Toll-like receptor 3 (TLR3), as an important pattern recognition receptor (PRR), dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases. Atherosclerosis is proved as an inflammatory disease, and inflammatory events involved in the entire process of initiation and deterioration. However, the contribution of TLR3 to atherosclerosis remains unclear. Herein, we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis. Besides, activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules. Conversely, silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation. Given the aberrance in TLR3 functions on atherosclerosis progression, we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy. Therefore, we developed the novel ellipticine derivative SMU-CX24, which specifically inhibited TLR3 (IC₅₀ = 18.87 ± 2.21 nmol/L). In vivo, atherosclerotic burden was alleviated in Western diet fed ApoE^-/- mice in response to SMU-CX24 treatment, accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion. Thus, for the first time, we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression, thereby proposing a new strategy and probe for atherosclerosis therapy.

Objective:To evaluate the effect of different anesthesia methods on the immune function in the patients with oral squamous cell carcinoma.Methods:Forty patients of both sexes, aged 31-64 yr, with body mass index of 19-23 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective radical resection of oral squamous cell carcinoma and repair of the defect with free flap, were enrolled and randomized to receive either combined intravenous-inhalational anesthesia (VICA group, n=20) or total intravenous anesthesia (TIVA group, n=20) using a random number table method.In group VICA, anesthesia was induced with intravenous propofol 1.5-2.0 mg/kg, remifentanil 1-2 μg/kg, and cisatracurium 0.2 mg/kg, sevoflurane was continuously inhaled to maintain MAC at 1.3, sevoflurane inhalation was stopped at 1 h before the end of surgery, sevoflurane was replaced with propofol, propofol 4-6 mg·kg -1·h -1 was continuously infused until the end of operation, and dexmedetomidine 0.4 μg·kg -1·h -1, remifentanil 0.2-0.3 μg·kg -1·min -1 and cisatracurium 0.1 mg·kg -1·h -1 were intravenously infused at the same time to maintain anesthesia.In group TIVA, anesthesia induction was the same as those previously described in group VICA, and anesthesia was maintained with intravenous dexmedetomidine 0.4 μg·kg -1·h -1, propofol 4-6 mg·kg -1·h -1, remifentanil 0.2-0.3 μg·kg -1·min -1 and cisatracurium 0.1 mg·kg -1·h -1.Venous blood samples were taken at 30 min before anaesthesia induction (T 0), 3 h after anaesthesia (T 1), at the end of operation (T 2), and at 6, 24 and 48 h after operation (T 3-5) for determination of the serum concentrations of immunoglobulins (IgA, IgM, IgG), interleukins (IL-2, IL-6, IL-10, sIL-2Rα) and soluble interleukin-2 receptor alpha (sIL-2Rα) by enzyme-linked immunosorbent assay. Results:Compared with the baseline at T 0, the concentrations of serum sIL-2Rα at T 1-5, IL-2 at T 1-4 and IL-10 at T 1 were significantly decreased, the concentrations of serum IL-6 at T 1-5 and IL-10 at T 2-4 were increased, and the concentrations of serum IgA and IgM at T 1-5 were decreased in two groups, and the concentrations of serum IgG at T 1-5 in TIVA group and at T 1, 2 and T 4, 5 in VICA group were significantly decreased ( P<0.05).Compared with group TIVA, the concentrations of serum sIL-2Rα at T 2, 5, IL-6 at T 4, 5 and IL-10 at T 3, IgA at T 4 and IgG at T 3 were significantly increased, and the concentrations of serum IL-2 at T 1-5 and IgA at T 5 were decreased in group VICA ( P<0.05). Conclusions:Both general anesthesia methods have significant inhibitory effects on intraoperative and postoperative cellular immune function and humoral immune function in the patients with oral squamous cell carcinoma, and combined intravenous-inhalational anesthesia produces higher inhibitory effects on cellular immune function than total intravenous anesthesia.

Objective: To explore the relationship between sialic-acid-binding immunoglobulin-like lectin 7 (Siglec-7) expressed on NK cells and hepatitis B virus-related cirrhosis. Methods: Peripheral venous blood samples were collected from 23 healthy controls and 31 patients with hepatitis B virus-related cirrhosis (Child-Pugh A, n = 7; Child-Pugh B, n = 12; Child-Pugh C, n = 12). Peripheral blood mononuclear cells (PBMCs) were obtained by using Ficoll-Hypaque density gradient centrifugation and the expression of Siglec-7 and NK cells phenotype and their subpopulations were detected by flow cytometry. Comparisons between various groups were performed using t -test, one-way analysis of variance (ANOVA), and correlations between variables were analyzed using Pearson’s-correlation coefficient. Results: (1) There was no significant difference in the percentage of NK cells and in their subpopulations with HBV-related cirrhosis and healthy controls. (2) Siglec-7 expression on NK cells in patients with HBV-related cirrhosis(62.44±13.45%)was significantly down-regulated than that to healthy controls(75.39±12.19%)while the frequency of Siglec-7⁺ NK cells were negatively correlated with Child-Pugh score. (3) Subpopulation analysis showed that Siglec-7 expression on CD56^brightCD16^-NK cells(66.99±15.93%)was significantly lower than CD56^dimCD16⁺NK cells(76.54±13.9%) in HBV-related cirrhosis. However, the expression of Siglec-7 in healthy controls showed no difference in these two NK cell subsets. (4) Phenotypic analysis showed that Siglec-7⁺ NK cells express higher levels of activating receptor CD16, CD38, NKp46 and lower levels of inhibitory receptor CD158b. Indeed, the frequency of CD16 and CD38 on Siglec-7⁺ NK cells in HBV-related cirrhosis was lower than that in healthy controls. Conclusion The disease progression in patients with hepatitis B virus-related cirrhosis is associated to decreased frequencies of Siglec-7⁺NK cells.

In order to search for new antiplatelet agents with higher potency, a series of tetramethylpyrazine ( TMP) /chalcone hybrids ( 2-26) were synthesized and evaluated based on the principle of bioisostere and hybrid-ization. They exerted inhibitory activity against adenosine diphosphate ( ADP )-induced and arachidonic acid ( AA)-induced platelet aggregation to varied extent. Among them, compound 8 was the most potent with IC50 of 0. 14 mmol/L on ADP-induced platelet aggregation ( 9. 1 folds of TMP and 10. 5 folds of chalcone ) and 0. 09 mmol/L on AA-induced platelet aggregation ( 8. 8 folds of TMP and 10. 0 folds of chalcone) , which was superior to clinically used anti-platelet drug aspirin ( ASP, IC50 =0. 15 mmol/L) .

OBJECTIVETo observe the effectiveness and safety of electrothermal acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in the cancerous patients of phlegm-stasis interaction in cisplatin-containing chemotherapy.

METHODSSixty cases of phlegm-stasis interaction in cisplatin-containing chemotherapy were randomized into a trial group and a control group, 30 cases in each one. In the control group, the intravenous drip of granisetron hydrochloride injection was adopted, 3 mg before and after cisplatin-containing chemotherapy 30 min, continuously for 3 days. 43 to 45℃ electrothermal acupuncture at zusanli(ST 36) for 30 min was used on the basis of the treatment as the control group in the trial group,once a day for 3 days. CINV, anti-nausea effects, Karnofsky score, the syndrome score of phlegm-stasis interaction, and relevant indices of safety were observed on the 1st and 7th days of cisplatin-containing chemotherapy separately.

RESULTS1.Regarding CINV and anti-nausea effect, CINV did not occur before chemotherapy in the patients of the two groups. On the 1st and 7th days of chemotherapy, CINV in the trial group were milder than those in the control group (both<0.05).The anti-nausea effects in the trail group were better than those of the control group.2.Regarding Karnofsky score and the syndrome score of phlegm-stasis interaction, the improvements on the 7th days of chemotherapy in the trial group were better than those in the control group, indicating the significant differences (both<0.05). 3.Regarding the safety indies, there was no adverse reaction during the treatment in the two groups.

CONCLUSIONSThe electrothermal acupuncture effectively relieves CINV, and improves self-care dbility and the symptoms of phlegm-stasis interaction.

Objective To evaluate the effect of dexmedetomidine on the mammalian target of rapamycin(mTOR)/tau protein signaling pathway in the hippocampus of aged rats after splenectomy.Methods One hundred and fifty pathogen-free healthy male Sprague-Dawley rats,aged 18 months,weighing 400-540 g,were divided into 5 groups(n=30 each)using a random number table:control group(group C),sham operation group(group S),operation group(group O),normal saline group(group NS)and dexmedetomidine group(group D).Group C received no treatment.Ten percent chloral hydrate 0.3 ml/100 g was injected intraperitoneally in group S.Group O underwent splenectomy.Dexmedetomidine 50 μg/kg was injected intraperitoneally at 5 min before splenectomy in group D.The equal volume of normal saline was injected intraperitoneally at 5 min before splenectomy in group NS.Morris water maze test was performed at day 7 after surgery.At days 1,3 and 7 after surgery,the rats were sacrificed,and the hippocampi were removed for examination of the pathological changes in the hippocampal CA3 region and for determination of the expression of mTOR protein and mRNA,tau protein mRNA and phosphor-tau protein(pS396 tau protein)(by real-time polymerase chain reaction or Western blot).Results Compared with group C,the escape latency and swimming distance were significantly prolonged,and the expression of mTOR protein and mRNA,tau protein mRNA and pS396 tau protein was up-regulated in O,D and NS groups(P<0.05),and no significant change was found in the parameters mentioned above in group S(P>0.05).Compared with group O,the escape latency and swimming distance were significantly shortened,and the expression of mTOR protein and mRNA,tau protein mRNA and pS396 tau protein was down-regulated in group D(P<0.05),and no significant change was found in the parameters mentioned above in group NS(P>0.05).The pathological changes in the hippocampal CA3 region were significantly attenuated in group D as compared with group O.Conclusion The mechanism by which dexmedetomidine improves postoperative cognitive function may be associated with inhibited activation of mTOR/tau protein signaling pathway in the hippocampus of aged rats.

OBJECTIVE:To study antibacterial activities of meropenem(MPN)combined with cefoperazone sulbactam(SCF) to 3 kinds of multidrug resistance (MDR) Gram-negative bacteria. METHODS:Each 50 strains of MDR-Escherichia coli (MDR-EC),MDR-Klebsiella pneumoniae (MDR-KPN) and MDR-Acinetobacter baumannii (MDR-AB) were isolated from spu-tum,blood,urine,ascites or drainage specimens of patients during Jan. to Dec. in 2016 from the affilidated hospital of Taishan medical university. The agar dilution method and board method were used to determine MIC50,MIC90 and MICG of MPN,SCF, MPN+SCF to MDR-EC,MDR-KPN,MDR-AB and calculate fractional inhibitory concentration (FIC). Drug sensitivity test was conducted by K-B disk method. RESULTS:In terms of the MICG to MDR-EC,MDR-KPN,MDR-AB,MPN alone were respec-tively 36.82,82.45,34.32 μg/mL;SCF alone were respectively 42.14,112.67,24.11 μg/mL;MPN combined with SCF were re-spectively 25.97,56.64,11.36 μg/mL. In terms of MICG to MDR-EC,MDR-KPN,MICG showed that MPN+SCF0-0.5 (78.00%),>0-0.5(72.00%),>0.5-1.0 (82.00%). CONCLUSIONS:MPN combined with SCF can effectively improve antibacterial activities to MDR Gram-negative bac-teria as MDR-EC,MDR-KPN,MDR-AB. MPN combined with SCF has synergistic effects.

Through an introduction to the importance of medical ethics education and the status quo, this paper discusses how to better combine the medical ethics education with medical students′medical practices. It puts for-ward some suggestions from the institutional arrangements, personnel allocation, and publicitymethods. The ulti-mate goal is that the medical students could get more effective, continue and integration medical ethics education in the process of medical practice.

In recent years , there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+LPD), and the name of EBV +LPD is used widely.However,the meaning of EBV+LPD used is not the same , which triggered confusion of the understanding and obstacles of the communication.In order to solve this problem.Literature was reviewed with combination of our cases to clarify the concept of EBV +LPD and to expound our understanding about it .In general, it is currently accepted that EBV +LPD refers to a spectrum of lymphoid tissue diseases with EBV infection , including hyperplasia , borderline lesions , and neoplastic diseases .According to this concept , EBV+LPD should not include infectious mononucleosis ( IM ) and severe acute EBV infection ( EBV +hemophagocytic lymphohistiocytosis, fatal IM, fulminant IM, fulminant T-cell LPD), and should not include the explicitly named EBV+lymphomas ( such as extranodal NK/T cell lymphoma , aggressive NK cell leukemia , Burkitt lymphoma, and Hodgkin lymphoma , etc.) either.EBV +LPD should currently include: ( 1 ) EBV +B cell-LPD:lymphomatoid granulomatosis , EBV +immunodeficiency related LPD , chronic active EBV infection-B cell type, senile EBV +LPD, etc.(2) EBV +T/NK cell-LPD:CAEBV-T/NK cell type, hydroa vacciniforme, hypersensitivity of mosquito bite, etc.In addition, EBV+LPD is classified, based on the disease process , pathological and molecular data , as 3 grades:grade1, hyperplasia ( polymorphic lesions with polyclonal cells ); grade 2, borderline ( polymorphic lesions with clonality ); grade 3, neoplasm (monomorphic lesions with clonality).There are overlaps between EBV +LPD and typical hyperplasia, as well as EBV+LPD and typical lymphomas .However , the most important tasks are clinical vigilance , early identification of potential severe complications , and treating the patients in a timely manner to avoid serious complications , as well as the active treatment to save lives when the complications happened .

Objective To investigate the effect of ramipril on urinary protein in elderly type 2 diabetic patients with nephropathy in different periods.Methods 120 type 2 diabetic patients with nephropathy (64 males, 56 females) with mean aged (68±3) years were randomized into treatment group and control group (n =60, each).According to test results of 24 h proteinuria and renal function, they were divided into 3 subgroups: the normal urine albumin (normal control) group, the early diabetic nephropathy group, and the clinical diabetic nephropathy group.The control group received conventional treatment, while the treatment group used conventional treatment combined with ramipril 2.5 mg/d.Both groups had treatment course of 3 months.The changes in 24 h urinary total protein and urinary albumin before and 1 and 3 months after treatment, and the changes in blood urea nitrogen and serum creatinine levels in patients with renal dysfunction before and 3 months after treatment were observed and compared.Results 24 h urinary total protein and urinary albumin were significantly decreased along with the extended treatment time (P＜0.05 or 0.01).The blood urea nitrogen and serum creatinine levels were significantly declined at 3 months after treatment versus pre-treatment (P＜0.05 for both).There were no significant differences in 24h urinary total protein and urinary albumin in control group before versus after treatment (P＞0.05 for both).At 1 and 3 months after treatment, there were significant differences both in the decrement of 24h urinary total protein and urinary albumin, and in the blood urea nitrogen and serum creatinine levels between the clinical diabetic nephropathy treatment group and the control group (P＜0.05 or 0.01).Conclusions Ramipril combined with conventional treatment can effectively reduce proteinuria and promote the recovery of renal function for type 2 diabetic patients with nephropathy.