CtBP1 Overexpression in Keratinocytes Perturbs Skin Homeostasis

Carboxyl-terminal–binding protein-1 (CtBP1) is a transcriptional corepressor with multiple in vitro targets, but its in vivo functions are largely unknown. We generated keratinocyte-specific CtBP1 transgenic mice with a keratin-5 promoter (K5.CtBP1) to probe the pathological roles of CtBP1. At transgene expression levels comparable to endogenous CtBP1 in acute skin wounds, the K5.CtBP1 epidermis displayed hyperproliferation, loss of E-cadherin, and failed terminal differentiation. Known CtBP1 target genes associated with these processes, e.g., p21 Brca1, and E-cadherin, were downregulated in K5.CtBP1 skin. Surprisingly, K5.CtBP1 pups also exhibited a hair loss phenotype. We found that expression of the Distal-less 3 (Dlx3), a critical regulator of hair follicle differentiation and cycling, was decreased in K5.CtBP1 mice. Molecular studies revealed that CtBP1 directly suppressed Dlx3 transcription. Consistently, K5.CtBP1 mice displayed abnormal hair follicles with decreased expression of Dlx3 downstream targets Gata3 Hoxc13, and hair keratins. In summary, this CtBP1 transgenic model provides in vivo evidence for certain CtBP1 functions predicted from in vitro studies, reveals—to our knowledge—previously unreported functions and transcriptional activities of CtBP1 in the context of epithelial–mesenchymal interplay, and suggests that CtBP1 has a pathogenic role in hair follicle morphogenesis and differentiation

An integrated model for evaluation of maternal health care in China.

In recent years, in the context of China's continuous medical and health reforms, the health status of Chinese women and children has been significantly improved through the continuous efforts of staff at all levels of maternal and child health care institutions. Many indicators in maternal health care have improved significantly, but the speed and magnitude of changes have varied. The purpose of this study is to evaluate the dynamic changes in China's maternal health status from 2004 to 2018, in order to determine whether China's medical and health reform measures in recent years have improved maternal health. A total of 6 evaluation indicators from the data of China Health Statistics Yearbook 2019 were selected. Then, based on the multi-criteria decision-making (MCDA) methodology, the entropy weighted technique for order preference by similarity to an ideal solution (TOPSIS), entropy weighted rank-sum ratio (RSR) method and the fuzzy comprehensive evaluation were employed in this study. In addition, sensitivity analysis was engaged to validate the stability and accuracy of the achieved results. The study results shows the ranking values of various methods were not exactly the same, but the overall trend was consistent. Overall, the maternal health care in China improved from 2004 to 2018 year by year, of which the top four were ranked from 2015 to 2018, and relatively poor from 2004 to 2006. This means that the policies and measures implemented in China's medical and health reform in the past few decades have effectively promoted China's maternal health care, and this will also provide a theoretical basis for future decisions to promote maternal health care

SERPINB4 Promotes Keratinocyte Inflammation via p38MAPK Signaling Pathway

Psoriasis is a chronic inflammatory skin disease characterized by infiltration of inflammatory cells and excessive proliferation of epidermal keratinocytes. SERPINB4, as a serine protease inhibitor, has been clearly expressed in the skin lesions and serum of patients with psoriasis, but the specific mechanism of action is not yet clear. Here, we showed that SERPINB4 expression was increased in skin lesions from the imiquimod (IMQ)-treated mice and M5-(a mixture of five proinflammatory cytokines: IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α) treated human immortalized keratinocyte (HaCaT). Knockdown of SERPINB4 by short hairpin RNA attenuated the M5-induced keratinocyte inflammation. Conversely, lentiviral expression of SERPINB4 promoted keratinocyte inflammation. Finally, we observed that SERPINB4 stimulation activated the p38MAPK signaling pathway. Taken together, these results suggest that SERPINB4 has a critical role in psoriasis pathogenesis

The Pro-inflammatory Role of TGFβ1: A Paradox?

TGF&#946;1 was initially identified as a potent chemotactic cytokine to initiate inflammation, but the autoimmune phenotype seen in TGF&#946;1 knockout mice reversed the dogma of TGF&#946;1 being a pro-inflammatory cytokine to predominantly an immune suppressor. The discovery of the role of TGF&#946;1 in Th17 cell activation once again revealed the pro-inflammatory effect of TGF&#946;1. We developed K5.TGF&#946;1 mice with latent human TGF&#946;1 overexpression targeted to epidermal keratinocytes by keratin 5. These transgenic mice developed significant skin inflammation. Further studies revealed that inflammation severity correlated with switching TGF&#946;1 transgene expression on and off, and genome wide expression profiling revealed striking similarities between K5.TGF&#946;1 skin and human psoriasis, a Th1/Th17-associated inflammatory skin disease. Our recent study reveals that treatments alleviating inflammatory skin phenotypes in this mouse model reduced Th17 cells, and antibodies against IL-17 also lessen the inflammatory phenotype. Examination of inflammatory cytokines/chemokines affected by TGF&#946;1 revealed predominantly Th1-, Th17-related cytokines in K5.TGF&#946;1 skin. However, the finding that K5.TGF&#946;1 mice also express Th2-associated inflammatory cytokines under certain pathological conditions raises the possibility that deregulated TGF&#946; signaling is involved in more than one inflammatory disease. Furthermore, activation of both Th1/Th17 cells and regulatory T cells (Tregs) by TGF&#946;1 reversely regulated by IL-6 highlights the dual role of TGF&#946;1 in regulating inflammation, a dynamic, context and organ specific process. This review focuses on the role of TGF&#946;1 in inflammatory skin diseases.</p

Prevalence of short stature among children in China: A systematic review

ABSTRACT Importance The prevalence and characteristics of short stature (SS) among children in China should be assessed to provide guidance for planning and implementation of nationwide public health policies. Thus far, there have been no accurate estimates of the prevalence of SS in China. Objective To analyze the prevalence of SS among children in China and to explore the influences of sex, area, age, study year, and study site on prevalence rates. Methods Relevant literature was identified by searching the following databases: PubMed, Embase, The Cochrane Library, Chinese Biomedical Literature, China Knowledge Resource Integrated, WeiPu, and WanFang databases. Meta‐analysis was carried out using STATA 11.2. Results This meta‐analysis included 39 studies with 348 326 Chinese participants; the studies covered 20 provinces, municipalities, and autonomous regions. The pooled prevalence of SS was 3.2% (95% confidence interval [CI], 2.6%–3.7%; I2 = 99.8%). The prevalence of SS in boys and girls were 3.1% (95% CI, 2.5%–3.7%) and 3.2% (95% CI, 2.6%–3.9%), respectively. The sex difference was not statistically significant (P > 0.05). The prevalence of SS was higher in rural areas than in urban areas (4.7% [95% CI, 3.6%–5.8%] vs. 2.8% [95% CI, 2.2%–3.4%]; P < 0.001). The prevalence of SS was higher in West China (5.2%; 95% CI, 4.4%–6.0%) than in Northeast China (0.6%; 95% CI, 0.3%–0.8%), East China (2.3%; 95% CI, 1.9%–2.8%), or Central China (2.9%; 95% CI, 1.9%–3.9%). Interpretation The prevalence of SS among children was higher in western and rural areas of China. Close attention to children’s growth and development is needed to prevent the occurrence of SS

Pressure Evolution Mechanism of Marine Shale Reservoirs and Shale Gas Accumulation Model: Evidence from Fluid Inclusions in the Wufeng&ndash;Longmaxi Formation in the Basin Margin Structural Transition Zone in Northern Guizhou Province, China

The Wufeng&ndash;Longmaxi Formation in northern Guizhou Province is the dominant shale gas exploration and development strata in China. This study investigates the Shixi and Daozhen synclines, which are located in the basin margin transition zone. This region experienced complex tectonic stages and superimposed transformations, resulting in heterogeneous preservation conditions and shale reservoir pressure evolution in different tectonic units of the Wufeng&ndash;Longmaxi Formation. Based on fluid inclusion analysis, the types of fluid inclusion and the fluid filling stages of the Wufeng&ndash;Longmaxi shale reservoir were determined by laser Raman analysis and homogenization temperature and salinity tests. It was found that the fluid inclusion density and paleopressure in each filling stage were then restored. The results confirm that: &#9312; Both the Shixi syncline and Daozhen syncline Wufeng&ndash;Longmaxi shale reservoirs experienced two fluid filling phases, in the early Yanshanian and late Yanshanian&ndash;Himalayan, respectively. In the course of tectonic evolution, the Wufeng&ndash;Longmaxi Formation in the Shixi and Daozhen synclines experienced pressure relief to some extent during the two aforementioned key fluid charging periods but remained in overpressurized states overall; &#9313; The Wufeng&ndash;Longmaxi Formations of the Shixi and Daozhen synclines are characterized by high-density methane inclusions; &#9314; Based on the differences in the structural preservation conditions, the pressure evolution mechanisms of the Wufeng&ndash;Longmaxi Formation Shales during the important tectonic evolution period in northern Guizhou Province were revealed. Furthermore, differential enrichment and accumulation models of shale gas were established and named &ldquo;facing thrust structural sealing type (Shixi syncline)&rdquo; and &ldquo;reverse fault lateral blocking type (Daozhen syncline)&rdquo;

Pressure Evolution Mechanism of Marine Shale Reservoirs and Shale Gas Accumulation Model: Evidence from Fluid Inclusions in the Wufeng–Longmaxi Formation in the Basin Margin Structural Transition Zone in Northern Guizhou Province, China

The Wufeng–Longmaxi Formation in northern Guizhou Province is the dominant shale gas exploration and development strata in China. This study investigates the Shixi and Daozhen synclines, which are located in the basin margin transition zone. This region experienced complex tectonic stages and superimposed transformations, resulting in heterogeneous preservation conditions and shale reservoir pressure evolution in different tectonic units of the Wufeng–Longmaxi Formation. Based on fluid inclusion analysis, the types of fluid inclusion and the fluid filling stages of the Wufeng–Longmaxi shale reservoir were determined by laser Raman analysis and homogenization temperature and salinity tests. It was found that the fluid inclusion density and paleopressure in each filling stage were then restored. The results confirm that: ① Both the Shixi syncline and Daozhen syncline Wufeng–Longmaxi shale reservoirs experienced two fluid filling phases, in the early Yanshanian and late Yanshanian–Himalayan, respectively. In the course of tectonic evolution, the Wufeng–Longmaxi Formation in the Shixi and Daozhen synclines experienced pressure relief to some extent during the two aforementioned key fluid charging periods but remained in overpressurized states overall; ② The Wufeng–Longmaxi Formations of the Shixi and Daozhen synclines are characterized by high-density methane inclusions; ③ Based on the differences in the structural preservation conditions, the pressure evolution mechanisms of the Wufeng–Longmaxi Formation Shales during the important tectonic evolution period in northern Guizhou Province were revealed. Furthermore, differential enrichment and accumulation models of shale gas were established and named “facing thrust structural sealing type (Shixi syncline)” and “reverse fault lateral blocking type (Daozhen syncline)”

Selective IgA Deficiency with Multiple Autoimmune Comorbidities: A Case Report and Literature Review

Individuals with Selective Immunoglobulin-A Deficiency (SIgAD) are often asymptomatic, and symptomatic SIgAD patients often have autoimmune comorbidities. A 48-year-old Han Chinese man presented with abdominal discomfort, hematochezia, and a large tumor in the anogenital region. The primary diagnosis of SIgAD was based on the patient’s age, serum IgA concentration (0.067 g/L), and the evidence of chronic respiratory infection. No other immunoglobulin deficiency or evidence of immunosuppression was present. The primary diagnosis of giant condyloma acuminatum was based on human papilloma virus-6-positive laboratory results and histological characteristics. The tumor and adjacent skin lesions were resected. Hemoglobin concentration fell to 5.50 g/dL, and an emergency erythrocyte transfusion was performed. The body temperature increased to 39.8 ºC, suggesting a transfusion reaction, and 5 mg dexamethasone was administered intravenously. Hemoglobin concentration stabilized at 10.5 g/dL. The clinical signs and laboratory results indicated autoimmune hemolytic anemia, systemic lupus erythematosus, and Hashimoto’s thyroiditis. Abdominal discomfort and hematochezia subsided. Though uncommon, the manifestation of multiple autoimmune comorbidities can occur in SIgAD patients. Further research is needed regarding the causes of SIgAD and the autoimmune disorders that often occur as comorbidities