ObjectiveTo investigate the risk factors associated with macrovascular disease in patients with newly-diagnosed type 2 diabetes. MethodsAccording to arterial intima-media thickness(IMT)measured by color duplex ultrasonography,232 cases of newly-diagnosed type 2 diabetic patients were divided into two groups:one group were 95 cases with macrovascular disease(MD),and the other group were 137 cases without macrovascular disease (non-MD).Then various clinical data between the two groups were compared and the correlated risk factors for macrovascular disease were analyzed. Results (1)95 patients(40.9%)showed macrovascular disease in 232 patients.(2)Age,BMI,SI,systolic blood pressure,diastolic blood pressure,TC,LDL-C,CRP and 24h UmAlb were significantly higher in MD group compared with those in non-MD group(all P＜0.05);But ISI was significantly lower in MD group compared with that in non-MD group(P＜0.05).(3)Pearson correlation analysis showed that risk factors were old age,BMI,smoking,higher systolic blood pressure,higher diastolic blood pressure,TC,LDL-C,CRP and microalbuminuria. ConclusionMacrovascular disease was related to many factors.It was important to control some risk factors earlier for preventing the happening and progress of macrovascular disease.

Background Studies show that regulatory T cells (Treg) are a kind of T cell subsets to negatively regulate immune response,and play an important role in maintaining immune homeostasis and immune tolerance.Autoimmune uveitis is an autoimmune disease,the regulation of Treg cells in pathogenesis and progression of autoimmune uveitis is not fully unelucidated.Objective This study was to observe the dynamic changes of Treg in experimental autoimmune uveitis (EAU) rats and explore the role of Treg cells in the pathological process of EAUrats.Methods Eighty four 6-8 week-old SPF Lewis rats were randomly divided into model group and control group.The mixed emulsifier of interphotoreceptor retinoid-binding protein (IRBP)1177-1191,tuberculin (TB),complete Freund adjuvant (CFA) and PBS (300 μl) was subcutaneously injected in double rear foot pad,abdominal side and back,and only equal amount of TB,CFA and PBS emulsifier was used in the same way in the control group.Ocular inflammation symptoms was examined at 9,13,18,23,28,35 and 48 days after modeling and scored based on the severity of the inflammatory.Six rats of each group were sacrificed in above time points respectively for the histopathological examination of iris,ciliary body and retinas by haematoxylin-eosin staining.The lymphocytes were isolated and cultured from rat spleens,and the proportion of Foxp3-labelled cells,a specific marker of Treg cells,was assayed by flow cytometry.The relative expression level of Foxp3 mRNA in the lymphocytes detected by using realtime quantitative PCR (RT-PCR).The use and care of the rats complied with the ARVO Statement.Results Eye inflammatory response appeared at 8 days after immunization,showing vasodilation and hyperemia of rat iris in the model group,and the response peaked at 13 days,with exudation and hypopyon in the anterior chamber.The highest inflammatory scores were 3.75±0.42 at day 13,and the ocular inflammation reaction was gradually relieved after that and disappeared at 23 days after immunity.A significant difference in ocular inflammatory scores of model rats was found among different time points (F =81.709,P ＜ 0.001);while no inflammatory symptom was observed in the control group.Histopathology examination showed obvious infiltration of inflammatory cells in the iris,ciliary body and retinas in model rats,including neutrophils,lymphocytes and mononuclear cells.The proportion of Foxp3-labelled cells in spleen lymphocytes was (5.50 ± 0.64)％,(13.36 ± 0.98)％,(10.34 ± 0.79)％,(9.58 ± 1.02)％,(6.73 ±0.81)％ and (5.58 ± 0.47) ％ in the model group on day 13,18,23,28,35,48 respectively,with statistically significant differences in comparison with (2.80 ± 0.38) ％,(3.36 ± 0.53) ％,(3.65 ± 0.57) ％,(3.37 ± 0.43) ％,(3.33±0.50)％ and (3.13±0.61)％ in the control group (t=-6.272,-15.556,-11.910,-9.753,-6.154,-5.491,all at P＜0.01).The change trend of Foxp3 mRNA expression was consistent to the dynamic change of the proportion of Foxp3-labelled cells.Conclusions The pathogenesis and development is closely associated with the dynamic changes of CD4+ CD25 + Foxp3+ Treg cells in EAU rats.

Objective To explore the influence of transcutaneous oximetry on septic shock-associated acute kidney injury (AKI) in intensive care unit (ICU).Methods Forty-nine patients with septic shock admitted in the ICU of Wuxi People's Hospital Affiliated to Nanjing Medical University were enrolled from January 2013 to December 2015.The 10 min oxygen challenge test was conducted using transcutaneous oximetry just before (0 h) and 6 h after initiation of fluid resuscitation,and 10 min oxygen challenge test data (10 min OCT) at 0 h and 6 h were then calculated,respectively.The enrolled patients were divided into low 10 min OCT group (10 min OCT ＜ 66 mmHg,L group) or high 10 min OCT group (10 min OCT ≥66 mmHg,H group) according to the 10 min OCT value at 6 h.The hemodynamic variables [mean arterial pressure (MAP),central venous pressure (CVP)],oxygen metabolism indexes [central venous oxygen saturation (ScvO2),arterial lactate (Lac)],dose of vasoactive agents,10 min OCT at 0 h and 6 h were recorded.APACHE Ⅱ score,incidence and severity of septic shock-associated AKI,frequency of CRRT,ICU mortality and 28 d mortality were compared between groups using SPSS 22.0 software,risk factors associated with prognosis were analyzed using COX regression model.Results There were 27 cases in L group and 22 cases in H group.The MAP,CVP,ScvO2,lactate level and dose of vasoactive agents were comparable between groups at 0 h or 6 h (P ＞ 0.05),while 10 min OCT at 6 h was higher in H group than that inLgroup [(77.6±18.5) mmHgvs.(51.3 ±21.6) mmHg,P＜0.05].The incidence of septic shock-associated AKI (77.8％ vs.50.0％,P ＜ 0.05),proportion of phase 3 AKI (44.4％vs.22.7％,P ＜0.05) and frequency of CRRT (48.1％ vs.22.7％,P ＜0.05) was higher in L group than those in H group,and similarly were the ICU mortality (51.8％ vs.22.7％,P ＜0.05) and 28 d mortality (63.0％ vs.31.8％,P ＜ 0.05).Therefore,the 6 h 10 min OCT ≥66 mmHg was a protective factor to improve the ICU mortality (RR =0.01,95％ CI:0.001-0.39,P ＜ 0.05) and 28 d mortality (RR =0.01,95％CI:0.001-0.27,P＜0.05) in patients with septic shock-associated AKI.Conclusions 10 min OCT imposes substantial influence on the incidence,severity and prognosis of patients with septic shockassociated AKI,oxygen challenge test could improve the treatment of septic shock-associated AKI.

Objective To determine the association between plasma concentrations of brain derived neurotrophic factor (BDNF), neuron-specific enolase (NSE), and S100β, and the occurrence of delirium in critically ill patients. Methods Totally 65 patients in Intensive Care Unit (ICU) of Wuxi People's Hospital of Nanjing Medical University between June 2015 and February 2016 were included in the present study. Delirium diagnosis was used by confusion assessment method for the ICU (CAM-ICU). Plasma BDNF, NSE, and S100β concentrations were determined on day 1(T1), 3(T3), and 10(T10) after ICU admission. The day of ICU admission was defined as T0. Results Compared with the plasma BDNF level on T1 (0.23±0.22) μg/L, the plasma BDNF level on T3 (0.59±0.34) μg/L and T10 (0.24±0.21) μg/L were higher, especially for that on T3 with a significant difference (F=21.58, P=0.018). Plasma NSE level on T3 (1.68±0.25) μg/L was significantly higher than that on T1 (1.22±0.32) μg/L (F=10.24, P=0.042). Compared with those without delirium, the delirious patients had lower BDNF, higher NSE and S100β on T1, T3 and T10, of which the difference of BDNF [T1: (0.23±0.22) μg/L vs. (1.02±0.24) μg/L, F=116.25,P<0.01; T3: (0.59±0.34) μg/L vs. (1.55±0.36) μg/L, F=82.39, P<0.01; T10: (0.24±0.21) μg/L vs. (1.09±0.55)μg/L, F=50.93, P=0.003, and NSE (T1: (1.22±0.32) μg/L vs. (0.47±0.23) μg/L, F=94.30, P<0.01;T3:(1.68±0.25) μg/L vs. (0.79±0.28) μg/L, F=78.63, P=0.017; T10: (0.98±0.37) μg/L vs. (0.51±0.22) μg/L, F=70.95, P=0.026) reached significant differences. Conclusions Plasma BDNF and NSE are closely related to the occurrence of delirium in critically ill patients, especially for BDNF. Clinical monitoring of plasma levels of BDNF can help to predict the outcome of brain function in critically ill patients.

Objective To explore the prognostic value of soluble triggering receptor expressed on myeloid cells-1(sTREM-1) in patients with ventilator-associated pneumonia (VAP).Methods A total of 103 VAP patients were enrolled from June 2013 to May 2015 in the ICU of Wuxi People's Hospital Affiliated to Nanjing Medical University.The demographics and clinical data were collected,while serum sTREM-1,procalcitonin (PCT),C-reactive protein(CRP),clinical pulmonary infection score(CPIS) and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) were measured.Patients were divided into the death group and the survival group according to 28 d survival.The differences in demographics and clinical data were compared between groups.The values of sTREM-1,PCT,CPIS and APACHE Ⅱ for predicting 28 d death were evaluated by receiver operating curves(ROC).The surviving curve was drawn by Kaplan-Meier method.The possible prognostic factors were analyzed by univadate and logistic multivariate analysis.Results There were 76 patients in the survival group and 27 patients in the death group,and there was no difference in demographics between two groups(P＞0.05).The serum sTREM-1,PCT,CPIS and APACHE Ⅱ were higher in the death group[(89.50±18.45) pg/mL,(823.86±182.74) pg/ mL,(7.20±1.74) and (19.58±3.43)] than those in the survival group[(54.09±12.71) pg/mL,(579.81±193.45) pg/mL,(4.79±1.93) and (17.23±3.12),all P＜0.05].The areas under the ROC of sTREM-1,PCT,CPIS and APACHE Ⅱ for predicting 28 d death were 0.84±0.04(95％CI:0.75-0.92,P＜0.01),0.65±0.05(95％CI:0.55-0.74,P=0.49),0.67±0.06(95％CI:0.55-0.79,P＜0.01),0.79±0.04(95％CI:0.70-0.87,P=0.03),respectively.Patients were assigned into two groups by the best cutoffpoint of sTREM-l=75.00 pg/mL,and Kaplan-Meier survival analysis showed that 28 d survival rate in the low sTREM-1 group was significantly higher than that in the high sTREM-1 group (82.5％ vs.63.4％,x2=3.96,P＜0.05).Multivariate logistic regression analysis showed that both sTREM-1 (OR=1.08,95％CI:1.04-1.13,P＜0.01) andAPACHE Ⅱ (OR=1.39,95％CI:1.15-1.67,P＜0.01) were risk factors associated with 28 d death.Conclusions Early serum sTREM-1 can be used as a reliable predictor for the outcome of patients with VAP.

Objective To evaluate the prognostic value of transcutaneous oximetry in patients with septic shock.Methods Fifty-three patients with septic shock were enrolled prospectively from January 2013 to December 2015.Transcutaneous oximetry were used to determine the results of 10 min oxygen challenge tests (OCT) carried out at beginning(0 h) and at 6 h after fluid resuscitation respectively.The 10-min OCT value (10 min OCT) and oxygen challenge index(OCI) were calculated.The APACHE Ⅱ and SOFA score,hemodynamic variables,oxygen metabolism indexes,dose of vasoactive agents,10 min OCT,and OCI at 0 h and at 6 h were recorded.Patients were assigned into survival group and death group according to the 28 d survival.The differences in demographics and clinical data were compared between groups.The role of 10 min OCT and OCI in predicting death was evaluated by receiver operating characteristic curves(ROC).The Kaplan-Meier surviving curve was created and the survival of the patients was analyzed by the Log-rank test.Risk factors associated with the prognosis were analyzed using the multiple logistic regression analysis.Results There were 29 patients in the survival group and 24 patients in the death group.Compared with death group,10 min OCT[(77.55±18.48)mmHg vs.(51.30±21.60)mmHg] and OCI [(0.78±0.13) vs.(0.59±0.15)] at 6 h in survival group were significantly higher(P＜0.05),while APACHE Ⅱ [(12.48±5.69) vs.(17.25±8.79)] and SOFA [(5.79±1.72) vs.(10.10±2.52)] in survival group were significantly lower than those in death group(P＜0.01).The area under the ROC curve of 10 min OCT at 6 h and OCI at 6 h for predicting 28 d death were 0.86±0.05(95％CI:0.76-0.87,P＜0.01) and 0.79±0.08(95％CI:0.64-0.95,P＜0.01),respectively.The optimal cutoff point for 10 min OCT at 6 h was 72.00 mmHg with the sensitivity of 76.84％ and specificity of 85.03％.The optimal cutoff point for OCI at 6 h was 0.76 with the sensitivity of 76.84％ and specificity of 77.47％.Kaplan-Meier survival analysis showed that 28 d survival rate in high level of 10 min OCT at 6 h and high level of OCI at 6 h were significantly higher than that in low level of 10 min OCT at 6 h(70.86％ vs.31.82％,x2=7.96,P＜0.01)and low level of OCI at 6 h (75.00％ vs.32.00％,x2=9.86,P＜0.01).Multivariate logistic regression analysis showed that both 10 min OCT at 6 h (OR=0.92,95％CI:0.88-0.96,P＜0.05) and OCI at 6 h (OR=0.01,95％CI:0.001-0.023,P＜0.05) were independent risk factors associated with 28 d mortality of patients with septic shock.Conclusions The 10 min OCT and OCI were reliable predictors for the prognosis of patients with septic shock.

Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.

Based on the theory of qi， blood and fluids， and taking into account of the pathogenesis evolution process from constraint to phlegm， stasis and then mass in pulmonary nodules， an attempt has been made to construct a three-dimensional differentiation system for pulmonary nodules from the dimensions of time and space. The temporal progression of the early， middle， and late stages of pulmonary nodules reflects the pathological changes from constraint to phlegm and then stasis in the metabolism disorders of qi， blood and fluid. The spatial structures such as size， density， and morphology of pulmonary nodules reflect the pathological states of the duration， severity， and primary and secondary conditions of qi， blood and fluid metabolism disorders. Based on the temporal progression， the therapeutic principles have been proposed， which are dispelling pathogenic factors and promoting the use of beneficial factors to interrupt the growth momentum in the early stage， removing turbidity and dispersing phlegm to reduce the degree of nodules in the middle stage， and dispersing nodulation and eliminating abnormalities in the late stage. Based on the spatial structures， the suggested therapeutic methods are using wind herbs， employing multiple approaches to treat phlegm， and promoting blood circulation to resolve stasis， so as to provide theoretical reference for the systematic diagnosis and treatment of pulmonary nodules in traditional Chinese medicine.

ObjectiveTo explore the effect and mechanism of Sishenwan-containing serum on aerobic glycolysis in human colon cancer HCT116 cells. MethodCell counting kit-8 （CCK-8） was used to detect the cell viability of colon cancer HCT116 cells after treatment with Sishenwan-containing serum （2.5%， 5%， and 10%） for 24， 48， 72 h. The concentration of lactic acid， the content of intracellular glucose， and the activity of hexokinase （HK） and fructose-6-phosphate kinase （PFK） in the cell culture medium were detected by the micro-method. The content of glucose transporter 1 （GluT1） mRNA was detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression of GluT1 and methyltransferase-like 3 （MettL3） was detected by Western blot. The expression of GluT1 in cells was detected by immunofluorescence and the level of N6-methyladenosine （m⁶A） RNA methylation was detected by colorimetry. ResultCompared with the normal serum， 2.5%， 5%， and 10% Sishenwan-containing serum had no significant effect on the viability of HCT116 cells at 24 h， while 10% Sishenwan-containing serum showed a significant inhibitory effect on the viability of HCT116 cells at 48 h （P<0.05）. Hence， 10% Sishenwan-containing serum was used in subsequent experiments， and the intervention time was 48 h. Compared with the normal serum， 10% Sishenwan-containing serum could reduce lactate production （P<0.05）， down-regulate glucose uptake （P<0.05）， and blunt the activities of HK and PFK， the key rate-limiting enzymes of glycolysis （P<0.05）. Meanwhile， 10% Sishenwan-containing serum could decrease the expression of GluT1 protein （P<0.01） and mRNA （P<0.05） and reduce the proportion of cells expressing GluT1 （P<0.01）. Compared with the normal serum， Sishenwan-containing serum also decreased the protein content of MettL3 （P<0.05） and the methylation level of m⁶A RNA （P<0.01）. ConclusionSishenwan can inhibit glycolysis in colon cancer cells， and its inhibitory mechanism may be related to reducing MettL3 overexpression， inhibiting m⁶A RNA methylation， and down-regulating GluT1 and the activities of intracellular aerobic glycolysis-related enzymes such as HK and PFK.

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8⁺ T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC.