OBJECTIVE To extract the-SH active fractions(SHF)from Bubali Cornu(water buffalo horn)and evaluate its an-tipyretic activity.METHODS SHF was extracted from Bubali Cornu by SDS-DTT,and the content of native thiols(-SH)was deter-mined by Ellman reagent method.SHF was identified based on nano LC-MS/MS technology.Evaluation of antipyretic activity of SHF was based on LPS-induced fever rat model.The levels of PGE2,IL-1β,and TNF-α in plasma as well as the levels of cAMP,PGE2,and TNF-α in the hypothalamus were measured by ELISA kits.An untargeted metabolomics approach was used to further investigate the intervention of SHF on plasma metabolites in febrile rats.RESULTS SDS-DTT could effectively extract SHF from Bubali Cornu,in which the main components were type Ⅰ,type Ⅱ keratins and keratin-associated proteins,which were rich in Cys,and the ratio of-SH to protein in SHF was increased about 20 times more than that of traditional decoction.SHF could significantly decrease(P＜0.01)the body temperature which lasted for 4.5 hours.SHF could also significantly decrease the levels of PGE2,IL-1β,TNF-α and cAMP in plasma and hypothalamic.A total of 137 potentially differential metabolites were identified from plasma samples of the control and model groups,of which 31 metabolites could be dialed back after SHF administration,including lysophosphatidic acid,phosphatidyli-nositol,phosphatidic acid,triglycerides,phosphatidylcholine and so on,which were mainly involved in the glycerophospholipid meta-bolic pathway.CONCLUSION SHF has precise antipyretic effect,and the dosage of 1/10 of the aqueous extract can show its com-parable antipyretic effect,which provides the direction and basis for the basic research on the antipyretic efficacy of Bubali Cornu.

Purpose To investigate the diagnostic criteria and prognostic significance of squamous cell components in pa-pillary thyroid carcinoma(PTC).Methods Twenty-three cases of PTC containing squamous cell components were collect-ed,and pathological sections were reviewed.p40,CK5/6,Ki-67,BRAF V600E,p53,PD-L1(22C3),PAX8,and CD10,markers related to diagnosis,prognosis,and treatment,were de-tected by immunohistochemistry.Histological characteristics and immunophenotype of squamous cell components were comprehen-sively evaluated.The squamous cell components were classified histologically.The relationship between squamous cell classifica-tion and clinicopathological parameters,and their prognostic im-pact were analyzed.Results The squamous cell components were divided into squamous differentiation(19 cases)and ana-plastic carcinoma(4 cases).In the latter,the squamous cell components were diffusely distributed in sheets;the cell atypia was moderate to severe;and the Ki-67 index was at least 30%.High expression of p53 was found only in anaplastic carcinoma.Compared with squamous differentiation,anaplastic carcinoma had a larger diameter,higher BRAF V600E positive rate,high PD-L1 combined positive score,and extremely worse progression-free survival and overall survival.Squamous differentiation had inconspicuous impact on survival,and only one case relapsed af-ter secondary surgery.Conclusion The cell atypia,distribu-tion,maximum diameter,Ki-67 and p53 expression of squamous cell components are helpful in differentiating squamous compo-nents from anaplastic carcinoma.Positive BRAF V600E and PD-L1 expression suggest the feasibility of targeted therapy and im-munotherapy for anaplastic carcinoma.

BACKGROUND: The expression of programmed cell death ligand 1 (PD-L1) as a biomarker for immunotherapy in non-small cell lung cancer (NSCLC) is routinely detected in clinical pathology department. However, the spatial heterogeneity of PD-L1 expression in intrapulmonary tumors and extrapulmonary metastases is still a challenge for the clinical testing. This study aims to explore the differences of PD-L1 expression in test samples obtaining from different sites of NSCLC. This study may contribute to the detection strategy of PD-L1 in patients with advanced lung cancer. METHODS: One hundred and thirty-one cases of consecutively detected PD-L1 (22c3 assay, Dako) staining in metastatic NSCLC and 972 cases of non-paired intrapulmonary NSCLC were collected. The discrepancies of tumor proportion score (TPS) of PD-L1 expression in intrapulmonary samples and extrapulmonary metastatic samples of different sites were compared. RESULTS: The positive expression rate of PD-L1 in extrapulmonary metastatic NSCLC (TPS ≥ 1%) was 61.83%, and the TPS was significantly higher than that in intrapulmonary tumors (P=0.03). The PD-L1 scores of the specimens obtained from different sites were significantly different (P=0.007). The positive rates of PD-L1 in liver and adrenal metastases were 85.71% and 77.78% respectively, and their TPS were significantly higher than that of the intrapulmonary samples (P<0.05). The positive rates of PD-L1 in lymph node, bone, brain, soft tissue, and pleural metastases was 40.00%-66.67%, with no significant differences compared to intrapulmonary tumors. The analysis of histological subtype and sample type showed that the PD-L1 score of extrapulmonary samples of adenocarcinoma subtype or surgical specimen was significantly higher than that of intrapulmonary tumors. The analysis of clinicopathological parameters showed that the PD-L1 positive expression or high expression were significantly correlated with male patients, smoking history, and epidermal growth factor receptor (EGFR) wild type. CONCLUSIONS The expression of PD-L1 in metastatic NSCLC is generally higher than that in intrapulmonary tumor, and the positive rate of PD-L1 expression was discrepant in different sites of specimen. The differences of PD-L1 score between extrapulmonary metastatic samples and intrapulmonary samples may be associated with different metastatic sites, histological subtype, and specimen type.
B7-H1 Antigen/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Immunohistochemistry ; Lung Neoplasms/drug therapy* ; Male

Objective:To study the clinicopathological features and PD-L1 expression of microsatellite instability-high (MSI-H) gastric cancer.Methods:The clinicopathological data of the 2 472 patients who had undergone radical surgical resection and been performed immunohistochemical staining of four major mismatch repair (MMR) proteins (MLH1, PMS2, MSH2 and MSH6) from March 2014 to December 2018 at Peking University Cancer Hospital were collected. One hundred and seventy-one patients showed mismatch repair-deficient (dMMR), and microsatellite instability of these patients were detected with polymerase chain reaction (PCR). Then, taken PCR results as the standard, PD-L1 was assessed using immunohistochemistry (IHC) in the MSI-H gastric cancers.Results:MSI-H (vs. MSI-L) in gastric cancers was associated with female gender, advanced age, gastric-antrum location, intestinal type, lesion diameter exceeding 5 cm, absence of lymph node metastasis and positive PD-L1 expression ( P<0.05, respectively). Combined positive score (CPS) was an independent risk factor ( P=0.026, HR=8.385, 95% CI=1.293-54.367). Although no relationship between PD-L1 expression pattern and prognosis was observed,"diffuse-pattern" of the PD-L1 expression was related to lymphatic-vascular invasion ( P=0.007) and infiltration depth ( P=0.04). Among the patients with MSI-H and PD-L1 positive gastric cancer, the patients who experienced recurrence or died all had the pattern of "diffuse" PD-L1 expression. Also, regarding the expression level and staining pattern of PD-L1, the metastasis lesion of lymph node had a high coincidence with primary site ( P=0.45). Conclusions:MSI-H gastric cancer shows distinctive clinicopathological characteristics. The CPS can be used as a prognostic indicator in MSI-H gastric cancers, while the "diffuse-pattern" of PD-L1 expression could possibly be used as a prognostic indicator. The patients with advanced gastric cancer could obtain the expression level and staining pattern of PD-L1 using the biopsy material of metastatic lesions.

Objective: To retrospectively analyze the distribution of non-fermentative bacteria causing bloodstream infection in hospitalized patients in Sichuan Province and their drug susceptibility to common antibiotics for better understanding their epidemiological characteristics. Methods: From January 1, 2015 to December 31, 2017, all of the non-fermentative bacteria isolated from patients with bloodstream infection in nine hospitals in Sichuan Province were collected. Species distribution and drug resistance test results were retrospectively analyzed. Results: A total of 6 291 strains of pathogenic bacteria were isolated, including 3 674 strains of gram-negative bacteria (58.4%) and 2 617 strains of gram-positive bacteria (41.6%). The gram-positive bacteria were 1 895 strains of Staphylococcus (30.1%), 372 strains of Streptococcus (5.9%), 317 strains of Enterococcus (5.1%) and 33 strains of other gram-positive bacteria (0.5%). The gram-negative bacteria were 3 191 Enterobacteriaceae strains (50.7%), 389 non-fermentative strains (6.2%) and 94 other gram-negative strains (1.5%). The isolated non-fermentative bacteria were mainly Pseudomonas aeruginosa (136 strains, 35.0%), Acinetobacter baumannii (126 strains, 32.0%) and Stenotrophomonas maltophilia (33 strains, 8.5%). There were 167 (42.9%), 112 (28.8%) and 82 (21.1%) non-fermentative bacteria isolated in internal medicine departments, ICUs and surgery departments, respectively. The drug resistance rates of Pseudomonas aeruginosa to cefepime, ciprofloxacin and gentamicin were 16.5%, 10.7% and 9.9%, respectively. Carbapenems-resistant Pseudomonas aeruginosa (CR-PA) accounted for 13.6%. No polymyxin-resistant Pseudomonas aeruginosa was found. The resistance rates of Acinetobacter baumannii to all antibiotics were over 30% except for minocycline and polymyxin and 75.7% of carbapenem-resistant Acinetobacter baumannii (CR-AB) were isolated. The drug resistance rates to levofloxacin, trimethoprim/sulfamethoxazole and ceftazidime were 0%, 0% and 37.0% in Stenotrophomonas maltophilia isolates and 10.5%, 4.2% and 19% in Burkholderia cepacia isolates, respectively. Conclusions Non-fermentative bacteria causing 6.2% of bloodstream infection in Sichuan, mainly by Pseudomonas aeruginosa and Acinetobacter baumannii. There were significant differences in the isolation rate of non-fermentative bacteria in different departments and most of the strains were isolated in internal medicine departments. The detection rate of Acinetobacter baumannii with multiple drug resistance was high, while other non-fermentative bacteria had good sensitivity to antibiotics.

Background and objective hTe bone and sotf tissue sarcoma can metastasize to distant sites, most commonly the lungs. Some cases can be cured by radical metastasectomy, but its role, indication and prognostic factors remains controversial. hTe rarity of the disease combined with the diverse number of subtypes can make bone and sotf tissue sarco-mas very diffcult to study. hTere are few randomized control studies or international high volume results, and such reports in China are seldom seen. hTe aim of this study is to investigate surgical treatment outcomes and prognostic factors of pulmonary metastatic bone and sotf tissue sarcoma patients.Methods From January 2007 to December 2015, patients with bone and sotf tissue sarcoma who underwent multimodality therapy including deifnitive surgery for the primary lesion and at least one pulmonary metastasectomy were enrolled in the retrospective study. All the relevant clinical variables were collected, and then statistically analyzed and interpreted with the aid of univariate and multivariateCox proportional hazard regression method. ResultsTotally 155 pulmonary metastasectomies in 144 patients were analyzed. Incomplete R0 resection, a less than 1-year interval from a previous surgery, more than three detected nodules; and the summed maximum diameter of more than 45 mm for pulmonary metastases were independent prognostic indicators by multivariate analysis.Conclusion We suggest that meta-static bone and sotf tissue sarcoma patients can beneift most from aggressive surgical intervention of pulmonary metastasec-tomy. Its prognostic factors include R0 resection, a longer interval from a previous surgery, smaller total number and total size of pulmonary metastases.

OBJECTIVETo investigate the expression level of COX-2, p16(INK4A) and p53 in patients with classic Hodgkin's lymphoma (cHL), and to evaluate their correlation with prognosis.

METHODSThe clinical data and samples of 52 cHL cases were collected. Immunohistochemical staining was performed to analyze the proteins level mentioned above and in situ hybridization of EBV encoded RNA (EBER) to clarify the tumor EBV infection state. Correlation between the protein expression and prognosis of patients was analyzed.

RESULTSOf 52 cases, the male and female ratio was 1.6∶1, the age was from 22 to 68 years old. All lesions located primarily in lymph nodes. All samples from 52 cases were stained with COX-2, p16(INK4A) and p53, and the positive expression of COX-2 was found in 28 cases (53.8%）, that of p16(INK4A) in 25 cases (48.1%)and p53 in 42 cases (80.8%）. All patients were divided into two groups according to differences in age (<40 years/ ≥ 40 years), gender (male/female), EBV infection (yes/no), B symptoms (yes/no), and the Ann Arbor staging (Ⅰ-Ⅱ/Ⅲ-Ⅳ), the correlation with COX-2, p16(INK4A) and p53 expression were analyzed, and only p53 expression was correlated with Ann Arbor staging (P=0.027). The statistical analysis of correlations between COX- 2, p16(INK4A) and p53 showed that the expression of COX-2 was strongly correlated with p53 (P=0.008), and p16 (INK4A) was not related to either COX-2 or p53 (P=0.246 and 0.958). Kaplan- Meier univariate OS analysis using SPSS17.0 software showed that only COX-2 expression was an adverse prognostic factor for patients'event free survival (EFS) (P=0.003). Meanwhile COX-2 expression was a unique independent prognostic factor analyzed by COX proportional hazards regression model (HR=0.091, 95% CI 0.017-0.505, P=0.006).

CONCLUSIONThe expression rate of COX-2, p16 (INK4A) and p53 in the cHL were relatively high; and they were not statistically correlated with tumor EBV infection status; the COX-2 positive group had poor prognosis, but only event free survival time becomes statistically significant shorter. COX proportional hazard regression model was used to analyze the COX-2 expression as a independent adverse prognostic factors for EFS.

Adult ; Aged ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; metabolism ; Cyclooxygenase 2 ; genetics ; metabolism ; Disease-Free Survival ; Epstein-Barr Virus Infections ; Female ; Hodgkin Disease ; diagnosis ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Young Adult

OBJECTIVETo summarize the mortality of esophagectomy in our series and compare the different mortalities based on 30-day deaths and 90-day deaths postoperatively.

METHODSA total of 954 patients undergoing esophagectomy by single-surgeon-team between January 2000 and December 2012 from our prospective database were enrolled. The mortalities based on 30-day and 90-day deaths postoperatively were compared, and the causes of deaths within 30 days and 90 days were analyzed.

RESULTSAmong all these 954 patients, a total of 20 postoperative deaths(2.1%) were observed: 11 within 30 days(1.1%) and 9 between 30 and 90 days after surgery(1.0%). The reasons for deaths within 30 days were as follows: 3 for respiratory failure related to anastomotic leakage,1 for bleeding after stenting due to anastomotic fistula, 1 for sepsis, 3 for respiratory failure from presenting preoperative respiratory morbidities, 2 for cardiac arrest caused by preoperative heart disorder, and 1 for multiple organ failure caused by early adjuvant chemotoxicity. The reasons for deaths between 30 and 90 days were as follows: 1 for respiratory failure related to anastomotic leakage, 1 for cardiac arrest from preoperative heart disorder, 1 for cerebrovascular accident, 1 for liver failure from liver cirrhosis presenting preoperatively, 1 for renal failure after operation, 1 for tumor progression and 2 for unknown reasons.

CONCLUSIONSince postoperative mortality calculated based on 30 days deaths postoperatively may underestimate the risk of esophagectomy, mortality calculated based on 90 days may be a better option.

Anastomotic Leak ; Cause of Death ; Esophageal Neoplasms ; surgery ; Esophagectomy ; mortality ; Humans ; Postoperative Period ; Prospective Studies ; Risk Factors ; Stents

Purpose To investigate the clinicopathologic features, diagnosis and differential diagnosis of primary gastric inflammatory myofibroblastic tumor ( IMT) . Methods Four cases of gastric IMTs were studied by clinicopathologic analysis, immunohistochemistry and in situ hybridization, and the related literature was reviewed. Results In four cases there are two males and two females, age range from 21 to 51 years old, and tumor size ranged from 1. 5 to 6. 5 cm in the greatest dimension. Histologically, these tumors were composed of varied spindle cells and chronic inflammatory cells, in a myxoid or hyalinized stroma. Occasionally, there were calcifica-tion and ossification areas. Most of the spindle cells had bland appearance and a minority of the tumor cells showed mild atypia. One to two mitotic figures were recognized in 10 high power fields ( HPFs) in 1 to 2 patients. Smooth muscle actin staining was observed in all tumors and ALK staining observed in two tumors. One tumor focally expressed CD34. S-100, desmin, CD68, CD117 and DOG1 was negative in all IMTs. The patients were followed up from 24 to 66 months, and none of them had tumor relapsed or metastasis. Conclu-sions Primary gastric IMTs have an intermediate behavior, and a few cases have malignant potential. It should be distinguished from other spindle cell lesions similar to IMT.

Objective To evaluate the myocardial protective effects of Histidine-TryptophanKetoglutarate (HTK) solution on infants with tetralogy of fallot in cardiac operation through comparison with St.Thomas Ⅱ cardioplegia(STH) and HTK cardioplegia in the operation of tetralogy of fallot.Methods Forty infants with tetralogy of fallot(TOF) were enrolled in this study.Their age ranged from 7 to 35 months,and body mass from 5.3 to 9.5 kg.The infants were randomly divided into HTK (n =20) group and STH (n =20) group who received HTK or STH solution respectively.Then 3 ml blood sample were got at 1,2,4,8,24 and 48 h after the opening of ascending aorta.The serum levels of cardiac troponin Ⅰ(cTnI),creatine kinase(CK) and creatine kinase MB(CK-MB) were measured.Results There was significant difference between two groups in terms of the level of cTnI at different time (F(inner group)=49.94,P＜0.001;F(between group) =10.23,P＜0.001;F (across group) =28.49,P＜0.001),and the level of cTnI in HTK group was lower than that of STH group at 1,2,4,8,24 and 48 h after the opening of ascending aorta (P＜0.05).There was significant difference between two groups in terms of the level of CK at different time (F(inner group) =58.85,P＜0.001;F(between group) =16.43,P＜0.001;F(across group)=18.32,P＜0.001),and the level of CK in HTK group was lower than that of STH group at 1,2,4,8,24 and 48 h after the opening of ascending aorta (P＜0.05).There was significant difference between two groups in terms of the level of CK-MB at different time (F(inner group)=34.51,P ＜0.001;F(between group)=11.03,P＜0.001;F(across group)=10.28,P＜0.001),and the level of CK-MB in HTK group was lower than that of STH group at 1,2,4,8,24 and 48 h after the opening of ascending aorta (P ＜0.05).Conclusion HTK is more valid than STK for improving the ability of anti ischemia of myocardium and cardiac function,reducing arrhythmia and ischemia reperfusion injury on infants with TOF in cardiopulmonary bypass.