Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Objective To compare the clinicopathological characteristics between primary and contralateral cancers in patients with metachronous bilateral breast cancer (MBBC) who carried a BRCA1/2 germline pathogenic variant. Methods A total of 496 BRCA1/2 carriers with primary unilateral breast cancer were included (196 with BRCA1 and 300 with BRCA2). Clinicopathological information of patients was collected, and the median follow-up for the entire cohort was 10.4 years (0.4-20.8 years). Results Among all patients, 31 (15.8%) of the 196 BRCA1 carriers and 49 (16.3%) of the 300 BRCA2 carriers had MBBC, respectively. Among the 31 BRCA1 carriers who developed MBBC, the proportion of triple-negative breast cancer (TNBC) in primary cancer and contralateral cancer was 61.3% and 67.7%, respectively. If the primary cancer of BRCA1-mutated MBBC was TNBC, the probability of the contralateral breast cancer with TNBC was 89.5% (17/19), which was significantly higher than that if the primary cancer was non-TNBC (33.3%, 4/12) (P=0.004). Among the 49 BRCA2 carriers who developed MBBC, the predominant molecular phenotype of the primary and contralateral cancers was HR+ & HER2- (77.6% and 67.3%, respectively; P=0.53). Conclusion Approximately 60% of BRCA1 carriers exhibit TNBC. If a BRCA1 carrier with a TNBC primary breast cancer had an MBBC, the probability of the contralateral breast cancer being TNBC phenotype is almost 89.5%.

Objective:To investigate the correlation between preterm infants with brain injury and the proportion of lymphocyte subsets, especially γδ-T cells in the postnatal peripheral blood, and to determine the predictive potential of γδ-T cells in the early peripheral blood in brain injury.Methods:It was a prospective study involving 106 preterm infants with gestational age less than 34 weeks who were delivered in the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University from January 1, to June 1, 2021.Relative levels of γδ-T , CD4 + T, CD8 + T, CD3 + T and total lymphocyte subsets in peripheral blood collected within the first 24 hours after birth were measured by flow cytometry.Recruited infants were divided into brain injury group (36 cases) and non-brain injury group (70 cases) according to serial cranial ultrasound and magnetic resonance imaging(MRI) at the corrected gestational age of 36-37 weeks.Differences in general conditions and the proportion of lymphocyte subsets between groups were compared by the t-test or Chi- square test.Patients in brain injury group were further divided into intracranial hemorrhage(ICH) group(8 cases), periventricular leukomalacia (PVL) group (6 cases)and diffuse white matter damage (WMD) group(22 cases). The proportion of lymphocyte subsets among the different groups was compared by One- Way ANOVA, followed by the LSD- t test. Results:The proportion of γδ-T cells in postnatal peripheral blood of preterm infants at 24 hours after birth in brain injury group was significantly lower than that of non-brain injury group [(0.09±0.12)% vs.0.15±0.13)%, t=-2.445, P=0.016]. No significant differences in the proportion of the CD4 + and CD8 + T cell subsets were found between them.Both preterm infants in PVL group and WMD group had a significantly lower proportion of γδ-T cells at 24 hours after birth compared to that of the non-brain injury group [(0.03±0.05)%, (0.07±0.09)% and (0.15±0.13)%], respectively, ( t=-2.190, -2.659, all P<0.05). Conclusions:γδ-T cells in early postnatal peripheral blood may be involved in the development of brain injury in preterm infants and they had early predictive value for preterm infants at high risk of brain injury, especially the leukomalacia and diffuse white matter injury.

Objective:To investigate the effect of peer support-based narrative therapy on postoperative self-image and stigma of patients with head and neck cancer, to provide reference for clinical nursing.Methods:A total of 78 head and neck cancer patients from August 2018 to August 2020 in Fudan University Shanghai Cancer Center were divided into experimental group and control group by random digits table method, each group were 39 cases. The control group was given conventional nursing, while the experimental group implemented support-based narrative therapy on the basis of routine nursing. The intervention time was 4 weeks. The self-image and stigma of the two groups before and after intervention were assessed by Body Image Scale (BIS) and Social Impact Scale (SIS), respectively.Results:Finally, 37 cases were included in the experimental group and 38 cases in the control group. There was no significant difference in BIS, SIS dimension scores and total scores between the two groups before intervention ( P>0.05). After intervention, the emotional demension scores, behavior dimension scores, cognitive dimension scores and total scores in BIS were 4.41 ± 1.04, 1.95 ± 0.51, 3.81 ± 0.63 and 10.16 ± 2.05 in the experimental group, significantly lower than in the control group 5.08 ± 1.08, 2.82 ± 0.60, 5.42 ± 0.76 and 13.32 ± 1.93, the differences were statistically significant ( t values were 2.76-6.86, all P<0.01); the social exclusion scores, internal shame scores, social isolation scores and total stigma scores in SIS were 17.57 ± 2.67, 9.08 ± 1.55, 12.14 ± 3.73 and 46.14 ± 4.95 in the experimental group, significantly lower than in the control group 19.18 ± 3.70, 10.68 ± 1.61, 14.18 ± 3.83 and 51.68 ± 6.09, the differences were statistically significant ( t values were 2.16-4.38, all P<0.05). Conclusions:Peer support-based narrative therapy can effectively alleviate the postoperative self-image problems and stigma of patients with head and neck cancer, which is worthy of clinical application.

Objective:To investigate the prevalence, gene variation and prognosis of very long chain acyl CoA dehydrogenase deficiency (VLCADD) in newborns in Henan Province.Methods:From January 2013 to December 2019, 867 103 newborns were investigated for VLCADD by tandem mass spectrometry.Children who diagnosed as VLCADD and their families were subjected to next-generation sequencing and Sanger sequencing.Clinical data, biochemical changes and gene variation characteristics of the confirmed cases of VLCADD were analyzed.Dietary guidance was given, and their growth and development were followed up.Results:Six neonates were diagnosed as VLCADD, and the prevalence of VLCADD in the Henan Province was 1/144 517.A total of 11 mutations in the ACADVL gene were found, including 5 new variants c. 692-2_692-1delAG, c.753-23_753-22del, c.960delG, c.1361A>G, and c. 1955C>T.The newborns were given a high-carbohydrate, low-fat diet, and followed up for 8-56 months.Except for two deaths, all patients had a good outcome. Conclusions:The prevalence of neonatal VLCADD in Henan Province is 1/144 517.This results has enriched the ACADVL gene mutation spectrum and provided an important basis for the screening and diagnosis of VLCADD.

Reducing the inflammatory response is a major goal in the therapy of rheumatoid arthritis (RA). Herein, we integrated palladium nanoparticles (Pd NPs) with selenium nanoparticles (Se NPs) and obtained a multiple nanosystem (Pd@Se-HA NPs) that could simultaneously scavenge hydroxyl radicals (⋅OH) and provide a photothermal effect. The Pd@Se-HA NPs were constructed by a simple self-assembly method in which Se NPs were electrostatically bonded to Pd NPs; hyaluronic acid (HA) was linked to the NPs by ester bonding to provide macrophage targeting ability. The experiments show that the combined therapy of eliminating ⋅OH with Se NPs and utilizing PTT with Pd NPs could effectively reduce the inflammatory response in macrophages more effectively than either individual NP treatment. In addition, the outer layer of HA could specifically target the CD44 receptor to enhance the accumulation of Pd@Se NPs at the lesion, further enhancing the therapeutic effect. After treatment for 15 days, the Pd@Se-HA NPs nearly eliminated the inflammatory response in the joints of mice in an induced RA model, and prevented joint damage and degradation.

Along with the develoipment of high-throughput sequencing technologies, both sample size and SNP number are increasing rapidly in genome-wide association studies (GWAS), and the associated computation is more challenging than ever. Here, we present a memory-efficient, visualization-enhanced, and parallel-accelerated R package called"rMVP"to address the need for improved GWAS computation. rMVP can 1) effectively process large GWAS data, 2) rapidly evaluate population structure, 3) efficiently estimate variance components by Efficient Mixed-Model Association eX-pedited (EMMAX), Factored Spectrally Transformed Linear Mixed Models (FaST-LMM), and Haseman-Elston (HE) regression algorithms, 4) implement parallel-accelerated association tests of markers using general linear model (GLM), mixed linear model (MLM), and fixed and random model circulating probability unification (FarmCPU) methods, 5) compute fast with a globally efficient design in the GWAS processes, and 6) generate various visualizations of GWAS-related information. Accelerated by block matrix multiplication strategy and multiple threads, the association test methods embedded in rMVP are significantly faster than PLINK, GEMMA, and FarmCPU_pkg. rMVP is freely available at https://github.com/xiaolei-lab/rMVP.

Objective:To explore the effects of K-ras gene on the expressions of oncogenes and cancer suppressor genes in human bronchial epithelial (HBE) cells which were exposed to PM 2.5. Methods:According to the mRNA sequence of K-ras gene provided by GenBank in September 2019, interference sequences were designed and synthesized, and the recombinant lentiviral vector was transfected into HBE cell to construct the K-ras gene-silenced cells. HBE cells and K-ras gene-silenced cells were exposed to 10 μg/ml, 50 μg/ml PM 2.5 suspension and 10 μmol/L Cr 6+. Real-time fluorescent quantitative PCR was used to detect the mRNA expression levels of c-myc, c-fos, N-ras, cyclin-D1, p16 and p53 genes, the expression levels of p53 and c-myc proteins were detected by Western blot. Results:In K-ras silenced cell group, K-ras mRNA expression level decreased (80.5%±3.6%) and K-ras protein level decreased (58.9%±4.7%) when compared with the control group ( P<0.01) . Compared with the correspoding cell control group without exposure, the mRNA expression levels of c-myc, c-fos, N-ras and cyclin-D1 genes in HBE cell group exposed to different concentrations of PM 2.5, K-ras silenced cell group exposed to different concentrations of PM 2.5, HBE cell group exposed to 10 μmol/L Cr 6+ and K-ras silenced cell group exposed to 10 μmol/L Cr 6+ were increased, the mRNA expressions of p16 and p53 genes were decreased ( P<0.01) . Compared with HBE cell group exposed to 10 μg/ml PM 2.5, the mRNA expressions of c-myc, c-fos and p16 genes in K-ras silenced cells exposed to 10 μg/ml PM 2.5 were decreased, and the p53 mRNA level was increased ( P<0.01) . Compared with HBE cell group exposed to 50 μg/ml PM 2.5, the mRNA expression levels of c-fos, N-ras, cyclin-D1, p16 and p53 genes in K-ras silenced cell group exposed to 50 μg/ml PM 2.5 were decreased ( P<0.01) . Compared with the HBE cell group without exposure, c-myc protein increased and p53 protein decreased in HBE cells exposed to 50 μg/ml PM 2.5 ( P<0.05) . Compared with the K-ras silenced cell group without exposure, c-myc protein increased in K-ras silenced cells exposed to 50 μg/ml PM 2.5 ( P<0.05) . Conclusion:PM 2.5 can increase the expression levels of oncogenes in HBE cells, and K-ras gene silencing can inhibit the expression levels of oncogenes in HBE cells treated with PM 2.5.

Objective:To explore the effects of K-ras gene on the expressions of oncogenes and cancer suppressor genes in human bronchial epithelial (HBE) cells which were exposed to PM 2.5. Methods:According to the mRNA sequence of K-ras gene provided by GenBank in September 2019, interference sequences were designed and synthesized, and the recombinant lentiviral vector was transfected into HBE cell to construct the K-ras gene-silenced cells. HBE cells and K-ras gene-silenced cells were exposed to 10 μg/ml, 50 μg/ml PM 2.5 suspension and 10 μmol/L Cr 6+. Real-time fluorescent quantitative PCR was used to detect the mRNA expression levels of c-myc, c-fos, N-ras, cyclin-D1, p16 and p53 genes, the expression levels of p53 and c-myc proteins were detected by Western blot. Results:In K-ras silenced cell group, K-ras mRNA expression level decreased (80.5%±3.6%) and K-ras protein level decreased (58.9%±4.7%) when compared with the control group ( P<0.01) . Compared with the correspoding cell control group without exposure, the mRNA expression levels of c-myc, c-fos, N-ras and cyclin-D1 genes in HBE cell group exposed to different concentrations of PM 2.5, K-ras silenced cell group exposed to different concentrations of PM 2.5, HBE cell group exposed to 10 μmol/L Cr 6+ and K-ras silenced cell group exposed to 10 μmol/L Cr 6+ were increased, the mRNA expressions of p16 and p53 genes were decreased ( P<0.01) . Compared with HBE cell group exposed to 10 μg/ml PM 2.5, the mRNA expressions of c-myc, c-fos and p16 genes in K-ras silenced cells exposed to 10 μg/ml PM 2.5 were decreased, and the p53 mRNA level was increased ( P<0.01) . Compared with HBE cell group exposed to 50 μg/ml PM 2.5, the mRNA expression levels of c-fos, N-ras, cyclin-D1, p16 and p53 genes in K-ras silenced cell group exposed to 50 μg/ml PM 2.5 were decreased ( P<0.01) . Compared with the HBE cell group without exposure, c-myc protein increased and p53 protein decreased in HBE cells exposed to 50 μg/ml PM 2.5 ( P<0.05) . Compared with the K-ras silenced cell group without exposure, c-myc protein increased in K-ras silenced cells exposed to 50 μg/ml PM 2.5 ( P<0.05) . Conclusion:PM 2.5 can increase the expression levels of oncogenes in HBE cells, and K-ras gene silencing can inhibit the expression levels of oncogenes in HBE cells treated with PM 2.5.

Objective:To analyze the pollution characteristics and source of fine particulate matter (PM 2.5) in Shenzhen and Taiyuan, two cities in the north and south of China. Methods:PM 2.5 samples were collected from the year of 2017 to 2018. The levels of 10 heavy metal elements (Pb, Al, As, etc.) , 10 water soluble ions (F -, Cl -, SO 42-, etc.) and 16 polycyclic aromatic hydrocarbons (PAHs) (Nap, Acy, Ace, etc.) in PM 2.5 were detected by inductively coupled plasma mass spectrometry (ICP-MS) , ion Chromatography and high Performance Liquid Chromatography respectively. USA commercial carbon analysis was applied to detect organic carbon (OC) and elemental carbon (EC) . Source of PM 2.5 was analyzed by Factor analysis method. Results:The concentrations of Pb, Mn, As, Ni, F -, OC and EC in PM 2.5 of Taiyuan city were significantly higher than those of Shenzhen City, and the concentrations of Na +, Cl -, and PO 43- were lower than those of Shenzhen City ( P<0.05) . Except naphthalene, the concentrations of PAHs in PM 2.5 of Taiyuan city were higher than those of Shenzhen City ( P<0.05) . The main sources of metal elements and water soluble ions in PM 2.5 in Shenzhen included: industry/vehicle exhaust factor (42.64%) , construction/soil factor (34.22%) and ocean factor (17.93%) . PAHs in PM 2.5 in Shenzhen mostly came from fuel oil/vehicle exhaust factor (38.58%) , coal combustion factor (30.78%) and biomass combustion factor (24.38%) . Differently, the main sources of metal elements and water soluble ions in PM 2.5 in Taiyuan included: construction factor (30.26%) , fuel oil and coal combustion factor (24.58%) , secondary particles/soil factor (22.03%) and industry factor (18.89%) . PAHs in PM 2.5 were from fuel oil/vehicle exhaust factor (54.71%) and coal combustion factor (43.54%) in Taiyuan. Conclusion:The sources of PM 2.5 pollution are different between Shenzhen and Taiyuan, the occupational health management must be continuously strengthened, measures should be strengthened contrapuntally on the basis of different pollution sources.