With the popularization of low-dose lung CT screening and the renewal of people's concept of physical examination, more and more pulmonary nodules are detected. This paper discusses some hot issues in the multidisciplinary diagnosis and treatment of pulmonary nodules from five perspectives: the concept and causes of pulmonary nodules, how to improve the diagnostic level of pulmonary nodules, the understanding of pulmonary nodules management in different specialties, the follow-up diagnosis of pulmonary nodules and the multidisciplinary diagnosis and treatment of pulmonary nodules.

ObjectiveTo investigate the value of aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) score, and gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in diagnosis of liver inflammation grade in patients with chronic hepatitis B (CHB). MethodsA total of 545 patients with CHB who underwent percutaneous liver biopsy and routine laboratory examinations during hospitalization in Shanghai Public Health Clinical Center Affiliated to Fudan University from October 2016 to October 2019 were enrolled. Inflammation grade (G) was determined according to the Scheuer scoring system, and APRI, FIB-4, and GPR were calculated based on related clinical indicators. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate the correlation between two variables. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of the three serum noninvasive diagnostic models in determining liver inflammation grade, and the Delong test was used for comparison of the area under the ROC curve (AUC). ResultsAmong the 545 patients, 224 had grade G0-1 liver inflammation, 209 had grade G2 liver inflammation, and 112 had grade G3 liver inflammation. The Spearman correlation analysis showed that APRI, FIB-4, and GPR were positively correlated with liver inflammation grade (r=0.611, 0.470, and 0.563, all P＜0.001). APRI, FIB-4, and GPR had an AUC of 0.820, 0.719, and 0782, respectively, in the diagnosis of G≥2 liver inflammation, with optimal cut-off values of 0.53, 1.48, and 0.20, respectively; for the diagnosis of G≥2 liver inflammation, GPR had a better performance than FIB-4 (P=0.01) and a slightly lower performance than APRI (P=0.048). The stratified analysis based on alanine aminotransferase (ALT) level showed that in the ≤1×upper limit of normal (ULN) group, the (1-2)×ULN group, and the (2-5)×ULN group, APRI had an AUC of 0.847, 0.786, and 0.724, respectively, in the diagnosis of G≥2 liver inflammation, FIB-4 had an AUC of 0.777, 0.729, and 0.626, respectively, and GPR had an AUC of 0.801, 0.781, and 0.607, respectively; the subgroup analysis showed that GPR had a similar diagnostic performance to APRI and FIB-4 in all ALT stratification groups except the (2-5)×ULN group, in which GPR had a lower diagnostic performance than APRI (P=0.042). APRI, FIB-4, and GPR had an AUC of 0.791, 0.725, and 0.801, respectively, in the diagnosis of G≥3 liver inflammation, with optimal cut-off values of 0.66, 1.49, and 0.25, respectively; in the diagnosis of G≥3 liver inflammation, GPR had a similar diagnostic performance to APRI and a better diagnostic performance than FIB-4 (P=0.006). The stratified analysis based on ALT level showed that in the ≤1×ULN group, the (1-2)×ULN group, and the (2-5)×ULN group, APRI had an AUC of 0.900, 0.742, and 0.693, respectively, in the diagnosis of G≥3 liver inflammation, FIB-4 had an AUC of 0.874, 0.683, and 0.644, respectively, and GPR had an AUC of 0.890, 0.805, and 0.668, respectively. The subgroup analysis showed that GPR had a similar diagnostic performance to APRI and FIB-4 in all ALT stratification groups except the (1-2)×ULN group, in which GPR had a better diagnostic performance than FIB-4(P=0.015). ConclusionAPRI, FIB-4, and GPR may accurately diagnose liver inflammation grade in CHB patients, which helps to monitor the progression of CHB and determine the timing of antiviral therapy.

Objective:To investigate the effect of hydroxysafflor yellow A(HSYA) preconditioning group on apoptosis induced by cold hypoxia/reoxygenation (cold H/R) injury in human renal tubular epithelial cells (HK2 cells).Methods:After digestion and passage, HK2 cell lines were divided into Sham group (control group), cold hypoxia and reoxygenation group (cold H/R group, cells cold hypoxia for 4 h, reoxygenation for 4 h), and HSYA preconditioning group (each HSYA subgroup was given different doses of HSYA 0.5 h before hypoxia, and the other operations were the same as the cold H/R group). The cell survival rate was measured by CCK-8 method.The expression of Bcl-2, Bax and Caspase-3 proteins in HK-2 cells were detected by immunocytochemistry and Western blotting.Results:(1) Compared with cold H/R group, different doses of HSYA could improve cell survival rate in different degrees, but only HSYA25 μmol/L group had the most significant effect (74.000±5.500 vs.59.000±3.800, P<0.05). (2) Immunocytochemistry semi-quantitative score: Compared with cold H/R group, the expression of Bax and Caspase-3 in HK2 cells of HSYA25 μmol/L group was significantly decreased(0(0, 1) vs. 8(6, 8), Z=2.041, P<0.05 and (3.400±0.548) vs.(7.800±1.095), t=11.000, P<0.01). The expression of Bcl-2 protein was increased significantly ((6.800±1.095) vs.(1.400±0.548), t=10.590, P<0.01). The ratio of Bcl-2/Bax increased significantly.(3)Western blot was used to detect protein: Compared with the cold H/R group, the protein levels of Bax, Cleaved-Caspase-3 and Pro-caspase-3 of HK2 cells in the HSYA25 μmol/L group were significantly decreased ((0.707±0.012) vs.(0.968±0.117), (0.480±0.009)vs.(0.735±0.005), (0.992±0.008)vs.(1.197±0.005), all P<0.01). The expression of Bcl-2 protein was significantly increased, and the ratio of Bcl-2/Bax was significantly increased ((0.410±0.009) vs.(0.273±0.008), (0.582±0.016) vs (0.282±0.080), all P<0.01). The experimental results were consistent with the immunocytochemistry. Conclusion:HSYA can effectively reduce the damage of HK2 cells after cold hypoxia and reoxygenation.

Objective To assess the diagnostic performance of liver stiffness measurement(LSM)and serum markers on hepatic fibrosis in chronic hepatitis B(CHB)patients with alanine aminotransferase(ALT)less than or equal to two times the upper limit of normal(≤2×ULN).Methods A total of 284 CHB patients with ALT≤2×ULN who were treated in Department of Hepatobiliary Medicine,Public Health Clinical Center,Shanghai from October 2015 to December 2017 were analyzed.FibroScan,routine blood tests and serum fibrosis markers were conducted on the day or one day before liver biopsy.The Scheuer scoring system was used for liver histologic assessment.Aspartate aminotransferase to platelet ration index(APRI)and FIB-4 were calculated.Based on the results of liver pathology,the area under receiver operating characteristic curve(AUROC)was used to evaluate the value of LSM and serum markers in the diagnosis of liver fibrosis stage.Non-normal distribution variables were expressed as M(QR)as appropriate,and compared by analysis of Kruskal-Wallis test as appropriate.The correlation between two variables was analyzed by Spearman correlation analysis.Results Of 284 CHB patients,175 were male and 109 were female.For inflammatory grading,175 cases were G1 grade,88 cases were G2,and 21 cases were G3.For fibrosis grading,153 cases were S1,53 cases were S2,34 cases were S3,and 44 cases were S4.Spearman correlation analysis showed that LSM,APRI and FIB-4 were positively correlated with hepatic fibrosis stage(r=0.650,0.484,and 0.317,respectively,all P<0.01).The AUC of LSM for predicting fibrosis≥S2,≥S3,and S4 were 0.840,0.902,and 0.942,respectively.The cut-off of LSM values were 6.10,8.40,and 10.10 kPa,respectively.The values of AUC of APRI and FIB-4 for predicting fibrosis≥S2 were 0.755 and 0.638,respectively,those for predicting fibrosis≥S3 were 0.737 and 0.657,respectively,and those for S4 were 0.804 and 0.694,respectively.The AUCs of LSM for predicting fibrosis≥S2 in patients with ALT≤1×ULN and those with ALT>1 -≤2×ULN were 0.857 and 0.813,respectively,those for fibrosis≥S3 were 0.890 and 0.892,respectively,and those for S4 were 0.925 and 0.908,respectively.The cut-off of LSM were 5.90 and 7.80 kPa,8.10 and 9.50 kPa,8.40 and 10.40 kPa,respectively.Conclusions LSM could accurately assess the degree of liver fibrosis in CHB patients with ALT≤2×ULN,which is superior to serum markers for predicting liver fibrosis stage.

Objective: To explore the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection who received entecavir alone or in combination with anluohuaxianwan for 78 weeks. Methods: Patients with chronic HBV infection were randomly treated with entecavir alone or in combination with anluohuaxian for 78 weeks. Ishak fibrosis score was used for blind interpretation of liver biopsy specimens. The improvement in liver fibrosis condition before and after the treatment was compared. Student's t test and non-parametric test (Mann-Whitney U-Test and Kruskal-Wallis test) were used to analyze the measurement data. The categorical variables were analyzed by Chi-square test method and Spearman’s rank correlation coefficient was used to test bivariate associations. Results: Liver fibrosis improvement rate after 78 weeks of treatment was 36.53% (80/219) and the progression rate was 23.29% (51/219). The improvement of liver fibrosis was associated to the degree of baseline fibrosis and treatment methods (P < 0.05). The improvement rate of hepatic fibrosis in patients treated with anluohuaxianwan combined with entecavir at baseline F < 3 (54.74%, 52/95) was significantly higher than that in patients treated only with entecavir (33.33%, 16/48), P = 0.016 and the progression rate of hepatic fibrosis (13.68%, 13/95) was lower than that in patients treated alone (18.75%, 9/48), P = 0.466. In patients with baseline F < 3, the proportion of patients with improved and stable liver fibrosis in the combined treatment group (68.1%, 32/47) was higher than that in the treatment group alone (51.7%, 15/29). Conclusion Combined anluohuaxianwan and entecavir treatment can significantly improve the improvement rate of liver fibrosis in patients with chronic hepatitis B virus infection. Furthermore, it has the tendency to improve the stability rate and reduce the rate of progression of liver fibrosis.

Objective To observe the effect of HIF-1a/iNOS signaling pathway on myocardial ischemia-reperfusion injury in rat heart transplantation and the protective mechanism of N-acetylcysteine (NAC) on donor heart after cardiac transplantation in rats.Methods Eighty healthy male Lewis rats were randomly divided into 3 groups,the control group (0.3 ml saline was infused via inferior vena cava 30 min before donor harvest or implantation),NAC donor pretreatment group [NAC (30 mg/kg.w) was injected into the vena cava of donor rat 30 min defore donor harvest],and the NAC receptor pretreatment group (NAC 300 mg/kg.w was injected into the vena cava of the recipient rats 30 min before transplantation.The 30 min was injected into the vena cava of the recipient rats).A transplant model was established and the graft was obtained after 24 h transplantation.The expression of iNOS,HIF-1a and mRNA in cardiac muscle tissue was detected by immunohistochemistry and Real time-PCR.Results HIF-1a protein expression in graft myocardial tissue was significantly lower in NAC donor pretreatment and recipient pretreatment group compared with control group (P ＜0.05),the differences were statistically significant (2.72±0.17 vs.2.24±0.23 vs.3.14.±0.16,F=56.26,P =0.000).The iNOS protein expression in NAC donor pretreatment group,and NAC recipient pretreatment group were lower than that in the control group (1.52±0.18 vs.1.61±0.19 vs.3.30±0.18,F=232.345,P =0.000),the differences were statistically significant (P ＜ 0.05).24 h after transplantation,the differences in graft myocardial tissue HIF-1a and iNOS mRNA among the three groups were statistically significant (F=7.467,16.490,P=0.003,0.000).The expression of iNOS mRNA in the NAC receptor pretreatment group was significantly lower than that in the control group (P＜0.05).Conclusion HIF-1a/iNOS signaling pathway can regulate ischemia reperfusion injury in rat heart transplantation,and the protective effect of NAC on donor heart maybe mediated via this pathway.

Objective To assess the clinical diagnostic performance of liver stiffness measurement (LSM) and aspartate transaminase (AST)-to-platelet (PLT) ratio index (APRI) for liver fibrosis in chronic hepatitis B (CHB) patients with alanine aminotransferase (ALT) less than or equal to five times of the upper limit of normal (≤5×upper limit of normal [ULN]).Methods FibroScan,blood routine and liver function test were conducted at the day or one day before liver biopsy in 383 CHB patients with ALT≤5 × ULN.The Scheuer scoring system was used for liver histologic assessment.APRI was calculated.Based on the results of liver pathology,the areas under receiver operating characteristic curve (AUC) of LSM and APRI for diagnosis of liver fibrosis stage were compared.Results The median LSM were 5.10 kPa for S0 fibrosis stage,5.20 kPa for S1,6.60 kPa for S2,10.10 kPa for S3,and 18.80 kPa for S4.The median APRI values were 0.36,0.38,0.63,0.61 and 1.27,respectively.The AUC of LSM were 0.817 for ≥S2,0.891 for ≥S3 and 0.913 for ≥S4.And the AUC of APRI were 0.717 for ≥S2,0.711 for ≥S3 and 0.746 for ≥S4.The cut-offs of LSM values were 6.8 kPa for ≥S2,8.7 kPa for ≥S3,and 10.9 kPa for ≥S4.Conclusion LSM can accurately assess the degree of liver fibrosis in CHB patients with ALT ≤5 × ULN,which is superior to APRI in clinical utility.

Objective:To explore the effect of sulforaphane (SFN) preconditioning on the cold myocardial ischemia-reperfusion injury (IRI) in the rats through PI3K/Akt signaling pathway.Methods:Sixty-four health male Sprague-Dawley (SD) rats were randomly divided into cold IRI group,SFN group,LY (LY294002) + cold IRI group,and LY+SFN group (n=16).The allogeneic heterotopic heart transplantation model was established by donor heart into recipient abdomen.The myocardium tissue was taken 24 h after reperfusion for the detection of histological changes using HE staining.The expression levels of Akt,p-Akt,Bax and Bcl-2 proteins were detected by immunohistochemistry and Western boltting methods.Results:The morphological results showed that the myocardium tissue damage was serious in cold IRI group and LY+cold IRI group,it was light in SFN group;the myocardium tissue damage of the rats in SFN+ LY group was ranged between cold IRI group and SFN group.Compared with IRI group,the expression levels of p-Akt protein and Bcl-2 protein in SFN group were increased (P＜0.05),and the expression level of Bax protein was decreased (P＜0.05).After treatment of blockage LY294002,compared with LY-+-cold IRI group,the expression level of p-Akt protein in LY-+-SFN group was not statistically significant (P＞0.05),the expression level of Bcl2 protein was increased (P＜0.05),the expression levels of Bax protein was decreased),and the ratio of Bcl-2/Bax was also increased (P＜0.05).Conclusion:SFN may attenuate cold IRI of heart transplantation through PI3K/Akt signaling pathway in the rats.

Objective To investigate the relationship between the plasma NT-proBNP level and the severity of acute asthmatic attack,and to provide a reference for the assessment of the severity of asthma and the prognosis of patients with acute asthmatic attack. Methods A total of 103 adult patients with mild,moderate,severe,and very severe acute asthmatic attack were enrolled in this study. The difference of plasma NT-proBNP level among groups,and the correlation between plasma NT-proBNP level and APACHE II score(Acute Physiology and Chron-ic Health Evaluation)were investigated.The correlation between plasma NT-proBNP level and Peak Expiratory Flow (PEF)was also studied in each group. Results There was significant difference in plasma NT-proBNP among groups(P < 0.05). Plasma NT-proBNP and APACHE II score was positive correlated(R = 0.767 1,P < 0.05). However,plasma NT-proBNP was negatively correlated with PEF(R =-0.709 7,P < 0.05). Conclusion NT-proBNP can be used as one of the indexes to evaluate the severity of acute asthmatic attack.

Objective To investigate the relationship between serum resistin,leptin and adiponectin with microangiopathy in the patients with type-2 diabetes mellitus(T2DM).Methods One hundred and twenty patients with T2DM in our hospital were selected and divided into the non-microangiopathy group (NON-MAP,60 cases) and microangiopathy group (MAP,60 cases) according to whether complicating microangiopathy.Other 60 individuals undergoing healthy physical examination were selected as the normal control group(NC).Fasting serum resistin,adiponectin and leptin levels were detected in each group.Fasting blood glucose,insulin and blood lipid levels were also detected.The insulin resistance was evaluated by using insulin resistance index(HOMA-IR).Results The levels of serum resistin,leptin,free fat acid(FFA) and hs-CRP in the NON-MVP group and MVP group were signifi cantly higher than those in the NC group,while the adiponectin level was sigrnificantly lower than that in the NC group,the difference was statistically significant(P＜0.05).The correlation analysis showed that serum resistin and leptin levels had positive correlation with hs-CRP,FFA,HOMA-IR and TG(P＜0.05),and had negative correlation with HDL-C(P＜0.05);the adiponectin level was negatively correlated with hs-CRP,FFA,HOMA-IR and TG,while positively correlated with HDL-C(P＜0.05);serum resistin and leptin levels had positive correlation,both had significantly negative correlation with adiponectin;with serum resistin,leptin and adiponectin as the dependent variables,the multiple stepwise linear regression analysis showed that HOMA-IR and waist to hip ratio had maximal influence on them.Conclusion Serum resistin and leptin levels increase and adiponectin level decrease in T2DM patients suggests that serum resistin,leptin and adiponectin are correlated with T2DM occurrence as well as microangiopathy occurrence.