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Background: Posterolateral decompression and fusion with internal fixation is a commonly used surgical approach for treating degenerative lumbar spinal stenosis (DLSS). This study aims to evaluate the impact of preserving a portion of the unilateral facet joint during decompression on surgical outcomes and long-term recovery in patients., Methods: This study analyzed 73 patients with DLSS accompanied by bilateral lower limb neurological symptoms who underwent single-level L4/5 posterolateral decompression and fusion surgery from January 2022 to March 2023. Patients were categorized into two groups based on the type of surgery received: Group A comprised 31 patients who underwent neural decompression without facet joint preservation, while Group B consisted of 42 patients who underwent neural decompression with preservation of partial facet joints on one side. Regular follow-up evaluations were conducted, including clinical and radiological assessments immediately postoperatively, and at 3 and 12 months thereafter. Key patient information was documented through retrospective chart reviews., Results: Most patients in both groups experienced favorable surgical outcomes. However, four cases encountered complications. Notably, during follow-up, Group B demonstrated superior 1-year postoperative interbody fusion outcomes (P < 0.05), along with a trend towards less interbody cage subsidence and slower postoperative intervertebral disc height loss. Additionally, Group B showed significantly reduced postoperative hospital stay (P < 0.05)., Conclusion: Under strict adherence to surgical indications, the posterior lateral lumbar fusion surgery, which preserves partial facet joint unilaterally during neural decompression, can offer greater benefits to patients., (© 2024. The Author(s).)

Solitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal neoplasm. The current classification has merged SFT and hemangiopericytoma (HPC) into the same tumor entity, while the risk stratification models have been developed to compensate for clinical prediction. Typically, slow-growing and asymptomatic, SFT can occur in various anatomical sites, most commonly in the pleura. Histologically, SFT consists of spindle to oval cells with minimal patterned growth, surrounded by stromal collagen and unique vascular patterns. Molecularly, SFT is defined by the fusion of NGFI-A-binding protein 2 (NAB2) and signal transducer and activator of transcription 6 (STAT6) genes as NAB2-STAT6. This fusion transforms NAB2 into a transcriptional activator, activating early growth response 1 (EGR1) and contributing to SFT pathogenesis and development. There are several fusion variants of NAB2-STAT6 in tumor tissues, with the most frequent ones being NAB2ex4-STAT6ex2 and NAB2ex6-STAT6ex16/ex17. Diagnostic methods play a crucial role in SFT clinical practice and basic research, including RT-PCR, next-generation sequencing (NGS), FISH, immunohistochemistry (IHC), and Western blot analysis, each with distinct capabilities and limitations. Traditional treatment strategies of SFT encompass surgical resection, radiation therapy, and chemotherapy, while emerging management regimes include antiangiogenic agents, immunotherapy, RNA-targeting technologies, and potential targeted drugs. This review provides an update on SFT's clinical and molecular aspects, diagnostic methods, and potential therapies., (© 2024. The Author(s).)

Importance: Previous studies on alcohol consumption and incident gout have mostly included men or combined both sexes, and the sex-specific associations between alcohol consumption and gout are poorly understood., Objective: To evaluate the consumption of total and specific alcoholic beverages in association with incident gout in men and women., Design, Setting, and Participants: This prospective cohort study included 401 128 participants in the UK Biobank aged 37 to 73 years who were free of gout at baseline (2006-2010). Participants were followed up through December 31, 2021, and data were analyzed between August 2023 and June 2024., Exposure: Questionnaire-based consumption of total alcohol and specific alcoholic beverages., Main Outcomes and Measures: The outcome was incident gout, identified using hospital records. Multivariable Cox proportional hazards regression models were used to estimate sex-specific hazard ratios (HRs) and 95% CIs of incident gout associated with alcohol consumption, with a particular consideration of reverse causation bias., Results: The main analysis included 179 828 men (mean [SD] age, 56.0 [8.2] years) and 221 300 women (mean [SD] age, 56.0 [8.0] years). Current drinkers showed a higher risk of gout than never drinkers among men (HR, 1.69; 95% CI, 1.30-2.18) but not among women (HR, 0.83; 95% CI, 0.67-1.03). Among current drinkers, higher total alcohol consumption was associated with a higher risk of gout among both sexes and more strongly among men than women (men: HR, 2.05 [95% CI, 1.84-2.30]; women: HR, 1.34 [95% CI, 1.12-1.61]). The most evident sex difference in the consumption of specific alcoholic beverages was observed for beer or cider (men: mean [SD], 4.2 [4.8] pints per week; women: mean [SD], 0.4 [1.1] pints per week). Consumption of champagne or white wine, beer or cider, and spirits each was associated with a higher risk of gout among both sexes, with beer or cider showing the strongest association per 1 pint per day (men: HR, 1.60 [95% CI, 1.53-1.67]; women: HR, 1.62 [95% CI, 1.02-2.57]). Some inverse associations between light to moderate consumption of specific alcoholic beverages and gout were eliminated after adjusting for other alcoholic beverages and excluding individuals who had reduced alcohol consumption for health reasons, self-reported poor health, or had cardiovascular disease, cancer, or kidney failure at baseline, or developed gout within the first 2 years of follow-up., Conclusions and Relevance: In this cohort study, higher consumption of several specific alcoholic beverages was associated with a higher risk of gout among both sexes. The sex-specific associations for total alcohol consumption may be associated with differences between men and women in the types of alcohol consumed.

Background : Gout is a nutrition-related, highly prevalent inflammatory arthritis with undesirable effects on the quality of life. The relationships between circulating fatty acids (FAs) and gout remain poorly understood. Method : We included 268 174 participants with plasma FAs measured using nuclear magnetic resonance at the baseline (2006-2010) from the UK Biobank, of which 15 194 participants had repeated measures of FAs between 2012 and 2013. Cox proportional hazards models were used to assess the association of the baseline and longitudinal changes in relative levels of plasma FAs ( % total FAs) with incident gout. Mendelian randomization (MR) analyses were conducted to assess the potential causality of the examined association. Results : Over a median follow-up of 12.8 years, 5160 incident cases of gout occurred. Baseline polyunsaturated fatty acids (PUFAs), n-6 PUFAs, and linoleic acids (LAs) were inversely associated with incident gout (all P -trend values < 0.0001). Baseline monounsaturated fatty acids (MUFAs), n-3 PUFAs, and docosahexaenoic acids (DHAs) were positively associated with incident gout (all P -trend values < 0.0001). Longitudinal increments of n-6 PUFAs and LAs were associated with a lower risk of subsequent gout, whereas an increment of n-3 PUFAs was associated with a higher risk. In two-sample MR analyses, genetically determined higher levels of PUFAs, n-6 PUFAs, and LAs were associated with a decreased risk of gout (all P values < 0.05). Conclusions : Our findings consistently indicate a causal relationship of elevated levels of n-6 PUFAs, especially LAs, with a reduced risk of gout.

Kv1.3 belongs to the voltage-gated potassium (Kv) channel family, which is widely expressed in the central nervous system and associated with a variety of neuropsychiatric disorders. Kv1.3 is highly expressed in the olfactory bulb and piriform cortex and involved in the process of odor perception and nutrient metabolism in animals. Previous studies have explored the function of Kv1.3 in olfactory bulb, while the role of Kv1.3 in piriform cortex was less known. In this study, we investigated the neuronal changes of piriform cortex and feeding behavior after smell stimulation, thus revealing a link between the olfactory sensation and body weight in Kv1.3 KO mice. Coronal slices including the anterior piriform cortex were prepared, whole-cell recording and Ca 2+ imaging of pyramidal neurons were conducted. We showed that the firing frequency evoked by depolarization pulses and Ca 2+ influx evoked by high K + solution were significantly increased in pyramidal neurons of Kv1.3 knockout (KO) mice compared to WT mice. Western blotting and immunofluorescence analyses revealed that the downstream signaling molecules CaMKII and PKCα were activated in piriform cortex of Kv1.3 KO mice. Pyramidal neurons in Kv1.3 KO mice exhibited significantly reduced paired-pulse ratio and increased presynaptic Cav2.1 expression, proving that the presynaptic vesicle release might be elevated by Ca 2+ influx. Using Golgi staining, we found significantly increased dendritic spine density of pyramidal neurons in Kv1.3 KO mice, supporting the stronger postsynaptic responses in these neurons. In olfactory recognition and feeding behavior tests, we showed that Kv1.3 conditional knockout or cannula injection of 5-(4-phenoxybutoxy) psoralen, a Kv1.3 channel blocker, in piriform cortex both elevated the olfactory recognition index and altered the feeding behavior in mice. In summary, Kv1.3 is a key molecule in regulating neuronal activity of the piriform cortex, which may lay a foundation for the treatment of diseases related to piriform cortex and olfactory detection., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Context: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases., Objective: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women., Methods: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders., Results: During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99)., Conclusion: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background : A healthy eating pattern characterized by a higher intake of healthy plant foods has been associated with a lower risk of premature mortality, but whether this applies to individuals with varying glycemic status remains unclear. Methods : This study included 4621 participants with diabetes and 8061 participants with prediabetes from the US National Health and Nutrition Examination Survey (2007-2016). Using the dietary data assessed by two 24 h dietary recalls, a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) were created based on 15 food groups and were assessed for their relationships with mortality risk. Results : Over a median follow-up of 7.2 years, there were 1021 deaths in diabetes and 896 deaths in prediabetes. A higher hPDI (highest vs. lowest quartile) was associated with a 41% (HR = 0.59, 95% CI: 0.49-0.72; P -trend < 0.001) lower risk of all-cause mortality in diabetes and a 31% (HR = 0.69, 95% CI: 0.55-0.85; P -trend < 0.001) lower risk in prediabetes. A higher uPDI was associated with an 88% (HR = 1.88, 95% CI: 1.55-2.28; P -trend < 0.001) higher risk of mortality in diabetes and a 63% (HR = 1.63, 95% CI: 1.33-1.99; P -trend < 0.001) higher risk in prediabetes. Mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.0% to 10.9% of the relationships between hPDI or uPDI and all-cause mortality among participants with diabetes. Conclusions : For adults with diabetes as well as those with prediabetes, adhering to a plant-based diet rich in healthier plant foods is associated with a lower mortality risk, whereas a diet that incorporates less healthy plant foods is associated with a higher mortality risk.

Objective: To identify the clinical characteristics of fractured hinges after open-door cervical laminoplasty for cervical canal stenosis and explore the relationship between hinge fractures and axial symptoms., Methods: This was a retrospective study of patients with cervical myelopathy who underwent open-door laminoplasty between November 2014 and November 2016 at the Affiliated Hospital of Qingdao University. Cervical CT scans were performed after surgery and the Takeuchi criteria were applied to evaluate the postoperative axial symptoms., Results: Of 223 opened laminae in 67 patients, 67 laminae (30.0%) in 30 patients (44.8%) showed fracture. The frequency of hinge fractures was higher at C6 (53.7%). Forty-nine fractured laminae (73.13%) were non-displaced and 18 were displaced. At 3 months, 33 fractured laminae (49.3%) showed bony union on CT, and union rates were 86.6% and 91.0% at 6 and 12 months, respectively, indicating that the union rate was lower for displaced fractures than for non-displaced fractures. Among the 67 patients, 14 had axial symptoms: three of 37 (8.1%) patients without hinge fractures and 11 of 30 (36.7%) patients with hinge fractures. One year later, the hinge fractures were healed in 24/30 patients. Among the six unhealed patients, five still suffered from axial symptoms. The frequency of axial symptoms was higher in the patients with three or more hinge fractures (66.7%) than in the patients with only one (16.7%) or two (46.7%) hinge fractures., Conclusions: Patients with hinge fractures may have an increased risk for axial symptoms after open-door cervical laminoplasty. The frequency of axial symptoms decreases with fracture healing.

Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignant tumors, and the mechanisms underlying the anti-ferroptosis of esophageal cancer cells are still largely unclear. This study aims to explore the roles of amplified protein kinase C iota (PKCiota) in the ferroptosis of ESCC cells. Cell viability, colony formation, MDA assay, Western blotting, co-IP, PLA, and RNA-seq technologies are used to reveal the roles and mechanisms underlying the PKCiota-induced resistance of ESCC cells to ferroptosis. We showed here that PKCiota was amplified and overexpressed in ESCC and decreased during RSL3-induced ferroptosis of ESCC cells. PKCiota interacted with GPX4 and the deubiquitinase USP14 and improved the protein stability of GPX4 by suppressing the USP14-mediated autophagy-lysosomal degradation pathway. PKCiota was negatively regulated by miR-145-5p, which decreased in esophageal cancer, and also regulated by USP14 and GPX4 by a positive feedback loop. PKCiota silencing and miR-145-5p overexpression suppressed tumor growth of ESCC cells in vivo, respectively; even a combination of silencing PKCiota and RSL3 treatment showed more vital suppressive roles on tumor growth than silencing PKCiota alone. Both PKCiota silencing and miR-145-5p overexpression sensitized ESCC cells to RSL3-induced ferroptosis. These results unveiled that amplified and overexpressed PKCiota induced the resistance of ESCC cells to ferroptosis by suppressing the USP14-mediated autophagic degradation of GPX4. Patients with PKCiota/USP14/GPX4 pathway activation might be sensitive to GPX4-targeted ferroptosis-based therapy.

Background: Wide phthalate exposure has been associated with both declines in renal function and an elevated risk of mortality. Whether phthalate-associated risk of premature mortality differs by renal function status remains unclear., Methods: This study included 9605 adults from the U.S. National Health and Nutrition Examination Survey. Urinary concentrations of 11 phthalate metabolites were assessed using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. According to estimated glomerular filtration rate (eGFR), participants were grouped as having normal or modestly declined renal functions, or chronic kidney disease (CKD). Multivariable Cox regression models estimated all-cause mortality associated with phthalate exposure, overall and by renal function status., Results: Overall, Mono-n-butyl phthalate (MnBP), Mono-benzyl phthalate (MBzP), Mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and Mono-(2-ethyl-5-carbox-ypentyl) phthalate (MECPP) were associated with an elevated risk of mortality (P-trend across tertile <0.05). Moreover, significant interactions were observed between eGFR and MEHHP, MEOHP, MECPP, DEHP in the whole population (P for interactions <0.05). After stratification by renal function, total Di (2-ethylhexyl) phthalate (DEHP) was additionally found to be associated with mortality risk in the CKD group (HR = 1.12; 95% CI: 1.01, 1.25). Co-exposure to the 11 phthalate metabolites was associated with a higher risk of all-cause mortality in the CKD (HR = 1.47; 95% CI: 1.18, 1.84) and modestly declined renal function group (HR = 1.25; 95% CI: 1.09, 1.44)., Conclusions: The associations between phthalate exposure and risk of all-cause mortality were primarily observed in CKD patients, reinforcing the need for monitoring phthalate exposure in this patient population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The standardization of quantification data is critical for ensuring the reliability and measurement traceability in the screening of neonatal inherited metabolic disorders. However, the availability of national certified reference materials is limited in China., Methods: In this study, we developed a series of dried blood spot (DBS) reference materials containing 9 amino acids (AA) and 10 acylcarnitines (AC) for neonatal screening. Four levels of the reference materials were measured with tandem mass spectrometry (MS/MS) by seven laboratories using different commercial In Vitro Diagnostic Device (IVD) kits. Then, 100 clinical samples were measured using both derivatization and non-derivatization methods by the same laboratory., Results: We found high homogeneity and stability at all levels of the reference materials, with the coefficient of variation (CV) of the analytes less than 15%. These reference materials can be used to assess the testing capabilities of different laboratories. Our test also revealed that the correction factors (CF) calculated by the reference materials, along with clinical samples, could increase the consistency for different kits., Conclusion: The DBS reference materials proposed in this study provide reliability for the harmonization in multi-center analysis for the screening of neonatal inherited metabolic disorders. And applying our correction method for the screening could improve the data consistency of the DBS samples prepared by different methods., (© 2023 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Ferroptosis is defined as an iron-dependent non-apoptotic form of programmed cell death. Dihydroorotate dehydrogenase (DHODH) is a newly discovered anti-ferroptosis molecule independent from the well-known GPX4 and AIFM2. However, the expression pattern and especially the functional roles of DHODH during cancer cell death are generally unknown., Methods: The databases of Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, and Tumor Immune Estimation Resource (TIMER), and methods of colony formation, Cell Counting Kit-8 (CCK-8), adenosine triphosphate (ATP) detection, RNA-seq, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blotting were used to analyze the expression level, prognostic role, and oncogenic roles of DHODH in cancers., Results: DHODH overexpression was identified in many types of cancers including esophageal carcinoma (ESCA), colon adenocarcinoma (COAD), rectum adenocarcinoma (READ), and so on. Silence and inactivation of DHODH decreased the abilities of cell proliferation, colony formation, and cellular ATP levels both in esophageal squamous cell carcinoma (ESCC) and colorectal cancer (CRC) cells. Z-VAD-FMK (an apoptosis inhibitor) partially rescued blockade of DHODH-induced death of ESCC cells, and ferroptosis inhibitors (ferrostatin-1 and liproxstatin-1) together with the necroptosis inhibitor (necrostatin-1) partially rescued inhibition of DHODH-induced death of CRC cells, respectively. Pathways including rheumatoid arthritis, salmonella infection, cytokine-cytokine receptor interaction, pertussis, and nuclear factor-κB (NF-κB) were enriched in DHODH-silenced ESCC cells., Conclusions: Overexpression of DHODH augments cell proliferation and suppresses cell death in ESCC and CRC, and DHODH might be developed as a potential anticancer target., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-136/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

Green innovation is currently recognized as a critical aspect for organizations to create economic value while contributing to ecological sustainability. Using the rationale of upper echelons theory, the present study introduces CEO narcissism, an important but underexplored psychological trait, and dynamic capability to probe the mechanisms driving green innovation. The regression findings show that enterprises with narcissistic CEOs do better in terms of green innovation. According to the mediation study findings, dynamic capability mediates between the CEO narcissism and corporate green innovation. In addition, the examination of mediated moderation reveals that top management risk aversion could negatively moderate this mediation effect. Such observations not only show that the CEO's personality has the potential to enhance corporate green achievements, but also discover the underlying mechanism which would provide guidance to help firms to be green., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Rheumatoid arthritis (RA) causes irreversible joint damage, but the pathogenesis is unknown. Therefore, it is crucial to identify diagnostic biomarkers of RA metabolism-related genes (MRGs). This study obtained transcriptome data from healthy individuals (HC) and RA patients from the GEO database. Weighted gene correlation network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), and random forest (RF) algorithms were adopted to identify the diagnostic feature biomarker for RA. In addition, biomarkers were verified by qRT-PCR and Western blot analysis. We established a mouse model of collagen-induced arthritis (CIA), which was confirmed by HE staining and bone structure micro-CT analysis, and then further verified the biomarkers by immunofluorescence. In vitro NMR analysis was used to analyze and identify possible metabolites. The correlation of diagnostic feature biomarkers and immune cells was performed using the Spearman-rank correlation algorithm. In this study, a total of 434 DE-MRGs were identified. GO and KEGG enrichment analysis indicated that the DE-MRGs were significantly enriched in small molecules, catabolic process, purine metabolism, carbon metabolism, and inositol phosphate metabolism. AKR1C3, MCEE, POLE4, and PFKM were identified through WGCNA, LASSO, and RF algorithms. The nomogram result should have a significant diagnostic capacity of four biomarkers in RA. Immune infiltration landscape analysis revealed a significant difference in immune cells between HC and RA groups. Our findings suggest that AKR1C3, MCEE, POLE4, and PFKM were identified as potential diagnostic feature biomarkers associated with RA's immune cell infiltrations, providing a new perspective for future research and clinical management of RA.

Background and Objective: In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC)., Material and Methods: Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People's Hospital [N = 150]) recruited 1376 patients with LA-NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S-1. Multivariate Cox regression was used to confirm optimal predictors of progression-free survival (PFS), and a nomogram was established to identify patients into low-risk and high-risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram., Results: After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high-risk cohort had greatly worse 5-year DMFS, LRFS, PFS and OS compared to low-risk cohort (all p < 0.05), and subgroup analysis found that the 5-year DMFS, PFS and OS of patients treated with IC+CCRT+AC/MC were better than those treated with IC+CCRT in high-risk cohort (all p < 0.05). Notably, the incidence of adverse effects for IC+CCRT+AC cohort was higher than that for IC+CCRT+MC cohort, especially leukocytopenia and neutropenia. IC+CCRT and IC+CCRT+MC were associated with similar incidences of adverse effects., Conclusions: The addition of AC or MC to IC+CCRT could improve the DMFS of patients with high-risk NPC and prolong their survival. Additionally, our findings suggest a potential role of AC/MC following IC plus CCRT in the treatment of high-risk LA-NPC., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: It is well established that discogenic low back pain (DLBP) is often caused by the inflammatory response during intervertebral disc degeneration (IDD). However, it remains unclear how inflammatory mediators such as Interleukin-6 (IL-6) are involved in discogenic pain caused by degeneration and intervertebral disc (IVD) metabolism. The purpose of this study is to study the relationship between IL-6 and Transmembrane protein 100 (TMEM100), and to analyze the different metabolites and metabolic pathways in various rat intervertebral discs by metabonomics., Methods: We established a rat model of IDD-DLBP by disc punctures and PBS infusion to examine the rat pain behaviors. Intervertebral disc tissues were harvested for molecular biology experiments to explore the relationship between IL-6 and TMEM100. High-resolution mass spectrometry (HRMS) was performed for untargeted metabolomics, and nuclear magnetic resonance spectroscopy metabolomics (MRS) for differential metabolites and metabolic pathways., Results: The results showed a significant decrease in vonFrey test, hot plate test and acetone test (P < 0.05). The expression of IL-6 and TMEM100 in DLBP model was significantly higher than that in sham control group and IDD discs without PBS infusion group (P < 0.05). There were 15 major contributing metabolites identified in the DLBP intervertebral discs through metabolomic studies, involving 6 major metabolic pathways. The main differential metabolites included nitric oxide (NO), ammonia, and lactic acid as the metabolic endpoints; and the differential metabolic pathways included the glycine-serine-threonine (Gly-Ser-Thr), which is gradually weakened with the progression of inflammation., Conclusion: The change of TMEM100 expression mediated by il-6 is related to the Gly-Ser-Thr metabolic axis and plays an important role in the relief of discogenic pain., Competing Interests: The authors declare no potential conflicts of interest., (© 2023 Guo et al.)

Mounting evidence has demonstrated that fatty acid binding protein 5 (FABP5) is commonly upregulated in many human malignancies. However, the mechanisms explaining the involvement of FABP5 in hepatocellular carcinoma (HCC) remain unclear. In this study, we demonstrated the involvement of FABP5 and its downstream signaling molecules in HCC progression. We first confirmed that FABP5 expression was upregulated in HCC. Additionally, FABP5 promoted HCC cells proliferation, migration, and invasion. Mechanistic investigation showed that FABP5 could improve cAMP-response element binding protein (CREB) phosphorylation. Meanwhile, CREB, as a transcription factor, upregulated the miR-889-5p expression by binding to the miR-889-5p promoter region. Consequently, miR-889-5p led to downregulation of Krüppel-like factor 9 (KLF9) by binding to the 3'-UTR of the KLF9 mRNA, potentiating the PI3K/AKT signaling pathway and promoting the proliferation, migration, and invasion of HCC cells. Our findings have identified a FABP5/CREB/miR-889-5p/KLF9 axis for HCC progression, and we postulate that blocking this key signaling pathway may represent a promising strategy for HCC treatment.

Introduction: Recently, large channel endoscopic systems and full endoscopic visualization technique have been used to perform unilateral laminotomy for bilateral decompression (ULBD) treatment for lumbar central spinal stenosis (LCSS). However, various endoscopic systems possess different design parameters, which may affect the technical points and treatment outcomes. The object of this retrospective study was to compare the efficiency, safety, and effectiveness of ULBD under the iLESSYS Delta system versus the Endo-Surgi Plus system., Methods: In the period from October 2020 to April 2021, ULBD was performed using the iLESSYS Delta system or Endo-Surgi Plus system to treat LCSS. Patients were classified into two groups based on the endoscopy system employed. Patient demographics, perioperative indexes, complications, and imaging characteristics were reviewed. Clinical outcomes were quantified using back and leg visual analog scale (VAS) scores and Oswestry Disability Index (ODI) at the time points of follow-up., Results: Thirty-two patients were assigned to the iLESSYS Delta system group and 37 to the Endo-Surgi Plus system group. In the comparison between the two groups, the Endo-Surgi Plus system possessed a shorter incision length and operation time (p < 0.005), and no statistical differences in other aspects were observed. The dural sacs of both groups were significantly expanded postoperatively compared to preoperatively (p < 0.001). Both groups experienced improvements in VAS and ODI scores at all time points (p < 0.001) and equally low frequency of complications., Conclusions: Current research suggests that both the Endo-Surgi Plus system and iLESSYS Delta system achieved favorable high safety and clinical outcomes in ULBD for treatment of LCSS. The use of a fully visualized trephine may have increased the efficiency of the Endo-Surgi Plus system. Moreover, the Endo-Surgi Plus system may be associated with a wider decompression range and indications., (© 2022. The Author(s).)

Objective: This study aimed to explore the clinical value of adjuvant chemotherapy (ACT) following concurrent chemo-radiotherapy (CCRT) and induction chemotherapy (ICT) in loco-regionally advanced nasopharyngeal carcinoma (LANC)., Methods: We included 839 newly diagnosed LANC patients in this study. ICT plus CCRT (ICT + CCRT group) was administered to 443 patients, and 396 patients received ACT after ICT plus CCRT (ICT + CCRT + ACT group). Univariate and multivariate Cox regression analyses were carried out. Furthermore, propensity score matching (PSM) was applied to balance the study and control groups., Results: A total of 373 pairs of LANC patients were obtained after PSM analysis. We found that ACT following ICT + CCRT has no significant effect on improving the survival of LANC patients. By further exploring the ICT + CCRT + ACT treatment protocol, we excluded N0-1-positive patients and re-performed PSM in the ICT + CCRT and ICT + CCRT + ACT groups. Each group consisted of 237 patients. Kaplan-Meier analysis revealed that there were differences between the ICT + CCRT and ICT + CCRT + ACT groups in terms of the 5-year overall survival (OS) (78.9% vs. 85.0%, P = 0.034), disease-free survival (DFS) (73.4% vs. 81.7%, P = 0.029), and distant metastasis-free survival (DMFS) (84.9% vs. 76.0%, P = 0.019). In addition, the ICT + CCRT + ACT group had a higher incidence of grade 3/4 acute leukocytopenia/neutropenia., Conclusion: Compared with ICT + CCRT, ACT following ICT plus CCRT can reduce distant metastasis of N2-3-positive LANC and improve the OS and DFS. The results demonstrated the feasibility and clinical utility of ACT following ICT plus CCRT., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Increasing contamination risk from oil/organic liquid leakage creates strong demand for the development of absorbents with excellent hydrophobicity and absorption capacity. Herein, bagasse was carbonized to form porous char with a special structure of array-style and vertically perforated channels, and then the activation process enlarged the pore volume of the char. With the cooperation of low-surface-energy polydimethylsiloxane and diatomaceous earth particles, the modified activated carbon aerogel (MACA) was fabricated by modifying the surface coating and mastoid structure on the bagasse char. Moreover, the MACA demonstrates high porosity oil-water separation, hydrophobicity, and considerable absorption capacity (4.06-12.31 g / g ) for gasoline and various organic solvents. This work converts agricultural waste into an efficient porous adsorbent, offering a scalable and commercially feasible solution to solving the leakages of oil/organic solvents.

Purpose: To investigate whether the addition of fluorouracil to docetaxel and cisplatin induction chemotherapy (IC) can truly improve the prognosis of patients with locoregionally advanced nasopharyngeal carcinoma (NPC)., Methods: A total of 801 patients newly diagnosed with non-metastatic locoregionally advanced NPC were included as the subjects. In this study, propensity score matching (PSM) was used for analysis of overall survival (OS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and locoregional relapse-free survival (LRRFS), and the chi-squared test or Fisher's exact test was used to investigate toxic reactions., Results: Patients received treatment with docetaxel and cisplatin (TP) or docetaxel, cisplatin and fluorouracil (TPF). With a median follow-up time of 60 months (range: 5-124 months), the TPF group had better 5-year OS (84.7% vs 79.0%; P = 0.037), PFS (84.6% vs 76.8%; P = 0.008) and DMFS (89.5% vs 82.3%; P = 0.004) than the TP group. After PSM, 258 patients were matched in each cohort. The Kaplan-Meier analysis showed that the 5-year OS, PFS and DMFS were 85.5%, 84.2% and 89.2%, respectively, in the TPF group, higher than the 80.8%, 75.0% and 81.4%, respectively, in the TP group (P = 0.048, 0.009 and 0.006, respectively). Moreover, the multivariate analysis revealed that different IC regimens were independent prognostic factors for PFS and DMFS (P = 0.014 and 0.010, respectively)., Conclusion: This study found that compared with the TP regimen, TPF induction chemotherapy is associated with improved survival in patients with locoregionally advanced NPC. TPF can produce more mucosal and nausea/vomiting adverse reactions than TP., (© 2021 The Authors. Asia-Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and apoptosis inducing factor mitochondria associated 2 (AIFM2) are the key regulators in ferroptosis. However, the expression patterns and prognostic roles of these genes in pan-cancer are still largely unclear. The expression patterns and prognostic roles of SLC7A11, GPX4, and AIFM2 and the relationships between the expression levels of these genes and immune infiltration levels in pan-cancer were analyzed by using TIMER, gene expression profiling interactive analysis (GEPIA), Oncomine, and Kaplan-Meier databases. Our results showed that both SLC7A11 and GPX4 were overexpressed in colorectal cancer, and SLC7A11 was overexpressed in lung cancer. High levels of SLC7A11 and AIFM2 were significantly linked with the shortened disease-free survival and overall survival (OS) in adrenocortical carcinoma (ACC), respectively. And high expression of SLC7A11, GPX4, and AIFM2 were significantly correlated with the shortened OS of acute myeloid leukemia patients. In esophageal carcinoma (ESCA), GPX4 expression was significantly associated with the infiltration of macrophage and myeloid dendritic cell, and AIFM2 expression was significantly associated with the infiltration of CD4 + T cell. Importantly, GPX4 expression was positively correlated with the expression levels of monocyte markers (CD14 and CD115) and M2 macrophage markers (VSIG4 and MS4A4A) both in ESCA and in head and neck squamous cell carcinoma (HNSC). In summary, SLC7A11, GPX4, and AIFM2 are dysregulated in many types of cancers, and are candidate prognostic biomarkers for many types of cancers, and can be used to evaluate the infiltration of immune cells in tumor tissues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shi, Tao, Fan, Song and Bai.)

Background: Surgery is often indicated for patients with massively prolapsed intervertebral disc herniation. The interlaminar endoscopic spine system (iLESSYS) Delta 6-mm working channel endoscope has advantages over other systems. The aim of this study was to explore the benefits and complications of using the iLESSYS Delta for the treatment of massively prolapsed intervertebral disc herniation., Aim: To explore the clinical benefits of treating massively prolapsed lumbar intervertebral disc herniation with the iLESSYS Delta endoscope., Methods: In this study, the data of 37 patients who underwent surgery with the iLESSYS Delta endoscope at The Affiliated Hospital of Qingdao University were retrospectively analyzed. Intraoperative blood loss, operation time, and complications were collected. The visual analog scale (VAS), oswestry disability index (ODI), and modified MacNab criteria were determined before and at 1 d, 3 mo, and 6 mo after surgery., Results: The mean intraoperative blood loss was 20.4 ± 1.2 mL. The mean operation time was 97.3 ± 12.4 min. The VAS scores for leg and back pain decreased from 68.0 ± 7.3, 34.4 ± 8.5 before operation to 2.5 ± 1.7, 5.5 ± 1.9 at 6 mo after surgery, respectively. The ODI also decreased from 60.2 ± 7.3 to 17.9 ± 3.4 at 6 mo after surgery. The improvement rate of the MacNab score was 86.4%, which was considered excellent. No spinal dural injury, nerve root injury, secondary protrusion of intervertebral disc, or myeloid hypertension was found during follow-up., Conclusion: The iLESSYS Delta 6-mm working channel endoscope has several advantages in terms of clinical and functional benefits, complications, and low risk of residual vertebral pulp in treating patients with massively prolapsed intervertebral disc herniation., Competing Interests: Conflict-of-interest statement: The authors of this work have nothing to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective : To investigate the clinical value of induction chemotherapy (IC) with docetaxel plus cisplatin (TP) followed by concurrent chemoradiotherapy (CCRT) with TP in locoregionally advanced nasopharyngeal carcinoma (NPC). Methods : A total of 544 patients with locoregionally advanced NPC that was newly diagnosed from January 2009 to December 2015 were included in this study. Among these patients, 251 were treated with TP induction chemotherapy followed by CCRT with cisplatin (DDP) alone (TP + DDP group), 167 were treated with TP followed by CCRT with TP (TP + TP group), and 126 were treated with docetaxel, DDP and fluorouracil (TPF) followed by CCRT with DDP alone (TPF + DDP group). Overall survival (OS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and locoregional relapse-free survival (LRRFS) were analyzed using the Kaplan-Meier method and a Cox proportional hazards model. Results : Survival analysis showed that the 5-year OS, PFS and DMFS rates in the TP + DDP group were significantly lower than those in the TP + TP group after propensity score matching (PSM). Multivariate analysis revealed that CCRT with TP was an independent prognostic factor for OS, PFS and DMFS. During CCRT, the incidence rates of grade 3/4 nausea/vomiting, oral mucositis, leukocytopenia and neutropenia were significantly increased in the TP + TP group compared with the TP + DDP group (all P < 0.05). To further explore the value of TP + TP, we performed PSM again with the TPF + DDP group. After PSM, there were 100 patients in each group. Survival analysis showed no significant differences in the 5-year OS, PFS, DMFS and LRRFS rates between the two groups. During IC and CCRT, the rate of grade 3/4 nausea/vomiting in the TPF + DDP group was higher than that in the TP+TP group (9.0% vs. 2.0%, P = 0.030; 18.0% vs. 8.0%, P = 0.036, respectively). No significant difference in the incidence of grade 3/4 hematologic toxicity was found between the two groups (all P > 0.05). Conclusion : TP + TP can reduce the distant metastasis of locoregionally advanced NPC and improve OS compared with TP + DDP; TP + TP has the same effect as TPF + DDP and is clinically feasible., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: Nasopharyngeal carcinoma (NPC) originates from the mucous epithelium of the nasopharynx. Although induction chemotherapy plus concurrent chemoradiotherapy is the major therapeutic protocol used for locally advanced NPC without metastasis, more research studies are needed to evaluate the curative effects. We aim to identify the therapeutic effects and prognosis after induction chemotherapy plus concurrent chemoradiotherapy in the treatment of locally advanced NPC under the intensity-modulated radiotherapy mode., Methods: The patients (N = 544) with locally advanced NPC (III and Iva, UICC 8th) after intensity-modulated radiotherapy with induction chemotherapy and concurrent chemoradiotherapy were included in this study. We analyzed the characteristics of patients including gender, age, smoking status, tumor node staging system, clinical stage, pathological type, the therapy protocol of induction chemotherapy and concurrent chemoradiotherapy, and chemotherapy prescription., Results: We have found the 5-year survival rates of overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 85.21%, 78.51%, 90.71%, and 85.21% in follow-up, and these data indicated that our therapeutic procedure provided beneficial effects on survival rates. Subsequently, the chemotherapy drug based on docetaxel (DOC) provided a more beneficial effect on survival rate compared with taxol (TXT) (all estimated HR >1; p = 0.005, 0.004, and <0.001 of OS, PFS, and DMFS), but there was no significant difference between chemotherapy drugs based on cisplatin (DDP) and nedaplatin (NDP) in treating NPC patients (p = 0.390, 0.549, 0.364, and 0.645 of OS, PFS, LRRFS, and DMFS). The therapeutic effects of induction chemotherapy revealed no difference between TPF and TP (T: DOC or TXT, P: DDP or NDP, and F: 5-fluorouracil) (p = 0.541, 0.897, 0.498, and 0.765 of OS, PFS, LRRFS, and DMFS). In addition, there was also no significant change between concurrent chemotherapy with TP dual drugs or a single platinum drug (being excluded in the multivariate model using forward [Wald] procedure). Moreover, the survival rate showed no difference between platinum accumulation dose of more or less than 150 mg/m2 for concurrent chemotherapy (being excluded in the multivariate model using forward [Wald] procedure)., Conclusion: Our results indicate that induction chemotherapy plus concurrent chemoradiotherapy under intensity-modulated radiotherapy which is the standard therapeutic method for locally advanced NPC provides beneficial therapeutic effects, and it is worthy of further study., (© 2021 S. Karger AG, Basel.)

Background: MNAT1 (menage a trois 1, MAT1), a cyclin-dependent kinase-activating kinase (CAK) complex, highly expressed in diverse cancers and was involved in cancer molecular pathogenesis. However, its deliverance profile and biological function in osteosarcoma (OS) remain unclear., Methods: The expression of MNAT1 in OS was detected by western blot (WB) and immunohistochemistry (IHC). The potential relationship between MNAT1 molecular level expression and OS clinical expectations were analyzed according to tissues microarray (TMA). Proliferation potential of OS cells was evaluated in vitro based on CCK8 and OS cells colony formation assays, while OS cells transwell and in situ tissue source wound healing assays were employed to analyze the OS cells invasion and migration ability in vitro. A nude mouse xenograft model was used to detect tumor growth in vivo. In addition, ordinary bioinformatics analysis and experimental correlation verification were performed to investigate the underlying regulation mechanism of OS by MNAT1., Results: In this research, we found and confirmed that MNAT1 was markedly over-expressed in OS tissue derived in situ, also, highly MNAT1 expression was closely associated with bad clinical expectations. Functional studies had shown that MNAT1 silencing could weaken the invasion, migration and proliferation of OS cells in vitro, and inhibit OS tumor growth in vivo. Mechanism study indicated that MNAT1 contributed to the progression of OS via the PI3K/Akt/mTOR pathway. We further verified that the MNAT1 was required in the regulation of OS chemo-sensitivity to cisplatin (DDP)., Conclusions: Taken together, the data of the present study demonstrate a novel molecular mechanism of MNAT1 involved in the formation of DDP resistance of OS cells.

Epigallocatechin gallate (EGCG), the most active monomer in green tea (GT), has demonstrated potential therapeutic and preventive effects on various tumors, including liver cancer. However, the anticancer mechanisms of EGCG in liver cancer remain to be elucidated. The abnormal expression of cell division cycle 25A (CDC25A) has been identified in liver cancer and is closely associated with malignancy and poor prognosis in patients with hepatocellular carcinoma (HCC). The present study used human hepatoma cell lines and rats with diethylnitrosamine (DEN)‑induced HCC as models to investigate the association between the effect of EGCG on liver cancer and regulation of the p21waf1/Cip1/CDC25A axis. The results demonstrated that EGCG can inhibit the proliferation of HepG2 and Huh7 cells, reduce the expression of CDC25A and increase the expression of p21waf1/Cip1 in HepG2. In vivo, HCC was induced by DEN in Sprague‑Dawley rats. EGCG significantly reduced tumor volume and improved the survival rates of rats with HCC. The expression levels of CDC25A mRNA and protein in liver tissues and the level of serum γ glutamyl transpeptidase in rats treated with EGCG were significantly decreased, while p21waf1/Cip1 mRNA and protein expression levels were increased compared with the HCC group, in the process of DEN‑induced HCC. No significant difference in the chemopreventive effects on liver cancer was observed between GT extract and EGCG under an EGCG equivalence condition. Thus, EGCG can suppress human hepatoma cell proliferation and prolong the survival of rats with HCC, and the potential mechanism may be involved in EGCG‑induced upregulation of p21waf1/Cip1 and downregulation of CDC25A.

Aims: This study aimed to investigate the clinical value of induction chemotherapy (IC) with docetaxel, 5-fluorouracil plus nedaplatin followed by concurrent chemoradiotherapy (CCRT) with nedaplatin for locoregional advanced nasopharyngeal carcinoma (NPC). Materials and Methods: In total, 269 patients diagnosed with locoregional advanced NPC between June 2012 and June 2017 were retrospectively included and divided into two groups: IC (docetaxel plus nedaplatin and 5-fluorouracil) followed by nedaplatin-based CCRT (TNF + N group, n = 146) and IC (docetaxel plus cisplatin and 5-fluorouracil) followed by cisplatin-based CCRT (TPF + P group, n = 123). The Kaplan-Meier method and Cox proportional hazards model were applied to analyse survival and prognosis. After propensity score-matched (PSM), 113 patients remained in each group. Toxicities were compared between the two groups using the Chi-square test or Fisher's exact test. Results: The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) rates of the TNF + N and TPF + P groups were 90.7% vs. 92.3% ( P = 0.315), 78.9% vs. 79.4% ( P = 0.715), 82.4% vs. 85.1% ( P = 0.441) and 96.1% vs. 93.3% ( P = 0.414), respectively, with no significant difference in 3-year survival outcome between the two groups, and this outcome was confirmed after using PSM analyses. In the PSM cohort, a significant higher frequency of grade 3/4 vomiting was observed in the TPF + P group compared to the TNF + N group (22.1% vs. 0%, P = 0.000). However, 15.9% of patients in the TNF + N group had grade 3/4 thrombocytopenia in comparison with 6.2% in the TPF + P group ( P = 0.020). Conclusions: The TNF regimen followed by CCRT with nedaplatin is an alternative treatment strategy to the standard TPF regimen followed by CCRT with cisplatin for patients with locoregional advanced NPC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background : There are limited studies on the medication regimen of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in China. This study compared the effectiveness of and adherence to two prophylactic HIV medication regimens, which provided evidence and guidance for the application and promotion of the PrEP strategy in the MSM population in China. Methods : We conducted an open, non-randomized, multicenter, parallel, controlled clinical intervention study in western China. Subjects were recruited by convenience sampling at research centers in Chongqing, Guangxi, Xinjiang and Sichuan, China from April 2013 to March 2015, and they were categorized into the daily PrEP, event-driven and blank control groups. Tenofovir disoproxil fumarate (TDF; 300 mg/dose) was administered to subjects in the daily PrEP and event-driven groups, and all subjects were followed up every 12 weeks for 96 weeks. Demographic, behavioral, psychological characteristics and AIDS-related attitudes were assessed using self-completed questionnaires. TDF serum concentrations in subjects in Chongqing and Sichuan were quantified after systematic sampling. Results : Of the 2422 enrolled MSM, 856 were eligible for statistical analysis (PrEP group: 385 and event-driven group: 471); 30 and 32 subjects in daily PrEP and event-driven groups, respectively, were HIV-positive; the incidence of HIV infection was as follows: daily PrEP group, 6.60 cases/100 person-years and event-driven group, 5.57 cases/100 person-years (relative risk (RR) 95% confidence interval (CI) was 0.844 (0.492-1.449)); HIV incidence did not differ significantly when stratified by medication adherence or sites. When the medication adherence rate was ≥80%, the median TDF serum concentrations were 0.458 mg/L, and 0.429 mg/L in the daily PrEP, and event-driven groups, respectively (not significant; p > 0.05); Subjects who were in the event-driven PrEP group (OR = 2.152, 95% CI: 1.566-2.957), had fewer male sexual partners in the last two weeks (OR = 0.685, 95% CI: 0.563-0.834), were one year older on average (OR = 1.022, 95% CI: 1.002-1.043), considered that medication kept them safe, were less worried about others knowing they took medicine and were more likely to have high adherence. Conclusions : The efficacies of daily TDF and event-driven TDF use were not significantly different in preventing new infections among HIV-negative MSM. Event-driven TDF use is economical and effective and is worth popularizing. Our results provide evidence for the application and promotion of the PrEP strategy in the MSM population in China.

Background: For coronal shear fractures of humeral capitellum, the lateral approach is the most commonly used surgical approach. However, exposure range of the anterior aspect of the distal humerus is inadequate. The anterolateral approach has also been adopted to overcome this disadvantage. However, this approach seems anatomically complex due to the risk of iatrogenic injury to the radial nerve. So far, the optimal approach for the treatment of capitellar shear fractures remains inconclusive. The purpose of this study is to prospectively review and compare the early clinical and radiographic outcomes of treated with open reduction and Herbert screw internal fixation through the lateral approach or the anterolateral approach., Methods: Twenty-six patients with isolated capitellar shear fractures were enrolled from January 2013 to December 2017, and randomly assigned to lateral approach group or anterolateral approach group. All the fractures were treated with open reduction and Herbert screw internal fixation through lateral approach or anterolateral approach. Operation time, wound healing complication, elbow joint function, and radiographic evidence were evaluated and compared between two groups., Results: The operation via the anterolateral approach took significantly shorter time than via lateral approach (p < 0.05). There were no wound healing problems and infection for both groups. One patient from anterolateral approach group sustained incomplete posterior interosseous nerve palsy, which recovered completely in 4 weeks without residual compromise. All fractures healed well in their normal anatomic position as seen on radiographs. At the final follow-up, no significant difference was found between two groups with respect to the ROM in supination-pronation, ROM in pronation-supination, loss of flexion-extension motion, or loss of pronation-supination motion (p > 0.05). There is no significant difference with respect to MEPI score of elbow joint between two groups (p > 0.05)., Conclusion: Based on our findings, both lateral approach and anterolateral approach with Herbert screw internal fixation are suitable for coronal shear fractures of capitellum with satisfactory early outcomes. Compared with the lateral approach, the anterolateral approach made the surgical procedure easier and time saving in current series. When the medial aspect of the trochlea is involved for capitellar coronal fractures, the anterolateral lateral approach should be preferred.

Several genetic tools have been developed for use in Bacillus anthracis, but there is still a need for a more marker-free gene inactivation protocols. Thus, we report a method to generate unmarked mutations in B. anthracis. This approach was based on the counter-selectable pheS* gene with assistance by the I-SceI homing endonuclease. Using this strategy, the NprR gene, a transcriptional activator of B. anthracis, was deleted at an extremely high efficiency. Our study indicates that mutated pheS is a useful counter-selective marker to design a valuable genetic tool for in-frame and unmarked gene deletions of B. anthracis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The aim of this paper is to investigate the effect of patchouli alcohol in enhancing Helicobater pylori's action in eradicating macrophages and its mechanism. H. pylori was co-cultured with macrophages at a ratio of MOI=100 in different concentrations of patchouli alcohol. The effect of patchouli alcohol in eradicating macrophages was detected by agar dilution method. The effect of patchouli alcohol on NO and myeloperoxidase (MPO) levels in macrophages were measured by H. pylori by biochemical methods. Patchouli alcohol effect on H. pylori-induced pro-inflammatory gene expression and protein secretion in macrophages were detected by RT-qPCR and ELISA method. The eradication of H. pylori has significantly enhanced, and the destabilization of lysosomes has been reversed. Meanwhile, patchouli alcohol has an effect in inhibiting pro-inflammation and oxidation. The mechanism of patchouli alcohol in eradicating H. pylori and resisting oxidative stress may be associated to the blocking of bacteria escape lysosome combination procedures., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Background: Due to the intraarticular and complex nature of the coronal shear fracture of the humeral capitellum and its rarity, it has been difficult to formulate a universally accepted method of surgical management. The purpose of this study is to retrospectively evaluate the clinical outcomes of 15 patients with isolated coronal shear fractures of the capitellum treated by Herbert screw fixation through anterolateral approach, and to address the safety and tips for this surgical procedure., Methods: This retrospective study included 15 isolated coronal shear fractures of the capitellum without posterior involvement, which were classified according to the Dubberley classification as 11 type 1A fractures and 4 type 3A fractures. All fractures were treated with Herbert screws fixation via the anterolateral approach. Clinical and radiographic evaluation was performed regularly, with a mean follow-up of 29 months., Results: The mean operative time was 81 min. There were no wound healing problems or infection. One incomplete posterior interosseous nerve injury occurred, which recovered soon without residual compromise. All fractures healed well. At the final follow-up, the average range of motion was 134°in flexion-extension and 172°in supination-pronation. There was no significant difference between the affected and the unaffected elbows with regard to motion in flexion-extension or flexion-extension. The average Mayo Elbow Performance Index Score was 93 with 11 excellent and 4 good. No evidence of avascular necrosis, posttraumatic osteoarthritis, or heterotrophic ossification was found., Conclusion: Open reduction and internal fixation using Herbert screws through a anterolateral approach is a reliable and effective treatment for coronal shear fractures of capitellum, and able to achieve stable fixation and restoration of a functional range of motion.

The Grainyhead-like 3 (GRHL3) is involved in epidermal barrier formation, neural tube closure and wound repair. Previous studies have suggested that GRHL3 has been linked to many different types of cancers. However, to date, its effects on human colorectal cancer (CRC) has not been clarified yet. Our microarray analysis has indicated predominant GRHL3 expression in CRC. The purpose of this study was to investigate the expression and significance of GRHL3 in CRC tumorigenesis using CRC tissues and paired paracancerous tissues, as well as using distinct CRC cell lines (HT29 and DLD1). We observed increased GRHL3 expression at both mRNA and protein levels in CRC tissues and CRC cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Moreover, silencing GRHL3 with siRNA could suppress CRC cell proliferation, viability and migration in vitro. We also found that knockdown of GRHL3 could promote cell cycle arrest at G 0 /G 1 phase in HT29 cells and DLD1 cells, and induce cell apoptosis in HT29 cells. Together, our study revealed the down-regulation of GRHL3 in vitro could inhibit CRC cell activity and trigger cell cycle arrest at G 0 /G 1 phase and apoptosis.

Background: The purpose of the study is to investigate whether autologous platelet-rich plasma (PRP) can serve as bone-inducing factors to provide osteoinduction and improve bone regeneration for tissue-engineered bones fabricated with bone marrow mesenchymal stem cells (MSCs) and beta-tricalcium phosphate (β-TCP) ceramics. The current study will give more insight into the contradictory osteogenic capacity of PRP., Methods: The concentration of platelets, platelet-derived growth factor-AB (PDGF-AB), and transforming growth factor-β1 (TGF-β1) were measured in PRP and whole blood. Tissue-engineered bones using MSCs on β-TCP scaffolds in combination with autologous PRP were fabricated (PRP group). Controls were established without the use of autologous PRP (non-PRP group). In vitro, the proliferation and osteogenic differentiation of MSCs on fabricated constructs from six rabbits were evaluated with MTT assay, alkaline phosphatase (ALP) activity, and osteocalcin (OC) content measurement after 1, 7, and 14 days of culture. For in vivo study, the segmental defects of radial diaphyses of 12 rabbits from each group were repaired by fabricated constructs. Bone-forming capacity of the implanted constructs was determined by radiographic and histological analysis at 4 and 8 weeks postoperatively., Results: PRP produced significantly higher concentration of platelets, PDGF-AB, and TGF-β1 than whole blood. In vitro study, MTT assay demonstrated that the MSCs in the presence of autologous PRP exhibited excellent proliferation at each time point. The results of osteogenic capacity detection showed significantly higher levels of synthesis of ALP and OC by the MSCs in combination with autologous PRP after 7 and 14 days of culture. In vivo study, radiographic observation showed that the PRP group produced significantly higher score than the non-PRP group at each time point. For histological evaluation, significantly higher volume of regenerated bone was found in the PRP group when compared with the non-PRP group at each time point., Conclusions: Our study findings support the osteogenic capacity of autologous PRP. The results indicate that the use of autologous PRP is a simple and effective way to provide osteoinduction and improve bone regeneration for tissue-engineered bone reconstruction.

The presence of a septum in the first extensor compartment is closely associated with the pathophysiology of de Quervain disease, and affects the efficacy of corticosteroid injection and surgical release. This study aimed to examine the incidence and length of the first extensor compartment septum.Forty sides of the wrists in 20 cadavers were used. The presence of a septum in the first extensor compartment was examined. The septum length was recorded with the radial styloid process as the reference point.The anatomical variations of the first extensor compartment were classified into 3 types. Type I compartment was found in 7 sides in males (29.2%) versus 6 sides in females (37.5%, P = .733), type II was found in 6 sides in males (25%) versus 1 side in females (6.25%, P = .21), and type III was found in 11 sides in males (45.8%) versus 9 sides in females (56.25%, P = .56). There was no significant difference in the septum length between males and females (5.3 ± 2.3 vs 4.8 ± 1.1 mm, P = .54).The incidence of a septum in the first extensor compartment is approximately 50%. The mean septum length is 5 mm. Injection at 5 mm proximal to the radial styloid process has a great chance of delivering the steroids into both subcompartments. Exposure to 5 mm proximal to the radial styloid process can avoid the overlook of subcompartment and achieve adequate decompression of the first extensor compartment.

Anaberrant Wnt/β-catenin signaling pathway is frequently implicated in tumorigenesis. However, whether the Wnt/β‑catenin pathway plays a role in resistance to antitumor chemotherapy drugs remains unknown. In the present study, the process of autophagy was assessed following overexpression of the autophagy‑associated gene Beclin 1 in gemcitabine‑induced MG63 human osteosarcoma cells. Autophagy‑associated gene expression was measured following activation or inhibition of the Wnt/β‑catenin pathway in gemcitabine‑induced MG63 cells using reverse transcription‑quantitative polymerase chain reaction. In addition, the percentage of MG63 cell apoptosis was measured by flow cytometry following Wnt/β‑catenin pathway activation or inhibition. The results demonstrated that Beclin 1 overexpression induced autophagy and reduced gemcitabine‑induced apoptosis in MG63 human cell line. Furthermore, activation of the Wnt/β‑catenin signaling pathway attenuated autophagy and enhanced gemcitabine‑induced apoptosis. Additionally, the expression of Beclin 1 was reduced following Wnt/β‑catenin signaling pathway activation. The present study demonstrated that activation of the Wnt/β‑catenin signaling pathway may rescue chemotherapy drug resistance by downregulating the expression of Beclin 1.

The sialyl Lewis X (SLe x ) antigen encoded by the FUT7 gene is the ligand of endotheliam-selectin (E-selectin). The combination of SLe x antigen and E-selectin represents an important way for malignant tumor metastasis. In the present study, the effect of the SLe x -binding DNA aptamer on the adhesion and metastasis of hepatocellular carcinoma HepG2 cells in vitro was investigated. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining were conducted to detect the expression of FUT7 at both transcriptional and translational levels. The SLe x expression in HepG2 cells treated with different concentrations of SLe x -binding DNA aptamer was detected by flow cytometry. Besides, the adhesion, migration, and invasion of HepG2 cells were measured by cell adhesion assay, and the Transwell migration and invasion assay. The results showed that the FUT7 expression was up-regulated at both mRNA and protein levels in HepG2 cells. SLe x -binding DNA aptamer could significantly decrease the expression of SLe x in HepG2 cells. The cell adhesion assay revealed that the SLe x -binding DNA aptamer could effectively inhibit the interactions between E-selectin and SLe x in the HepG2 cells. Additionally, SLe x -binding DNA aptamers at 20 nmol/L were found to have the similar effect to the monoclonal antibody CSLEX-1. The Transwell migration and invasion assay revealed that the number of penetrating cells on the down-side of Transwell membrane was significantly less in cells treated with 5, 10, 20 nmol/L SLe x -binding DNA aptamer than those in the negative control group (P<0.01). Our study demonstrated that the SLe x -binding DNA aptamer could significantly inhibit the in vitro adhesion, migration, and invasion of HepG2 cells, suggesting that the SLe x -binding DNA aptamer may be used as a potential molecular targeted drug against metastatic hepatocellular carcinoma.

Aim: To study the impact on cleavage of tumor necrosis factor receptor-associated factor 1 (TRAF1) regulated by Helicobacter pylori ( H. pylori )., Methods: Cleavage of TRAF1 was detected by western blotting in the human gastric cancer cell line AGS following treatment with an apoptosis inducer. Cleavage of TRAF1 mediated by caspase was examined in vitro using specific caspase inhibitors. The effect of the COOH-terminal TRAF1 fragment on gastric cell apoptosis during H. pylori infection was measured using flow cytometry. The impact of H. pylori infection on TRAF1 cleavage was detected in the presence of apoptosis inducer. The roles of H. pylori virulence factors that may regulate TRAF1 cleavage were analyzed using isogenic cagA-, vacA- and cagE- null mutants., Results: TRAF1 was found to be cleaved in AGS cells treated with the apoptosis inducer, and caspase-8 was the major caspase involved in the cleavage of TRAF1. The COOH-terminal TRAF1 fragment significantly induced cell apoptosis ( P < 0.05) as well as promoted H. pylori -induced cell apoptosis ( P < 0.05). H. pylori infection was found to significantly inhibit the cleavage of TRAF1 and to inhibit the activation of caspase-8 in the presence of the apoptosis inducer at specific infection times and different cell/bacteria ratios. We also found that the effects of cagE- and cagA- null mutants on the inhibition of TRAF1 cleavage and activation of caspase-8 were significantly attenuated, compared with wild-type H. pylori , in the presence of the apoptosis inducer, showing that the virulence factor CagA was mainly involved in the inhibition of TRAF1 cleavage., Conclusion: H. pylori infection significantly inhibits the cleavage of TRAF1 via a CagA-dependent mechanism, which would increase the relative amounts of full-length TRAF1 and exert an antiapoptotic effect on H. pylori -infected cells., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest.

Background: Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a member of the TRAF family and is dysregulated in diseases, such as atheroma, lymphoma, and solid tumors, but the role of TRAF1 in gastric cancer remains unknown. This study was aimed to investigate the role of TRAF1 in Helicobacter pylori (H. pylori)-related cell apoptosis and gastric carcinogenesis., Materials and Methods: The mRNA and protein expression levels of TRAF1 were measured in a panel of gastric cancer cell lines and in H. pylori -infected mice by quantitative real-time PCR (qPCR) and Western blotting. The transcription factor that mainly affects transcription of TRAF1 during H. pylori infection was identified. The roles of H. pylori virulence factors that regulate TRAF1 expression were analyzed using isogenic cagA-, vacA-, and cagE-null mutants. The effects of TRAF1 on gastric cell viability and apoptosis during H. pylori infection were detected using the standard MTS (cell viability) assay and flow cytometry, respectively., Results: H. pylori infection induced TRAF1 overexpression in both gastric epithelial cells and mice. The expression of TRAF1 in response to H. pylori infection was majorly regulated by the activation of NF-κB and was strongly related to H. pylori virulence factor CagA. The upregulation of TRAF1 inhibited cell apoptosis and increased the viability of infected cells., Conclusions: H. pylori infection induces the overexpression of TRAF1 in gastric epithelial cells. The upregulation of TRAF1 plays an antiapoptotic role in H. pylori -infected gastric cells and may contribute to the gastric carcinogenesis., (© 2016 John Wiley & Sons Ltd.)

Allogeneic bone marrow mesenchymal stem cell (BMSC) transplantation has been investigated worldwide. However, few reports have addressed the survival status of human BMSCs in the intervertebral discs (IVDs) in vivo following transplantation. The current study aimed to observe the survival status of human BMSCs in rabbit IVDs. The IVDs of 15 New Zealand white rabbits were divided into three groups: Punctured blank control group (L1-2); punctured physiological saline control group (L2-3); and punctured human BMSCs transfected with green fluorescent protein (GFP) group (L3-4, L4-5 and L5-6). One, 2, 4, 6 and 8 weeks after transplantation the IVDs were removed and a fluorescence microscope was used to observe the density of GFP-positive human BMSCs. The results indicated that in the sections of specimens removed at 1, 2, 4, 6 and 8 weeks post-transplantation, no GFP-positive cells were observed in the control groups, whereas GFP-positive cells were apparent in the nucleus pulposus at all periods in the GFP-labeled human BMSCs group, and the cell density at 6 and 8 weeks was significantly less than that at 1, 2 and 4 weeks post-transplantation (P<0.001). Thus, it was identified that human BMSCs were able to survive in the rabbit IVDs for 8 weeks.

To investigate the surface display of the anthrax protective antigen (PA) on attenuated Bacillus anthracis, a recombinant B. anthracis strain, named AP429 was constructed by integrating into the chromosome a translational fusion harboring the DNA fragments encoding the cell wall-targeting domain of the S-layer protein EA1 and the anthrax PA. Crerecombinase action at the loxP sites excised the antibiotic marker. Western blot analysis, fluorescence-activated cell sorting and immunofluorescence analysis confirmed that PA was successfully expressed on the S-layer of the recombinant antibiotic marker-free strain. Notwithstanding extensive proteolytic degradation of the hybrid protein SLHs-PA, quantitative ELISA revealed that approximately 8.1 × 10(6) molecules of SLHs-PA were gained from each Bacillus cell. Moreover, electron microscopy assay indicated that the typical S-layer structures could be clearly observed from the recombinant strain micrographs.

Background: Epidural fibrosis (EF) is a common complication after laminectomy. Salvianolic acid B (Sal B) is a major bioactive component of a traditional Chinese medical agent, Salvia miltiorrhiza, which has shown anti-inflammatory, anti-fibrotic and anti-proliferative properties. The object of this study was to investigate the effect of Sal B on the prevention of epidural fibrosis in laminectomy rats., Methods: A controlled double-blinded study was conducted in sixty healthy adult Wistar rats that underwent laminectomy at the L1-L2 levels. The rats were randomly divided into 3 groups of 20: (1) Sal B treatment group; (2) Vehicle group; (3) Sham group (laminectomy without treatment). All rats were sacrificed 4 weeks post-operatively. The extent of epidural fibrosis, fibroblast proliferation and the expression of vascular endothelial growth factor (VEGF) and inflammatory factors were analyzed., Results: The recovery of all rats was uneventful. In the laminectomy sites treated with Sal B, the dura mater showed no adhesion. Collagen deposition was significantly lower in the Sal B group than the other two groups. In addition, both fibroblast and inflammatory cell counting in the laminectomy sites treated with Sal B showed better grades than the other two groups. The expression of VEGF and inflammatory factors in operative sites also suggested better results in the Sal B group than the other two groups., Conclusions: Sal B inhibits fibroblast proliferation, blood vessel regeneration, and inflammatory factor expression. Thus, Sal B is able to prevent epidural scar adhesion in post-laminectomy rats.

Background: The purpose of this study was to clarify the treatment value of zoledronic acid (ZA) and/or strontium-89 (Sr-89) in patients with non-small-cell lung cancer (NSCLC) with asymptomatic bone metastases (BMs)., Patients and Methods: Eligible patients were those with resectable NSCLC and asymptomatic BMs. These candidates were randomized into 4 groups: group A was treated with ZA and Sr-89 simultaneously, group B was treated with ZA, group C was treated with Sr-89, and group D was untreated. Patients were monitored and analyzed for the first skeletal-related event (SRE), overall survival (OS), and annual incidence of SREs., Results: One hundred eighty patients were enrolled. Time to first SRE in group A was 15 months (95% confidence interval [CI], 14.0-16.0 months), in group B it was 12 months (95% CI, 11.1-13.0 months), in group C it was 9 months (95% CI, 8.5-9.5 months), and in group D it was 8 months (95% CI, 7.1-8.9 months) (P = .000). The overall survival (OS) in group A was 17 months (95% CI, 16.0-18.1 months); in group B, it was 16 months (95% CI, 14.2-17.8 months); in group C, it was 12 months (95% CI, 11.1-12.9 months); and in group D, it was 12 months (95% CI, 10.8-13.2 months). The annual incidence of SREs in group A was 24.4%; in group B, it was 55.6%; in group C, it was 75.6%; in group D, it was 91.1% (P = .000)., Conclusions: Treatment with ZA and/or Sr-89 significantly extended the time to first SRE as well as survival time and reduced the annual incidence of SREs. Treatment with the combined use of ZA and Sr-89 was safe and well tolerated and achieved the best effect on asymptomatic BMs of NSCLC., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The treatment methods for the failed internal fixation in elderly patients suffering from several osteoporostic fractures are still inconclusive. We aimed to evaluate the clinical effects of endoprosthetic replacement for failure treatment of intertrochanteric fracture., Methodology: A total of 13 patients with failed internal fixation for intertrochanteric fracture were collected between January 2002 and October 2009. All of them were treated with endoprosthetic replacement and followed up till October 2010. Four of them received total hip replacement and the remained nine received artificial bipolar femoral head replacement. Clinical and functional outcomes of patients were assessed., Results: Of 13 patients, nine were females and four were males with the mean age of 76.5 years (SD, 11.7, range, 58-92 years) at the time of fracture. The average time of operation and follow-up was 124 minutes (89-187minutes) and 31 months (14-68 months), respectively. The average blood loss during the operation was 631 ml (450-1560 ml). All patients showed good pain relief and functional improvement. Final post-operative Harris and WOMAC scores were significantly improved from pre-operative levels (P<0.05). Only five patients showed operative complications., Conclusions: Our finding indicated that endoprosthetic replacement is an effective salvage procedure for failed internal fixation of intertrochanteric fracture in elderly patients with effective pain relief and functional improvement as well as few serious complications.

Objective: To establish a novel and useful rabbit model of lumbar disc degeneration using microinjection of fibronectin fragment (Fn-f)., Methods: Thirty-two New Zealand white rabbits underwent injection of N-terminal 30 kDa Fn-f (experimental group) or phosphate buffered saline (PBS) (control group) into the central region of L1-2, L2-3, L3-4, L4-5 discs using a 32-gauge microsyringe. Two rabbits (blank group) with no treatments were sacrificed to examine the proteoglycan synthesis of neucleus pulposus (NP) using (35)S-sulfate incorporation assay. At the 4-, 8-, 12-, and 16-week time points, the discs were examined histologically, radiographically, and with proteoglycan synthesis., Results: Histology demonstrated a progressive loss of the cell numbers in NP and architecture destruction in NP and anulus fibrosus (AF) in Fn-f-injected discs over the 16-week study period. The NP regions in Fn-f-injected discs shrinked distinctly after the 4-week time point, and were not discernible with the inner AF by the 16-week time point. Protoglycan synthesis in Fn-f-injected discs decreased progressively (F = 263.241, P = 0.000). At each time point, the Fn-f-injected discs showed significantly decreased proteoglycan synthesis compared with controls (t = -27.010 - -2.833, P < 0.05). The DHI% of the Fn-f-injected discs at the 4-, 8-, 12-, and 16-week time points were 96.5% ± 1.7%, 85.6% ± 3.8%, 77.2% ± 3.5% and 65.5% ± 5.6%, respectively. Comparing with the DHI% of PBS-injected discs (97.4% ± 1.2%), the Fn-f-injected discs exihibited no significant differences in disc heights at the 4-week time point (P > 0.05), but significant decreases in disc heights at the 8-, 12-, and 16-week time points (t = -21.225 - -10.795, P < 0.01). Apparent anterior osteophytes formed at the 12-week time point and enlarged remarkablely by the 16-week time point in the experimental spines., Conclusions: Fn-f can induce a progressively degenerative process in rabbit discs which is ethical, cost-effective, reproducible, and consistent with the spontaneous degeneration in human. And it seem to be a novel and useful model for the study of disc degeneration at the molecular level.

Bone marrow mesenchymal stem cells were isolated from New Zealand white rabbits, culture-expanded and differentiated into Schwann cell-like cells. Autologous platelet-rich plasma and Schwann cell-like cells were mixed in suspension at a density of 1 × 10(6) cells/mL, prior to introduction into a poly (lactic-co-glycolic acid) conduit. Fabricated tissue-engineered nerves were implanted into rabbits to bridge 10 mm sciatic nerve defects (platelet-rich plasma group). Controls were established using fibrin as the seeding matrix for Schwann cell-like cells at identical density to construct tissue-engineered nerves (fibrin group). Twelve weeks after implantation, toluidine blue staining and scanning electron microscopy were used to demonstrate an increase in the number of regenerating nerve fibers and thickness of the myelin sheath in the platelet-rich plasma group compared with the fibrin group. Fluoro-gold retrograde labeling revealed that the number of Fluoro-gold-positive neurons in the dorsal root ganglion and the spinal cord anterior horn was greater in the platelet-rich plasma group than in the fibrin group. Electrophysiological examination confirmed that compound muscle action potential and nerve conduction velocity were superior in the platelet-rich plasma group compared with the fibrin group. These results indicate that autologous platelet-rich plasma gel can effectively serve as a seeding matrix for Schwann cell-like cells to construct tissue-engineered nerves to promote peripheral nerve regeneration.

Aim: To investigate the association between the tag single nucleotide polymorphisms (TagSNPs) of NOD1 and NOD2 and the risk of developing gastric cancer., Methods: We conducted a hospital-based case-control study including 296 incident gastric cancer patients and 160 gastritis controls. Eight TagSNPs in the NOD1 and NOD2 genes were selected from the Hapmap database using the haploview software and genotyped by the Sequenom MassArray system. The serum levels of anti-Helicobacter pylori (H. pylori) IgG were measured by enzyme-linked immunosorbent assay to indicate H. pylori infection. The odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression, including sex and age as confounding factors., Results: The NOD1 rs2907749 GG genotype showed a decreased risk for gastric cancer (OR 0.50, 95% CI: 0.26-0.95, P = 0.04) while the rs7789045 TT genotype showed an increased risk (OR 2.14, 95% CI: 1.20-3.82, P = 0.01). An elevated susceptibility to gastric cancer was observed in the subjects with H. pylori infection and the NaOD1 rs7789045 TT genotype (OR 2.05, 95% CI: 1.07-3.94, P = 0.03) or the NOD2 rs7205423 GC genotype (OR 2.52, 95% CI: 1.05-6.04, P = 0.04). Haplotype analysis suggested that the distribution of AGT (rs2907749, rs2075820 and rs7789045) in NOD1 between the cases and control groups was significantly different (P corrected: 0.04), and the diplotype AGT/AGT was associated with an elevated gastric cancer risk (OR 1.98, 95% CI: 1.04-3.79, P = 0.04). The association of the NOD1 rs7789045 TT genotype and the diplotype AGT/AGT was significant with H. pylori-related diffuse-type gastric cancer (OR 3.00, 95% CI: 1.38-6.53, P = 0.01; OR 4.02, 95% CI: 1.61-10.05, P < 0.01, respectively)., Conclusion: Genetic polymorphisms in NOD1 and NOD2 may interact with H. pylori infection and may play important roles in promoting the development of gastric cancer in the Chinese population.

To identify linear B-cell epitopes of urease B (UreB), a series of 19 partially overlapping fragments of the UreB gene were expressed. Three MAbs against UreB of Helicobacter pylori (H. pylori), A1H10, A3C10, and B3D9, were tested for their reactivity to the truncated proteins by Western blot and enzyme-linked immunosorbent assay (ELISA). Three linear B-cell epitopes were identified covering a stretch of 15 amino acid (aa) residues and localized in the aa regions 158-172, 181-195, and 349-363 of UreB. ELISA also showed that the three synthetic peptides containing epitope sequences (UP32: GGGTGPADGTNATTI, UP35: WMLRAAEEYSMNLGF, and UP38: TLHDMGIFSITSSDS) were recognized by the corresponding MAbs and H. pylori positive sera from H. pylori infected patients. Mice immunized with glutathione S-transferase (GST) fusion peptides showed that epitope-specific antibodies were capable of inhibiting urease enzymatic activity. These results should be useful in clinical applications and highlight the potential importance of these epitopes as the targets for development of epitope-based vaccines against H. pylori., ((c) 2010 Elsevier Ltd. All rights reserved.)