Development and Application of Global Health Events-Mental Stress Scale for Assessment of Medical Staff's Acute Mental Stress Responses.

Background: Medical workers have been increasingly involved in emergent public health events, which can lead to severe stress. However, no standardized, officially recognized, unified tool exists for mental distress measurement in medical workers who experienced the public health events. Purpose: In the present study, we propose the Global Health Events-Mental Stress Scale (GHE-MSS), as a revised version of the Impact of Event Scale-Revision (IES-R), for assessment of medical workers' acute mental stress responses within one month and their chronic mental stress responses within six months after major health events. Patients and methods: The IES-R was slightly modified, developed, and its reliability and validity were tested using the Delphi survey, primary survey with 115 participants, formal survey with 300 participants, and clinical evaluation with 566 participants. Results: Exploratory factor analysis and confirmatory factor analysis confirmed a promising validity of the scale. The values of Cronbach's alpha coefficient, the Spearman-Brown coefficient, and the retested Cronbach's alpha coefficient of the scale applied for the clinical evaluation were 0.88, 0.87, and 0.98, respectively, which confirmed a good internal consistency and stability. The results of the goodness-of-fit test indicated a good adaptation of the model. A correlation analysis was conducted to assess the correlation between the GHE-MSS and the PCL-C, which had a correlation coefficient of 0.68 (P<0.01). Conclusion: GHE-MSS can be applied with a promising reliability and validity for the assessment of the acute mental stress response of medical workers experiencing public health events. This method can also be used for the screening of mental stress-associated disorders.

Confirming the TMEM232 gene associated with atopic dermatitis through targeted capture sequencing.

Atopic dermatitis (AD) is a common and complex skin disorder, and the 5q22.1 region had been reported to be associated with AD. To confirm the susceptibility gene for AD in the 5q22.1 region by haplotype and targeted capture sequencing. The haplotypes were reconstructed with the genotyping data of four SNPs and six deletions from 3624 Chinese Hans AD patients and 5076 controls. The targeted capture sequencing spanning 5q22.1 region was performed in the selected samples. The gene level enrichment analysis was done using loss of function variants. A total of 62 haplotypes were found, and the H15 haplotype had the strongest association with AD (P = 3.92 × 10-10, OR 0.17, 95% CI 0.09-0.32). However, no co-segregation mutation sites were found in the sequencing analysis within the 16 selected samples, while the enrichment analysis indicated that TMEM232 was significantly associated with AD (P = 7.33 × 10-5, OR 0.33, 95% CI 0.19-0.58). This study confirms previous findings that the TMEM232 gene is associated with AD by haplotype analysis and targeted capture sequencing.

Chronic Progression of Lung Cancer Recurrence After Surgery: Warning Role of Postoperative Pneumonia.

PURPOSE: The association between the process of postoperative pneumonia and lung cancer recurrence remains elusive in lung cancer surgery. Herein, the association between postoperative pneumonia and lung cancer recurrence was investigated, emphasizing the warning role of postoperative specific pneumonia in primary lung cancer resection patients. METHODS: The occurrence of postoperative pneumonia was assessed in 4-6 months (PPFS), 7-12 months (PPST), and lung cancer recurrence within 1 year (LRO) in 332 patients. The primary outcome was the development of PPST and LRO according to PPFS occurrence. The relevant risk factors of PPFS, PPST, and LRO were identified through multivariable regression analysis. RESULTS: During follow-up, 151 (45.48%) participants experienced PPFS. Irrespective of the existing postoperative pneumonia in 1-3 months (PPOT), PPFS significantly increased the risk of PPST (P < 0.01) and LRO (P < 0.01), and persistent PPST further increased the risk of LRO (P < 0.001). The generalized estimating equation identified chemotherapy as an independent risk factor for PPFS and PPST. CONCLUSION: PPFS was associated with the increased risk of PPST and LRO. Postoperative pulmonary inflammation assessed 4 months post-surgery also significantly influenced LRO development, indicating a need for close follow-up of lung inflammatory conditions to improve patient outcomes.

Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing.

Neurofibromatosis (NF) is an autosomal genetic disorder for which early and definite clinical diagnoses are difficult. To identify the diagnosis, five affected probands with suspected NF from unrelated families were included in this study. Molecular analysis was performed using multigene panel testing and Sanger sequencing. Ultradeep sequencing was used to analyze the mutation rate in the tissues from the proband with mosaic mutations. Three different pathogenic variants of the NF1 gene were found in three probands who mainly complained of café-au-lait macules (CALMs), including one frameshift variant c.5072_5073insTATAACTGTAACTCCTGGGTCAGGGAGTACACCAA:p.Tyr1692Ilefs in exon 37, one missense variant c.3826C > T:p.Arg1276Ter in exon 28, and one splicing variant c.4110 + 1G > T at the first base downstream of the 3'-end of exon 30. One NF1 gene mosaic variant was found in a proband who complained of cutaneous neurofibroma with the frameshift variant c.495_498del:p.Thr165fs in exon 5, and ultradeep sequencing showed the highest mutation rate of 10.81% in cutaneous neurofibromas. A frameshift variant, c.36_39del:p.Ser12fs in exon 1 of the NF2 gene, was found in a proband who presented with skin plaques and intracranial neurogenic tumors. All of these pathogenic variants were heterozygous, one was not reported, and one not in Chinese before. This study expands the pathogenic variant spectrum of NF and demonstrates the clinical diagnosis.

Validation of Susceptibility Loci for Vitiligo Identified by GWAS in the Chinese Han Population.

Forty-nine susceptible loci have been reported to be significantly associated with vitiligo by genome-wide association studies (GWASs) in European-derived whites. To date, some of these reported susceptibility loci have not yet been validated in the Chinese Han population. The purpose of this study was to examine whether the 16 reported susceptible loci in European-derived whites were associated with vitiligo in the Chinese Han population. Imputation was performed using our previous GWAS dataset by IMPUTE v2.2.2. The 16 imputed top single-nucleotide polymorphisms (SNPs) with suggestive signals, together with the reported SNPs, were genotyped in a total of 2581 patients and 2579 controls by the Sequenom MassARRAY system. PLINK 2.0 software was used to perform association analysis. The dbSNP database, HaploReg, and eQTL data were adopted to annotate the biological function of the SNPs. Finally, four SNPs from three loci were significantly associated with vitiligo, including rs3747517 (P = 1.29 × 10-3, OR = 0.87) in 2q24.2, rs4807000 (P = 7.78 × 10-24, OR = 0.66) and rs6510827 (P = 3.65 × 10-5, OR = 1.19) in 19p13.3, and rs4822024 (P = 6.37 × 10-10, OR = 0.67) in 22q13.2. According to the dbSNP database, rs3747517 is a missense variant of IFIH1, rs4807000 and rs6510827 are located in TICAM1, and rs4822024 is located 6 kb upstream of TEF. Further bioinformatics analysis by HaploReg and eQTL found that rs4807000, rs6510827, and rs4822024 are involved in regulating gene expression. Our study revealed the strong association of 2q24.2 (rs3747517), 19p13.3 (rs4807000, rs6510827), and 22q13.2 (rs4822024) with the risk of vitiligo in the Chinese Han population, which implicates common factors for vitiligo across different ethnicities, and helps expand the understanding of the genetic basis of this disease.

Comparison of a Novel Muscle Training Device with Conventional Rehabilitation Training in Motor Dysfunction of Lower Limb Patients: A Pilot Study.

BACKGROUND: Postoperative functional training for fracture or osteoarthritis is mainly focused on functional self-exercise, which aims to recover the function of the lower limbs. PURPOSE: To compare the function and life quality recovery in patients with fracture or arthritis treated with novel muscle training device (NMT) or conventional rehabilitation training (CRT) following surgery. PATIENTS AND METHODS: A total of 32 fracture patients were randomly divided into the NMT or the CRT groups. The evaluation was performed on the first and 7th day after surgery. The outcome measurements included the incidence of foot drop, Deep Vein Thrombosis and pressure ulcers, Hospital for Special Surgery knee score (HSS scores), pain scores for the Visual Analogue Scale (Pain scores for VAS), Zung self-rating anxiety scale (SAS), Pittsburgh sleep quality index (PSQI) and the Barthel Index score. RESULTS: The comparison of the change scores between the two groups indicated significant differences on day 7 following surgery in the Barthel Index score (P<0.01). The Pain scores for VAS between the two groups indicated a significant difference (P<0.05, U=20.0). The HSS scores between the two groups indicated a significant difference (P<0.05, U=19.0). The HSS scores exhibited a highly significant difference in the NMT group (P<0.01). The Mann-Whitney test was used to analyze the various components of the HSS scores. The comparison of the change scores on the function between the two groups indicated a significant difference (P<0.05). The Range of Motion difference between groups exhibited highly significant differences (P<0.01). CONCLUSION: The novel muscle training device positively influenced the decrease in pain score, which resulted in a range increase of knee joint movement and a significant overall improvement in motion.

Optimal concentration of necrostatin-1 for protecting against hippocampal neuronal damage in mice with status epilepticus.

Hippocampal neurons undergo various forms of cell death after status epilepticus. Necrostatin-1 specifically inhibits necroptosis mediated by receptor interacting protein kinase 1 (RIP1) and RIP3 receptors. However, there are no reports of necroptosis in mouse models of status epilepticus. Therefore, in this study, we investigated the effects of necrostatin-1 on hippocampal neurons in mice with status epilepticus, and, furthermore, we tested different amounts of the compound to identify the optimal concentration for inhibiting necroptosis and apoptosis. A mouse model of status epilepticus was produced by intraperitoneal injection of kainic acid, 12 mg/kg. Different concentrations of necrostatin-1 (10, 20, 40, and 80 µM) were administered into the lateral ventricle 15 minutes before kainic acid injection. Hippocampal damage was assessed by hematoxylin-eosin staining 24 hours after the model was successfully produced. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, western blot assay and immunohistochemistry were used to evaluate the expression of apoptosis-related and necroptosis-related proteins. Necrostatin-1 alleviated damage to hippocampal tissue in the mouse model of epilepsy. The 40 µM concentration of necrostatin-1 significantly decreased the number of apoptotic cells in the hippocampal CA1 region. Furthermore, necrostatin-1 significantly downregulated necroptosis-related proteins (MLKL, RIP1, and RIP3) and apoptosis-related proteins (cleaved-Caspase-3, Bax), and it upregulated the expression of anti-apoptotic protein Bcl-2. Taken together, our findings show that necrostatin-1 effectively inhibits necroptosis and apoptosis in mice with status epilepticus, with the 40 µM concentration of the compound having an optimal effect. The experiments were approved by the Animal Ethics Committee of Fujian Medical University, China (approval No. 2016-032) on November 9, 2016.

GWAS Follow-up Study Discovers a Novel Genetic Signal on 10q21.2 for Atopic Dermatitis in Chinese Han Population.

Atopic dermatitis (AD) is a common inflammatory skin disease with high heritability. Two susceptibility loci have been confirmed in our previous AD genome-wide association study (GWAS). To look for additional genetic factors in Chinese Han ethnicity, we performed a large-scale GWAS follow-up study. Forty-nine top single nucleotide polymorphisms (SNPs) that had never been reported previously were genotyped using Sequenom Massarray system in an independent cohort, which consist of northern Chinese (1634 cases and 1263 controls) and southern Chinese (2985 cases and 9526 controls). Association analyses were performed using PLINK 2 software. Three SNPs in northern and ten SNPs in southern were found exhibiting association evidence with AD (P < 0.05). Finally, SNP rs224108 on 10q21.2 showed high significance for AD in joint analysis of GWAS and replication study (P meta = 4.55 × 10-9, OR = 1.21), and was confirmed as an independent genetic marker by Linkage disequilibrium calculation and conditional logistic regression analysis. Bioinformatics analysis strongly suggested that rs224108 may have the potential to alter the target gene expression through non-coding epigenetic regulation effects. Meanwhile, SNP rs11150780 on 17q25.3 was also found suggestive association with AD (P meta = 7.64 × 10-7, OR = 1.18). Our findings confirmed a novel susceptibility signal on 10q21.2 for AD in Chinese Han population and advanced the understanding of the genetic contribution to AD.

A variant on chromosome 2p13.3 is associated with atopic dermatitis in Chinese Han population.

BACKGROUND: Multi-ancestry genome-wide association study (GWAS) has recently identified 11 new susceptibility loci for Atopic dermatitis (AD). The replication of these new susceptibility loci in different populations should not be ignored. OBJECTIVE: To examine whether these 11 new identified susceptibility loci are also associated with AD in the Chinese Han population. METHODS: These 11 variants were imputed using our genome-wide array dataset. The selected SNPs with suggestive signals were genotyped in a large-scale replication study with a total of 4619 cases and 10,789 controls using the Sequenom Massarray system. Association analyses were performed using PLINK 1.07 software. Results were combined across our previous AD-GWAS stage and the replication stage by meta-analysis. Bioinformatic analysis was done to predict the possible causal gene. RESULTS: Of the 11 SNPs investigated, four SNPs showed suggestive association (P<0.05) in our previously published GWAS datasets. Association evidence for an intergenic variant rs112111458 at 2p13.3 with AD was replicated in Chinese Han population (P=7.37×10-7, OR=0.86), showing significance in Meta analysis of GWAS and replication study (Pmeta=8.18×10-08, OR=0.69). Further functional annotation by HaploReg indicated that transcriptional regulation activity exists at this locus for the CD207 gene in skin tissue. CONCLUSIONS: Our study confirmed a previously reported susceptibility loci in the Chinese Han population, which implicates CD207 might be a new susceptibility gene for AD and highlights the crucial role of immune responses in AD.