BackgroundBrain innate immunity is vital for maintaining normal brain functions. Immune homeostatic imbalances play pivotal roles in the pathogenesis of neurological diseases including Parkinson’s disease (PD). However, the molecular and cellular mechanisms underlying the regulation of brain innate immunity and their significance in PD pathogenesis are still largely unknown.MethodsCre-inducible diphtheria toxin receptor (iDTR) and diphtheria toxin-mediated cell ablation was performed to investigate the impact of neuron-glial antigen 2 (NG2) glia on the brain innate immunity. RNA sequencing analysis was carried out to identify differentially expressed genes in mouse brain with ablated NG2 glia and lipopolysaccharide (LPS) challenge. Neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice were used to evaluate neuroinflammatory response in the presence or absence of NG2 glia. The survival of dopaminergic neurons or glial cell activation was evaluated by immunohistochemistry. Co-cultures of NG2 glia and microglia were used to examine the influence of NG2 glia to microglial activation.ResultsWe show that NG2 glia are required for the maintenance of immune homeostasis in the brain via transforming growth factor-β2 (TGF-β2)-TGF-β type II receptor (TGFBR2)-CX3C chemokine receptor 1 (CX3CR1) signaling, which suppresses the activation of microglia. We demonstrate that mice with ablated NG2 glia display a profound downregulation of the expression of microglia-specific signature genes and remarkable inflammatory response in the brain following exposure to endotoxin lipopolysaccharides. Gain- or loss-of-function studies show that NG2 glia-derived TGF-β2 and its receptor TGFBR2 in microglia are key regulators of the CX3CR1-modulated immune response. Furthermore, deficiency of NG2 glia contributes to neuroinflammation and nigral dopaminergic neuron loss in MPTP-induced mouse PD model.ConclusionsThese findings suggest that NG2 glia play a critical role in modulation of neuroinflammation and provide a compelling rationale for the development of new therapeutics for neurological disorders.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on 2'-fucosyllactose/difucosyllactose (2'-FL/DFL) mixture as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is a powdered mixture mainly composed of two oligosaccharides, 2'-FL and DFL, which are produced together by fermentation with a genetically modified strain of Escherichia coli K12. The information provided on the manufacturing process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF in a variety of foods, including infant and follow-on formula, foods for infants and young children, foods for special medical purposes and food supplements. The target population is the general population except for food supplements, for which the target population is individuals above 1 year of age. Since the intake of 2'-FL and DFL from the NF at the proposed use levels is unlikely to exceed the intake level of naturally occurring 2'-FL and DFL in breastfed infants per kilogram body weight, the Panel concludes that the NF, a mixture of 2'-FL and DFL, is safe under the proposed conditions of use for the proposed target population.

Many studies have investigated the association between hormonal and reproductive factors and thyroid cancer risk but provided contradictory and inconclusive findings. This review was aimed at precisely estimating this association by pooling all available epidemiological studies. 25 independent studies were retrieved after a comprehensive literature search in databases of PubMed and Embase. Overall, common hormonal factors including oral contraceptive and hormone replacement therapy did not alter the risk of thyroid cancer. Older age at menopause was associated with weakly increased risk of thyroid cancer in overall analysis (RR = 1.24, 95% CI 1.00–1.53, P = 0.049); however, longer duration of breast feeding was related to moderately reduced risk of thyroid cancer, suggested by pooled analysis in all cohort studies (RR = 0.7, 95% CI 0.51–0.95, P = 0.021). The pooled RR in hospital-based case-control studies implicated that parous women were more susceptible to thyroid cancer than nulliparous women (RR = 2.30, 95% CI 1.31–4.04, P = 0.004). The present meta-analysis suggests that older age at menopause and parity are risk factors for thyroid cancer, while longer duration of breast feeding plays a protective role against this cancer. Nevertheless, more relevant epidemiological studies are warranted to investigate roles of hormonal and reproductive factors in thyroid carcinogenesis.

We investigated all-inside ankle arthroscopy for Tillaux-Chaput fractures. We retrospectively evaluated 19 patients (12 males [63.2%] and 7 [36.8%] females; 11 right [57.9%] and 8 left [42.1%] ankles) treated from May 2013 to January 2016. Their mean age was 28.1 (range 10 to 55) years. Sixteen (84.2%) had single Tillaux-Chaput fractures and 3 (15.8%) had combined proximal fibular fractures; 17 (89.5%) were diagnosed radiographically and 2 (10.5%) by computed tomography. Anterolateral and anteromedial ankle arthroscopy was used for closed reduction and internal fixation with 1 or 2 Herbert screws. Joint function was evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale. All 19 patients healed by first intention without nerve, vessel, or tendon injuries. The follow-up was 19.0 (range 12 to 25) months; fracture union was achieved by 23.5 (range 12 to 36) weeks. At the last follow-up, the 19 patients had no restrictions in ankle function and range of motion, with no ankle or walking pain. The AOFAS score changed from 52.8 to 91.7 points, with an excellent/good rate of 100%. These results suggest that anterolateral and anteromedial all-inside ankle arthroscopy is a precise and effective method for closed reduction and internal fixation of Tillaux-Chaput fractures.

The potential advantages for fermentation production of chemicals at high temperatures are attractive, such as promoting the rate of biochemical reactions, reducing the risk of contamination and the energy consumption for fermenter cooling. In this work, we de novo engineered the thermophile Geobacillus thermoglucosidasius to produce riboflavin, since this bacterium can ferment diverse carbohydrates at an optimal temperature of 60°C with a high growth rate. We first introduced a heterogeneous riboflavin biosynthetic gene cluster and enabled the strain to produce detectable riboflavin (28.7 mg l À1). Then, with the aid of an improved gene replacement method, we preformed metabolic engineering in this strain, including replacement of ribC Gtg with a mutant allele to weaken the consumption of riboflavin, manipulation of purine pathway to enhance precursor supply, deletion of ccpN Gtg to tune central carbon catabolism towards riboflavin production and elimination of the lactate dehydrogenase gene to block the dominating product lactic acid. Finally, the engineered strain could produce riboflavin with the titre of 1034.5 mg l À1 after 12-h fermentation in a mineral salt medium, indicating G. thermoglucosidasius is a promising host to develop hightemperature cell factory of riboflavin production. This is the first demonstration of riboflavin production in thermophilic bacteria at an elevated temperature.

Background. To investigate the efficacy and safety of MEBO combined with Jinhuang powder for the treatment of diabetic foot with infection. Methods. From August 2015 to August 2019, patients with diabetic foot in our hospital were divided into the treatment group and control group. The treatment group was treated with moist exposed burn ointment (MEBO) combined with Jinhuang powder, while the control group was treated with MEBO only. Results. After one week of treatment, the effective rate in the treatment group was 100%, and the effective rate in the control group was only 76%. The difference between the two groups was statistically significant ( P < 0.05 ). The wound pain score was 2.40 ± 1.38 in the treatment group and 3.76 ± 1.85 in the control group. The difference was statistically significant ( P < 0.01 ). After one month of treatment, the effective rate of wound healing was 92.0% in the treatment group and 68% in the control group. The difference between the two groups was statistically significant ( P < 0.05 ). Conclusion. MEBO combined with Jinhuang powder is effective in treating diabetic foot with infection wound.

Background: The all-inside arthroscopic Broström-Gould technique gained particular attention among clinicians and researchers due to its high rate of satisfactory results. Thus far, there is a lack of evidence regarding the differences in clinical outcomes between the use of 1 anchor and 2 anchors. The purpose of this study was to compare the differences in clinical function and activity levels in patients treated with 1 or 2 anchors in all-inside arthroscopic Broström-Gould surgery for chronic lateral ankle instability (CLAI). Methods: The data of 75 patients with CLAI (unilateral) admitted from May 2013 to July 2016 were retrospectively analyzed. All patients were treated with all-inside arthroscopic Broström-Gould surgery. The patients were divided into a single-anchor group ( n = 36) and double-anchor group ( n = 39) according to the number of anchors used. There was no statistical difference in general characteristics between the 2 groups before surgery. After 36 to 72 months of follow-up, the pain visual analog scale (VAS) score, American Orthopaedic Foot & Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (KAFS), and Foot and Ankle Outcome Score (FAOS) were used to evaluate and compare the clinical function results between the 2 groups. Results: The incidence of wound complications; reaction to the suture; injury to the nerve, blood vessel, or tendon; and length of postoperative hospitalization were similar between the 2 groups. At the last follow-up, there was no significant difference in the VAS and AOFAS scores between single- and double-anchor groups, but the KAFS and FAOS in the double-anchor group were significantly higher than in the single-anchor group. Additionally, more patients in the double-anchor group returned to preinjury sports activities. Conclusion: All-inside arthroscopic Broström-Gould surgery for the treatment of CLAI yielded a better functional effect and better recovery to preinjury mobility when 2 anchors were used instead of a single anchor. Level of Evidence: Level III, comparative study.

ObjectiveThe neutrophil-to-lymphocyte ratio (NLR) is recognised as a suitable prognostic biomarker in patients with breast cancer. Nevertheless, the efficacy of this biomarker in predicting the pathological complete response (pCR) and survival in patients with breast cancer receiving neoadjuvant chemotherapy (NACT) is still controversial. This meta-analysis aimed to identify the association between baseline NLR and the prognosis of patients with breast cancer treated with NACT.DesignMeta-analysis.Data sourcesRelevant literature published before 1 May 2021 was searched using the Cochrane Library, Embase, PubMed and the Web of Science databases.Eligibility criteriaAll studies involving patients with breast cancer treated with NACT and peripheral blood pretreatment NLR recorded as a dichotomous variable were included.Data extraction and synthesisTwo researchers independently extracted and evaluated OR/HR and its 95% CIs of survival outcomes and clinicopathological parameters.ResultsA total of 19 studies were identified. From each study, the impact of NLR on the pCR, OR and HR, with their 95% CIs were extracted and combined using either a random or fixed-effects model. The results indicate that a higher pCR in patients with a low NLR (OR 1.620, 95% CI 1.209 to 2.169, p＜0.001). In addition, an elevated NLR predicted lower disease-free survival (HR 2.269, 95% CI 1.557 to 3.307, p<0.001) and overall survival (HR 1.691, 95% CI 1.365 to 2.096, p<0.001) in patients with breast cancer treated with NACT.ConclusionsNLR is a suitable biomarker for predicting pCR and survival in patients with breast cancer receiving NACT.