrombin and ADP groups(P＜0.05).ELISA results showed that the concentrations of FGF(P＜0.001)and EGF(P＜0.05)in the supernatant of PRP stored at-80 ℃ for more than 20 months and 10-20 months were significantly higher than those in the group stored at less than 10 months after CaCl2 activation,and the expressions of CD86(P＜0.01),CD163(P＜0.001)and CD206(P＜0.001)in macrophages cocultured with the supernatant of the two groups were significantly increased.Conclusion:PRP activated by different activators has different effects on the phenotype of macrophages.Meanwhile,the storage time will also affect the growth factor concentration and effect of PRP.

BACKGROUND: It remains unclear whether the outcomes of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) during off-hours are as favorable as those treated during on-hours, especially those with a first medical contact-to-device (FMC-to-device) time within 90 min. We aimed to determine whether off-hours admission impacted late outcomes in patients undergoing PPCI and with an FMC-to-device time ≤90 min. METHODS: This multicenter retrospective study included 670 STEMI patients who underwent successful PPCI and had an FMC-to-device time ≤90 min from 19 chest pain centers in Beijing from January 2018 to December 2018. Patients were divided into on-hours group and off-hours group based on their arrival time. Baseline characteristics, clinical data, and key time intervals during treatment were collected from the Quality Control & Improvement Center of Cardiovascular Intervention of Beijing by the "Heart and Brain Green Channel" app. RESULTS: Overall, the median age of the patients was 58.8 years and 19.9% (133/670) were female. Of these, 296 (44.2%) patients underwent PPCI during on-hours and 374 (55.8%) patients underwent PPCI during off-hours. Compared with the on-hours group, the off-hours group had a longer FMC-to-device time and fewer patients with FMC-to-device time ≤60 min (P < 0.05). During the mean follow-up period of 24 months, a total of 64 (9.6%) participants experienced a major adverse cardiovascular event (MACE), with 28 (9.1%) in the on-hours group and 36 (9.6%) in the off-hours group (P > 0.05). According to the Cox regression analyses, off-hours admission was not a predictor of 2-year MACEs (P = 0.788). Similarly, the Kaplan-Meier curves showed that the risks of a MACE, all-cause death, reinfarction, and target vessel revascularization were not significantly different between the two groups (P > 0.05). CONCLUSIONS This real-world, multicenter retrospective study demonstrated that for STEMI patients who underwent PPCI within 90 min, off-hours admission was safe, with no difference in the risk of 2-year MACEs compared with those with on-hours admission.
Beijing ; Female ; Humans ; Middle Aged ; Percutaneous Coronary Intervention ; Retrospective Studies ; Risk Factors ; ST Elevation Myocardial Infarction/surgery* ; Treatment Outcome

OBJECTIVE: To perform dried blood spots thalassemia gene detection in patients with positive blood phenotypes by microarray technology, and evaluate its value in clinical detection. METHODS: DNA samples were extracted from dried blood spots of 410 patients. Microarray technology was used to detect 3 deletion and 3 non-deletion types of α-thalassemia and 19 β-thalassemia point mutations which were common gene mutions in China. RESULTS: There were 357 positive cases in all the 410 tested samples with the positive rate 87.07%, among which 299 cases (72.93%) carried deletion or point mutations of α-thalassemia, 29 cases (7.07%) carried point mutations of β-thalassemia and 29 cases (7.07%) carried gene mutations of complex αβ-thalassemia syndrome. The mutations of α-thalassemia were involved with -- CONCLUSION The most common genetic mutations are --
China ; Humans ; Mutation ; Oligonucleotide Array Sequence Analysis ; alpha-Thalassemia/genetics* ; beta-Thalassemia/genetics*

Objective: This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B (AFB ) in rats. Methods: Forty Sprague Dawley rats were randomly divided into control, AFB , AFB + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB and AFB + PCB2 groups were intraperitoneally injected with AFB (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured. Results: AFB significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB . Conclusion Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB .
Aflatoxin B1 ; toxicity ; Animals ; Biflavonoids ; administration & dosage ; pharmacology ; Catechin ; administration & dosage ; pharmacology ; Chemical and Drug Induced Liver Injury ; drug therapy ; etiology ; Male ; Poisons ; toxicity ; Proanthocyanidins ; administration & dosage ; pharmacology ; Protective Agents ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

BACKGROUNDSinonasal inverted papilloma (IP) is a rare benign tumor of the nasal cavities and paranasal sinuses. It is destructive or bone-remodeling, tends to recur after surgical resection, and has a significant malignant potential. The present study aimed to perform a retrospective analysis of patients with squamous cell carcinoma (SCC) arising from IP, including characteristics, survival outcome, and predictors of associated malignancy.

METHODSThe medical records of 213 patients diagnosed with IP from January 1970 to January 2014 were retrospectively reviewed. Eighty-seven patients were diagnosed with SCC/IP; their clinical characteristics, treatments, and survival outcomes were analyzed.

RESULTSOf the 87 patients with SCC/IP, the 5- and 10-year overall survival outcomes were 39.6% and 31.8%, respectively. Twenty-nine of these patients received surgery and 58 received combined surgery and radiation. Of the patients with stages III-IV, the 5-year survival rate was 30.7% for those treated with surgery only and 39.9% for those given the combination treatment (P = 0.849). Factors associated with significantly poor prognosis were advanced-stage, metachronous tumors, or with cranial base and orbit invasion. Age, synchronous or metachronous tumors, and pathological stage were independent risk factors for mortality, shown by multivariate analysis.

CONCLUSIONPatients with SCC/IP had low overall survival outcomes. Advanced age, stage, and metachronous tumors are the main factors affecting prognosis. Treatment planning should consider high-risk factors to improve survival outcome.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; etiology ; mortality ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Papilloma, Inverted ; complications ; mortality ; Retrospective Studies ; Young Adult

OBJECTIVETo explore the effects of bisphenol A (BPA) exposure on toxicity characteristic and OCT4 and SOX2 gene expression of mouse embryonic stem cells (mESC).

METHODSmESC were cultured, and treated with the doses of 10(-8), 10(-7), 10(-6), 10(-5), 10(-4) mol/L respectively of BPA and DMSO (the solvent control group)for 24 hours, and three groups of cells were treated with the same method. The morphological changes of mESC in the control and exposure groups were observed through an inverted microscope. Cell counting kit 8 (CCK8) was used to detect the effects of BPA on proliferation of mESC, and based on the results, the half inhibitory concentration (IC50) was calculated. Real-time fluorescent quantitative polymerase chain reaction (RT-QPCR) and western blotting were used to detect the expression of OCT4 and SOX2.

RESULTSBPA had certain toxicity on mESC, the treatment of BPA significantly increased cell toxicity in a concentration-dependent manner, and the IC50 was 4.3×10(-4) mol/L, combined with the BPA exposure concentration of the environment and the related literature, eventually taking the five concentrations of 10(-8), 10(-7), 10(-6), 10(-5), 10(-4) mol/L as the experimental groups. The mESC morphology were effected after the treatment of BPA for 24 h, compared with the control group, the number of cells decreased, appearing some floating cells, and the cell cloning became irregular and differentiation in the higher concentration groups. The OCT4 mRNA expression level in the 10(-7) mol/L (1.146 ± 0.087), 10(-6) mol/L (1.156 ± 0.030), 10(-5) mol/L (1.158 ± 0.103) and the 10(-4) mol/L (1.374 ± 0.053) dose group were all significantly higher than the control group (1.000 ± 0.000) (t values were -2.384, -2.953, -3.203, -4.021 respectively, P value all < 0.05). Meanwhile, the SOX2 mRNA expression level in the 10(-4) mol/L (1.113 ± 0.052) were higher than the control group (1.000 ± 0.000) (t value was -2.765, P value < 0.05). Moreover, the OCT4 protein expression level in the 10(-5) mol/L (1.360 ± 0.168) and 10(-4) mol/L (1.602 ± 0.151) were all significantly higher than the control group (1.000 ± 0.000) (t values were -3.538, -4.002 respectively, P value all < 0.05), while no obvious change of the SOX2 protein expression level was detected in all treated groups.

CONCLUSIONBPA in a certain dose range could upregulate the expression of OCT4 gene in mouse embryonic stem cells while had no significant effect on the expression of SOX2 gene.

Animals ; Benzhydryl Compounds ; toxicity ; Cells, Cultured ; Embryonic Stem Cells ; drug effects ; metabolism ; Gene Expression ; Mice ; Octamer Transcription Factor-3 ; genetics ; Phenols ; toxicity ; SOXB1 Transcription Factors ; genetics ; Signal Transduction ; drug effects

OBJECTIVETo study in vitro sperm damage caused by trichloroethylene in male rats.

METHODSSperms of Sprague-Dawley (SD) rats were collected 4 hours after being contaminated by trichloroethylene of 0, 2, 4, 6, 8, and 10 mmol/L in vitro. Giemsa staining was performed to observe the morphological changes of sperms, and flow cytometer was used to detect the changes in mitochondrial membrane potential.

RESULTSThe sperm motilities in 6, 8, and 10 mmol/L trichloroethylene groups decreased significantly compared with that in control group (P <0.01); the sperm aberration rates in 8 and 10 mmol/L trichloroethylene groups were significantly higher than that in control group (P<0.01). With the increase in exposure dose, the proportion of sperms with reduced mitochondrial membrane potential increased, and there were significant differences in sperm apoptosis rate between the 4, 6, 8, and 10 mmol/L trichloroethylene groups and control group (P<0.01).

CONCLUSIONIn vitro exposure to trichloroethylene can reduce sperm motility and increase the aberration rate and apoptosis rate of sperms in male SD rats.

Animals ; Apoptosis ; drug effects ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Spermatozoa ; cytology ; drug effects ; Trichloroethylene ; toxicity