Objective To investigate epidermal growth factor receptor(EGFR)expression and tumor residual to the prognostic value in patients with nasopharyngeal cancer(NPC).Methods 200 patients with NPC were examined for EGFR expression by immunohistochemistry analysis,neck cancer and nasopharyngeal residual.Results In 200 cases with NPC,expression of EGFR of positive and negative were 160 cases(80.0%) and 40 cases (20.0%);the rate of overall survival(OS),disease-free survival (DFS),loeoregional relapse-free survival (LRFS) and distant metastasis-free survival(DMFS)in patients with positive EGFR were 72.3%,63.6%,72.2%,63.8% and negative EGFR were 90.0%,90.0%,90.0%,90.0%,respectively in 3-year(X2=3.95,X2=4.12,X2=3.98,X2=4.15,P＜0.05),the rate of local recurrence,distant metastasis rate in residual were 26.6%,32.5% which is significantly higher than 8.1%,18.1% in without residual(X2=4.75,X2=4.94,P＜0.05);the hish expression of EGFR with DFS,OS were significantly correlated(r=6.457,P＜0.05).Conclusion The overexpress of EGFR had the tendency of poor prognosis.tumor residual after radiotherpy can be a prognostic indicator for patients with NPC.

Objective To observe the effects of resveratrol on blood pressure and cardiac function in the rats with vascular calcification induced by vitamin D3 plus nicotine.Methods 32 male SD rats were randomly divided into the following groups for treatment:Control (Con), calcified (Cal), Cal+Res low dose [L] and Cal+Res high dose [H] groups.Blood pressure, cardiac function, alkaline phosphatase ( ALP ) activity in serum or aorta were detected and HE staining was used for pathological examination at 6 weeks after treatment.Results Compared with the Con group, LVW/BW, heart rate, systolic aortic pressure, pulse pressure, mean blood pressure, left ventricular systolic pressure and ALP activity in serum or aorta of rats in the Cal group were increased by 27.3%, 8.8%, 22.8%, 47.5%, 13.6%, 19.0%, 280%and 265%( P<0.05 or P<0.01) , respectively.Compared with the Cal group, pulse pressure and ALP activity in serum or aorta of rats in the Cal+Res [L] group were decreased by 8.5%, 34.5%and 29.5%(P<0.05 or P<0.01), respectively, and LVW/BW, systolic aortic pressure, pulse pressure, mean blood pressure, left ventricular systolic pressure and ALP activity in serum or aorta of rats in the Cal +Res [ H] group were decreased by 14.2%, 13.6%, 23.7%,10.0%, 9.0%, 53.1%and 45.9%(P<0.05 or P<0.01), respectively.Compared with the Cal+Res [L] group, systolic aortic pressure, pulse pressure, left ventricular systolic pressure and ALP activity in serum or aorta of rats in the Cal+Res [H] group were decreased by 8.3%, 16.7%, 5.8%, 28.4% and 23.2% (P<0.05 or P<0.01), respectively.Compared with the aorta in the Con group, pathological examination revealed thickened vessel walls and disordered elastic fibers in the calcified aortas.However, the thickness of aortic wall in the Cal+Res [ L] and Cal+Res [ H] groups was reduced and elastic fibers were regularly arranged.Conclusion Resveratrol can effectively reduce the blood pressure and improve the cardiac function in rats with vascular calcification.

Objective To analyze clinical features of and hypertrophy-related factors in patients with hypertrophic port-wine stains (PWS). Methods Patients with PWS were enrolled into this study from Anhui Provincial Hospital and the First Affiliated Hospital of Anhui Medical University between January 2010 and August 2014. Clinical features of hypertrophic PWS were investigated. The factors related to hypertrophy in PWS were analyzed by univariate and multivariate unconditional logistic regression analyses. Results A total of 262 patients with PWS were enrolled, 82 (30 males and 52 females)of whom had hypertrophic PWS with a median age of 32.5 years (range, 18 - 54 years). Among the 82 patients, 66(80.48%)had plaque-like hypertrophic PWS, 9(10.98%)had papular or nodular type, and 7 (8.54%)had mixed type; 56.10% (46/82)were aged ≥ 30 years, 41.46% (34/82)varied from 11 to 30 cm2 in lesional area, and 85.36% (70/82)showed purple lesions. There was a significant difference between patients with hypertrophic PWS and those with flat PWS in the distribution of age, lesional area and color(χ2 = 25.559, 10.580, 90.630, respectively, all P < 0.05), while gender, Fitzpatrick′s skin type, lesional site and distribution were unrelated to hypertrophy in PWS (all P > 0.05). Multivariate unconditional logistic regression analysis revealed that an age ≥ 30 years(OR = 2.889, 95%CI: 1.459 - 5.721)and purple lesions(OR = 19.984, 95% CI: 5.704 - 70.023)were factors related to skin hypertrophy in PWS. Conclusion An age ≥ 30 years and purple lesions seem to be hypertrophy-related factors in PWS.

Objective To evaluate the changes of platelet-derived growth factor(PDGF) and vascular endo-thelial growth factor(VEGF) in infectious and autoimmunity diseaases. Methods The growth factors were measured by ELISA in 149 patients for seven times in different periods,and the levels and duration were compared. Results PDGF was (6.32±2.54) μg/ml and (2.57±1.65) μg/ml (P<0.05), and VEGF was (179.5±53.30) ng/ml and (221.4±70.04) ng/ml(P<0.05) in the two groups before treatment;There was statistical significance in dif-ferent time points between groups and within groups for PDGF(P<0.05) and significant difference for time chan-ging to the peak and changed duration between two groups for VEGF(P<0.05). For the two groups,the peak time of PDGF were (2.6±1.1) and (5.4±3.3) days;The peak time of VEGF were (2.4±0.7) and (7.2±3.3) days respectively(P<0.05 for each). However in the two groups, the change duration were (6.7±3.1) and (15.4±6.1) days for PDGF and (8.1±3.4) and (16.7±7.2) days for VEGF (P<0.05 for each). Conclu-sions There is significant difference for serum levels of PDGF and VEGF and the level change duration as well in the two groups, which maybe correlated with inflammatory nature and outcome.

Objective Several studies have indicated that miR-15a,miR-15b and miR-16 may be the important regulators of apoptosis.Since attenuate apoptosis could protect myocardium and reduce infarction size,the present study was aimed to find out whether these miRNAs participate in regulating myocardial ischemia reperfusion (I/R) injury.Methods Apoptosis in mice hearts subjected to I/R was detected by TUNEL assay in vivo,while flow cytometry analysis followed by Annexin V/PI double stain in vitro was used to detect apoptosis in cultured cardiomyocytes which were subjected to hypoxia/reoxygenation (H/R).Taqman real-time quantitative PCR was used to confirm whether miR-15a/15b/16 were involved in the regulation of cardiac I/R and H/R.Results Compared to those of the controls,I/R or H/R induced apoptosis of cardiomyocytes was significantly iucreased both in vivo (24.4％ ± 9.4％ vs.2.2％ ± 1.9％,P ＜ 0.01,n =5) and in vitro (14.12％ ±0.92％ vs.2.22％ ± 0.08％).The expression of miR-15a and miR-15b,but not miR-16,was increased in the mice I/R model,and the results were consistent in the H/R model.Conclusions Our data indicate miR-15 and miR-15b are up-regulated in response to cardiac I/R injury,therefore,down-regulation of miR- 15a/b may be a promising strategy to reduce myocardial apoptosis induced by cardiac I/R injury.

OBJECTIVE:To establish HPLC fingerprint of Qingbi granules.METHODS:HPLC method was adopted.The determination was performed on Diamonsil C18 column with mobile phase consisted of methanol-0.3％ phosphoric acid (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 260 nm,and column temperature was 25 ℃.The sample size was 10 μL.Using baicalin as reference,HPLC chromatograms of 10 batches of samples were determined.Common peak identification and similarity evaluation were performed by using TCM Chromatographic Fingerprint Similarity Evaluation Software (2.0 edition).RESULTS:There were 29 common peaks in HPLC chromatograms of 10 batches of samples.The similarity among the 10 batches was more than 0.90.After validation,HPLC chromatograms of 10 batches of samples were in line with control fingerprints.CONCLUSIONS:Established fingerprints can provide reference for identification and quality evaluation of Qingbi granules.

Objective To examine the expression profile of programmed death-ligand 1 (PD-L1) on lung endothelial or epithelial cells,and to determine the specific role of PD-L1 in mouse model of indirect acute lung injury (i-ALI).Methods Eighty male C57BL/6 mice were randomly divided into two parts (both n =40).The effects of different administration routes on the expression of PD-L1 were observed.The mice in each part were randomly divided into sham,i-ALI,i-ALI+small interfering RNA (siRNA) random sequence control,and i-ALI+PD-L1 siRNA which could specifically inhibit PD-L1 expression groups,with l0 mice in each group.i-ALI was reproduced in a mouse model of hemorrhagic shock in combination with a subsequent cecal ligation and puncture (CLP).In sham group,only bilateral femoral arteries were ligated without catheterization or bleeding,and only cecum was separated but perforation was not ligated.Intravenous or intratracheal delivery of PD-L1 siRNA was performed 2 hours following the resuscitation to suppress the expression of PD-L1 on lung endothelial or epithelial cells.The mice in i-ALI+siRNA random sequence control group were given siRNA random sequence without inhibition effect on PD-L1 expression,and those in sham group and i-ALI group were given 100 μL phosphate buffered saline (PBS).The mice were sacrificed at 24 hours after CLP,and samples of blood,lung tissue and bronchoalveolar lavage fluid (BALF) were harvested.Expressions of PD-L1 were determined with flow cytometry.Cytokines and chemokines in plasma,lung tissue and BALF were determined by enzyme linked immunosorbent assay (ELISA).The protein concentration in plasma and BALF and the activity of myeloperoxidase (MPO) in lung tissue were quantitatively measured.The pathological changes in lung tissue were observed under light microscope.Results ① Compared with sham group,PD-L1 expression on lung endothelial or epithelial cells were significantly elevated in i-ALI group [endothelial cells:(27.88 ± 1.53)％ vs.(19.64 ± 1.03)％,epithelial cells:(58.70 ± 8.21)％ vs.(29.23 ± 3.94)％,both P ＜ 0.05].② Mice received intravenous delivery of liposomal-encapsulated siRNA had significantly lower expression of PD-L1 on lung endothelial cells as compared with that of i-ALI group [(21.37 ± 0.76)％ vs.(27.88 ± 1.53)％,P ＜ 0.05].Intratracheal delivery of naked PD-L1 siRNA mainly inhibited the PD-L1 expression on epithelial cell as compared with that of i-ALI group [(31.23±4.71) ％ vs.(58.70±8.21) ％,P ＜ 0.05].The expression of PD-L1 in pulmonary microvascular endothelial cells or pulmonary epithelial cells of i-ALI mice was not affected by siRNA random sequence.③ PD-L1 silencing on pulmonary endothelial cells induced by intravenous delivery of PD-L1 siRNA led to a lower protein ratio of BALF/plasma [(4.48 ± 0.35) × 10-3 vs.(6.11 ± 0.56) × 10-3,P ＜ 0.05] and a decreased MPO activity in lung tissue (U · μg-1 · min-1:2.48 ± 0.47 vs.4.56 ± 0.52,P ＜ 0.05) as compared with that of i-ALI group.Moreover,inflammatory mediator levels such as interleukin-6 (IL-6),monocyte chemoattractant protein-1 (MCP-1),macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) in lung tissue or plasma were significantly reduced following PD-L1 suppression on endothelial cells as compared with those of i-ALI group [IL-6 (ng/g):177.4±23.2 vs.287.9±57.3,MCP-1 (ng/g):839.6±91.7 vs.1 395.7±211.9,MIP-2 (ng/g):923.7± 107.3 vs.1 700.9±240.2 in lung tissue;IL-6 (ng/L):950.2±192.7 vs.1 828.2±243.6,TNF-α (ng/L):258.7±29.1 vs.443.0 ± 58.1,MCP-1 (ng/L):2 583.8±302.3 vs.4 328.1 ±416.4,MIP-2 (ng/L):1 512.9± 165.6 vs.2 005.9 ± 85.7 in plasma,all P ＜ 0.05],however,there was no significant change in the levels of inflammatory factors in BALF.It was shown in lung tissue histology that PD-L1 silencing on pulmonary endothelial cells induced by intravenous delivery of PD-L1 siRNA led to lessened pulmonary edema and reduced immune cells emigration.Intratracheal delivery of PD-L1 siRNA for PD-L1 suppression on epithelial cells had minimal effects on protein ratio of BALF/plasma,MPO activity,inflammatory mediator expressions in lung tissue,plasma,and BALF as well as lung tissue histology.Conclusion PD-L1 silencing on endothelial cells but not epithelial cells protected mice against hemorrhagic shock-sepsis induced i-ALI.

Objective:To evaluate the early diagnostic value of tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) in acute kidney injury induced by sepsis.Methods:A total of 85 sepsis patients admitted to the EICU and GICU in Shanghai East Hospital from September 2017 to June 2019 were divided into theAKI group ( n=37) and the non-AKI group ( n=48) according to KIDGO diagnostic criteria, and 20 healthy volunteers were served as the control group. The clinical data were recorded and samples of urine were collected at 0 h, 6 h, 12 h, 1 d, 3 d and 7 d post sepsis. The levels of TIMP-2 and IGFBP-7 in the urine were analyzed with ELISA at different time points. Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC), the early diagnostic value of urinary TIMP-2 and IGFBP-7 in sepsis-induced AKI patients was determined. Results:Compared with the control group, the levels of TIMP-2 and IGFBP-7 of the AKI group were significantly higher at the above time points ( P<0.05), while those of the non-AKI group showed no significant differences. The levels of TIMP-2 and IGFBP-7 of the AKI group were significantly higher than the those of the non-AKI group ( P<0.05). ROC analysis showed that when the AUC of urine TIMP-2 peaked at 1 d, the sensitivity and specificity reached 97.5% and 81.2%, separately with the cutoff value of 151.23 ng/mL. Furthermore, when the AUC of urine IGFBP-7 peaked at 12 h, the sensitivity and specificity reached 100% and 72.8%, separately with the cutoff value of 14.91 ng/mL. Interestingly, when the AUC of combined TIMP-2×IGFBP-7 peaked at 12 h, the sensitivity reached 98.0% and specificity reached 91.5% with the cutoff value of 2.09 [(ng/mL) 2/1 000]. There was no significant correlation between the levels of TIMP-2 and IGFBP-7 with SOFA and APACHEⅡ score at 1 d, 3 d and 7 d post sepsis in the AKI group ( P>0.05). Conclusions:Urine TIMP-2 and IGFBP-7 have early diagnostic value in sepsis-induced AKI. Besides, the combination of the two biomarkers have superior predictive value than each single of them.

OBJECTIVE To explore the effects of irbesartan（Irb）combined with 5-fluorouracil（5-FU）on the proliferation and extracellular signal-regulated kinase （ERK）/peroxidase proliferator-activated receptor γ（PPARγ）signaling pathway of Lewis lung cancer cells. METHODS Lewis lung cancer cells from mice were divided into normal control （NC）group，Irb low-dose （LD）group（1×10－3 mmol/L），Irb high-dose （HD）group（1×10－1 mmol/L），5-FU group （10 μmol/L），Irb LD+ 5-FU group （Irb 1×10－3 mmol/L+5-FU 10 μmol/L）and Irb HD+ 5-FU group （Irb 1×10－1 mmol/L+5-FU 10 μmol/L）. MTT method was used to measure the activity of cell proliferation in each group. Plate colony formation experiment was used to determine the number of cell colonies formed in each group ；Western blot method was used to detect the expression levels of proliferating cell nuclear antigen （PCNA），p53，ERK1/2，p-ERK1/2 and PPAR γ protein in each group. RESULTS Compared with the NC group ，the cell proliferation activity ，the number of colonies formed and the protein levels of PCNA ，p-ERK1/2，and PPARγ were significantly reduced in the other five groups ，and the protein level of p 53 was significantly increased （P＜0.05）；the protein expression of ERK1/2 had no significant difference （P＞0.05）. The changes of above indexes in Irb LD+ 5-FU group and Irb HD+ 5-FU group were more significant than Irb LD group ，Irb HD group and 5-FU group （P＜0.05）. CONCLUSIONS Irb combined with 5-FU can inhibit the proliferation of Lewis lung cancer cell ，and the effect is better than that of the two alone. The mechanism may be related to the inhibition of ERK/PPARγ signal pathway.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.