Dectin-1-CD37 association regulates IL-6 expression during Toxoplasma gondii infection

Toxoplasma gondii can establish chronic infection and is characterized by the formation of tissue cysts in the brain. Although T. gondii can infect any kind of nucleated cells, macrophages and related mononuclear phagocytes are its preferred targets in vivo. Microglial cells are the resident macrophages in the central nervous system. It has been reported that CD37, a tetraspanin molecule, is expressed exclusively in the immune system; Dectin-1, an important pattern-recognition receptor, is expressed on the surface of murine primary microglia. The Dectin-1-CD37 association can affect Dectin-1-mediated IL-6 secretion. However, there is no report concerning the relationship among the expressions of Dectin-1, IL-6, and CD37 during T. gondii infection. In the present study, Kunming outbred mice were infected with Prugniaud (Pru), a type II strain of T. gondii by oral gavage, and BV-2 murine microglial cells were cocultured with RH tachyzoites of T. gondii. By H&E and immunohistochemical staining, the results showed that marked inflammation and a significantly increased activation of Iba1-positive microglial cells were observed in the brain tissues of mice infected with T. gondii Pru strain at 5 weeks postinfection (p.i.) in comparison of uninfected controls. Using quantitative real-time PCR detection, Dectin-1 messenger RNA (mRNA) expressions were significantly upregulated in both brains at 3 (P?<?0.01), 5 (P?<?0.01), 7 (P?<?0.01), and 9 (P?<?0.05) weeks p.i. and spleens at 3, 5, 7, and 9 weeks p.i. (P?<?0.01). IL-6 expressions showed similar dynamic tendency as that of Dectin-1 in both the brains and spleens at the same times in comparison of uninfected controls; CD37 expressions were significantly increased in the brain tissues at all the times (P?<?0.01) and no significant differences in the spleens at 3 weeks p.i. but significantly downregulated in the spleens at 5, 7, and 9 weeks p.i. (P?<?0.01). In vitro study showed that compared with uninfected controls, the mRNA expressions of Dectin-1 at 2, 4, 8, and 10 h (P?<?0.01); IL-6 at 8 and 10 h (P?<?0.01); and CD37 at 4 (P?<?0.05), 8 (P?<?0.01), and 10 h (P?<?0.01) were significantly upregulated in BV-2 murine microglial cells stimulated with RH tachyzoites of T. gondii. Our data suggested that the expression of Dectin-1 was positively correlated with that of IL-6 in toxoplasmic encephalitis (TE) mouse model; Dectin-1 interaction with tetraspanin CD37 regulated IL-6 expression in both the brain tissues of TE mouse model and in the T. gongdii-infected BV-2 murine microglial cells.     

A label-free RTP sensor based on aptamer/quantum dot nanocomposites for cytochrome c detection

Given the outstanding room-temperature phosphorescence (RTP) of Mn–ZnS quantum dots (QDs) and the specific recognition performance of the aptamer, we built phosphorescent composites from aptamers conjugated with polyethyleneimine quantum dots (PEI-QDs) and applied them to cytochrome c (Cyt c) detection. Specifically, QDs/CBA composites were generated from the electrostatic interaction between the positively-charged PEI-QDs and the negatively-charged Cyt c binding aptamer (CBA). With the presence of Cyt c, the Cyt c can specifically bind with the QDs/CBA composites, and quench the RTP of QDs through photoinduced electron-transfer (PIET). Thereby, an optical biosensor for Cyt c detection was built, which had a detection range of 0.166–9.96 μM and a detection limit of 0.084 μM. This aptamer-mediated phosphorescent sensor with high specificity and operational simplicity can effectively avoid the interference of scattering light from complex substrates. Our findings offer a new clue for building biosensors based on QDs and aptamers.

In this study, the nanocomposites from polyethyleneimine-capped Mn-doped ZnS QDs (PEI-QDs) and Cyt c binding aptamer (CBA) were prepared and used as Cyt c RTP sensors..     

Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE) and hepatic arterial infusion chemotherapy(HAIC) have shown promising local benefits for advanced hepatocellular carcinoma(HCC). S-1, a composite preparation of a 5-fluorouracil prodrug, has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC.AIM To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC.METHODS In this single-center, open-label, prospective, randomized controlled trial, 117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with(TACE/HAIC + S-1, n = 56) or without(TACE/HAIC, n = 61) oral S-1 between December 2013 and September 2017. Two participants were excluded from final analysis for withdrawing consent. The primary endpoint was progression-free survival(PFS) and secondary endpoints included overall survival(OS), objective response rate, disease control rate and safety.RESULTS In total, 115 participants(100 males and 15 females; mean age, 57.7 years ± 11.9) were analyzed. The median PFS and OS were 5.0 mo(0.4–58.6 mo)(95% confidence interval(CI): 3.82 to 6.18) vs 4.4 mo(1.1–54.4 mo)(95%CI: 2.54 to 6.26; P = 0.585) and 8.4 mo(0.4–58.6 mo)(95%CI: 6.88 to 9.92) vs 8.3 mo(1.4–54.4 m)(95%CI: 5.71 to 10.96; P = 0.985) in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. The objective response rate and disease control rate were 30.9% vs 18.4% and 72.7% vs 56.7% in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. Grade 3/4 adverse events had a similar frequency in both treatment groups.CONCLUSION No improvements in tumor response rates, PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC. Both treatment regimens had a similar safety profile.     

Admission hyperglycemia predicts poorer short‐ and long‐term outcomes after primary percutaneous coronary intervention for ST‐elevation myocardial infarction

Aims/Introduction

Admission hyperglycemia is associated with poor outcome in patients with myocardial infarction. The present study evaluated the relationship between admission glucose level and other clinical variables in patients with ST‐elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Materials and Methods

The 959 consecutive STEMI patients undergoing primary PCI were divided into five groups based on admission glucose levels of <100, 100–139, 140–189, 190–249 and ≥250 mg/dL. Their short‐ and long‐term outcomes were compared.

Results

Higher admission glucose levels were associated with significantly higher in‐hospital morbidity and mortality, the overall mortality rate at follow up, and the incidence of reinfarction or heart failure requiring admission or leading to mortality at follow up. The odds ratios (95% confidence interval) for in‐hospital morbidity, in‐hospital mortality, mortality at follow up and re‐infarction or heart failure or mortality at follow up of patients with admission glucose levels ≥190 mg/dL, compared with those with admission glucose levels <190 mg/dL, were 2.12 (1.3–3.4, P = 0.001), 2.74 (1.4–5.5, P = 0.004), 2.52 (1.2–5.1, P = 0.01) and 1.70 (1.03–2.8, P = 0.04), respectively. Previously non‐diabetic patients with admission glucose levels ≥250 mg/dL had significantly higher in‐hospital morbidity or mortality (44 vs 70%, P = 0.03). Known diabetic patients had higher rates of reinfarction, heart failure or mortality at follow up in the 100–139 mg/dL (8 vs 27%, P = 0.04) and 140–189 mg/dL (11 vs 26%, P = 0.02) groups.

Conclusions

Admission hyperglycemia, especially at glucose levels ≥190 mg/dL, is a predictor of poor prognosis in STEMI patients undergoing primary PCI.     

血清miR-27与老年2型糖尿病下肢血管病变及25（OH）D3水平的关系

目的分析血清miR-27与老年2型糖尿病下肢血管病变及25(OH)D3水平的关系。方法选取2017年10月-2019年5月河北省沧州市人民医院内分泌科确诊老年2型糖尿病患者86例为T2DM组,并以有无下肢血管病变分为下肢血管病变(LLPAD)亚组44例和非下肢血管病变(Non-LLPAD)亚组42例;选择同期医院门诊健康体检者76例为对照组,测定比较各组血清miR-27 mRNA表达及TC、TG、HDL-C、LDL-C、HbA1c、FPG、25(OH)D3、hs-CRP、Fib水平。结果 T2DM组miR-27 mRNA、TC、TG、LDL-C、Fib、HbA1c、hs-CRP、FPG水平高于对照组,25(OH)D3、HDL-C水平低于对照组(t=13.371、13.036、25.364、19.698、29.326、38.489、95.524、66.547,66.241、8.698,P均=0.000);LLPAD亚组miR-27 mRNA、TC、TG、LDL-C、Fib、HbA1c、hs-CRP、FPG水平高于Non-LLPAD亚组,25(OH) D3、HDL-C水平低于Non-LLPAD亚组(t=5.275、13.541、26.541、8.965、20.146、14.548、14.369、23.654、7.711、9.491,P均=0.000);miR-27 mRNA与25(OH)D3、HDL-C呈负相关(r=-0.486、-0.483,P=0.039、0.039),与TC、TG、LDL-C、Fib、HbA1c、hs-CRP、FPG呈正相关(r=0.651、0.572、0.494、0.747、0.438、0.523、0.591,P均<0.05);高水平的miR-27 mRNA、TC及低水平的25(OH)D3均为老年2型糖尿病合并下肢血管病变发生的危险因素(OR=2.43.7、4.268、13.625,P<0.05);miR-27 mRNA、25(OH)D3两者的AUC相近,均小于TC;miR-27 mRNA、25(OH)D3诊断老年2型糖尿病下肢血管病变的敏感度、特异度相近(P>0.05),均小于TC(P<0.05)。结论老年2型糖尿病下肢血管病变患者血清miR-27 mRNA水平升高,与25(OH)D3呈负相关;miR-27、25(OH)D3诊断2型糖尿病下肢血管病变具有较高的敏感度、特异度,可作为判定2型糖尿病下肢血管病变的生物学标志物。     

“热证用灸”的历史源流

"热证用灸"的思想基础上溯《黄帝内经》。秦汉时期有灸法补泻理论;魏晋时期灸疗用于痈疽肿痛;隋唐时期"热证用灸"应用已从外科阳热痈肿疮疡拓展到内科急证、热证的治疗;宋金元时期"热证用灸"理论的愈加丰富,并广泛应用于临床;明清医家对前人"热证用灸"的理论和应用做了全面继承和总结,同时出现了灸、熨法和药末相结合的神灯照法、太乙神针、雷火神针,提高了灸法用于疮疡肿毒的临床疗效;近现代出现了"热证贵灸"、灸感三相、腧穴热敏化灸、动力灸法、灯火灸、脐灸等理论和方法,有助于"热证用灸"的规范化研究。一方面,历史上还有不少医家持热证禁灸的观点。"热证用灸"的临床适应证和禁忌证尚缺乏系统、完善的研究总结,限制其理论的广泛传播和应用,故在临床诊疗和研究中,应该求同存异,探索和总结其临床适应证。另一方面,随着灸法的现代化研究不断深入,应用科学手段探究灸法疗效的客观化、规范化也越来越多,这也有助于我们更加深入地理解"热证用灸"的作用机理。     

The harmonic scalpel versus electrocautery for parotidectomy: A meta - analysis

ObjectiveParotidectomy is the most classic and unequivocal intervention for parotid neoplasm. The operative outcomes and postoperative complications of parotidectomy between harmonic scalpel and electrocautery gained more prominence in physician. In spite of much research work within the past years, there was an obvious lack of randomized controlled trial to resolve this question. Hence, a quantitative and qualitative meta-analysis was essential to evaluate the differences in these two types of hemostasis method.MethodThe major electronic databases, including Pubmed, Embase, Cochrane library, Google Scholar, China National Knowledge Infrastructure and Chinese Scientific and Technological Journal databases were using the key words “electrocautery”, “electrocoagulation”, “harmonic scalpel”, “ultrasonic scalpel”, “ultrasonic dissector”, “parotidectomy” and “parotid surgery”. 9 articles were included in our systematic review and meta-analysis. The operative time, intraoperative blood loss, hospital stay, salivary fistula and transient facial nerve paralysis were the outcome measures. Odds ratios (ORs) with 95% confidence intervals (CIs) were employed to evaluate the effect size for categorical outcomes and mean differences (MDs) with 95% confidence intervals (CIs) for continuous outcomes.ResultsIn our meta-analysis, there was a significant reduction in operation time [mean difference: ?20.97; 95%CI=(?24.02,?17.92); P < 0.00001], intraoperative blood loss [mean difference: ?20.75, 95%CI=(?22.32,?19.18); P < 0.00001], hospital stay [mean difference: ?0.83; 95%CI=(?1.10,?0.57); P < 0.00001], salivary fistula [ORs: 0.30, 95%CI=(0.08,1.14)] and transient facial nerve paralysis [OR:0.33, 95%CI=(0.19,0.58),P = 0.0001] in harmonic scalpel group compared with electrocautery group.ConclusionThis meta-analysis indicated that compared with electrocautery, harmonic scalpel (HS)was transcendent in the aspects of operative time, intraoperative blood loss, hospital stay, salivary fistula and transient facial nerve paralysis. The harmonic scalpel, as an efficient and useful instrument, was advocated in parotidectomy.     

新型冠状病毒肺炎130例CT分布特点及征象研究

目的探讨2019新型冠状病毒肺炎(COVID-19)影像学表现。方法根据纳入标准和排除标准收集2020年1月20日至2月5日来自全国多家医院确诊COVID-19病例130例,按分布特点进行分型,分析其影像学特征。结果(1)分布:单侧14例(10.7%),双侧116例(89.3%);胸膜下型(102例78.4%),小叶核心型99例(76.1%),弥漫型8例(6.1%);(2)数目:单发病灶9例(6.9%),多发病灶113例(86.9%),弥漫8例(6.1%);(3)密度:仅为磨玻璃影(GGO)70例(53.8%),GGO与实变影兼有60例(46.2%);(3)伴随征象:血管增粗100例(76.9%),胸膜平行征98例(75.3%),"细网格征"100例(76.9%),"晕征"13例(10%),"反晕征"6例(4.6%),3例胸腔积液(2.3%),2例肺气囊(1.5%)。未见空洞。35患者行CT复查,21例(60%)好转,14例(40%)加重。结论COVID-19影像学特点主要以胸膜下及小叶核心分布为主,两者均可融合成片,重症者发展为双肺弥漫;最有价值的特征是"胸膜平行征";恢复期表现为边缘收缩的实变影,支气管扩张,胸膜下线或纤维条索影。     

Coexpression of SGLT1 and EGFR is associated with tumor differentiation in oral squamous cell carcinoma

Overexpression of epidermal growth factor receptor (EGFR) is associated with resistance to chemotherapy and radiotherapy, advanced tumor stage, invasion, metastasis and poor prognosis in malignant tumors. EGFR, therefore, has been an attractive molecular target for chemotherapy. However, the results of clinical studies using inhibitors of its kinase activity have not been promising because the response rates were at most 20%. Sodium-glucose co-transporter 1 (SGLT1) is a membrane protein that mediates the transport of glucose across cellular membranes. EGFR physically associates with and stabilizes SGLT1 to promote glucose uptake into cancer cells through a kinase-independent process. The purpose of this study was to investigate the coexpression of SGLT1 and EGFR and its relationships with clinicopathological features in oral squamous cell carcinoma (OSCC). SGLT1 and EGFR were detected in all OSCC cell lines, and the expression levels of SGLT1 were significantly correlated with those of EGFR. Pearson product?Cmoment correlation coefficient of SGLT1 and EGFR was 0.89 (P?=?0.016). The immunohistochemical study using the surgical specimens in 52 patients with tongue SCC also showed a significant correlation between SGLT1 and EGFR. Moreover, SGLT1/EGFR expression was inversely related to tumor differentiation among the 5 clinicopathological factors (P?=?0.004). SGLT1/EGFR coexpression might be required in the de-differentiation of OSCC, but further study is needed to clarify the implication of these proteins in the manifestation of malignancy and clinical significance.