Voluntary running wheel exercise induces cognitive improvement post traumatic brain injury in mouse model through redressing aberrant excitation regulated by voltage-gated sodium channels 1.1, 1.3, and 1.6.

Traumatic brain injury (TBI) leads to disturbed brain discharge rhythm, elevated excitability, anxiety-like behaviors, and decreased learning and memory capabilities. Cognitive dysfunctions severely affect the quality of life and prognosis of TBI patients, requiring effective rehabilitation treatment. Evidence indicates that moderate exercise after brain injury decreases TBI-induced cognitive decline. However, the underlying mechanism remains unelucidated. Our results demonstrate that TBI causes cognitive impairment behavior abnormalities and overexpression of Nav1.1, Nav1.3 and Nav1.6 proteins inside the hippocampus of mice models. Three weeks of voluntary running wheel (RW) exercise treatments before or/and post-injury effectively redressed the aberrant changes caused by TBI. Additionally, a 10% exercise-conditioned medium helped recover cell viability, neuronal sodium current and expressions of Nav1.1, Nav1.3 and Nav1.6 proteins across cultured neurons after injury. Therefore, the results validate the neuroprotection induced by voluntary RW exercise treatment before or/and post-TBI. The RW exercise-induced improvement in cognitive behaviors and neuronal excitability could be associated with correcting the Nav1.1, Nav1.3, and Nav1.6 expression levels. The current study proves that voluntary exercise is an effective treatment strategy against TBI. The study also highlights novel potential targets for rehabilitating TBI, including the Navs proteins.

The oncolytic bacteria-mediated delivery system of CCDC25 nucleic acid drug inhibits neutrophil extracellular traps induced tumor metastasis.

BACKGROUND: Neutrophil extracellular traps (NETs), antibacterial weapons of neutrophils (NEs), have been found to play a crucial role in cancer metastasis in recent years. More and more cancer research is focusing on anti-NETs. However, almost all anti-NETs treatments have limitations such as large side effects and limited efficacy. Therefore, exploring new anti-NETs therapeutic strategies is a long-term goal. RESULTS: The transmembrane protein coiled-coil domain containing 25 (CCDC25) on tumor cell membranes can bind NETs-DNA with high specificity and affinity, enabling tumor cells to sense NETs and thus promote distant metastasis. We transformed shCCDC25 into VNP20009 (VNP), an oncolytic bacterium, to generate VNP-shCCDC25 and performed preclinical evaluation of the inhibitory effect of shCCDC25 on cancer metastasis in B16F10 lung metastasis and 4T1 orthotopic lung metastasis models. VNP-shCCDC25 effectively blocked the downstream prometastatic signaling pathway of CCDC25 at tumor sites and reduced the formation of NETs while recruiting more neutrophils and macrophages to the tumor core, ultimately leading to excellent metastasis inhibition in the two lung metastasis models. CONCLUSION: This study is a pioneer in focusing on the effect of anti-NET treatment on CCDC25. shCCDC25 is effectively delivered to tumor sites via the help of oncolytic bacteria and has broad application in the inhibition of cancer metastasis via anti-NETs.

[Expert consensus on the prenatal diagnosis and genetic counseling for uniparental disomy-related imprinting disorders].

Uniparental disomy (UPD)-related imprinting disorders are a group of congenital disorders which can lead to severe birth defects. Their molecular etiology is the occurrence of UPD in the genomic imprinting regions, which may cause disturbed expression of parent-of-origin imprinted genes. With the widespread applications of genetic testing techniques, the prenatal diagnosis of UPD-related imprinted diseases has gradually become clinical routines. However, due to the complicated pathogenesis of such disorders, currently there is still a lack of standards and norms for the understanding, diagnosis, management and genetic counseling. By referring to the relevant guidelines and consensus, the latest progress of research, and opinions from experts in the relevant fields, the writing group has formulated a consensus over the prenatal diagnosis and genetic counseling for UPD-related imprinting disorders, with an aim to provide a more accurate and rational evaluation in prenatal clinics.

[Genetic analysis of a case with Al Kaissi syndrome and a literature review].

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.

Extracorporeal cardiopulmonary resuscitation versus conventional cardiopulmonary resuscitation for patients with refractory out-of-hospital cardiac arrest: A retrospective propensity matching analysis.

OBJECTIVE: The incidence of out-of-hospital cardiac arrest (OHCA) is high. Though extracorporeal cardiopulmonary resuscitation (ECPR) has been considered a potential treatment for refractory cardiac arrest after failure of conventional cardiopulmonary resuscitation (CCPR), the benefit of ECPR in refractory OHCA remains uncertain. METHODS: In this retrospective cohort study, we included patients with refractory OHCA who visited the Emergency Department of the Aerospace Center Hospital between January 2018 and April 2023. We divided the patients into the ECPR Group and the CCPR Group. The primary endpoint of the study was the neurological function of the patients in both groups 3 months after the cardiac arrest. We used propensity score matching to reduce selection bias and identified factors associated with good neurological function when OHCA was treated with ECPR by performing univariate and multivariate correlation analyses on surviving patients with good neurological function in the ECPR group. RESULTS: During the study period, we enrolled 133 patients, consisting of 33 in the ECPR group and 100 in the CCPR group. The survival rate of patients with good neurological function at discharge was 18.2% (6/33 cases) in the ECPR group and 9% (9/100 cases) in the CCPR group, p = .20. Three months after discharge, the survival rate of patients with good neurological function was 15.2% (5/33 cases) in the ECPR group and 8% (8/100 cases) in the CCPR group, p = .31. Using propensity score matching, we identified 22 pairs of patients for further analysis. Among these, 3 months after discharge, the survival rate of patients with good neurological function was 13.6% (3/22 cases) in the ECPR group and 4.5% (1/22 cases) in the CCPR group, p = .61, and the survival rate at discharge was 18.2% (4/22 cases) in the ECPR group and 4.5% (1/22 cases) in the CCPR group, p = .34. The univariate analysis of patients with good neurological function in the ECPR group showed that time without perfusion, hypoperfusion time, and PCI treatment were associated factors affecting the prognosis of neurological function in patients, while multivariate analysis showed that hypoperfusion time was independently associated with good neurological function, with an OR (95% CI) of 1.06 (1.00-1.14) and p = .05. CONCLUSION: Our findings suggested that ECPR failed to significantly improve neurological outcome in patients with refractory OHCA; however, the small sample size in this study may be insufficient to detect clinically relevant differences. In addition, hypoperfusion time may be a key predictive factor in identifying candidates for ECPR.

[Genetic analysis of a pregnant woman with moderate intellectual disability due to variant of DLG4 gene].

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for a woman featuring moderate intellectual disability (ID). METHODS: The patient had presented at the First Affiliated Hospital of Zhengzhou University on April 28, 2021. With informed consent, peripheral blood and amniotic fluid samples were collected for the extraction of genomic DNA. Pathogenic copy number variations (CNVs) were detected with CNV-seq, and single gene variants were detected by whole exome sequencing (WES) and Sanger sequencing. Candidate variant was verified by Sanger sequencing, and CNV-seq and multiplex ligation-dependent probe amplification (MLPA) were used to detect fetal CNVs. RESULTS: The 23-year-old woman had moderate ID, sideway walking, and unstable holding. Ultrasonography at 18+3 weeks' gestation had revealed no fetal abnormality. No pathogenic CNV was detected in the woman by CNV-Seq, while WES revealed that she has harbored a heterozygous c.1675C>T (p.Arg559*) variant of the DLG4 gene, which was verified by Sanger sequencing. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PVS1+PM2_supporting). Sanger sequencing has confirmed that the fetus has inherited this variant, and CNV-Seq also revealed that that fetus has harbored a 0.1 Mb heterozygous deletion at Xp21.1, which has encompassed the DMD gene, and the result was verified by MLPA. CONCLUSION: The heterozygous c.1675C>T variant of the DLG4 gene probably underlay the mental retardation in this woman, and her fetus was found to harbor the same variant in addition with deletion of the DMD gene, which may predispose to ID type 62.

Reduced Expression of Voltage-Gated Sodium Channel Beta 2 Restores Neuronal Injury and Improves Cognitive Dysfunction Induced by Aß1-42.

Voltage-gated sodium channel beta 2 (Nav2.2 or Navß2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Navß2 in amyloid-ß 1-42- (Aß1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Navß2 knockdown restored neuronal viability of Aß1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including Aß42, sAPPα, and sAPPß, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating Aß degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Navß2 plays crucial roles in the repair of neuronal injury induced by Aß1-42 both in vivo and in vitro.

Comparison of paper-based nucleic acid extraction materials for point-of-care testing applications.

Cheap, rapid, simple and equipment-free nucleic acid extraction (NAE) is highly preferred for implementing nucleic acid detection at point-of-care (POC). Paper-based NAE materials have been extensively utilized due to their low cost, abundance, portability, biocompatibility and ease of chemical modification. However, it is challenging for users to choose the proper one from existing paper-based NAE materials for specific POC applications, which is determined by their physical and chemical properties. Additionally, building the relationship between the physical and chemical properties and the NAE efficiency of paper-based materials is instructive for development of new paper-based NAE materials. In this study, we first systematically compared the physical and chemical properties of six widely used paper-based NAE materials (namely Whatman filter paper #1, FTA card, FTA elute card, Fusion 5, silica membrane and polyethersulfone (PES) membrane), and then evaluated their NAE efficiency. The obtained results indicated that pore uniformity, wet strength, porosity and functional groups are key parameters to affect the efficiency of NAE. The NAE performance of FTA card is the best with high concentration and purity. Finally, we envision that more cost-effective paper-based NAE materials will be developed for POCT application in the future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10570-022-04444-6.

[Genetic testing and prenatal diagnosis for a Chinese pedigree affected with mitochondrial DNA depletion syndrome due to variant of MPV17 gene].

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree affected with infantile hepatitis syndrome. METHODS: Genes associated with liver diseases subjected to high-throughput sequencing. Candidate variants were validated by Sanger sequencing of the proband and his parents. The pathogenicity of the variants was analyzed through bioinformatic analysis. RESULTS: High-throughput sequencing revealed that the proband has harbored c.182T>C (p.F61S) and c.293C>T (p.P98L) variants of the MPV17 gene, which were verified by Sanger sequencing to be inherited from his parents. The variant c.182T>C (p.F61S) was unreported previously and predicted to be likely pathogenic by bioinformatic analysis. CONCLUSION: The proband was caused by the compound heterozygous variations of MPV17 gene including c.182T>C (p.F61S) and c.293C>T (p.P98L). Discovery of the novel variant has enriched the spectrum of pathogenic variants of the MPV17 gene.

[Genetic analysis of a case with Dubin-Johnson syndrome due to two novel variants of ABCC2 gene].

OBJECTIVE: To explore the genetic etiology and differential diagnosis for a patient with jaundice. METHODS: Clinical data of the patient and his parents were collected. Genes associated with metabolic liver diseases were subjected to high-throughput sequencing. The pathogenicity of the candidate variants was predicted by using bioinformatics software. RESULTS: High-throughput sequencing revealed that the proband has harbored two variants of the ABCC2 gene (NM_000392) including c.3011C>T (p.T1004I) and c.3541C>T (p.R1181X), which were respectively inherited from his father and mother. Both variants have been previously unreported and predicted to be pathogenic by bioinformatics analysis. CONCLUSION: The proband was diagnosed with Dubin-Johnson syndrome due to the compound heterozygous variants of the ABCC2 gene. Genetic testing has enabled accurate differential diagnosis of Dubin-Johnson syndrome in this patient.

[Genetic analysis of a child with glycogen storage disease type IXa due to a novel variant in PHKA2 gene].

OBJECTIVE: To explore the genetic etiology of a patient with glycogen storage diseases. METHODS: Clinical data of child and his parents were collected. The genes associated with glycogen storage diseases were subjected to high-throughput sequencing to screen the variants. Candidate variant was validated by Sanger sequencing. Pathogenicity of the variant was predicted by bioinformatic analysis. RESULTS: High-throughput sequencing results showed that the boy has carried a hemizygous c.749C>T (p.S250L) variant of the PHKA2 gene. Sanger sequencing verified the results and confirmed that it was inherited from his mother. This variant was unreported previously and predicted to be pathogenic by bioinformatic analysis. CONCLUSION: The patient was diagnosed with glycogen storage disease type IXa due to a novel c.749C>T (p.S250L) hemizygous variant of the PHKA2 gene. High-throughput sequencing can facilitate timely and accurate differential diagnosis of glycogen storage disease type IXa.

Liquid biopsy for ALK-positive early non-small-cell lung cancer predicts disease relapse.

Background: We aimed to determine whether circulating tumor cells (CTCs) and cell-free DNA (cfDNA) aids in prognosis of relapse-free survival (RFS). Methods: Non-small cell lung cancer patients with ALK mutations were recruited prospectively. CTCs and cfDNA were quantified at different time points. RFS was estimated and correlated. Results: Baseline median CTCs and cfDNA were 16 cells and 57 ng/mL and declined to nine cells and 30 ng/mL, respectively, postsurgery in 150 patients. Interestingly, patients without detectable CTCs postsurgery fared better for RFS. cfDNA monitoring showed deviations within 7 months of surgery that were significant predictors for RFS. Conclusion: Short-term monitoring of CTCs and cfDNA variations shows promise for early risk detection and may aid in better disease control.

[Variant analysis and therapeutic prospect for Chinese pedigrees affected with Duchenne/Becker muscular dystrophy from a single center over the past 15 years].

OBJECTIVE: To summarize the result of genetic testing and therapeutic prospect of 2042 unrelated Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD) from a single center from 2005 to 2019. METHODS: Peripheral blood samples of the pedigrees were collected for the detection of DMD gene variants with combined multiple ligation-dependent probe amplification (MLPA), next generation sequencing (NGS) and Sanger sequencing. RESULTS: DMD and BMD have respectively accounted for 78.60% and 21.40% of the pedigrees, which included 33 female probands. Variants of the DMD gene were detected in 1986 pedigrees (97.26%). Large deletions, duplications and small-scale mutations have respectively accounted for 71.85%, 8.76% and 19.39%. Common deletions and duplications have included deletion of exons 45-50 and duplications of exon 2, while no hot spot was found with small-scale mutations. For 1595 pedigrees affected with DMD, 935 (58.62%) were hereditary and 660 (41.38%) were de novo in origin. 34.28% (700/2042) of the patients had symptoms which could be relieved by gene therapy. CONCLUSION: This has been the largest single-center study of DMD pedigrees, which has attained definite diagnosis in 97.26% of the patients. The results have enabled genetic counseling and prenatal diagnosis for the affected families upon their subsequent pregnancies, enriched the spectrum of DMD gene variants, as well as facilitated study of the mechanism of DMD gene mutations and exploration of clinical treatment.

[Non-invasive prenatal detection of ocutaneous albinism type I based on cfDNA barcode-enabled single-molecule test].

OBJECTIVE: To assess the value of non-invasive prenatal testing based on cfDNA barcode-enabled single-molecule test (cfBEST) for the prenatal diagnosis of oculocutaneous albinism type I in a family. METHODS: Prenatal genetic diagnosis was carried out by using the cfBEST-based method as well as invasive prenatal diagnosis through amniocentesis. The outcome of the pregnancy was followed up. RESULTS: Non-invasive prenatal testing based on cfBEST showed a fetal DNA concentration of 6.6%, with the proportion of c.929_930insC (p.Arg311Lysfs*7) and c.1037-7T>A mutations being 45.7% and 0%, respectively. The posterior frequency of the negative results was 1, suggesting that the fetus carried neither of the two mutations. The result was consistent with that of invasive prenatal diagnosis, and the follow-up found that the fetus was normal. CONCLUSION: Non-invasive prenatal testing based on cfBEST can be used to detect maternal and fetal genotypes in maternal cell-free DNA, which is clinically feasible.

[Genetic screening and prenatal diagnosis in high-risk families with tuberous sclerosis complex syndrome].

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for 29 Chinese pedigrees affected with tuberous sclerosis complex (TSC) and assess efficacy of combined next generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) for the diagnosis. METHODS: NGS and MLPA were used in conjunct to detect variants of TSC1 and TSC2 genes among the probands of the pedigrees. Paternity test was carried out to exclude maternal DNA contamination. Prenatal diagnosis was provided to 14 couples based on the discoveries in the probands. RESULTS: Twenty-seven variants were identified in the TSC1 and TSC2 genes among the 29 pedigrees, which yielded a detection rate of 93.1%. Respectively, 5 (18.5%) and 22 (81.5%) variants were identified in the TSC1 and TSC2 genes. Twelve variants were unreported previously. Prenatal diagnosis showed that five fetuses were affected with TSC, whilst the remaining nine were unaffected. CONCLUSION: Above finding has expanded the spectrum of TSC1 and TSC2 gene variants. Combined NGS and MLPA has enabled diagnosis of TSC with efficiency and accuracy.

[Simultaneous determination of six pyrrolizidine alkaloids in different parts of Emilia sonchifolia by UPLC-MS/MS].

This study aims to develop a UPLC-MS/MS method for simultaneous determination of six pyrrolizidine alkaloids(PAs)--intermedine N-oxide(ImNO), lycopsamine N-oxide(LyNO), seneciphylline(Sp), seneciphylline N-oxide(SpNO), senecionine N-oxide(SnNO), and senkirkine(Sk) in different parts of Emilia sonchifolia. UPLC conditions are as follows: ACQUITY UPLC HSS T3 column(2.1 mm×100 mm, 1.8 µm), mobile phase consisting of 0.05% formic acid and 2.5 mmol·L~(-1) ammonium formate in water(A)-0.05% formic acid and 2.5 mmol·L~(-1) ammonium formate in acetonitrile(B) for gradient elution. MS conditions are as below: electrospray ionization(ESI) in the positive ion mode, multiple reaction monitoring(MRM), and the content of the six PAs was calculated with the external standard method. The results suggested the differences in the six PAs among different parts of E. sonchifolia. Sk was detected in all the four parts, with similar content. SnNO also existed in all the four parts, but the content in roots was significantly higher than that in other parts. Sp and SpNO were found in both roots and flowers, with the content higher in the former than in the later. ImNO and LyNO were only found in leaves, and the content was low. Among the six components detected, ImNO, LyNO, and SpNO were found and determined for the first time, which enriched the toxic components and laid a scientific basis for the quality and safety evaluation of E. sonchifolia.

Decreased Expression of Semaphorin 3A and Semaphorin 7A Levels and Its Association with Systemic Lupus Erythematosus.

A growing body of data suggests that semaphorins are involved in both normal and pathological immune responses, as well as autoimmune pathologies. To investigate the plasma semaphorin 3A (Sema3A) and semaphorin 7A (Sema7A) levels in systemic lupus erythematosus (SLE) patients and their correlation with clinical manifestations and laboratory indexes, a two-step method was applied. First, 80 SLE patients and 80 healthy controls were recruited for comparing serum Sema3A and Sema7A concentrations. Second, 40 rheumatoid arthritis (RA) patients and 40 sjögren's syndrome (SS) patients were then included as disease controls. Plasma Sema3A and Sema7A concentrations were detected by ELISA. There were significant differences in Sema3A and Sema7A among four groups. When compared to healthy controls, both Sema3A and Sema7A levels were decreased in SLE and increased in RA; increased Sema3A level and decreased Sema7A level were found in SS. There were significant differences in Sema3A concentration between SLE and RA, SLE and SS. Moreover, there were significant differences in Sema7A level between SLE and RA, SS and RA. However, no significant differences in Sema3A between SS and RA and no significant differences in Sema7A between SS and SLE were observed. Both plasma Sema3A and Sema7A levels were correlated with anti-SSA and IgM. Area under curve (AUC) of the receiver operating characteristic (ROC) curve for Sema3A and Sema7A were 0.535 (0.455-0.613) and 0.671 (0.594-0.742), respectively. Aberrant Sema3A and Sema7A expression and their clinical associations in SLE suggest their important role in this disease.

MYB-QKI rearrangement in angiocentric glioma.

AIMS: To evaluate the occurrence and diagnostic value of MYB-QKI rearrangement status in angiocentric glioma (AG) in Chinese patients. MATERIALS AND METHODS: 27 cases were collected from six hospitals, followed by a retrospective analysis of clinical, radiological, and morphological data. MYB protein expression was assessed by immunohistochemical staining (IHC), and the MYB-QKI rearrangement was detected by fluorescence in situ hybridization (FISH). RESULTS: Among the 27 cases (16 males), the median age at surgery was 17 years (range 3 - 43 years); 24 (88.9%) cases had a history of refractory epilepsy, and the mean history of pre-surgical epilepsy was 13 years (range 1.5 - 27 years); 26 (96.3%) cases had lesions located in the superficial cerebrocortical regions, and 1 (3.7%) case had a lesion in the brainstem. Except for the classic histological features, the involvement of superficial cortex extending to the leptomeninges, microcalcification, and cystic pattern with microcystic formations was observed in 11 (40.7%), 3 (11.1%), and 4 (14.8%) cases, respectively. IHC showed that all 27 cases were positive for glial fibrillary acidic protein (GFAP) and vimentin, and negative for neuronal nuclear antigen (NeuN). The positive rates of epithelial membrane antigen (EMA) and D2-40 were 81.5% (22/27) and 74.1% (20/27), respectively. A total of 14 (51.9%) cases were positive for MYB. The rate of Ki-67 proliferation was 1 - 5% in 25 cases, and in 2 cases with anaplastic features it was 10 and 20%. MYB-QKI rearrangement was revealed by FISH examination in 95.8% (23/24) of the AGs, including 3 cases with atypical histological appearance. CONCLUSION: Compared to IHC, FISH was more appropriate for detecting MYB-QKI rearrangement. MYB-QKI rearrangement was detected in the majority of Chinese AG cases, and therefore represents a potential diagnostic biomarker for AG.

Seasonality and global public interest in psoriasis: an infodemiology study.

OBJECTIVE: Although patients with psoriasis frequently report seasonal changes in their symptoms, the seasonality of psoriasis has rarely been explored. This study aims to investigate the seasonal pattern of and global public interest in psoriasis using Google search data. METHODS: Internet search data were collected from Google Trends. Data on the relative search volume (RSV) from January 2004 to December 2018 were retrieved using the term psoriasis. Cosinor analyses were conducted to examine the seasonality of psoriasis using data from two southern hemisphere countries (Australia and New Zealand) and four northern hemisphere countries (USA, Canada, UK and Ireland). RESULTS: Overall, searches for psoriasis steadily decreased between 2004 and 2010, and then rose from 2011 to 2018. On cosinor analyses, RSV of 'psoriasis' displayed a significant seasonal variation worldwide (p<0.025). Further analyses confirmed the seasonality of psoriasis-related RSV in Australia, New Zealand, USA, Canada, UK and Ireland (p<0.025 for all), with peaks in the late winter/early spring months and troughs in the late summer/early autumn months. The top 11 rising topics were calcipotriol/betamethasone dipropionate, ustekinumab, apremilast, shampoo, eczema, guttate psoriasis, seborrhoeic dermatitis, dermatitis, psoriatic arthritis, atopic dermatitis and arthritis. CONCLUSION: There was a significant seasonal pattern for psoriasis, with peaks in the late winter/early spring and troughs in the late summer/early autumn. Further studies are warranted to confirm the seasonal pattern of psoriasis using clinical data and to explore the underlying mechanisms.

Simulation stress model of the undersea environment activates the central nervous, neuroendocrine and immune systems and anxiety in rats.

The present study was designed to assess the stress responses to a simulation model of the undersea environment that is similar to some undersea working conditions such as submarine rescue, underwater salvage and underwater construction. Restraint, hyperbaric air and immersion were chosen to produce the simulation stress model in rats for four hours. Rats were randomized into five groups: control group, restraint (R) group, hyperbaric air (H) group, restraint plus hyperbaric air (RH) group, and restraint plus hyperbaric air plus immersion (RHI) group. The results showed that the responses to the simulation stress model of the undersea environment induced by R, H, RH and RHI involved the upregulated norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) of the central nervous system (CNS), upregulated adrenocorticotropic hormone (ACTH), corticosterone (CORT) and blood glucose of the neuroendocrine system, upregulated interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) of the immune system, and increased anxiety in rats. Compared with hyperbaric air, restraint tended to activate stronger stress responses. Conclusively, this work established a simulation stress model of the undersea environment induced by restraint, hyperbaric air and immersion. It further provided experimental data of such a model that showed significant activation of the CNS, neuroendocrine and immune systems and anxiety in rats. In this experiment we provided an experimental basis for undersea work such as working aboard a submarine.