SERPINB3/B4 is Increased in Psoriasis and Rosacea Lesions and has Pro-inflammatory Effects in Mouse Models of these Diseases.

Psoriasis and rosacea are both chronic inflammatory skin disorders resulted from aberrant keratinocyte-immune cell crosstalk, but the common molecular foundations for these two conditions are poorly understood. Here, we reveal that both psoriasis and rosacea patients, as well as their mice models, have significantly elevated expressions of SERPINB3/B4 (members of serine protease inhibitor) in the lesional skin. Skin inflammation in mice that resembles both psoriasis and rosacea is prevented by SERPINB3/B4 deficiency. Mechanistically, we demonstrate that SERPINB3/B4 positively induces NF-κB signaling activation, thereby stimulating disease-characteristic inflammatory chemokines and cytokines production in keratinocytes, and promoting the chemotaxis of CD4+ T cells. Our results suggest that, in keratinocytes, SERPINB3/B4 may be involved in the pathogenesis of both psoriasis and rosacea by stimulating NF-κB signaling, and they indicate a possible treatment overlap between these two diseases.

Assessing the association of leukocyte telomere length with ankylosing spondylitis and rheumatoid arthritis: A bidirectional Mendelian randomization study.

Background: Telomere length shortening can cause senescence and apoptosis in various immune cells, resulting in immune destabilization and ageing of the organism. In this study, we aimed to systematically assess the causal relationship of leukocyte telomere length (LTL) with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) using a Mendelian randomization study. Methods: LTL (n=472174) was obtained from the UK Biobank genome-wide association study pooled data. AS (n=229640), RA (n=212472) were obtained from FinnGen database. MR-Egger, inverse variance weighting, and weighted median methods were used to estimate the effects of causes. Cochran's Q test, MR Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots were used to look at sensitivity, heterogeneity, and multiple effects. Forward MR analysis considered LTL as the exposure and AS, RA as the outcome. Reverse MR analysis considered AS, RA as the exposure and LTL as the outcome. Results: In the forward MR analysis, inverse variance-weighted and weighted median analysis results indicated that longer LTL might be associated with increased risk of AS (IVW: OR = 1.55, 95% CI: 1.14-2.11, p = 0.006). MR Egger regression analysis showed no pleiotropy between instrumental variables (IVs) (Egger intercept= 0.008, p = 0.294). The leave-one-out analysis showed that each single nucleotide polymorphism (SNP) of AS was robust to each outcome. No significant causal effects were found between AS, RA and LTL in the reverse MR analysis. Conclusion: Longer LTL may be related with an increased risk of developing AS, and these findings provide a foundation for future clinical research on the causal association between LTL and AS.

Coexistence of anomalous muscle, persistent median artery, bifid median nerve causing carpal tunnel syndrome: A case report and literature review.

Carpal tunnel syndrome (CTS) is an upper extremity median nerve entrapment disorder that is rare in children and adolescents. Anatomical variations of the wrist, such as anomalous muscles, persistent median artery (PMA), and bifid median nerves (BMN), are rare etiology of CTS. Coexistence of all three variants combined with CTS in adolescents has been rarely reported. Case description: A 16-year-old right-hand dominant male presented to our clinic with several years of bilateral thenar muscle atrophy and weakness but no paresthesia or pain in his both hands. Ultrasonography showed that the right median nerve become significantly thinner, and the left median nerve was split into two branches by PMA. Magnetic resonance imaging (MRI) revealed that anomalous muscles in the bilateral wrist extending to the carpal tunnel, causing compression of the median nerve. Considering the possibility of CTS clinically, the patient underwent bilateral open carpal tunnel release without resection of anomalous muscles and PMA. The patient has no discomfort after 2 years. This suggests that anatomical variations of the carpal tunnel may contribute to CTS, which can be confirmed by preoperative ultrasonography and MRI, and the possibility of carpal tunnel anatomical variations should be considered when CTS occurs in adolescents. Open carpal tunnel release is an effective treatment for juvenile CTS without the need to resect abnormal muscle and PMA during the operation.

[Clinical Value of Translocator Protein Gene in Evaluating the Efficacy of FLT3-ITD/DNMT3A R882 Double-Mutated Acute Myeloid Leukemia].

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION: TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.

Cerebral Gray Matter Volume Changes in Patients with Neuropathic Pain from Total Brachial Plexus Injury.

INTRODUCTION: Total brachial plexus injury not only significantly affects the motor and sensory function of the affected upper limbs but also causes further physical and mental damage to patients with long-term intractable pain. Previous studies mainly focused on the surgical treatment, while only a few paid attention to the intractable neuropathic pain caused by this injury. Changes in the volume of gray matter in the brain are thought to be associated with chronic neuropathic pain. METHODS: Voxel-based morphometry analysis was used to compare the difference in cerebral gray matter volume between total brachial plexus injury patients with neuropathic pain and healthy controls. Correlations between pain duration, pain severity, and GM changes were analyzed. RESULTS: The volume of cerebral gray matter in the patient group was decreased significantly in multiple regions, including the parahippocampal gyrus, paracentric lobule, inferior frontal gyrus, auxiliary motor cortex, middle occipital gyrus, right middle temporal gyrus, while it was increased in the insular, pons, middle frontal gyrus, cingulate gyrus, inferior parietal lobule, bilateral thalamus, and globus pallidus. There were no significant correlations between pain duration and rGMV changes, while a positive correlation was observed between pain severity and rGMV changes in one specific region, involving the anterior cingulate cortex. CONCLUSION: Total brachial plexus injury patients with chronic pain have widespread regions of gray matter atrophy and hypertrophy. The only positive correlation was observed between pain severity and rGMV changes in one specific region, suggesting that nociceptive stimuli trigger a variety of nonpain-specific processes, which confirms the multidimensional nature of pain.

Study on the relationship between the risk of Parkinson's disease complicated with cerebral infarction and the serum level of tyrosine hydroxylase and its potential influencing factors / 公共卫生与预防医学

Objective To explore the relationship between serum levels of tyrosine hydroxylase (TH) and the risk of cerebral infarction in Parkinson's patients. Methods A total of 129 patients with confirmed Parkinson's disease who were hospitalized in our hospital were selected, among the 58 patients had Parkinson's disease complicated with cerebral infarction (complicated with cerebral infarction group), and the remaining 71 patients had Parkinson's disease alone (control group). Blood TH levels and other potential related information were collected retrospectively at the time of diagnosis. Comparative analysis of data was performed using SPSS software. Results Comparing the serum TH expression levels in patients with Parkinson's disease and patients with cerebral infarction at admission , the serum TH level in patients with cerebral infarction was lower. Results also showed that the levels of CRP, IL-6, MDA, and Hcy were higher in patients with cerebral infarction, while PON-1 level was lower. In addition, patients with cerebral infarction had lower motor ability (higher UPDRS Ⅲ score). Further regression analysis was carried out with the occurrence of Parkinson's disease complicated with cerebral infarction as the dependent variable and the potential influencing factors as the independent variable. The results indicated that factors such as low expression of TH, high expression of inflammatory factors, and high expression of oxidative stress factors were positively correlated with the risk of complications of the two diseases. Conclusion The low expression of TH, inflammatory state and high oxidative stress state are the potential risk factors for Parkinson's disease complicated with cerebral infarction, which deserves clinical attention.

Lithocholic acid promotes rosacea-like skin inflammation via G protein-coupled bile acid receptor 1.

BACKGROUND: Rosacea is a chronic inflammatory skin disorder with unclear etiology. Evidence showed that immunoinflammatory dysregulation was involved in the pathogenesis. Bile acids, as important participants of hepatoenteric circulation, play a vital role in immunoinflammatory regulation through peripheral blood circulation. However, whether it has effects on rosacea remains unknown. METHODS: Here, we performed a bile acid analysis on the serum samples of rosacea patients and healthy controls. Then we gavage G protein-coupled bile acid receptor 1 (TGR5) knockout mice with lithocholic acid (LCA) based on a LL37-induced rosacea-like model. We further overexpress TGR5 in HaCaT keratinocytes to figure out the downstream pathway. RESULTS: We found varied bile acid profile in the peripheral blood circulation of patients, especially the most significant increase in LCA. LCA promoted skin inflammation in LL37-induced rosacea-like mouse model. Our in vivo and in vitro results further demonstrated that LCA induced inflammatory cytokines and chemokines, thus exacerbated rosacea-like skin inflammation, via TGR5 in keratinocytes and LL37-induced rosacea-like mouse model. CONCLUSIONS: Therefore, we conclude that LCA promotes skin inflammation of rosacea via TGR5, and LCA-TGR5 axis may be a novel therapeutic target for rosacea.

Analyzing Prognostic Hub Genes in the Microenvironment of Cutaneous Melanoma by Computer Integrated Bioinformatics.

Cutaneous melanoma (CM) is attracting increasing attention due to high mortality. In response to this, we synthetically analyze the CM dataset from the TCGA database and explore microenvironment-related genes that effectively predict patient prognosis. Immune/stromal scores of cases are calculated using the ESTIMATE algorithm and are significantly associated with overall patient survival. Then, differentially expressed genes are identified by comparing the immune score and stromal score, also prognostic genes are subsequently screened. Functional analysis shows that these genes are enriched in different activities of immune system. Moreover, 19 prognosis-related hub genes are extracted from the protein-protein interaction network, of which four unreported genes (IL7R, FLT3, C1QC, and HLA-DRB5) are chosen for validation. A significant negative relationship is found between the expression levels of the 4 genes and pathological stages, notably T grade. Furthermore, the K-M plots and TIMER results show that these genes have favorable value for CM prognosis. In conclusion, these results give a novel insight into CM and identify IL7R, FLT3, C1QC, and HLA-DRB5 as crucial roles for the diagnosis and treatment of CM.

Long-term follow-up of one-stage artificial dermis reconstruction surgery for fingertip defects with exposed phalanx.

Fingertip injuries are among the most common injuries of the hand. Although numerous treatment methods have been described in detail in the literature, there are a few alternatives that require exploration. We analyzed 24 patients who underwent one-stage artificial dermis (Pelnac®) reconstruction surgery between 2012 and 2016 to assess the effectiveness of this alternative reconstruction method for extensive fingertip injury with exposed phalanx. There were 16 males and 8 females, with ages ranging from 2 to 75 years. There were 16 type III injuries, 6 type IV, and 2 type II on the Allen classification. Complete epithelialization was achieved by the 4th week in 19 cases and by the 6th week in 5. The wounds of all patients healed completely, without infection. All the injured fingers developed various levels of hooked nail and length shortening except for the 2 type II injuries. There was nail spicule formation in 1 case. There were no cases of cold intolerance, but 2 cases of hypersensitivity and 5 of numbness. Overall 2-point discrimination ceased improving by the 2nd postoperative year. This technique is simple, allows spontaneous healing of the fingertips, and is mostly free from the major complications associated with other treatment methods.

Increased serum levels of CCL3, CXCL8, CXCL9, and CXCL10 in rosacea patients and their correlation with disease severity.

Rosacea is a common chronic inflammatory skin disease involving millions of patients worldwide. Previous studies have highlighted the upregulation of a variety of chemokines in the skin lesions of both rosacea patient and rosacea-like mouse model. However, the serum levels of these chemokines and their clinical significance have not been explored before. In this study, we aimed at examining the serum levels of a series of chemokines (including CCL2, CCL3, CCL20, CXCL1, CXCL8, CXCL9, CXCL10, and CXCL12) implicated in rosacea and their correlation with disease severity. Bio-Plex Pro Human Chemokine Assays were used to measure the serum levels of these chemokines. Investigator's Global Assessment (IGA) was applied for assessing the papules/pustules of rosacea patients, while persistent erythema was evaluated by the Clinician's Erythema Assessment (CEA). Our results revealed that the serum concentration of CCL3, CXCL8, CXCL9, and CXCL10 were markedly elevated in rosacea patients compared to healthy controls. Among them, the levels of CCL3, CXCL8, and CXCL9 were positively correlated with the IGA score, while serum CXCL9 and CXCL10 were positively related with the CEA score of rosacea patients. What's more, the expression of the corresponding receptors of CCL3 (Ccr1), CXCL8 (Cxcr1 and Cxcr2), CXCL9, and CXCL10 (Cxcr3) were all significantly increased in the skin lesions of rosacea-like mouse model with CXCR2 and CXCR3 highly expressed in rosacea patient skins. Our results indicated that CCL3, CXCL8, CXCL9, and CXCL10 might potentially serve as serum indicators for rosacea and could assist the severity evaluation of disease. Findings in this study would also potentially help to develop new targeted therapies for rosacea in future. © 2022 Japanese Dermatological Association.

Powerful Identification of Large Quantitative Trait Loci Using Genome-Wide R/glmnet-Based Regression.

R/glmnet has been successfully applied to jointly mapped multiple quantitative trait loci for linkage analysis, along with statistical inference for quantitative trait loci candidates with nonzero genetic effects using R/lm for normally distributed traits, R/glm for discrete traits, and R/coxph for survival times. In this study, we extended R/glmnet to a genome-wide association study by means of parallel computation. A multi-locus genome-wide association study for high-throughput single-nucleotide polymorphisms was implemented in the "Multi-Runking" software written within the R workspace. This software can better detect common and large quantitative trait nucleotides and more accurately estimate than genome-wide mixed model analysis for one single-nucleotide polymorphism at a time and linear mixed models-least absolute shrinkage and selection operator. Its applicability and utility were demonstrated by multi-locus genome-wide association studies for the simulated and real traits distributed normally, binary traits, and survival times.

Androgen Receptor-Mediated Paracrine Signaling Induces Regression of Blood Vessels in the Dermal Papilla in Androgenetic Alopecia.

Androgenetic alopecia (AGA), also known as male pattern baldness, is associated with androgen and androgen receptor (AR) signaling; however, the pathogenesis of AGA remains largely unknown. In this study, we show that nuclear localization of AR is elevated in the dermal papilla (DP) of balding scalp in patients with AGA. Transcriptome analysis identifies microvascular abnormalities in the DP of balding scalp compared with nonbalding scalp of patients with AGA. We provide further evidence that blood vessels regress in the DP of balding scalp at the early stage of hair follicle miniaturization in AGA development. Consistently, we find that microvascular vessels accumulate around the DP on anagen initiation, and angiogenesis is required for hair regeneration in mice. Mechanistically, we show that AR-mediated paracrine signaling, mainly TGFß signaling, from DP cells induces apoptosis of microvascular endothelial cells in the DP of balding scalp of AGA. These findings define a role of AR-mediated regression of blood vessels in DP in AGA and support the notion that early anti-AR treatment is better than late treatment.

N2-Polarized Neutrophils Reduce Inflammation in Rosacea by Regulating Vascular Factors and Proliferation of CD4+ T Cells.

The infiltration of neutrophils is implicated in rosacea, which is a common chronic inflammatory facial disease. This study explores the biological function of neutrophils and their underlying mechanism in rosacea. A rosacea-like mouse model was established to explore the polarization of neutrophils. RNA sequencing was used to investigate the underlying mechanisms. Our results show that neutrophils partly switched to N2 phenotypes in both patients with rosacea and rosacea-like mouse models. The rosacea-like phenotype and inflammation in both a genetic mutation (Genista mice) and the Gr-1 antibody‒induced neutropenia mice were significantly aggravated compared with that in the control groups. In vitro, lipopolysaccharide + IFN-γ and IL4 stimulation of neutrophils successfully induced the N1 and N2 polarization of neutrophils, respectively. Replenishment of N2 neutrophils in the lesions of wild-type and Genista mice ameliorated the rosacea-like phenotype and inflammation. RNA sequencing suggested that N2 neutrophils relieved the rosacea-like phenotype, possibly by regulating the expression of blood circulation‒associated factors, such as ACE, AGTR2, and NOS1. Finally, N2 neutrophils regulated the proliferation of CD4+ lymphocytes, which could explain the remission of inflammation in mice. Our results suggest that N2 polarization of neutrophils in rosacea exerts anti-inflammatory effects by regulating vascular factors and proliferation of CD4+ T cells.

Aspirin alleviates skin inflammation and angiogenesis in rosacea.

Rosacea is a chronic, relapsing inflammatory skin disease featured by abnormal activation of immune responses, vascular dysfunction and prominent permeability barrier alterations. Aspirin, as the first nonsteroidal anti-inflammatory drug (NSAID), is widely used for various inflammatory conditions due to its anti-inflammatory and anti-angiogenic properties. However, its effects on rosacea are unclear. In this study, we demonstrated that aspirin dramatically improved pathological phenotypes in LL37-induced rosacea-like mice. The RNA-sequencing analysis revealed that aspirin alleviated rosacea-like skin dermatitis mainly via modulating immune responses. Mechanically, we showed that aspirin decreased the production of chemokines and cytokines associated with rosacea, and suppressed the Th1- and Th17-polarized immune responses in LL37-induced rosacea-like mice. Besides, aspirin administration decreased the microvessels density and the VEGF expression in rosacea-like skin. We further demonstrated that aspirin inhibited the activation of NF-κB signaling and the release of its downstream pro-inflammatory cytokines. Collectively we showed that aspirin exerts a curative effect on rosacea by attenuating skin inflammation and angiogenesis, suggesting a promising therapeutic candidate for the treatment of rosacea.

A positive feedback loop between mTORC1 and cathelicidin promotes skin inflammation in rosacea.

Rosacea is a chronic inflammatory skin disorder whose pathogenesis is unclear. Here, several lines of evidence were provided to demonstrate that mTORC1 signaling is hyperactivated in the skin, especially in the epidermis, of both rosacea patients and a mouse model of rosacea-like skin inflammation. Both mTORC1 deletion in epithelium and inhibition by its specific inhibitors can block the development of rosacea-like skin inflammation in LL37-induced rosacea-like mouse model. Conversely, hyperactivation of mTORC1 signaling aggravated rosacea-like features. Mechanistically, mTORC1 regulates cathelicidin through a positive feedback loop, in which cathelicidin LL37 activates mTORC1 signaling by binding to Toll-like receptor 2 (TLR2) and thus in turn increases the expression of cathelicidin itself in keratinocytes. Moreover, excess cathelicidin LL37 induces both NF-κB activation and disease-characteristic cytokine and chemokine production possibly via mTORC1 signaling. Topical application of rapamycin improved clinical symptoms in rosacea patients, suggesting mTORC1 inhibition can serve as a novel therapeutic avenue for rosacea.

mTORC1-Mediated Angiogenesis is Required for the Development of Rosacea.

Although multiple evidences suggest that angiogenesis is associated with the pathophysiology of rosacea, its role is still in debate. Here, we showed that angiogenesis was enhanced in skin lesions of both rosacea patients and LL37-induced rosacea-like mice. Inhibition of angiogenesis alleviated LL37-induced rosacea-like features in mice. Mechanistically, we showed that mTORC1 was activated in the endothelial cells of the lesional skin from rosacea patients and LL37-induced rosacea-like mouse model. Inhibition of mTORC1 decreased angiogenesis and blocked the development of rosacea in mice. On the contrary, hyperactivation of mTORC1 increased angiogenesis and exacerbated rosacea-like phenotypes. Our in vitro results further demonstrated that inhibition of mTORC1 signaling significantly declined LL37-induced tube formation of human endothelial cells. Taken together, our findings revealed that mTORC1-mediated angiogenesis responding to LL37 might be essential for the development of rosacea and targeting angiogenesis might be a novel potential therapy.

Platelet factor 4 inhibits human hair follicle growth and promotes androgen receptor expression in human dermal papilla cells.

Platelet-rich plasma (PRP) has been reported recently as a potential therapeutic approach for alopecia, such as androgenetic alopecia, but the exact mechanisms and effects of specific components of this recipe remain largely unknown. In this study, we identified that platelet factor 4 (PF4), a component of PRP, significantly suppressed human hair follicle growth and restrained the proliferation of human dermal papilla cells (hDPCs). Furthermore, our results showed that PF4 upregulated androgen receptor (AR) in human dermal papilla cells in vitro and via hair follicle organ culture. Among the hair growth-promoting and DP-signature genes investigated, PF4 decreased the expression of Wnt5a, Wnt10b, LEF1, HEY1 and IGF-1, and increased DKK1 expression, but did not affect BMP2 and BMP4 expression. Collectively, Our data demonstrate that PF4 suppresses human hair follicle growth possibly via upregulating androgen receptor signaling and modulating hair growth-associated genes, which provides thought-provoking insights into the application and optimization of PRP in treating hair loss.

ADAMDEC1 promotes skin inflammation in rosacea via modulating the polarization of M1 macrophages.

Rosacea is a chronic inflammatory cutaneous disease which mainly affects central face, leading to cosmetic disfigurement and compromised social psychology in billions of rosacea patients. Though the exact etiology of rosacea remains elusive, accumulating evidence has highlighted the dysfunction of innate immunity and inflammation in rosacea pathogenesis. Disintegrin Metalloprotease ADAM-like Decysin-1 (ADAMDEC1) is an orphan ADAM-like metalloprotease which is believed to be closely related to inflammation. Here for the first time, we reported that Adamdec1 expression was significantly increased in the skin lesions of rosacea patients and LL37-induced rosacea-like mouse models. Immunofluorescence analysis revealed co-localization of ADAMDEC1 and macrophages in patient and mouse biopsies. In cellular experiment, the expression of ADAMDEC1 was prominently elevated in M1 but not M2 macrophages. Knocking down of ADAMDEC1 significantly blunted M1 polarization in macrophages induced from human monocytes and THP-1 cell lines. Furthermore, silencing of Adamdec1 in LL-37-induced mouse model also suppressed the expression of M1 signature genes such as IL-6, iNOS and TNF-α, resulting in attenuated rosacea-like phenotype and inflammation. Taken together, our results demonstrate that ADAMDEC1 plays a pro-inflammatory role in rosacea via modulating the M1 polarization of macrophages.

Thalidomide ameliorates rosacea-like skin inflammation and suppresses NF-κB activation in keratinocytes.

BACKGROUND: Rosacea is a chronic inflammatory skin disorder of uncertain etiology. Evidence suggests the underlying pathogenesis is modulated by abnormal inflammatory and vascular responses. Thalidomide is a synthetic derivative acid with anti-inflammatory and anti-angiogenic properties. However, its effects on rosacea remain unknown. OBJECTIVES: To investigate the effects of thalidomide on the lesional alterations and molecular mechanisms in rosacea. METHODS: Mice were intradermally injected with LL37 to induce rosacea-like features and intraperitoneally administered with thalidomide. The severity of skin inflammation was evaluated. The mRNA levels of cytokines and chemokines associated with rosacea were assessed by qPCR. The number of CD4 positive infiltrated T helper cells and CD31 positive microvessels, and related-genes were measured by immunofluorescence, qPCR and ELISA. Moreover, the effect of thalidomide on inhibiting NF-κB activation was determined by immunofluorescence and western blot. RESULTS: Our results showed that thalidomide significantly alleviated erythema and reduced inflammatory cell infiltration in dermis of LL37-induced rosacea-like mice. The production of cytokines and chemokines induced by LL37 was decreased by thalidomide in mice skin and HaCaT keratinocytes. Particularly, we showed thalidomide reduced CD4+ T helper cell infiltration and downregulated Th1- and Th17-polarizing genes. In addition, thalidomide treatment lowered the microvessel density and vascular endothelial growth factor (VEGF) expression. We further demonstrated that thalidomide suppressed NF-κB activation in LL37-treated skin and in TNF-α-stimulated HaCaT keratinocytes in vitro. CONCLUSIONS: Our findings suggest thalidomide attenuates the inflammation and represses NF-κB activation in skin, which leads to assumptions that thalidomide may be a new therapeutic agent for rosacea.

Traumatic brachial plexus injury: a study of 510 surgical cases from multicenter services in Guangxi, China.

BACKGROUND: Traumatic brachial plexus injuries are severe lesions, and the incidence of these injuries has been increasing in recent years. METHODS: The clinical data of 510 operated patients with brachial plexus injury recruited from 74 hospitals in Guangxi from 2004 to 2016 were retrospectively studied. RESULTS: Our study included 447 males and 63 females, with an average age of 29.04 years. Traffic accidents were the most common cause of injury (64.71%), especially motorcycle accidents. Closed injuries accounted for 88.24% of cases, and 83.53% of patients had associated injuries, the most common of which were fractures (76.27%). The preoperative predictive value of root injury of MRI and CT was 74.71% and 71.28%, respectively. 44.71% of patients underwent an initial operation within 6 months after the trauma. Regarding the surgery, neurolysis alone, brachial plexus reconstruction, and free functioning gracilis graft accounted for 16.67%, 75.50%, and 4.51%, respectively. A total of 415 patients were followed up with an average time of 47.95 (25-68) months, and anxiety or depression were found among 81.20% of them. Two hundred seventy-six patients suffered from nerve pain, with mild pain present in 67.03% of patients. Additionally, 347 patients were followed up for more than 3 years, 76.81% of patients with C5-C6 injury recovery to useful function, and the procedure of neurolysis alone demonstrated the best efficacy (79.45%). CONCLUSIONS: Brachial plexus injury is still a challenging trauma for surgeons, and traffic accidents are the dominant cause. Timely and effective surgery is important for functional limb recovery.