The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear. In this study, we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates. Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes. Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo. Furthermore, bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7 (SETD7) as a significant CHAF1B target gene. In addition, CHAF1B competitively binds to the SETD7 promoter region and represses its transcription. Altogether, these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.
Humans ; Lung Neoplasms/metabolism* ; Histone-Lysine N-Methyltransferase/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Gene Expression Regulation, Neoplastic ; Disease Progression ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Chromatin Assembly Factor-1/metabolism* ; Animals ; Mice ; Male ; Female

Objective:To explore the feasibility of bibliometric analysis of research papers on human metapneumovirus based on Web of Science database.Methods:The human metapneumovirus (HMPV) causes a serious disease burden worldwide. This article used bibliometric analysis method to search for papers using the keyword " metapneumovirus" , and searched for HMPV papers published from 2001 to 2023 in the Web of Science database. Statistical analysis of the distribution of papers on HMPV by year, country, journal, research institution, author, etc., in order to understand the current research status and development trends of HMPV in the international community.Results:A total of 3 282 papers were retrieved, of which 97% were in English. HMPV was first reported in 2001, and since then, research papers have been increasing year by year. The United States has the highest number of published papers, with China, the United Kingdom, France, and the Netherlands ranked 2nd, 3rd, 4th, and 5th respectively. The field of virology-general had the highest number of papers. In terms of research institution distribution, Vanderbilt University in the United States has published 135 papers, ranked the first. The journal which had the highest number of published papers was JOURNAL OF MEDICAL VIROLOGY, with a total of 143 papers. The author Williams JV of Vanderbilt University in the United States has published 92 papers, indicating its high international status in the field of HMPV research.Conclusions:Among the retrieved HMPV related papers, research institutions and universities in European and American countries have published more papers.

Objective:To investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

Objective:To investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

The passing of ethical review is a necessary conditions and prerequisite for the development of life science and medical research involving humans. At present, some medical and health institutions have no or insufficient ethical review capabilities. The lack of ethical review ability has become a bottleneck restricting the development of life science and medical research involving humans. According to documents such as Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical and Medical Devices, Opinions on Strengthening the Ethical Governance of Science and Technology, institutions can entrust competent institutional ethics review committees or regional ethics review committees in writing to conduct ethical review. Entrustment ethical review provides a viable solution for institutions that need to carry out life science and medical research involving humans but do not have an ethics (review) committee or the ethics (review) committee is not competent to review. To conduct the entrustment ethical review, the entrustment between the principal and the trustee is required. According to The Measures for Ethical Review of Life Sciences and Medical Research Involving Humans, if medical and health institutions and their ethical review committees do not accept the formal entrustment to provide the ethical review opinions for other institutions, the local health authorities at or above the county level will impose administrative penalties and sanctions on the relevant institutions and personnel in accordance with the law. Signing the entrustment ethical review contract, implementing legal compliance entrusted ethical review to protect the rights and interests of the trustee and the principal, and protect the research participants.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

Objective:To evaluate the efficacy and safety of heating physiotherapy goggles in the treatment of meibomian gland dysfunction (MGD).Methods:A randomized controlled study was performed.Forty-four MGD patients were recruited in Wenzhou Medical University Eye Hospital from July 2021 to January 2022.Two patients were lost to follow-up.The patients were randomly divided into experimental group treated with heating physiotherapy goggles and control group treated with hot towels according to the random envelope method, with 21 patients (21 eyes) in each group.Throughout the study, the examiner was blinded.The data of the worse eye were analyzed.At baseline, 2 weeks and 4 weeks after treatment, the Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), fluorescein breakup time (FBUT), corneal fluorescein staining score (CFS), lid margin hyperemia score and meibomian gland function scores were measured to evaluate the efficacy; visual acuity, intraocular pressure and slit lamp microscopy were examined to assess the safety.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Wenzhou Medical University Eye Hospital (No.2021-177-K-153-01).Results:There were significant differences in OSDI scores between before and after treatment ( Ftime=16.528, P<0.001). No significant difference was found in OSDI scores between 30.46±17.31 at 2 weeks after treatment and 35.43±18.22 before treatment in control group ( P=0.405). The OSDI score at 2 weeks after treatment was 26.27±16.47, which was significantly lower than 39.24±17.96 before treatment in experimental group ( P=0.001). The eyelid margin hyperemia score was 0.0(1.0, 2.0) at 4 weeks after treatment in experimental group, which was significantly lower than 2.0(1.0, 3.0) in control group (Wald χ2=11.444, P=0.001). The morphologic scores of meibomian gland orifices at 2 and 4 weeks after treatment were both 1.0(0.0, 1.0) in experimental group, which were significantly lower than 2.0(1.0, 3.0) and 2.0(1.0, 2.5) in control group (Wald χ2=15.082, 23.172; both at P<0.001). The scores of meibum quality at 2 and 4 weeks after treatment were 1.0(0.5, 2.0) and 1.0(0.0, 1.5) in experimental group, which were significantly lower than 2.0(1.0, 2.0) and 2.0(1.0, 2.5) in control group (Wald χ2=4.638, 9.395; both at P<0.05). The scores of upper meibomian gland expressibility at 2 and 4 weeks after treatment were both 2.0(1.0, 2.0) in experimental group, which were significantly lower than 3.0(2.0, 3.0) and 2.0(2.0, 2.5) in control group (Wald χ2=6.489, 11.562; both at P<0.05). The score of lower meibomian gland expressibility at 4 weeks after treatment in experimental group was 1.0(0.5, 2.0), which was significantly lower than 2.0(2.0, 3.0) in control group (Wald χ2=24.085, P<0.001). The FBUT at 2 and 4 weeks after treatment were 3.00(1.75, 3.50) and 3.00(2.00, 4.00) seconds in experimental group, which were significantly longer than 1.00(0.75, 2.00) and 2.00(1.00, 3.00) seconds in control group (Wald χ2=8.576, 8.539; both at P<0.05). There were significant differences in TMH among different time points ( Ftime=8.874, P<0.001). In control group, the TMH at 4 weeks after treatment was (0.24±0.09) mm, which was significantly higher than (0.18±0.05) mm before treatment ( P<0.05). In experimental group, the TMH at 4 weeks after treatment was (0.23±0.09) mm, which was significantly higher than (0.17±0.05) mm before treatment ( P<0.05). Significant differences were found in CFS score among different time points (Wald χ2time=10.116, P=0.006). There was no statistically significant differences in CFS score between before and after treatment in control group (Wald χ2=1.781, P=0.410). In experimental group, the CFS scores at 2 and 4 weeks after treatment were 0.0(0.0, 1.5) and 0.0(0.0, 0.0), which were significantly decreased in comparison with 0.00(0.00, 4.00) before treatment (both at P<0.05). In experimental group, the visual acuity converted to the logarithm of the minimum angle of resolution at 2 and 4 weeks after treatment were 0.10(0.00, 0.22) and 0.10(0.00, 0.22), which was significantly better than 0.10(0.00, 0.40) before treatment (both at P<0.05). There was no significant change in intraocular pressure at different time points between the two groups ( Fgroup=0.432, P=0.515; Ftime=0.329, P=0.721). No serious adverse effects occurred in both groups during the follow-up period. Conclusions:Compared with hot towel therapy, the use of heating physiotherapy goggles can relieve ocular discomfort of MGD patients more rapidly and improve the function and status of the meibomian gland more significantly.Heating physiotherapy goggles can treat MGD safely and effectively.

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Objective Tostudy the influence of pipe structures on the mixing uniformity of airborne effluents from nuclear power plant chimneys. Methods We used the computational fluid dynamics (CFD) method to simulate the velocity distribution and gas mixing in long straight pipes (I type) with square section and circular section, 90° single-bend pipes (L type) with square section and circular section, and 90° double-bend pipes (S type and U type) with square section and circular section. Results For the long straight pipe, due to the lack of flow disturbance caused by structural changes, the mixing effect was not good; when the pipe section was circular, it might take mixing distance 20 times the hydraulic diameter to achieve the uniformity index required by the relevant standard; for the square pipe, the distance might be longer. In the single bend pipe with square section, the velocity uniformity was improved more greatly after the bend, and the tracer gas met the mixing uniformity at a shorter distance (11 times the hydraulic diameter), as compared with the single bend pipe with circular section. For the S-type double-bend pipe, the tracer gas appeared uniformly mixed after a distance 6 times the hydraulic diameter in the square pipe, and 7 times the hydraulic diameter in the circular pipe. For the U-type double-bend pipe, the gas in the square pipe also achieved uniform mixing ata shorter distance downstream, and the airflow showed greater disturbance when passing through the bend. Conclusion The CFD method can make an accurate prediction for the change patterns of gas mixing uniformity in pipes with different structures, and can partially replace physical experiments to study the factors affecting the mixing uniformity of airborne effluents from the chimney of nuclear power plants.

Objective:The purpose of this study was to explore the association between gene in the potassium recycling pathway 4 (KCNQ4) polymorphisms and the susceptibility to noise-induced hearing loss (NIHL) , and analysis the effect of cumulative noise exposure (CNE) and noise exposure duration on this association.Methods:A nested case-control study with 1∶1 matched was used based on the cohort of noise exposure in a steel factory. A total of 286 cases were selected as the group of hearing loss and 286 controls were chosen according to the matching standards of same gender, same type of work, age difference ≤ 5 years, noise exposure duration ≤ 2 years. The single nucleotide polymorphisms (SNPs) of rs4660468, rs4660470, rs34287852 in KCNQ4 were genotyped by SNPscan TM method. The codominant, dominant and recessive models were established to study KCNQ4 polymorphisms and the susceptibility to NIHL by single-factor conditional logistic regression analysis. The COX regression analysis was used to analyze the risk of developing NIHL in individuals with different genotypes along with the extending of noise exposure duration or CNE. Results:In the case of CNE≤96 dB (A) ·year, the risk of developing NIHL in individuals with TA genotype of rs4660470 was 2.197 times than individuals with TT genotypes (95% CI: 1.032~4.677) , and those with TA+AA and TT genotypes (HR=2.467, 95% CI: 1.025~5.934) With the increase of noise exposure duration, in rs4660470, individuals with TA genotype had a higher risk of suffering NIHL than those with TT genotype (HR=1.461, 95% CI: 1.061~2.011) , individuals with TA and/or AA genotype had a earlier risk of suffering NIHL than those with TT genotype. Conclusion:The mutant allele A of rs4660470 in KCNQ4 may be a risk factor for developing NIHL, CNE≤100 dB (A) ·year or the increase of noise exposure duration may further increase the risk of NIHL.