Prospective evaluation of cardiovascular risk and mortality in patients with psoriasis: An American population-based study.

The association between psoriasis and cardiovascular disease (CVD) has long been discussed and continually refined. However, there is currently a lack of prospective studies on the cardiovascular risk attributed to psoriasis in the United States general population. Representative adult participants were selected from the National Health and Nutrition Examination Survey (NHANES). Risks of cardiovascular symptoms and diseases prevalence were evaluated between participants with and without psoriasis. The hazards for all-cause mortality and CVD mortality were stratified by psoriasis status. Mediation analysis was then conducted to identify potential mediators between psoriasis and cardiac death. Overall, 19 741 participants were included in the current study, 542 (2.7%) had psoriasis and 19 199 (97.3%) did not have psoriasis. After adjusting for known CVD risk factors, odds for hypertension (OR = 1.37, 95% CI: 1.13-1.66, p = 0.001), hypercholesterolemia (OR = 1.37, 95% CI: 1.13-1.64, p < 0.001) and angina pectoris (OR = 1.74, 95% CI: 1.11-2.60, p = 0.011) were higher in psoriasis patients. Compared with participants without psoriasis, moderate/severe but not mild patients showed significantly higher CVD mortality (HR = 2.55, 95% CI: 1.27-5.15, p = 0.009). This result was supported by subgroup analyses. Mediation analysis further suggested that the direct effect of moderate/severe psoriasis on CVD mortality accounted for 81.4% (65.8%-97.1%). Besides, the indirect effect might derive from disturbance of serum albumin, urea nitrogen and uric acid. Moderate-to-severe psoriasis is an independent risk factor for cardiovascular disease, making it necessary to regularly conduct cardiovascular disease-related examinations for patients with higher severity of psoriasis in clinical settings.

The pharmacological properties and corresponding mechanisms of farrerol: a comprehensive review.

CONTEXT: Farrerol, a typical natural flavanone isolated from the traditional Chinese herb 'Man-shan-hong' [Rhododendron dauricum L. (Ericaceae)] with phlegm-reducing and cough-relieving properties, is widely used in China for treating bronchitis and asthma. OBJECTIVE: To present the anti-inflammatory, antioxidant, vasoactive, antitumor, and antimicrobial effects of farrerol and its underlying molecular mechanisms. METHODS: The literature was reviewed by searching PubMed, Medline, Web of Knowledge, Scopus, and Google Scholar databases between 2011 and May 2021. The following key words were used: 'farrerol,' 'flavanone,' 'anti-inflammatory,' 'antioxidant,' 'vasoactive,' 'antitumor,' 'antimicrobial,' and 'molecular mechanisms'. RESULTS: Farrerol showed anti-inflammatory effects mainly mediated via the inhibition of interleukin (IL)-6/8, IL-1ß, tumour necrosis factor(TNF)-α, NF-κB, NO, COX-2, JNK1/2, AKT, PI3K, ERK1/2, p38, Keap-1, and TGF-1ß. Farrerol exhibited antioxidant effects by decreasing JNK, MDA, ROS, NOX4, Bax/Bcl-2, caspase-3, p-p38 MAPK, and GSK-3ß levels and enhancing Nrf2, GSH, SOD, GSH-Px, HO-1, NQO1, and p-ERK levels. The vasoactive effects of farrerol were also shown by the reduced α-SMA, NAD(P)H, p-ERK, p-Akt, mTOR, Jak2, Stat3, Bcl-2, and p38 levels, but increased OPN, occludin, ZO-1, eNOS, CaM, IP3R, and PLC levels. The antitumor effects of farrerol were evident from the reduced Bcl-2, Slug, Zeb-1, and vimentin levels but increased p27, ERK1/2, p38, caspase-9, Bax, and E-cadherin levels. Farrerol reduced α-toxin levels and increased NO production and NF-κB activity to impart antibacterial activity. CONCLUSIONS: This review article provides a theoretical basis for further studies on farrerol, with a view to develop and utilise farrerol for treating of vascular-related diseases in the future.

Genetic spectrum of dyschromatosis symmetrica hereditaria in Chinese patients including a novel nonstop mutation in ADAR1 gene.

BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder caused by the mutations of adenosine deaminase acting on RNA1 (ADAR1) gene. We present a clinical and genetic study of seven unrelated families and two sporadic cases with DSH for mutations in the full coding sequence of ADAR1 gene. METHODS: ADAR1 gene was sequenced in seven unrelated families and two sporadic cases with DSH and 120 controls. Functional significance of the observed ADAR1 mutations was analyzed using PolyPhen 2, SIFT and DDIG-in. RESULTS: We describe six novel mutations of the ADAR1 gene in Chinese patients with DSH including a nonstop mutation p.Stop1227R, which was firstly reported in ADAR1 gene. In silico analysis proves that all the mutations reported here are pathogenic. CONCLUSION: This study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene. A three-generation family exhibiting phenotypic variability with a single germline ADAR1 mutation suggests that chilblain might aggravate the clinical phenotypes of DSH.

[Analysis of ATP2A2 gene mutations in a pedigree and a sporadic case with Darier disease].

OBJECTIVE: To detect mutations of ATP2A2 gene in a pedigree and a sporadic case with Darier disease (DD) and explore the underlying molecular mechanism. METHODS: Clinical data of the pedigree and the sporadic case were collected. Genomic DNA was extracted from blood samples of four members from the pedigree (including three patients and one healthy member), the sporadic case and 100 healthy controls. PCR was performed to amplify all coding exons of the ATP2A2 gene. And the products were directly sequenced to detect mutations. RESULTS: A missense mutation c.1484C>T (p.S495L) in exon 12 was detected in all patients of the pedigree. For the sporadic case, a novel splicing mutation c.325-2A>G was detected at the junction between intron 4 and exon 5. The same mutations were not found in the 100 healthy controls. CONCLUSION: Mutations of the ATP2A2 gene may lead to the occurrence of DD in both familial and sporadic cases with DD.

[Mutation analysis of FLG gene in 10 Chinese families with ichthyosis vulgaris].

OBJECTIVE: To detect FLG gene mutations in 10 families affected with ichthyosis vulgaris and to explore mutational hot spot of the FLG gene in Chinese Han population. METHODS: PCR and direct sequencing were carried out to identify potential mutations of the FLG gene in above families. One hundred healthy individuals were analyzed as normal controls. RESULTS: Three mutations (3321delA, 5757delCCAG and S2706X) were identified in 7 families. A homozygous mutation 3321delA was also detected in two unrelated patients. No mutations were found in the remaining three families. Neither of the null mutations (5757delCCAG and S2706X) was found in the 100 controls. However, for 3321delA, a heterozygous mutation was also found in two of the controls. CONCLUSION: Three FLG mutations have been identified in the selected families with ichthyosis vulgaris, and the 3321delA mutation was most prevalent (46.9%). Mutations 5757delCCAG and S2706X were first found in patients with ichthyosis vulgaris. Other candidate genes may underlie the disease in those without a FLG mutation.

Association Between Trichoscopic Features and Serum Hormone Levels and Vitamin D Concentration in Patients with Androgenetic Alopecia in Eastern China: A Cross-Sectional Study.

Purpose: Androgenetic alopecia (AGA) is a common dermatological condition, with reported associations between serum vitamin D and sex hormone levels. However, the relationship between these factors and the severity of hair loss remains unclear. Patients and Methods: Our cross-sectional study included 310 AGA patients who visited the dermatology clinic and underwent trichoscopy examinations throughout 2021. We collected data on serum sex hormones and 25(OH)D levels during their consultations. TrichoScan analysis was used to characterize and quantify AGA severity based on hair density and vellus hair proportions in the central scalp area, which were then correlated with the collected indicators. Results: The study findings reflect the basic demographic characteristics of AGA patients in the Chinese population. We discovered a significant negative correlation between serum SHBG levels and AGA severity in women, but no association was found in men. Serum testosterone, estradiol, dehydroepiandrosterone sulfate, and 25(OH)D levels showed no significant correlation with the severity of androgenetic alopecia, regardless of gender. Conclusion: To our knowledge, this is the first study to investigate the relationship between serum sex hormones, vitamin D, and AGA severity using trichoscopic scalp hair features.

Down-regulation of connexin 43 contributes to structure and function of pulmonary artery in nicotine-administered mice.

Dysregulated connexin signaling is implicated in the pathophysiology of pulmonary artery hypertension (PAH). Nicotine affects pulmonary vascular remodeling. However, the potential mechanistic link between connexin signaling and nicotine-induced pulmonary artery remodeling remains unclear. We aimed to investigate the role of connexin 43 (Cx43) in pulmonary artery remodeling in nicotine-administered C57BL/6 J wild-type (WT) and Cx43 heterozygous (Cx43+/-) mice. Hemodynamic parameters and right ventricle pathology were assessed in the mice. Serum biochemical indices of hepatic and renal function were measured. The RT-PCR, immunofluorescence, and western blotting were conducted to evaluate Cx43 mRNA and protein levels. We performed histological staining to identify pulmonary arteries. Wire myography was used to examine contraction and relaxation responses in the pulmonary arteries. Pulmonary vascular permeability was assessed through Evans blue staining. Compared with the WT group, the Cx43+/- group showed lower Cx43 mRNA and protein expression in the pulmonary arteries (P < 0.01). Nicotine treatment significantly increased Cx43 expression (P < 0.01) and induced morphological changes in the pulmonary arteries (P < 0.01). Our findings suggest that Cx43 plays a crucial role in pulmonary artery reactivity and permeability in mice. Furthermore, downregulation of Cx43 expression may contribute to alterations in pulmonary artery structure and function.

[Control study on colonoscopy skills acquiring from endoscopic simulation system transfering to patients].

OBJECTIVE: To explore the feasibility of transferring the skills from the AccuTouch flexible endoscopy simulator colonoscopy training to clinical practices. METHODS: The novice colonoscopies were divided into 2 groups.Group A (control group) including 4 trainees for traditional training, Group B (experimental group) including 4 trainees for simulator training. After training, we compared the number of cases for achieving independent competence, assisted competence and incompetence in the first ten patients. RESULTS: No significant differences existed between two groups in terms of age and gender (both P > 0.05). Significant differences existed in educational background and the controlled group was better than the experimental group (Z = -2.005, P = 0.04). The cases of independent completion, assisted competence and incompetence of the control and experimental groups were 2, 4, 9 and 21, 29, 15 respectively. Rank tests show that the simulator training was better than the traditional counterpart (average rank: 56.14 vs 24.86, Z = -6.393, P = 0.00). CONCLUSIONS: The skills acquired from AccuTouch Endoscopy Simulator may be well transferred into the clinical colonoscopy environment. It clearly supports the scheme of integrating simulator training into colonoscopic education curricula.

Application of CT Multimodal Images in Rehabilitation Monitoring of Long-Distance Running.

In order to monitor the rehabilitation of athletes injured in long-distance running, the author proposes a method for rehabilitation monitoring of long-distance running based on CT multimodal images. This method combines the latest multimodal image technology, integrates multimodal technology into CT images to improve the accuracy, performs image segmentation on CT multimodal images through medical segmentation methods, and analyzes the segmented images; finally, it can achieve the effect of rehabilitation treatment for athletes in long-distance running. Experimental results show that the total time taken by the authors' method is 10.9 hours, with an average time of 8 seconds, which is much shorter than the other two control methods. In conclusion, the authors' method allows for better rehabilitation monitoring of long-distance running sports injuries.

Frontal fibrosing alopecia: A review of disease pathogenesis.

Frontal fibrosing alopecia (FFA) is a primary patterned cicatricial alopecia that mostly affects postmenopausal women and causes frontotemporal hairline regression and eyebrow loss. Although the incidence of FFA has increased worldwide over the last decade, its etiology and pathology are still unclear. We cover the latest findings on its pathophysiology, including immunomodulation, neurogenic inflammation, and genetic regulation, to provide more alternatives for current clinical treatment. A persistent inflammatory response and immune privilege (IP) collapse develop and lead to epithelial hair follicle stem cells (eHFSCs) destruction and epithelial-mesenchymal transition (EMT) in the bulge area, which is the key process in FFA pathogenesis. Eventually, fibrous tissue replaces normal epithelial tissue and fills the entire hair follicle (HF). In addition, some familial reports and genome-wide association studies suggest a genetic susceptibility or epigenetic mechanism for the onset of FFA. The incidence of FFA increases sharply in postmenopausal women, and many FFA patients also suffer from female pattern hair loss in clinical observation, which suggests a potential association between FFA and steroid hormones. Sun exposure and topical allergens may also be triggers of FFA, but this conjecture has not been proven. More evidence and cohort studies are needed to help us understand the pathogenesis of this disease.

Association of the NFKBIA gene polymorphisms with susceptibility to autoimmune and inflammatory diseases: a meta-analysis.

OBJECTIVE: To quantitatively summarize the association of NFKBIA gene polymorphisms with autoimmune and inflammatory diseases. METHODS: We surveyed studies on the association of NFKBIA gene polymorphisms with autoimmune and inflammatory diseases in PubMed. Meta-analysis was performed in a fixed/random effect model. RESULTS: We identified 14 studies using a PubMed search. Meta-analysis was performed for NFKBIA gene polymorphisms at positions 2758 (A/G, 5 studies), -881 (A/G, 3 studies), -826 (C/T, 3 studies), and -297 (C/T, 3 studies). We did not detect associations of NFKBIA gene polymorphisms at positions 2758, -881, -297 with autoimmune and inflammatory diseases. An association of NFKBIA gene -826C/T polymorphism with autoimmune and inflammatory diseases was found (C vs. T: OR = 1.81, 95% CI = 0.97-3.36, P = 0.06; CT + TT vs. CC: OR = 2.11, 95% CI = 1.07-4.19, P = 0.03; TT vs. CC + CT: OR = 2.20, 95% CI = 0.78-6.21, P = 0.06; TT vs. CC: OR = 2.87, 95% CI = 0.78-10.62, P = 0.11; CT vs. CC: OR = 2.02, 95% CI = 1.22-3.36, P = 0.006). CONCLUSION: This meta-analysis demonstrates that autoimmune and inflammatory diseases are associated with NFKBIA gene -826C/T polymorphism, but not with 2758A/G, -881A/G, and -279C/T.

Extramammary Paget's disease mimicking acantholytic squamous cell carcinoma in situ: a case report.

BACKGROUND: Extramammary Paget's disease (EMPD) is an uncommon skin neoplasm characterized by Paget's cells with pale-staining cytoplasm in the epidermis, and cases with distinguished acantholysis but lacking characteristic Paget's cells were rarely reported in the literature. METHODS: An 80-year-old male with lesion on scrotum was screened histologically and immunohistologically for the diagnosis of his tumor. RESULTS: Histological examination showed acanthosis with cellular atypia and focal acantholysis, consistent with acantholytic squamous cell carcinoma in situ (SCCIS). No characteristic Paget's cells were observed in low magnification. Immunohistochemical staining showed carcinoembryonic antigen (CEA), cytokeratin 7 (CK7) and cytokeratin 8 (CK8) to be strongly expressed in the nests and singly arranged large tumor cells, and the surrounding epidermis was positive for CK5/6 and negative for CEA. Sporadic periodic acid-schiff (PAS)-positive cells could be seen in some areas. CONCLUSIONS: These findings strongly indicated the diagnosis of EMPD mimicking acantholytic SCCIS.

[Mutation analysis of ATP2C1 gene in a Chinese family with Hailey-Hailey disease].

OBJECTIVE: To study a Chinese pedigree with Hailey-Hailey disease (HHD) and identify the ATP2C1 gene mutation in this family. METHODS: All exons of the ATP2C1 gene were analyzed with polymerase chain reaction and DNA sequencing in all patients of this family and 80 unrelated population-matched controls. RESULTS: We identified a nonsense mutation 163C to T, resulting in a premature termination codon in ATP2C1 gene. The mutation was not found in normal individuals of the family and controls. CONCLUSION: The mutation can affect the result of transcription and translation of ATP2C1 gene, and it is firstly reported in the Chinese pedigree with HHD.

[An incontinentia pigmenti family with deletion in both NEMO gene and pseudogene DeltaNEMO].

OBJECTIVE: To detect the genomic deletion mutation in the NEMO gene of a family with incontinentia pigmenti (IP; MIM 308310). METHODS: A pedigree of IP was investigated. By using long PCR, the Delta4-10 deletion in NEMO gene was tested with specific primers In2/JF3R, and Delta4-10 deletion in pseudogene DeltaNEMO was investigated with primers Rev-2/JF3R. NEMO gene of 80 normal controls was also tested. RESULTS: The deletion of exons 4-10 in both NEMO gene and the pseudogene DeltaNEMO was detected in all the patients in the family, but was not found in the normal individuals in this IP family and 80 unrelated controls. CONCLUSION: The study showed that the family with IP, which showed anticipation, was caused by NEMODelta4-10 deletion in the NEMO gene. Long PCR analysis is proven to be an efficient tool for identification of NEMO rearrangements. It could provide useful information for the genetic counseling of the family involved.

Functional training on ankle sprain rehabilitation in soccer players / Treinamento funcional sobre a reabilitação da entorse de tornozelo nos jogadores de futebol / Entrenamiento funcional en la rehabilitación del esguince de tobillo en los jugadores de fútbol

ABSTRACT Introduction An ankle sprain is a common soccer injury. Functional training is used to rehabilitate muscle strength with undiscovered benefits on soccer players' recovery. Objective Explore the functional training effects on ankle injury recovery in soccer players. Methods 29 amateur soccer players were randomly assigned to control (n=15) and experimental (n=14) groups with no statistical difference in age or sex (P>0.05). The experimental group used functional rehabilitation training, while the control group was treated with traditional rehabilitation methods. Both groups practiced 30 to 40 minutes of rehabilitation, three times a week, for two months. Mathematical statistics were used to analyze the effects of different injury rehabilitation on the two groups, estimating the ankle joint continuous motion angle by the tibialis anterior muscle electromyogram responses. Results The ankle instability assessment questionnaires were statistically different between the two groups of patients after rehabilitation training (P<0.05). There was a statistical difference in the agility test after the intervention. The ankle capacity score and agility test score were better in the experimental group (P<0.05). Conclusion Functional rehabilitation training can improve ankle performance after a sprain. This training can also help athletes avoid future sprains and is recommended as preventive training. Evidence Level II; Therapeutic Studies - Investigating the result.

RESUMO Introdução Entorse no tornozelo é uma lesão comum no futebol. O treinamento funcional é utilizado na reabilitação da força muscular com benefícios ainda explorados sobre a recuperação dos jogadores de futebol. Objetivo Explorar os efeitos do treinamento funcional na recuperação das lesões no tornozelo em jogadores de futebol. Métodos 29 jogadores de futebol amador foram aleatoriamente distribuídos em grupo controle (n=15) e experimental (n=14) sem diferença estatística de idade ou sexo (P>0,05). O grupo experimental utilizou treinamento de reabilitação funcional enquanto o grupo controle foi tratado com os métodos tradicionais de reabilitação. Ambos os grupos praticaram 30 a 40 minutos de reabilitação, três vezes por semana, durante dois meses. Estatísticas matemáticas foram utilizadas para analisar os efeitos da reabilitação de lesões diferentes nos dois grupos por estimativa do ângulo de movimento contínuo na articulação do tornozelo com as respostas do eletromiograma do músculo tibial anterior. Resultados Os questionários de avaliação da instabilidade do tornozelo entre os dois grupos de pacientes após o treinamento de reabilitação foram estatisticamente diferentes (P<0,05). Houve diferença estatística no teste de agilidade após a intervenção. A pontuação na capacidade do tornozelo e o escore no teste de agilidade foram melhores no grupo experimental (P<0,05). Conclusão O treinamento de reabilitação funcional pode melhorar o desempenho do tornozelo após a entorse. Este treinamento também pode ajudar os atletas a evitarem futuros entorses, sendo recomendado como treino preventivo. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción El esguince de tobillo es una lesión común en el fútbol. El entrenamiento funcional se utiliza en la rehabilitación de la fuerza muscular con beneficios aún explorados en la recuperación de los jugadores de fútbol. Objetivo Explorar los efectos del entrenamiento funcional en la recuperación de lesiones de tobillo en jugadores de fútbol. Métodos 29 jugadores de fútbol amateur fueron distribuidos aleatoriamente en los grupos de control (n=15) y experimental (n=14) sin diferencias estadísticas en cuanto a edad o sexo (P>0,05). El grupo experimental utilizó un entrenamiento de rehabilitación funcional mientras que el grupo de control fue tratado con métodos de rehabilitación tradicionales. Ambos grupos practicaron entre 30 y 40 minutos de rehabilitación, tres veces por semana, durante dos meses. Se utilizó la estadística matemática para analizar los efectos de las diferentes rehabilitaciones de lesiones en los dos grupos mediante la estimación del ángulo de movimiento continuo en la articulación del tobillo con las respuestas del electromiograma del músculo tibial anterior. Resultados Los cuestionarios de evaluación de la inestabilidad del tobillo entre los dos grupos de pacientes después del entrenamiento de rehabilitación fueron estadísticamente diferentes (P<0,05). Hubo una diferencia estadística en la prueba de agilidad después de la intervención. La puntuación de la capacidad del tobillo y la puntuación de la prueba de agilidad fueron mejores en el grupo experimental (P<0,05). Conclusión El entrenamiento de rehabilitación funcional puede mejorar el rendimiento del tobillo tras un esguince. Este entrenamiento también puede ayudar a los atletas a evitar futuros esguinces y se recomienda como entrenamiento preventivo. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Diagnostic value of horizontal versus vertical sections for scarring and non-scarring alopecia: a systematic review and meta-analysis.

Histopathological diagnosis of scalp biopsies remains a challenging area in dermatopathology. Published studies have described the benefits of different sectioning techniques although the application of these techniques is still under clinical investigation. To review published literature and evaluate the value of horizontal sections compared to vertical sections in the diagnosis of alopecia. Databases, such as PubMed and EMBASE, among others, were searched for published articles; to identify additional relevant studies, the literature search was performed manually. The total number of cases and diagnosed cases, and diagnostic rates, were extracted from each included study. Pooled diagnostic rates with 95% confidence intervals (CI) were used to evaluate the value of different sectioning techniques, and we tested for publication bias and heterogeneity. Most studies had a suboptimal design. With regards to non-scarring alopecia, there were eight horizontal and eight vertical section studies. The pooled diagnostic rates were 0.81 (95% CI: 0.70-0.92) and 0.76 (95% CI: 0.60-0.93), respectively, and extensive heterogeneity existed among these studies. For the diagnosis of scarring alopecia, there were three horizontal and five vertical sectioning studies. The pooled diagnostic rates were 0.86 (95% CI: 0.66-1) and 0.90 (95% CI: 0.82-0.98), respectively, and heterogeneity was also observed. Based on published studies, no significant difference exists between horizontal and vertical sectioning techniques in the diagnosis of alopecia. Whereas most studies had a suboptimal design, future studies in this area would benefit from a scientific approach and standardised measurements to explore the value of horizontal and vertical sectioning.

Clinical and Molecular Characterization of NF1 Patients: Single-Center Experience of 32 Patients From China.

Neurofibromatosis type 1 (NF1) is a hereditary disorder caused by mutations in the NF1 gene. Detecting mutation in NF1 is hindered by the gene's large size, the lack of mutation hotspots, and the presence of pseudogenes.Our goal was to establish a sensitive, feasible, and comparatively economical protocol to detect NF1 mutations using blood samples.We developed a method to screen patients for mutations. Thirty-two NF1 patients from 32 unrelated families and 120 unrelated population-match controls were investigated in this study. Specific primers were designed for NF1 to avoid pseudogenes. NF1 mutations were detected by sequencing at the deoxyribonucleic acid (DNA) and complementary DNA (cDNA) levels, and multiplex ligation-dependent probe amplification (MLPA) and familial segregation analyses were used.Forty-four specific primers designed according to the NF1 structure were successfully used for polymerase chain reaction (PCR) and DNA sequencing, which was more feasible and useful than cDNA sequencing. Thirty distinct NF1 mutations were identified in 32 patients. Thirteen mutations were novel and most were frameshift mutations (33.3%). Mutations were detected at a rate of 93.8%.Our study suggests that this sensitive, feasible, and comparatively economical protocol is effective for the detection of NF1 mutations.