BACKGROUND: Recent studies have provided compelling evidence that exposure to brominated flame retardants (BFRs) can adversely affect human health. We aim to explore the potential impact of BFRs on adiposity and central obesity. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) cycles conducted between 2009 and 2014 was used to study the connections between variables. After filtering, we analyzed a sample of 4,110 adults aged 20 years and above. Our goal was to examine the potential association between BFRs and consequences and investigate the part played by oxidative stress and inflammatory markers as intermediaries. To achieve this, we used advanced statistical methods such as weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and the Bayesian kernel machine regression (BKMR). RESULTS: The findings showed that among the examined chemicals, exposure to PBDE85 (weight: 41%), PBDE100 (24%), and PBB153 (23%) may be the dominant contributors to general obesity risk. Upon controlling for all variables that could impact the results, it was found that the QGC outcomes indicated a positive correlation between exposure to mixtures of brominated flame retardants and the occurrence of abdominal obesity (OR = 1.187, 95% CI: 1.056-1.334, p = 0.004). Significant contributions were made by PBDE85 (52%), PBB153 (27%), and PBDE100 (21%). Mediation analysis shows that lymphatic cells (LC) and albumin (ALB) partially mediate the link between brominated flame retardants and obesity. The results of BKMR are generally consistent with those of WQS and QGC. CONCLUSION At a population level, our research has revealed a noteworthy correlation between BFRs and obesity. However, further investigation is required through prospective cohort studies and in-depth mechanistic exploratory studies.
Humans ; Flame Retardants/adverse effects* ; Oxidative Stress/drug effects* ; Adult ; Male ; Female ; Middle Aged ; Inflammation/epidemiology* ; Obesity/chemically induced* ; Biomarkers/blood* ; Nutrition Surveys ; Mediation Analysis ; Young Adult ; United States/epidemiology* ; Environmental Exposure/adverse effects* ; Aged ; Environmental Pollutants/adverse effects* ; Halogenated Diphenyl Ethers/adverse effects*

Objective:To explore the genetic etiology of a child with delayed growth and development and carry out a literature review.Methods:A child suspected for Al Kaissi syndrome at the First Affiliated Hospital of Zhengzhou University on March 6, 2021 was selected as the study subject. Following extraction of genomic DNA, the child was subjected to copy number variation sequencing (CNV-seq) and whole exome sequencing (WES), and candidate variants were verified by PCR-agarose gel electrophoresis and quantitative real-time PCR (qPCR). Prenatal diagnosis was conducted on chorionic villi sample upon subsequent pregnancy.Results:The child, a 6-year-and-4-month-old boy, has dysmorphic features including low-set protruding ears and triangular face, delayed language and intellectual development, and ventricular septal defect. CNV-seq result has found no obvious abnormality, whilst WES revealed homozygous deletion of exons 1 and 2 of the CDK10 gene, which was confirmed by PCR -agarose gel electrophoresis and qPCR. Both of his parents were heterozygous carriers. Prenatal diagnosis using chorionic villi samples suggested that the fetus also carried the heterozygous deletion.Conclusion:The clinical features of Al Kaissi syndrome in this child can probably be attributed to the homozygous deletion of exons 1 and 2 of the CDK10 gene.

Clinical application of serological screening and non-invasive prenatal testing (NIPT) both have difficulties to attain high detection rate and low cost. For its advantages of high detection rate, high sensitivity, simplicity, short turnaround time and low cost, digital PCR (dPCR) has provided a new choice for prenatal screening of trisomies 21, 18 and 13. To standardize the application of dPCR for prenatal screening, we have formulated this consensus by referring to relevant guidelines, expert consensus and latest literature, which has covered the basic requirements, application scope, pre-testing service, testing procedure, report interpretation, genetic counseling, and limitations for this technology.

Objective:To explore the application of triplet-primer PCR (TP-PCR) for the genetic testing and prenatal diagnosis in patients with Myotonic dystrophy type 1 (DM1).Methods:A total of 60 individuals from 48 pedigrees undergoing genetic testing at the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from May 2018 to October 2022 were selected as the study subjects. TP-PCR combined with capillary electrophoresis was applied to determine the number of CTG repeats of the DMPK gene, and prenatal testing was provided to four DM1 pedigrees. This study was approved by Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. KS-2018-KY-36). Results:A total of 52 DM1 patients were detected, mostly with muscle weakness, muscular atrophy and myotonia as the initial symptoms, along with typical myotonic potentials. Some patients also had abnormalities of other systems. The number of abnormal CTG repeats of the DMPK gene was > 50, whilst the number of CTG repeats on the normal allele had ranged from 5 to 18. The number of the most common normal CAG repeats was 6 (30.77%, 16/52). Among the four DM1 pedigrees undergoing prenatal diagnosis, one fetus was healthy, whilst three fetuses were found to have abnormal CTG repeats (> 50 times) and diagnosed with DM1. Conclusion:TP-PCR can diagnose DM1 patients with speed and accuracy. However, this method cannot accurately determine the number of CTG repeats when it exceeds 50.

Objective:To explore the genetic basis for a Chinese pedigree affected with Fragile X syndrome (FXS) through Nanopore long-read sequencing.Methods:A FXS pedigree who had undergone genetic counseling at the First Affiliated Hospital of Zhengzhou University in April 2023 was selected as the study subject. Nanopore long-read sequencing, triplet-repeat primed PCR (TP-PCR), methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) and trinucleotide polymorphism genotyping of androgen receptor (AR) gene were used to analyze the FMR1 CGG repeat number, methylation, and X chromosome inactivation of the pedigree members. This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No. KS-2018-KY-36). Results:Full mutation and CpG island hypermethylation were detected in the proband. The elder sister of the proband had full mutation of the FMR1 gene on one X chromosome and hypermethylation of CpG island, while the FMR1 gene on the other X chromosome was normal. FMR1 premutation was detected in the proband′s mother. Conclusion:Nanopore long-read sequencing can simultaneously detect the dynamic mutation and methylation status of the FMR1 gene on the two X chromosomes of females, which has important value for the diagnosis of FXS in different genders.

Objective:To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality.Methods:This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone.Results:A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa), P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg, P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg, P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions:RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Objective:To study the effects of metformin on marginal bone resorption of implants in patients with type 2 diabetes melli-tus(T2DM)and exercise habit.Methods:63 cases with 73 implants were included.Among them,there were 41 cases(47 implants)without T2DM in group N,10 cases(13 implants)with T2DM and without exercise habit in group M,12 cases(12 implants)with T2DM and exercise habit in the MR group.The patients were followed up at 6 months,1 and 2 years after implantation.The marginal bone loss(MBL).Implantation success rate and peri-implantitis incidence rate were compared among the groups.Results:The bone resorption of the proximal and median margins of the long-term bone level of the implants in the N and MR groups were significantly lower than that in the M group(P=0.001 and P=0.000 5,respectively).The implant success rates of group N,MR and M were 95.74％,100％and 76.92％,respectively.The incidence of peri-implantitis of the three groups was 2.13％,0 and 15.38％,respec-tively.Conclusion:Metformin is more effective in the improvement of the long-term marginal bone resorption of implants,increase the success rate of implants,and reduce the incidence of peri-implantitis in patients with T2DM and exercise habit in the mandibular first molar area.

Objective To use color Doppler ultrasound to measure the hemodynamic indexes,and to es-tablish the diagnostic prediction model of inflammatory fetal distress.Methods A total of 213 pregnant women admitted to the obstetrics department of the First Affiliated Hospital of Air Force Military Medical U-niversity were collected as the research subjects and divided into the control group and case group according to whether or not fetal distress occurred,including 93 cases in the control group and 120 cases in the case group.The predictive value of PI,RI,S/D values of middle cerebral artery,umbilical artery and uterine artery for pre-dicting fetal distress was analyzed The diagnostic model was constructed by logistic regression analysis.The receiver operating characteristic(ROC)curve,calibration curve and clinical decision curve were adopted to an-alyze and evaluate the diagnostic efficiency of the model for adverse perinatal outcome and the clinical benefit of the patients.Results The univariate analysis results showed that MCA-PI,MCA-RI,MCA,S/D and CPR in the case group were lower than those in the control group,while UA-RI,UA,S/D and UtA-RI were higher than those in the control group.The multivariate regression analysis further showed that MCA-PI,MCA-RI and CPR were the independent protective factors for predicting fetal distress,while UA-R1 and UA-S/D served as the independent risk factors affecting the fetal outcome.Based on five independent influencing fac-tors,the risk prediction model was constructed,and the area under the receiver operating characteristic curve was 0.880(95％CI:0.834-0.925).The sensitivity,specificity and accuracy were 0.93,0.70 and 0.83 respec-tively,and the goodness of fit was good.Conclusion The hemodynamic indexes measured by color Doppler ul-trasound have good predictive value for the diagnosis of fetal distress.The risk prediction model established by the combined indexes has a certain reference value for the intervention in advance of pregnant women with fe-tal distress occurence.

OBJECTIVE To determine the prevalence of frontal recess cells variations in patients with frontal sinus associated headache according to the International Frontal Sinus Anatomy Classification(IFAC).METHODS A retrospective study was conducted on the CT scans of sinuses in patients with frontal sinus associated headache.We reviewed 46 patients with frontal sinus-related headache who had clinical symptoms and were relieved after nasal endoscopic surgery.The development of frontal recess cells in the frontal recess drainage area was analyzed,and the variation of middle meatus and sinus involvement were analyzed in the same time.The Anatomical variations and imaging characteristics of frontal recess cells development in patients with frontal sinus associated headache were analyzed.RESULTS A total of 92 sinus CT profiles were analyzed in 46 patients.The most common cells were agger nasi cell(ANC)(100%,92/92),followed by supra bulla cell(SBC)(78.3%,72/92),supra agger cell(SAC)(67.4%,62/92),supra bulla frontal cell(SBFC)(27.2%,25/92),supra agger frontal cell(SAFC)(20.7%,19/92),frontal septal cell(FSC)(8.7%,8/92)and supraorbital ethmoid cell(SOEC)(0%,0/92).In the conventional frontal sinus drainage area,SAFC(P=0.0108),SAC(P=0.0104)and SAFC(P=0.0088)in the IFAC classification were significantly associated with the occurrence of frontal sinus associated headache.At the same time,the middle concha bullosa also showed a significant correlation with the occurrence of frontal sinus associated headache in the lower segment of the frontal recess drainage channel(P=0.0390).CONCLUSION In the frontal recess drainage channel,the abnormal development of SAC,SAFC,SBFC and the middle concha bullosa are significantly correlated with frontal sinus associated headache.

Objective:To investigate the expression levels of miRNA-21 (miR-21) and miRNA-330 (miR-330) in serum exosomes of non-small cell lung cancer (NSCLC) patients with brain metastases, and the correlation of the two with the prognosis of patients.Methods:A prospective cohort study was conducted. A total of 125 NSCLC patients who were admitted to the Affiliated People's Hospital of Shandong First Medical University from March 2021 to September 2022 were prospectively selected, and the brain metastasis was determined by CT, contrast-enhanced magnetic resonance imaging of the head, or surgical pathology. The NSCLC patients were divided into the metastatic group (58 cases) and the non-metastatic group (67 cases) according to whether they had brain metastases, and 50 patients with benign lung diseases and 50 healthy subjects who underwent physical examination in the same period were selected as benign group and healthy control group respectively. Serum samples were collected from all subjects (including patients' pre-treatment samples), the exosomes were extracted, and real-time fluorescence quantitative polymerase chain reaction was used to determine the relative expression of miR-21 and miR-330 in exosomes at the transcriptional level, and electrochemiluminescence immunoassay was used to detect the levels of serum tumor markers [neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA)]. The levels of miR-21 and miR-330 in serum exosomes and serum tumor markers in the 4 groups were compared, and the correlation between miR-21 and miR-330 in serum exosomes of NSCLC patients with brain metastases before treatment and the correlation between miR-21, miR-330 and serum tumor markers were analyzed by Pearson method. Using brain metastases identified by CT, contrast-enhanced magnetic resonance imaging of the head or surgical pathology as the gold standard, the receiver operating characteristic (ROC) curves were drawn to determine the occurrence of brain metastases in NSCLC patients based on the levels of miR-21, miR-330 and their combination in the serum exosomes before treatment. NSCLC patients were divided into the poor prognosis group and the good prognosis group according to whether or not they died of tumor during the follow-up period, and the clinical characteristics and levels of miR-21 and miR-330 in serum exosomes before treatment were compared between the two groups. The independent influencing factors of death due to tumor in NSCLC patients were analyzed by multivariate logistic regression.Results:Among 125 NSCLC patients, 68 (54.4%) were male and 57 (45.6%) were female; the age was (63±5) years old, ranging from 49 to 82 years old; 89 patients (71.2%) were adenocarcinoma and 36 patients (28.8%) were squamous cell carcinoma. The transcriptional level relative expression of miR-21 in serum exosomes of healthy control group, benign group, non-metastatic group and metastatic group increased sequentially, the transcriptional level relative expression of miR-330 decreased sequentially, the protein concentrations of NSE, CEA and SCCA increased sequentially, and the differences between each two groups were statistically significant (all P<0.001). Pearson correlation analysis showed that in the serum exosomes of NSCLC patients with brain metastases before treatment, miR-21 was positively correlated with serum NSE, CEA and SCCA levels ( r values were 0.641, 0.785 and 0.612, respectively; P values were 0.015, 0.011 and 0.019, respectively), miR-330 in the serum exosomes before treatment was negatively correlated with serum NSE, CEA, and SCCA levels ( r values were -0.612, -0.689 and -0.587, respectively; P values were 0.016, 0.021 and 0.013, respectively), and miR-21 was positively correlated with miR-330 in the serum exosomes before treatment ( r = -0.529, P = 0.023). ROC curve analysis showed that the area under the curve of miR-21, miR-330 and their combination in serum exosomes before treatment for determining the occurrence of brain metastases in NSCLC patients were 0.861 (95% CI: 0.792-0.931), 0.894 (95% CI: 0.840-0.947) and 0.906 (95% CI: 0.849-0.963), and the differences were statistically significant (all P < 0.001). The optimal cut-off value of miR-21 relative expression was 1.625, and the corresponding sensitivity and specificity were 77.4% and 71.5%, respectively; the optimal cut-off value of miR-330 was 0.611, and the corresponding sensitivity and specificity were 81.1% and 74.9%, respectively; the sensitivity and specificity when the two were combined to reach the optimal cut-off value were 84.5% and 73.8%, respectively. NSCLC patients were followed up for a median time of 19 months (95% CI: 17-21 months), and 23 cases (18.4%) died due to the tumor during the follow-up period. The proportions of patients with age ≥60 years old, clinical stage Ⅲ-Ⅳ and brain metastases and the relative expression of miR-21 in serum exosomes before treatment in the poor prognosis group were higher than those in the good prognosis group, the relative expression of miR-330 in the serum exosomes before treatment was lower than that in the good prognosis group, and the differences were all statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that the high age (≥60 years old vs. <60 years old, OR = 3.750, 95% CI: 1.191-11.806, P = 0.024), late clinical stage (stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ, OR = 4.667, 95% CI: 1.303-16.716, P = 0.018), brain metastasis (with metastasis vs. non-metastasis, OR = 2.573, 95% CI: 1.008-6.611, P = 0.049), and elevated relative expression of miR-21 in serum exosomes before treatment ( OR = 2.585, 95% CI: 1.198-6.152, P = 0.008) were the independent risk factors for death due to tumor in NSCLC patients, and elevated relative expression of miR-330 in serum exosomes before treatment was an independent protective factor for death due to tumor ( OR = 0.821, 95% CI: 0.715-0.954, P < 0.001). Conclusions:miR-21 level is high and miR-330 level is low in serum exosomes of NSCLC patients with brain metastases before treatment, and there is a negative correlation between them, and they are closely related to various serum tumor markers of NSCLC patients with brain metastases and NSCLC patients' prognosis; the combination of the two may predict the occurrence status of brain metastases in NSCLC.