Objective:To investigate the molecular features of hand, foot and mouth disease (HFMD) caused by coxsackievirus A10 (CVA10) in Qingdao and analyze the clinical features of mild and severe cases.Methods:A total of 6 677 cases of HFMD routinely monitored by Qingdao Women and Children Hospital from 2014 to 2021 were enrolled. Throat swab samples were collected. Clinical data of these cases were retrospectively analyzed. Virus nucleic acid was extracted from the samples and the serotypes of enteroviruses were identified. The VP1 genes of CVA10 strains were amplified and sequenced. A phylogenetic tree based on the VP1 gene sequences was constructed using MEGA7. 0 software. SPSS23.0 software was used for statistical analysis.Results:There were 285 cases positive for CVA10, including 183 males and 102 females, and children under five years old accounted for 89.8%. Most of CVA10 infection occurred between the months of April to September. The count of white blood cells, the percentage of neutrophils, the concentration of hemoglobin, and the levels of aspartate aminotransferase and alanine transaminase were significantly higher in severe patients than in mild patients. Besides, chest radiography and brain CT revealed more abnormalities in severe patients, and the duration of ECG monitoring was longer in them. Compared with mild cases, severe cases developed rash early than fever with rash mostly on buttocks ( P<0.05). Phylogenetic analysis showed that most of the CVA10 strains circulating in Qingdao between 2014 and 2021 belonged to clade Ⅰ, and there were two variations A23V and I283V in the amino acid sequence of clade Ⅰ. Conclusions:This study showed that children of all ages were susceptible to CVA10, especially those under five years old. CVA10 showed complex and diverse epidemic trends in different regions and years.

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1β release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.

Objective:To explore the effect of match between childhood stress and adulthood stress on mental health status.Methods:Adult healthy volunteers( n=239) and adult mental disorder patients were examined by questionnaires or telephone interviews.Childhood trauma questionnaire (CTQ) and lifetime stress event list were used for measure of CS and AS, DSM5-level-1-cross-cutting-symptom-measure (DSM5-L1CCSM) and self-rating depression scale (SDS) for mental health outcomes.Subjects were grouped according to positive (+ ) / negative (-) stress events into five groups: CS+ AS+ Matched ( n=108), CS+ AS+ mismatched( n=240), CS-AS+ ( n=100), CS+ AS-( n=79), and CS-AS-( n=99). The data of stress and mental health status were compared and analyzed among stress groups. Results:The distributions of positive stress events among 626 volunteers were 68.2% with CS+ , 71.6% with AS+ , 17.3% with C+ A+ M+ .There were differences among groups in all parameters (all P<0.05) except for gender.Age, years of education, CS and emotional abuse were influencing factors of onset of AS( P<0.01). MANCOVA analysis showed that factors about the interaction of AS and CS had attribution on DSM5-L1CCSM and SDS ( P<0.01). Conclusion:CS has a facilitatory effect on AS.The match of CS-AS is an important risk factor of adulthood mental health outcomes.Re-experiencing the same type of CS in adulthood would worsen adulthood mental health status.

Objective:To investigate the mechanism of crush syndrome (CS) induced by crush injury on myocardial cells in rats.Methods:Thirty two male Sprague Dawley (SD) rats were randomly divided into control group, CS-0 group, CS-12 group and CS-24 group with 8 rats in each group. CS model was made by self-made extruder and perfused with 4% paraformaldehyde for 0, 12 and 24 h. The morphological changes of myocardial tissue were observed by hematoxylin staining. The apoptosis of cardiomyocytes was detected by terminal dexynucleotide transferase-mediated nick end labeling (TUNEL). The levels and activities of malondialdehyde (MDA), superoxide dismutase (SOD), lactose dehydrogenase (LDH), interleukin-6 (IL-6), interleukin-1 β (IL-1 β), tumor necrosis factor-α (TNF- α) in myocardial homogenate were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Caspase-3, Bax, Bcl-2 and necrosis factor-κB (NF-κ B) were detected by Western blot.Results:Compared with the control group, the myocardial tissue of CS model group had different degrees of morphological damage; compared with the control group, the apoptosis rate, Caspase-3 and Bax protein expression levels of CS-0 group, CS-12 group and CS-24 group were significantly increased ( P<0.05), and the expression level of Bcl-2 protein was significantly decreased ( P<0.05); compared with the control group, the levels of MDA, LDH, IL-6, IL-1β, TNF-α and p65 protein phosphorylation in the myocardial homogenate of CS-0 group, CS-12 group and CS-24 group were significantly increased ( P<0.05), and SOD activity was significantly decreased ( P<0.05). Conclusions:CS may inhibit oxidative stress and induce inflammatory reaction by activating NF-κ B pathway, thus damaging myocardial cells in rats.

Objective To explore the effect of childhood trauma on escitalopram treatment of adult depression. Methods There were 68 adult patients with major depression disorder recruited. All patients were assessed with Childhood Trauma Questionnaire ( CTQ ) and given 8 weeks of standardized treatment with escitalopram. Beck Depression Inventory ( BDI) and HAMD-17 were assessed at the end of the 2nd,4th and 8th week respectively. The changes of BDI score and HAMD-17 score in patients with different CTQ fac-tors were observed. Results ( 1) The overall effect of intervention was 25. 0％ at the end of 4th week and 45. 6％ at the end of 8th week. The total effective rate was 94. 1％. At the end of 4th week,there was no sig-nificant difference in the clinical recovery rate between the positive group(19. 5％) and the negative group (33. 3％)(χ2=1. 66,P>0. 05). There was no significant difference in clinical recovery between the two groups at the end of 8th week(positive group :39. 0％,negative group :55. 6％,χ2=1. 79,P>0. 05). (2) The total score reduction rate of HAMD-17((46. 26±24. 79)％,(58. 39±23. 25)％) and BDI((51. 63± 16. 03)％,(66. 28±18. 05)％) at the end of 4th week and the total score reduction rate of BDI at the end of 8th week ((59. 13±15. 42)％,(68. 50±20. 91)％)in the positive group were lower than those in the nega-tive group (P<0. 05) . ( 3) Except for sexual abuse,there was a significant negative correlation between CTQ scores and the reduction rate of BDI scores at end of 4th and 8th week( r=-0. 46--0. 06,P<0. 05) . Conclu-sion Childhood trauma has adverse effects on the efficacy of escitalopram in the treatment of adult depres-sion.

OBJECTIVE: The aims of the present study were to explore the occurrence of childhood trauma and importantly to determine the impacts of childhood trauma on psychosocial features in a Chinese sample of young adults. METHODS: A survey was carried out in a group of 555 university students by using Childhood Trauma Questionnaire (CTQ), Self-rating Depression Scale (SDS), Self-rating Anxiety Scale (SAS), Dysfunctional Attitudes Questionnaire (DAS), Eysenck Personality Questionnaire (EPQ), and Social Support Rating Scale (SSRS). The moderate-severe cut-off scores for CTQ were used to calculate the prevalence of childhood trauma, and then psychosocial features were compared between individuals with and without childhood trauma. RESULTS: A proportion of 18.6% of university students had self-reported childhood trauma exposures. Subjects with childhood trauma reported higher scores of SDS, SAS, DAS, and psychoticism and neuroticism dimensions of EPQ (t=4.311–5.551, p < 0.001); while lower scores of SSRS and extraversion dimension of EPQ (t=-4.061– -3.039, p < 0.01). Regression analyses further revealed that scores of SAS and DAS were positively (Adjusted B=0.211–0.230, p < 0.05), while scores of SSRS were negatively (Adjusted B=-0.273– -0.240, p < 0.05) associated with specific CTQ scores. CONCLUSION: Childhood trauma is still a common social and psychological problem. Individuals with childhood trauma show much more depression, anxiety, distorted cognition, personality deficits, and lower levels of social support, which may represent the social and psychological vulnerability for developing psychiatric disorders after childhood trauma experiences.
Anxiety ; Asian Continental Ancestry Group* ; Cognition ; Depression ; Extraversion (Psychology) ; Humans ; Prevalence ; Young Adult*

BACKGROUND:MicroRNAs (miRNAs) play an important role in a variety of diseases. Investigation of miRNA expression profile in degenerative lumbar scoliosis is beneficial for understanding its pathogenesis, providing a novel therapeutic target. Therefore, we tested the hypothesis that miRNAs promote intervertebral disc degeneration through the interleukin-10/STAT3 signaling pathway, a potential regulator of intervertebral disc degeneration.
OBJECTIVE:To compare the differentialy expressed miRNAs in the intervertebral disc tissues from patients with degenerative lumbar scoliosis and normal controls and to identify specific miRNAs in degenerative lumbar scoliosis folowed by functional validation.
METHODS: An initial screening of miRNA expression in nucleus pulposus tissues by miRNA Solexa Sequencing was performed in samples from 10 patients with degenerative lumbar scoliosis and 10 controls, respectively. Subsequently, differentialy expressed miRNAs were validated using qRT-PCR. The level of differentialy expressed miRNAs in degenerative nucleus pulposus tissues was investigated. Then, functional analysis of the miRNAs in regulating type II colagen expression was carried out. Western blot and luciferase reporter assay were used to further confirm the target gene.
RESULTS AND CONCLUSION: We identified 30 miRNAs that were differentialy expressed (16 upregulated and 14 downregulated) in patients with degenerative lumbar scoliosis compared with controls. Folowing qRT-PCR confirmation, Has-let-7f was significantly down-regulated in degenerative nucleus pulposus tissues as compared with controls. Moreover, its level was correlated with the severity of disc degeneration. Overexpression of Has-let-7f promoted type II colagen expression in nucleus pulposus cels. Knockout of interleukin-10 induced effects on nucleus pulposus cels similar to Has-let-7f. Bioinformatics target prediction identified interleukin-10 as a putative target of Has-let-7f. Furthermore, luciferase reporter assays demonstrated that Has-let-7f altered the expression of STAT3 and matrix metaloproteinase-2. These findings indicate that the downregulation of Has-let-7f induces type II colagen loss by directly targeting inleukin-10, thereby resulting in intervertebral disc degeneration and degenerative lumbar scoliosis. Has-let-7f is likely to be a novel therapeutic target for degenerative lumbar scoliosis.

BACKGROUND:MicroRNAs are widely involved in the regulation of protein expression, and play a critical role in many physiological and pathological processes in the body. But microRNA expression profile in degenerative lumbar scoliosis is rarely reported and understood. OBJECTIVE:To compare the microRNA expression profile in the normal intervertebral disc and degenerative lumbar scoliosis and to identify degenerative lumbar scoliosis-specific microRNAs, folowed by functional validation. METHODS: Total RNA samples were extracted from the nucleus pulposus tissues of 57 patients with degenerative lumbar scoliosis as experimental groups and the normal nucleus pulposus tissues of 42 patients with lumbar fractures as control group. An initial screening of differentialy expressed microRNAs in the nucleus pulposus tissues by microRNA microarray was performed in 10 samples from each group. Subsequently, differentialy expressed microRNAs were validated using real-time quantitative RCR. The level of differentialy expressed microRNAs in the degenerative nucleus pulposus tissues was investigated. Then, the functional analysis of microRNAs in regulating colagen II expression was carried out. Western blot and luciferase reporter assay were also used to detect target genes. RESULTS AND CONCLUSION:We identified 22 microRNAs that were differentialy expressed (17 upregulated and 5 downregulated) in degenerative lumbar scoliosis patients compared with the controls. Folowing real-time quantitative RCR confirmation, miR-491-5p was significantly down-regulated in degenerative nucleus pulposus tissues in comparison with the controls. Moreover, its level was closely correlated with the pathological grading of disc degeneration. Overexpression of miR-491-5p promoted type II colagen expression in nucleus pulposus cels. Bioinformatics target prediction identified matrix metaloproteinase-9 as a putative target of miR-491-5p. Furthermore, luciferase reporter assays demonstrated that miR-491-5p directly targeted matrix metaloproteinase-9 and affected its protein expression in nucleus pulposus cels. These results show that the downregulation of miR-491-5p induces type II colagen loss by directly targeting matrix metaloproteinase-9, thereby resulting in degeneration of the intervertebral disc and degenerative lumbar scoliosis. This study also underscores the potential of miR-491-5p as a novel therapeutic target in degenerative lumbar scoliosis.

Aim To screen the potential inhibitors of post-transcriptional activity of pro-inflammatory media-tor TNF-α from the lipophilic constituents in Chinese Medicine Salvia miltiorrhiza Bunge ( Danshen) , we es-tablished dual luciferase reporter gene system pGL3-TNF-α3′UTR ( 3′untranslated region ) co-transfected with Renilla control gene. Methods Complementary DNA ( cDNA) template was obtained from human um-bilical vein endothelial cells ( HUVECs ) . The full length DNA of TNF-α 3′-UTR was amplified through PCR, and then connected the luciferase reporter vector pGL3-control after enzyme digestion. pGL3-TNF-α 3′UTR constructs were co-transfected with pSVRenilla into the mononuclear macrophages RAW264. 7 cells. The relative activity of reporter genes was measured by dual luciferase reporter ( DLR ) assay system after the stimulus of lipopolysaccharide ( LPS ) in presence or absence of tanshinones compounds. Results The pGL3-TNF-α3′UTR luciferase reporter gene was suc-cessfully constructed. The cloning DNA fragment and sequence were both consistent with the GENBANK da-tabase. LPS significantly induced the relative reporter activityof RAW264 . 7 cells transfected with pGL3-TNF-α 3′UTR. Among four tanshinones compounds, we found only cryptotanshinone could significantly de-crease LPS-induced relative reporter activity. Conclu-sion The pGL3-TNF-α 3′UTR construct combined with DLR assay system was successfully established, which can be used to discover the agents such as cryp-totanshinone that regulate the post-transcription of TNF-α in treatment of inflammatory and malignant dis-eases.