Circular RNA PDK1 targets miR-4731-5p to enhance TNXB expression in ligamentum flavum hypertrophy.

Hypertrophic ligamentum flavum (LF) is a main factor responsible for lumbar spinal stenosis (LSS); however, the exact mechanisms of the pathogenesis of these processes remain unknown. This study aimed to elucidate whether circular RNAs and microRNAs regulate the pathogenesis of LF and LSS, especially focusing on circPDK1 (hsa_circ_0057105), a circRNA targeting pyruvate dehydrogenase kinase 1 and differentially expressed in LF tissues between lumbar disk herniation and LSS patients. The circPDK1/miR-4731 and miR-4731/TNXB (Tenascin XB) interactions were predicted and validated by luciferase reporter assay. Colony formation, wound-healing, and MTT assays were used for estimating cell proliferation and migration. Protein expression levels were evaluated using Western blotting. TNXB expression was verified using immunohistochemistry (IHC). Overexpressing circPDK1 promoted the proliferation, migration, and expression of fibrosis-related protein (alpha smooth muscle actin (α-SMA), lysyl oxidase like 2 (LOXL2), Collagen I, matrix metalloproteinase-2 (MMP-2) and TNXB) in LF whereas miR-4731-5p showed opposite effects. The expression of TNXB was promoted by circPDK1; contrary results were observed with miR-4731-5p. Co-overexpression of miR-4731-5p partially reversed the proliferative and fibrosis-prompting effects of circPDK1 or TNXB. The circPDK1-miR-4731-TNXB pathway may be proposed as a regulatory axis in LF hypertrophy, which might shed light on in-depth research of LSS, as well as providing a novel therapeutic target for LF hypertrophy-induced LSS.

Reliability and Validity Analysis of Pelvic Sagittal Inclination Calculated by Inverse Cosine Function Method on Pelvic Anteroposterior Radiographs.

OBJECTIVE: Evaluation of sagittal pelvic tilt is significant for hip surgeons. However, the accurate measurement of pelvic sagittal inclination (PSI) is still a challenge. The objective of this study is to propose a new method for measurement of PSI from pelvic anteroposterior radiograph based on the inverse cosine function obtained from individualized pelvic model. METHODS: Collecting the imaging data of 30 patients with both pelvic CT and full-length spine radiographs. Establishing pelvic model by customized 3D reconstruction software. The length of three groups of longitudinal and transverse line segments (A'p and B') were measured from full-length spine anteroposterior radiographs. The corresponding anatomical parameters, including A, B, b, ∠α, ∠γ, were measured and calculated on the same patient's pelvic model. The estimated PSI (ePSI) based on three groups of anatomical landmarks, including ePSI-1, ePSI-2, and ePSI-3, were calculated by equation, ePSI = arccos A ' p b * B ' - ∠ α , and compared with the actual PSI (aPSI) measured by Surgamap software. For the reliability and validation evaluation, three observers measured these parameters in two rounds. Intra-class correlation and inter-class correlation were both calculated. Bland-Altman method was used to evaluate the consistency between the estimated PSI (ePSI) and the actual PSI (aPSI). RESULTS: ePSI-1 and ePSI-2 showed excellent intra-observer reliability (0.921-0.997, p < 0.001) and inter-observer reliability (0.801-0.977, p < 0.001). ePSI-3 had a fair inter-observer reliability (0.239-0.823, p < 0.001). ePSI-1 showed the strongest correlation with aPSI (r = 0.917, p < 0.001). Mean (maximum) absolute difference of ePSI-1, ePSI-2, and ePSI-3 is 2.62° (7.42°), 4.23° (13.78°), and 7.74° (31.47°), respectively. The proportion of cases with absolute difference less than 5° in three groups were 86.7% (ePSI-1), 66.7% (ePSI-2), 56.7% (ePSI-3). CONCLUSION: This new method based on inverse cosine function has good reliability and validity when used in the evaluation of PSI on pelvic anteroposterior radiographs.

Circadian rhythm disruption exacerbates Th2-like immune response in murine allergic airway inflammation.

BACKGROUND: Chronic jet lag (CJL)-induced circadian rhythm disruption (CRD) is positively correlated with an increased risk of allergic diseases. However, little is known about the mechanism involved in allergic rhinitis (AR). METHODS: Aberrant light/dark cycles-induced CRD mice were randomly divided into negative control (NC) group, AR group, CRD+NC group, and CRD+AR group (n = 8/group). After ovalbumin (OVA) challenge, nasal symptom scores were recorded. The expression of Occludin and ZO-1 in both nasal mucosa and lung tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-PCR) and immunohistochemical staining. The level of OVA-specific immunoglobulin E (sIgE) and T-helper (Th)-related cytokines in the plasma was measured by enzyme-linked immunosorbent assay (ELISA), and the proportion of Th1, Th2, Th17, and regulatory T cell (Treg) in splenocytes was evaluated by flow cytometry. RESULTS: The nasal symptom score in the CRD+AR group was significantly higher than those in the AR group with respect to eosinophil infiltration, mast cell degranulation, and goblet cell hyperplasia. The expression of ZO-1 and Occludin in the nasal mucosa and lung tissues in the CRD+AR group were significantly lower than those in the AR group. Furthermore, Th2 and Th17 cell counts from splenocytes and OVA-sIgE, interleukin 4 (IL-4), IL-6, IL-13, and IL-17A levels in plasma were significantly increased in the CRD+AR group than in the AR group, whereas Th1 and Treg cell count and interferon γ (IFN-γ) level were significantly decreased in the CRD+AR group. CONCLUSION: CRD experimentally mimicked CJL in human activities, could exacerbate local and systemic allergic reactions in AR mice, partially through decreasing Occludin and ZO-1 level in the respiratory mucosa and increasing Th2-like immune response in splenocytes.

Subdural fluid collection rather than meningitis contributes to hydrocephalus after cervical laminoplasty: A case report.

BACKGROUND: Hydrocephalus following dural tear after spinal surgery is rare. Although a few cases of obstructive hydrocephalus caused by subdural fluid collection and communicating hydrocephalus associated with meningitis have been reported, the mechanism remains uncertain. Herein we describe a patient complicated with hydrocephalus after cervical laminoplasty in whom subdural fluid collection in the cervical spine and posterior cranial fossa rather than chronic meningitis was the main mechanism. CASE SUMMARY: A 45-year-old man underwent cervical laminoplasty for cervical spondylotic myelopathy at a local hospital. Ten days postoperatively, a high fever occurred and magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) leakage. Pseudomeningocele liquid test showed high levels of protein and white blood cell (WBC) count with negative bacterial culture. The patient was treated with short-term intravenous antibiotic and discharged with normal body temperature. The patient was uneventful during the first 8 mo follow-up although repeated MRI showed persistent pseudomeningocele. At the 9th mo postoperatively, the patient gradually presented with dizziness and headache accompanied by recurrent weakness of his left arm. Imaging examinations demonstrated hydrocephalus and a cystic lesion around the cervical spinal cord. CSF test from lumbar puncture indicated chronic meningitis. MRI on 1 d after pseudomeningocele drainage showed a significant decrease in the cystic volume, suggesting that the cystic lesion would be subdural fluid collection rather than adhesive arachnoiditis. After dural defect repair, the patient's symptoms completely resolved and hydrocephalus gradually disappeared. CSF analysis at the 21-mo follow-up revealed significantly decreased protein level and WBC count. CONCLUSION: Subdural fluid collection rather than meningitis contributes to the hydrocephalus formation after cervical laminoplasty.

[Study on mechanism of salidroside against liver fibrosis by regulating CXCL16].

In order to investigate the effect of salidroside on inhibiting liver fibrosis and its relationship with CXC chemokine ligand 16(CXCL16) in vivo and in vitro, totally 45 C57 BL/6 J male mice were randomly divided into normal group, model group and salidroside group, with 15 mice in each group. The mice in model group and salidroside group were injected intraperitoneally with 15% carbontetrachloride(CCl_4) olive oil solution to establish liver fibrosis model, and the mice in normal group were injected intraperitoneally with the same dose of olive oil. Salidroside group was given with 100 mg·kg~(-1 )salidroside by gavage, while the normal group and model group received the same amount of double distilled water by gavage. All mice were sacrificed after 5 weeks of intragastric administration. The pathological changes of mouse liver were observed by hematoxylin-eosin(HE) staining, and the degree of liver fibrosis was observed by sirius red staining. The protein expressions of collagen Ⅰ(ColⅠ), α-smooth muscle actin(α-SMA), fibronectin(FN), CXCL16, phosphorylated Akt(p-Akt), Akt in liver tissues were detected by Western blot. Hepatic stellate cell line JS 1 was cultured in vitro and divided into control group, model group(100 µg·L~(-1) CXCL16) and salidroside group(100 µg·L~(-1) CXCL16+1×10~(-5) mol·L~(-1) salidroside). Cell migration was detected by cell scratch, the mRNA expressions of ColⅠ and α-SMA were detected by RT-PCR, and the protein expressions of p-Akt and Akt were detected by Western blot. As compared with the normal group, the protein expressions of ColⅠ, α-SMA, FN, CXCL16, and p-Akt in the model group were significantly increased, and salidroside could reduce the expression of these indicators(P<0.05 or P<0.01). In vitro, CXCL16 could promote the migration of JS 1, increase the mRNA expressions of ColⅠ and α-SMA in JS 1, and enhance Akt phosphorylation in JS 1(P<0.05 or P<0.01). As compared with the model group, salidroside could inhibit the migration of JS 1 induced by CXCL16(P<0.05), and reduce the high expression of ColⅠ and α-SMA mRNA and the phosphorylation of Akt in JS 1 induced by CXCL16(P<0.05). In conclusion, salidroside might attenuate CCl_4-induced liver fibrosis in mice by inhibiting the migration, activation and Akt phosphorylation of hepatic stellate cells induced by CXCL16.

A nationwide survey of otolaryngologists' compliance with Chinese guidelines for diagnosis and treatment of allergic rhinitis.

BACKGROUND: A higher compliance with clinical guidelines helps improve treatment outcomes. But the clinical practice of otolaryngologists is not always consistent with guidelines. OBJECTIVE: To describe otolaryngologists' compliance with guidelines about allergic rhinitis (AR) management and identify factors responsible for the discordance between clinical practice and guideline recommendations in China. METHODS: A cross-sectional nationwide survey was designed and conducted via an online platform. Recruitment was done by emailing otolaryngologists registered in the Chinese Society of Otorhinolaryngology-Head and Neck Surgery or by inviting otolaryngologists to scan a Quick Respond (QR) code that linked to the questionnaire at various academic meetings. RESULTS: A total of 2142 otolaryngologists were eligible and completed the survey. Of them, 64.7% had over 10 years work experience and 97.4% had a bachelor's degree or higher. About 18.3% of the participants strictly copied the guideline in clinical practice, while 73.7% used the guideline that had been adjusted according to their clinical experience. Otolaryngologists were most concerned about the efficacy, safety, and minimum age of AR medications, and least concerned about patient preferences. Regarding the use of intranasal steroids (INS), leukotriene receptor antagonists (LTRA), and H1-antihistamines, 86.8%, 55.7% and 51.2% of otolaryngologists complied with the guideline recommendations, respectively. Educational background was a factor affecting the compliance with guidelines and acceptance of INS. CONCLUSION: A vast majority of Chinese otolaryngologists complied with the current Chinese AR guidelines. A difference still existed between the otolaryngologists' real-world and guideline-recommended management. The otolaryngologists should pay more attention to patient preferences. A higher education could improve otolaryngologists' adherence to the guidelines.

Livin in synergy with Ras induces and sustains corticosteroid resistance in the airway mucosa.

Rationale: Corticosteroid resistance (CR) seriously affects the therapeutic effects of steroids on many chronic inflammatory disorders, including airway allergy. The mechanism of CR development is unclear. Recent research indicates that livin, an apoptosis inhibitor, is associated with the regulation in cell activities. This study investigates the role of livin in the inducing and sustaining CR in the airway mucosa. Methods: Nasal epithelial cells (NECs) were isolated from surgically removed nasal mucosal tissues of patients with allergic rhinitis (AR) and nasal polyps with or without CR. Differentially expressed genes in NECs were analyzed by the RNA sequencing. A CR mouse model was developed to test the role of livin in CR development. Results: The results showed that NECs of AR patients with CR expressed high levels of livin, that was positively correlated with the thymic stromal lymphopoietin (TSLP) expression and the high Ras activation status in NECs. Livin and Ras activation mutually potentiating each other in the inducing and sustaining the TSLP expression in NECs. TSLP induced eosinophils and neutrophils to express glucocorticoid receptor-ß (GRß). Eosinophils and neutrophils with high CRß expression were resistant to corticosteroids. Depletion of livin or inhibition of TSLP markedly attenuated CR and airway allergy. Conclusions: Livin facilitates CR development in the airways by promoting TSLP expression in epithelial cells and the GRß expression in eosinophils and neutrophils. Depletion of livin or inhibiting TSLP attenuates CR development and inhibits airway allergy, this has the translational potential to be used in the treatment of airway allergy.

Role of FcγRI in Antigen-Dependent Eosinophil Activation in Patients With Allergic Rhinitis.

BACKGROUND: The eosinophil (Eo) activation is a crucial factor evoking allergic rhinitis (AR) attacks; factors; the mechanism of triggering Eo activation remains to be further investigated. The interaction of antigen (Ag) and antibody plays a critical role in evoking allergy attacks. This study aims to elucidate the role of FcγRI, the high affinity receptor of IgG, in the Ag-mediated Eo activation. METHODS: Nasal lavage fluids (NLF) were collected from AR patients and healthy control (HC) subjects. Eos were isolated by flow cytometry cell sorting and analyzed by pertinent immunological approaches. RESULTS: Eos composed more than 60% of the cellular components in AR NLF. Exposure to specific Ags (sAgs) in the culture triggered Eos to release inflammatory mediators. High levels of FcγRI were detected on the surface of AR NLF Eos. Exposure to lipopolysaccharide markedly increased the FcγRI expression in naive Eos, which could be bound by Ag-specific IgG (sIgG) to form complexes on the surface of Eos; this made Eos at the sensitized status. Eos bore with the sIgG/FcγRI complexes could be activated upon exposure to sIgG in the culture; these Eos can be designated as Ag-specific Eos. Passive transfer of Ag-specific Eos resulted in profound AR response in mice upon sAg challenge. Depletion of FcγRI on Eos efficiently abolished AR response in mice. CONCLUSIONS: AR Eos express high levels FcγRI, that can be bound by sIgG to make Eos sensitized. Re-exposure to specific Ags can activate the sensitized Eos.

Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage.

Salvianolic acid B (Sal B) is one of the main active ingredients of Salvia miltiorrhiza, with strong antioxidant effects. Recent findings have shown that Sal B has anti-inflammatory, anti-apoptotic, anti-fibrotic effects and can promote stem cell proliferation and differentiation, and has a beneficial effect on cardiovascular and cerebrovascular diseases, aging, and liver fibrosis. Reactive oxygen species (ROS) include oxygen free radicals and oxygen-containing non-free radicals. ROS can regulate cell proliferation, survival, death and differentiation to regulate inflammation, and immunity, while Sal B can scavenge oxygen free radicals by providing hydrogen atoms and reduce the production of oxygen free radicals and oxygen-containing non-radicals by regulating the expression of antioxidant enzymes. The many pharmacological effects of Sal B may be closely related to its elimination and inhibition of ROS generation, and Nuclear factor E2-related factor 2/Kelch-like ECH-related protein 1 may be the core link in its regulation of the expression of antioxidant enzyme to exert its antioxidant effect. What is confusing and interesting is that Sal B exhibits the opposite mechanisms in tumors. To clarify the specific target of Sal B and the correlation between its regulation of oxidative stress and energy metabolism homeostasis will help to further understand its role in different pathological conditions, and provide a scientific basis for its further clinical application and new drug development. Although Sal B has broad prospects in clinical application due to its extensive pharmacological effects, the low bioavailability is a serious obstacle to further improving its efficacy in vivo and promoting clinical application. Therefore, how to improve the availability of Sal B in vivo requires the joint efforts of many interdisciplinary subjects.

Fuzheng Huayu Recipe Prevented and Treated CCl4-Induced Mice Liver Fibrosis through Regulating Polarization and Chemotaxis of Intrahepatic Macrophages via CCL2 and CX3CL1.

BACKGROUND: Fuzheng Huayu recipe (FZHY) is an original Chinese patent medicine which was developed and marketed by our institute. It could markedly improve liver tissue inflammation and ameliorate hepatic fibrosis in the clinical study. The intrahepatic macrophages recruitment and polarization play an important role in the progress of liver inflammation and fibrosis. Whether FZHY exerted its antiliver fibrosis effects through regulating intrahepatic macrophages phenotypic ratios is still unknown. This study aims to explore the antifibrosis mechanism of FZHY on regulating the recruitment and polarization of intrahepatic macrophages. METHODS: C57/B6 mice were used for the establishment of the CCl4-induced mice liver fibrosis model. Liver inflammation and fibrosis were evaluated by HE and Sirius red staining, hydroxyproline assays, and biochemical tests. The levels of chemokines and inflammatory cytokines in liver tissue were measured by RNA-Seq transcriptome analysis, western blot assay, RT-qPCR, and immunofluorescence assay. The macrophages recruitment and phenotypic polarization were observed by flow cytometry. RESULTS: FZHY significantly improved liver inflammation and reduced liver fibrosis degree. TNF signaling pathway, involved in macrophages recruitment and phenotypic polarization, was discovered by RNA-Seq transcriptome analysis. In TNF signaling pathway, CCL2 expression was significantly decreased and CX3CL1 expression was significantly upregulated by FZHY in liver tissue and primary intrahepatic macrophages. The ratio of proinflammatory hepatic resident macrophage-Kupffer cells (F4/80+CD11b-CD86+) was downregulated by FZHY, while the proportion of anti-inflammatory Kupffer cells (F4/80+CD11b-CD206+) was upregulated. Meanwhile, the ratio of proinflammatory Ly6Chigh macrophages (F4/80+CD11b+Ly6Chigh) which were recruited from blood circulation by CCL2 was reduced by FZHY, while the ratio of restorative Ly6Clow macrophages (F4/80+CD11b+Ly6Clow) which were recruited from blood circulation or induced from Ly6Chigh macrophages polarization by CX3CL1 was significantly increased. CONCLUSIONS: FZHY could regulate the recruitment and polarization of intrahepatic macrophages via CCL2 and CX3CL1, so as to play its anti-inflammation and antifibrosis pharmacological effects in the liver.

Histological Outcome of Fuzheng Huayu plus Entecavir Combination Therapy in Chronic Hepatitis B Patients with Significant Liver Fibrosis.

Background and Aims: To evaluate the efficacy of Fuzheng Huayu (FZHY), a Chinese herbal formula, plus entecavir (ETV) in regression of liver fibrosis in chronic hepatitis B (CHB) patients with significant fibrosis/cirrhosis. Methods: The current study was a two-center, randomized, double-blind and placebo-controlled pilot study. Fifty-two currently untreated chronic hepatitis B patients with Ishak fibrosis score ≥3 points were identified and 1:1 randomized into FZHY plus ETV combination and placebo plus ETV groups. The second liver biopsy was performed after 48-week treatment. Necroinflammatory improvement and regression of fibrosis were assessed. Fine changes in different collagen features in paired liver biopsies were evaluated by dual-photon microscopy for both groups. Results: Forty-nine patients completed the full course of treatment; forty-six of them underwent second liver biopsy (for which twenty-two were in the combination group and twenty-four were in the control group). Compared to those in the control group, patients in the combination group had significantly higher rate of fibrosis regression (82% vs. 54%) (p<0.05). Furthermore, the necroinflammatory improvement was greater in the combination group than in the control group (59% vs. 25%, p<0.05). Among the more than 80 collagen parameters in the dual-photon analysis, 5 decreased significantly in the combination group compared to the control group (p<0.05). However, no significant improvement was detected in either biochemical, virologic or serologic responses between these two groups at week 48. Conclusions: The combination therapy of FZHY plus ETV for 48 weeks resulted in a higher rate of necroinflammatory improvement and fibrosis regression than ETV alone in chronic hepatitis B patients with significant fibrosis/cirrhosis. The clinical trial number is ChiCTR-TRC-11001377.

Period2 gene regulates diurnal changes of nasal symptoms in an allergic rhinitis mouse model.

BACKGROUND: Allergic rhinitis (AR) symptoms exhibit prominent 24-hour variations associated with the biological clock. Although endogenous glucocorticoids synchronize circadian oscillator in the nasal mucosa, the precise mechanism of AR remains unclear. Therefore, using a mouse model, we investigated the association between circadian-clock genes and AR symptoms at various time-points. METHODS: Based on the rhythmic secretion of corticosterone levels, we chose 2 time-points, ZT4 (10:00 AM) and ZT16 (10:00 PM), to observe dynamic changes of nasal symptoms, immunologic responses, and circadian-clock gene period (Per) expressions. RESULTS: In the AR group, nasal symptom scores at ZT4 were significantly higher than at ZT16, with a greater increase in eosinophils, mast cells, and total immunoglobulin E levels at ZT4. The scores had a negative correlation with fluctuation of corticosterone levels. T-helper 1 (Th1) cell counts and interferon-γ levels decreased significantly at ZT4 compared with ZT16 in the AR group, whereas Th2 cells; Th17 cells; and interleukin (IL)-4, -13, and -17A levels increased significantly at ZT4 compared with ZT16. Furthermore, Per2 gene expression levels were attenuated at ZT4 and elevated at ZT16, but correlated negatively with Th2 and Th17 responses associated with Gata3 and Rorγt expression levels that were enhanced at ZT4 and reduced at ZT16 in the AR group. CONCLUSION: Our results suggest that the Per2 gene may influence diurnal variations of AR symptom severity, partially through its possible anti-inflammatory effect on the circadian regulation of GATA3 and RORγt levels in immune cells. This further demonstrates the neural-immune-endocrinal mechanism of circadian rhythm in AR and sheds new light on chronotherapeutic approaches to AR.

Probiotic extracts ameliorate nasal allergy by inducing interleukin-35-producing dendritic cells in mice.

BACKGROUND: The therapeutic efficacy of allergic rhinitis (AR) needs to be improved. Probiotics have immunoregulatory functions. In this study we evaluated the effects of protein extracts of probiotics in the amelioration of AR. METHODS: Extracts of Bifidobacterium infantis (EBI) were prepared by lysing the live probiotics. AR mice were developed to be used to evaluate the therapeutic efficacy of EBI. RESULTS: The results show that EBI induced interleukin (IL)-10-producing dendritic cells (DCs) via increasing IL-35 and signal transducer and activator of transcription 3 (STAT3) phosphorylation. IL-10-expressing DCs induced IL-10-producing B cells (B10 cells), with the latter showing immunosuppressive functions. After challenge with specific antigens, AR mice showed sneezing, nasal itch, and increases in serum-specific immunoglobulin E (IgE) and mouse mast cell protease-1; higher levels of T helper 2 (Th2) cytokines (IL-4, 67.17 ± 10.66; IL-5, 62.83 ± 9.70; IL-13, 51.00 ± 6.69, before treatment) in nasal mucosal protein extracts, which were significantly suppressed (IL-4, 27.00 ± 6.66; IL-5, 23.86 ± 4.53; IL-13, 25.67 ± 4.93, after treatment (p < 0.001) by administration with EBI nasal drops. CONCLUSION: EBI can suppress AR via inducing B10 cells. Thus, after carrying out required preclinical experiments and tests, EBI has the translational potential to be used in the treatment of AR and other allergic diseases.

Effects of HGF and KGF gene silencing on vascular endothelial growth factor and its receptors in rat ultraviolet radiation­induced corneal neovascularization.

Hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF), two paracrine growth factors, modulate corneal epithelial cell metabolism, apoptosis and survival. Vascular endothelial growth factor (VEGF) serves as a proangiogenic factor in corneal neovascularization (CNV), which is a major cause of vision impairment and corneal blindness. The aim of the present study was to evaluate the ability of HGF and KGF to influence VEGF and its receptor, kinase insert domain receptor (Flk­1) in corneal injury and CNV in rats induced by ultraviolet radiation (UVR). An UVR­induced corneal injury rat model was successfully established to characterize the expression patterns of KGF, HGF, VEGF and Flk­1 in corneal tissues. Corneal epithelial cells were extracted and treated with small interfering RNAs (siRNAs) targeting KGF, HGF or both (si­KGF, si­HGF or si­HGF/KGF). The effects of HGF and KGF were examined through detection of the expression of KGF, HGF, VEGF and Flk­1, and the evaluation of cell proliferation, cell cycle and cell apoptosis. The expression levels of KGF, HGF, VEGF and Flk­1 in corneal tissues were increased in the rat model. In the cell experiments, the transfection of si­HGF/KGF resulted in reductions in VEGF, Flk­1, KGF and HGF. In addition, decreased cell proliferation and elevated cell apoptosis were found in the corneal epithelial cells from the rat model following KGF and HGF gene silencing. Taken together, these findings suggest that HGF and KGF gene silencing inhibits UVR­induced corneal epithelial proliferation and CNV and may function as novel targets for corneal wound healing.

Survivin facilitates T-helper 2-biased inflammation in the airway.

BACKGROUND: The biased T helper 2 (Th2) responses play a critical role in the pathogenesis of allergy. The underlying mechanism is not fully understood yet. Survivin can regulate multiple cellular activities. This study aims to elucidate the role of survivin in the development and maintenance of Th2 polarization. METHODS: CD4+ T cells were isolated from blood samples collected from patients with allergic asthma (AS) and HS control (HS) subjects. Mice carrying CD4+ T cells with survivin knockout (KO mice) were employed to test the role of survivin in the development of the biased Th2 responses. RESULTS: KO mice failed to induce airway allergy. Peripheral CD4+ T cells expressed survivin, which was higher in the AS group than that in the HS group. Naive CD4+ T cells with higher expression of survivin were prone to differentiating into Th2 cells. Survivin bound to the Il4 promoter in CD4+ T cells to enhance Il4 gene transcription. The expression of Fas was lower in CD4+ T cells of the AS group than that in the HS group. Overexpression of survivin suppressed the expression of Fas and impaired the activation-induced cell death (AICD) of CD4+ T cells. CONCLUSION: Survivin facilitates the development of biased Th2 polarization through promoting expression of interleukin 4 (IL-4) and impairing the AICD machinery of CD4+ T cells. To modulate the expression of survivin in CD4+ T cells has the translational potential in the treatment of allergic diseases.

Alcohol consumption analysis among patients with liver disease in China.

BACKGROUND: Alcohol consumption has been observed to be a contributing factor in liver damage. However, very few studies have tried to decipher the correlation between patients with liver disease and alcohol consumption. Therefore, this study was planned to determine the prevalence of alcohol consumption among patients with liver disease, and to evaluate the risk factors, liver diseases, and chronic medical conditions associated with alcohol drinking. METHODS: A cross-sectional study was conducted among patients with liver disease in 30 provinces, autonomous regions, and municipalities across China. All participants answered the questionnaire, which led to the calculation of Alcohol Use Disorders Inventory Test (AUDIT) score for each patient. Based on this score, low-risk drinkers, hazardous drinkers, and harmful drinkers were defined as having AUDIT score of <8, between 8 and 15, and ≥16, respectively. RESULTS: A total of 1489 participants completed the questionnaire. Based on this information, 900 (60.44%) participants were classified as alcohol drinkers. Among these, 8.66% were ex-drinkers, 22.10% were low-risk drinkers, 17.13% were hazardous drinkers, and 12.56% were harmful drinkers. Further investigation of the association between alcohol consumption and other baseline characteristics of patients with liver disease revealed that usually men <40 years old, participants having higher family annual income, having college degree or higher education, living alone, having higher body mass index (BMI), current smokers, and ex-smokers had significant association with higher risk of alcohol consumption. In addition, among the 18.07% of the participants with cirrhosis, it was observed that risk of cirrhosis increased with higher alcohol consumption. Furthermore, harmful drinkers showed greater odds of hypertension and heart diseases, while hazardous drinkers and harmful drinkers, both had greater odds of hyperlipidemia. CONCLUSIONS: Overall our analyses indicated that among the patients with liver disease in China, there was high rate of alcohol consumption and dependence. Alcohol consumption usually associated with men <40 years old, higher family income, education level, living alone, high BMI, and smoking. Increased alcohol consumption not only increased the risk of cirrhosis, but also enhanced the risk of hypertension, heart diseases, and hyperlipidemia.

Pelvic incidence measurement using a computed tomography data-based three-dimensional pelvic model.

OBJECTIVES: To introduce a new method of pelvic incidence (PI) measurement based on three-dimensional (3D) pelvic models reconstructed from CT images and to report the normal distribution of PI in normal pelvic anatomy. METHODS: CT images of 320 subjects with normal pelvic anatomy who visited the Radiology Department between 2006 and 2017 were retrospectively selected and saved in Digital Imaging and Communications in Medicine (DICOM) format. A computerized method was employed to determine the bony landmarks required for the measurement of PI. To quantify the method's accuracy and reliability, the intraclass correlation coefficient (ICC) was calculated. A subgroup of 30 DICOM files was randomly selected to perform a validation study. Three independent testers performed all procedures. All measurements were performed twice independently by the three testers on all 10 subjects with an interval of 2 weeks. Independent samples t tests were used to identify statistically significant differences in the PI value between sexes. Pearson correlation coefficient was employed to determine the relationship between PI and age. RESULTS: PI measurement using the new method resulted in an excellent intraobserver reliability (0.9612, range 0.8917-0.9893; p < 0.001) and interobserver reliability (0.9867, range 0.9611-0.9964; p < 0.001). PI was significantly different between sexes, with larger PI in women (p = 0.019). PI was significantly larger in the 40-80-year age group (45.94 ± 9.08°) than the < 40-year age group (43.50 ± 7.39°). We did not find any linear correlation between PI and age in the male (r = 0.140, p = 0.105) or female subgroup (r = 0.119, p = 0.107). A weak correlation between PI and age overall was observed (r = 0.142, p = 0.011). CONCLUSION: Accurate PI measurement could be achieved by a CT data-based 3D pelvic model.

B cell lymphoma-2-like protein-12 association with T-helper 2 inflammation in chronic rhinosinusitis with allergy.

BACKGROUND: T-helper 2 (Th2) polarization plays a critical role in the pathogenesis of chronic rhinosinusitis (CRS) with accompanying nasal allergy. Recent studies indicate that B cell lymphoma-2-like protein-12 (Bcl2L12) is associated with immune dysregulation. The purpose of this study was to elucidate the role of Bcl2L12 in the pathogenesis of Th2 polarization of CRS patients. METHODS: CRS patients with nasal allergy (CRSa) and without nasal allergy (CRSna) were recruited into this study. CD4+ T cells were isolated from the blood samples of human subjects. A variety of immunologic molecular strategies were used to assess Th2 polarization and Bcl2L12 expression. RESULTS: Twenty CRSa patients, 20 CRSna patients, and 20 healthy subjects were recruited into this study. High levels of immunoglobulin E (IgE), interleukin 4 (IL-4), IL-5, IL-13, and Bcl2L12 were detected in nasal extracts of CRSa patients, but not in CRSna patients. The levels of Bcl2L12 were positively correlated with Th2 cytokines. CD4+ T cells from CRSa patients were prone to differentiate into Th2 cells, in which Bcl2L12 was required. CONCLUSION: Bcl2L12 is positively correlated with Th2 cytokine levels in the nasal mucosa of CRSa patients. Bcl2L12 contributes to the Th2 polarization, which may be a novel therapeutic target in the treatment of CRSa.

Optimal medial transforaminal lumbar interbody fusion approach with five extensive options: A simulated study on three-dimensional digital reconstructed images.

OBJECTIVE: The objective of this study is to use 3D digital lumbar models to investigate and simulate the optimal posterior operative approach for safe decompression and insertion of an interbody cage. METHODS: Thirty lumbar spine (L3-S1) computed tomography data are collected for 3D reconstruction. We cut medial half part of the superior facet and define the distance between the margin of the operative side of the spinous process and the medial margin of the cut superior facet as "medial distance (MD)". Then, we cut the total superior facet and define the distance between the margin of the operative side of the spinous process and the lateral side of the junction of the pedicle and the vertebral body as "extend distance (ED)". The feasible insertion of the current standard width size (10 mm and 12 mm) interbody cages was assessed by the two aforementioned MD and ED approaches. Besides the ED, we also simulate four other extensive options of lateral upper, lateral lower, vertical upper and lower and transmedian contralateral decompression on 3D digital lumbar model. RESULTS: The MD increased from 13.48 ± 1.28 mm at L3/4 to 18.05 ± 1.43 mm at L5/S1, and the ED increased from 16.64 ± 1.34 mm at L3/4 to 21.12 ± 1.62 mm at L5/S1. To insert a 10-mm-wide cage, 16.7% (left) and 13.3% (right) of MD for L3/4 is not enough, 60.0% (left) and 46.7% (right) of MD for L3/4 is subsafe, 13.3% (left) and 16.7% (right) of MD for L4/5 is subsafe and all others are safe. To insert a 12-mm-wide cage, 76.7% (left) and 60.0% (right) of MD for L3/4 is not enough, 20.0% (left) and 30.0% (right) of MD for L3/4 is subsafe, 13.3%% (left) and 16.7% (right) of MD for L4/5 is not enough, 63.3% (left) and 56.7% (right) of MD for L4/5 is subsafe and 6.7% (left) and 10.0% (right) of MD for L5/S1 is subsafe, whereas 33.3%% (left) and 30.0% (right) of ED for L3/4 is subsafe, 3.3% (left) and 3.3% (right) of ED for L4/5 is subsafe and all others are safe. Besides the ED, on 3D models, four other extensive options could be simulated too and may need to be performed for different special individuals. CONCLUSION: Our 3D digital image study provides a feasible optimal medial transforaminal lumbar interbody fusion approach with five extensive options on lower lumbar region. It can provide safe lumbar decompression and interbody fusion in most population. In addition, surgeons can choose the different extensive options for special individual conditions. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Transforminal lumbar interbody fusion is very common used for lumbar degenerative diseases. The optimal medial transforminal lumbar interbody fusion with five options provide a safe and precise approach for surgeons in treatment of lumbar degenerative diseases.

The compression of L5 nerve root, single or double sites?-radiographic graded signs, intra-operative detect technique and clinical outcomes.

BACKGROUND: The L5 nerve root could be compressed at both L4-5 and L5-S1 regions. If L5 nerve root has confirmed compression at L4-5 level and questionable compression at L5-S1 foramina, performing both surgeries at L4-5 and L5-S1 levels may induce unnecessary extra surgery on L5-S1; however, ignoring foraminal stenosis of L5/S1 may require re-exploration. METHODS: Two hundred seventeen patients with L5 nerve root compressed at L4-5 lateral access were performed with L4-5 decompression and interbody fusion. Lee et al. grade classification was used to assess the foraminal stenosis of L5-S1 preoperatively. Nerve root probe was designed and used to detect if there were foraminal stenosis at L5-S1 level that compressing the exiting L5 nerve root. Visual analog scale (VAS) of low back pain, leg pain and Oswestry Disability Index (ODI) were used to assess clinical outcomes. RESULTS: For all of 217 patients who underwent L4-5 surgery, L5-S1 foramina were preoperatively assessed as: grade 0: 125 cases, grade 1: 58 cases, grade 2: 23 cases, and grade 3: 11 cases. After intra-operative L5 nerve root detection, 11/11 patients with grade 3 radiographic foraminal stenosis, 6/23 (26.1%) with grade 2 and 2/58 (3.4%) who had grade 1 underwent L4-5 and L5-S1 transforaminal lumbar interbody fusion (TLIF), the others received only L4-5 TLIF. Compared to pre-operative baseline data, both L4-5 TLIF and L4-5 and L5-S1 TLIF groups had significant decreased VAS of low back pain and leg pain, and ODI at 3 and 24 months after operation. CONCLUSIONS: We suggested that our novel nerve root probe combined with pre-operative radiographic grade may be helpful to surgeons to identify the single or double compression of L5 nerve root and make a more precise surgical strategy to improve surgical outcome than the method depended on pre-operative radiographic grade alone.