Objective To investigate the expression and clinical significance of leptin receptor (OBR) and phosphorylation of signal transducer and activator of transcription (p-STAT3) in patients with diffuse large B-cell lymphoma (DLBCL).Methods Immunohistochemical analysis was used to detect the expression of OBR and p-STAT3 in 80 patients with DLBCL and 10 patients with reactive lymphoid hyperplasia (RLH).Using a panel of immunohistochemical markers (CD10,bcl-6 and Mum-1),all cases of DLBCL were further divided into two groups,GCB (germinal center B-cell-like) or non-GCB.Results Immunohistochemistry revealed high expression of OBR and p-STAT3 in 45.0 ％ (36/80) and 28.8 ％ (23/80) cases of DLBCL,respectively,and minimal straining in 100.0 ％ (10/10) cases of RLH (P ＜ 0.05).Compared with GCB group (8.7 ％,2/23),non-GCB group had higher p-STAT3 high expression rate (36.8 ％,21/57) (P ＜ 0.05).There was no significant difference in the expression of OBR between these two groups.Compared with clinical stage Ⅰ-Ⅱ [46.2 ％ (18/39) and 25.6 ％ (10/39)],stage Ⅲ-Ⅳ had higher OBR and p-STAT3 high expression rate [61.9 ％ (13/21) and 38.1％ (8/21)] (P ＞ 0.05).The expression of OBR and p-STAT3 were not correlated with age,gender,extranodal infiltrations,LDH level,B-symptoms and IPI(international prognostic index)(P ＞ 0.05).The expression of OBR was positively related with that of p-STAT3 in DLBCL patients (r =0.232,P =0.039).Conclusion OBR could stimulate the JAK-STAT signaling pathway and induces the phosphorylation of STAT3.This may be involved in carcinogenesis and prognosis of DLBCL.

Purpose To investigate the expression of TET2 and DNMT3A in patients with peripheral T cell lymphoma (PTCL) and the relationship to immunophenotypes of PTCL.Methods Using a panel of immunohistochemical markers (CD3,CD4,CD10,BCL-6,CXCL-13,CD30,ALK),all cases of PTCLs were further divided into four groups,including angioimmunoblastic T cell lymphoma (AITL),peripheral T cell lymphoma,not otherwise specified (PTCL-NOS),anaplastic lymphoma kinase negative anaplastic large cell lymphoma (ALK-ALCL) and anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK + ALCL).The expression of TET2 and DNMT3A in 89 cases of PTCL was detected by immunohistochemical analysis.Results 89 cases were divide into four subtypes,AITL (36/89),PTCL-NOS (26/89),ALKALCL (18/89),and ALK + ALCL (9/89).Immunohistochemistry staining revealed higher cytoplasmic expression of TET2 and DNMT3A in AITL than that of in PTCL-NOS and ALCL (P ＜ 0.05).And the nuclear expression of DNMT3A in patients with AITL was higher than that of PTCL-NOS and ALCL (P ＜ 0.05).The cytoplasmic expression of TET2 was positively related with both cytoplasmic and nuclear expression of DNMT3A in patients with AITL (P ＜ 0.05).Conclusion TET2 combined with DNMT3A could be used as markers in AITL diagnosis,which could provide new strategy for AITL diagnosis.

Objective To investigate the expressions of CXCR4,MMP-2 and VEGF in pancreatic carcinoma and the relationship with biological behavior of pancreatic carcinoma.Methods Immunohistochemical PV6000 technique was used to detect the expression of CXCR4,MMP-2 and VEGF in 47 cases of pancreatic carcinoma tissues,and the relationship between the expressions and pathologic parameters,and the relationship among the expressions of the 3 proteins were analysed.Results The expression rates of CXCR-4,MMP-2 and VEGF were 72.3%,66.O%and 61.7%in pancreatic carcinoma tissues,and all these proteins were correlated with metastasis,clinical staging and prognosis(X2=5.84～12.69;P＜0.05).The expression of CXCR-4,MMP-2 and VEGF was not correlated with sex,age,tumor size and differentiation(X2=0.03～4.27;P＞0.05).There was a positive relationship between the expression of CXCR-4 and MMP-2 or VEGF in pancreatic carcinoma(r=0.587,0.521;P＜0.01).Conclusions CXCR-4 could up-regulate the expression of MMP-2 and VEGF in pancreatic carcinoma,and they may contribute to metastasis and invasion of pancreatic carcinoma.

Cryptotanshinone (CPT) is a natural compound isolated from traditional Chinese medicine Salvia miltiorrhiza Bunge. In the present study, the regulatory effect and potential mechanisms of CPT on tumor necrosis factor alpha (TNF-α) induced lectin-like receptor for oxidized low density lipoprotein (LOX-1) were investigated. Human umbilical vein endothelial cells (HUVECs) were cultured and the effect of TNF-α on LOX-1 expression at mRNA and protein levels was determined by Real-time PCR and Western blotting respectively. The formation of intracellular ROS was determined with fluorescence probe CM-DCFH2-DA. The endothelial ox-LDL uptake was evaluated with DiI-ox-LDL. The effect of CPT on LOX-1 expression was also evaluated with SD rats. TNF-α induced LOX-1 expression in a dose- and time-dependent manner in endothelial cells. TNF-α induced ROS formation, phosphorylation of NF-κB p65 and ERK, and LOX-1 expression, which were suppressed by rotenone, DPI, NAC, and CPT. NF-κB inhibitor BAY11-7082 and ERK inhibitor PD98059 inhibited TNF-α-induced LOX-1 expression. CPT and NAC suppressed TNF-α-induced LOX-1 expression and phosphorylation of NF-κB p65 and ERK in rat aorta. These data suggested that TNF-α induced LOX-1 expression via ROS activated NF-κB/ERK pathway, which could be inhibited by CPT. This study provides new insights for the anti-atherosclerotic effect of CPT.
Animals ; Aorta ; Blotting, Western ; Endothelial Cells* ; Fluorescence ; Human Umbilical Vein Endothelial Cells ; Lipoproteins ; Medicine, Chinese Traditional ; Phosphorylation ; Rats ; Reactive Oxygen Species* ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Rotenone ; Salvia miltiorrhiza ; Tumor Necrosis Factor-alpha

ABSTARCT Purpose To investigate the clinicopathologic characteristics and genetic mutations of metastatic follicular thy-roid carcinoma(FTC).Methods A total of 22 cases of meta-static FTC were collected,including previous medical history,imaging,treatments and outcomes,and next-generation sequen-cing study and Sanger sequencing were performed in 12 cases.Results There were 16 women and 6 men.Sixteen cases were older than 50 years.Seven cases presented with metastases as the first symptom.Fourteen cases developed metastases 3 to 12 years after thyroid surgery.Sixteen cases developed bone metas-tasis,10 cases had lung metastasis,and 3 cases had brain me-tastasis.Those patients with multiple bone metastases progressed during the follow-up period.The common gene mutations in me-tastases were NRAS p.Q61R(6 cases),HRAS p.Q61R(2 ca-ses)and KRAS p.Q61R(1 case),followed by TERT promoter mutation(8 cases).Other mutated genes included KEL,BRCA1/2,ALK,ROS1,ErbB4,etc.Conclusion FTC has a high misdiagnosis rate.Those diagnosed with FTC should under-go regular systemic examinations to detect potential metastasis,especially in bone,lung,and brain.Further research on the sig-nificance of NRAS and other molecular indicators in FTC metas-tasis will help to better predict its biological behaviors.

Objective To survey on training for general practice backbone mentors in tertiary hospitals of Hebei province.Methods A questionnaire survey on training status was conducted among general practice backbone mentors in tertiary hospitals of Hebei Province.The survey items included the basic information,knowledge of general practice and its training,suggestions for mentors training and general practice discipline construction in tertiary hospitals.Results Total 208 questionnaires were distributed and 208 were retrieved with a recovery rate of 100％.Among 208 participants,all of them were over the age of 30;202 (97.1％) had bachelor degree or above;202 (97.1％) were attending doctors or above;165 (79.3％) had worked for more than 10 years;169 (81.3％) had no or little knowledge of general practice;159 (76.4％)had not received general practice training before;124 (59.6％) thought that general practitioners were not qualified as "gatekeeper" at present;and 192 (92.3％) worked in the hospitals providing standardized residency training.The training contents in general section were prioritized as clinical skills,community health service development and policy,rules for general practice standardized training,theoretical training,the present situation and countermeasure of general teaching,the doctor-patient relationship and medical ethics.The contents in training method section were prioritized as lecture series of clinical medicine,case discussion,seminar,distance education with classroom teaching.The suggestions for mentors training included:the exploration of standardized training model,perfecting continuing education system for general practice mentors,more attention to the training at community health service centers and the consummation of general practice system.The suggestions for general practice discipline construction were that more attentions should be paid by the government and the hospitals leaders,the general practice departments in tertiary hospitals should closely cooperate with community health service centers in training ofqualified general practitioners.Conclusions The specialists in tertiary hospitals of Hebei province do not have enough knowledge about general practice and do not quite understand the necessity of establishment of general practice department,so the training for general practice mentors should be strengthened and improved.Properly policy and more social resources from the government and the hospitals leaders will be helpful for construction of general practice discipline in general hospital.

Objective:To investigate the relationship between electrocardiographic (ECG) changes and prognosis of paraquat poisoning patients, so as to provide evidence for the condition assessment in paraquat poisoning patients.Methods:In January 2022, The clinical data of paraquat poisoning patients were retrospectively analyzed in the First Affiliated Hospital of Wenzhou Medical University from January 1, 2016 to December 31, 2021. The patients' basic information (age, sex, underlying disease, and occupation) and the ECG within 24 hours were collected, and the data were statistically analyzed by SPSS 22.0. One variable analysis and multivariable logistic regression analysis were used to analyze the risk factors related to prognosis determine in their ECG. The receiver operating characteristic (ROC) curve were used to evaluate the diagnostic value of ECG indexes in patients with paraquat poisoning.Results:A total of 145 patients with paraquat poisoning were finally enrolled in this study, there were 84 patients survived and 60 patients died. One variable analysis revealed that heart rate ( P=0.000) , QTc changes ( P=0.000) , and ST-T changes ( P=0.007) of ECG had statistically significant differences in the prognosis of paraquat poisoning patients between the survival group and the death group. Multifactorial logistic results showed that heart rate ( OR=1.059, 95% CI: 1.033~1.086) and QTc ( OR=1.015, 95% CI: 1.000~1.029) were independent risk factors for death diagnosis of patients with paraquat poisoning ( P<0.05) . ROC curve analysis revealed that the area under the cure (AUC) of the prediction model constructed based on heart rate and QTc was 0.832 (95% CI: 0.765~0.899) , with the best diagnostic efficacy. Conclusion:Heart rate, QTc and the prediction model constructed based on both can be used as prognostic indicators for the diagnosis of patients with paraquat poisoning, and which have reference value for clinical prognosis diagnosis.

Objective:To investigate the relationship between electrocardiographic (ECG) changes and prognosis of paraquat poisoning patients, so as to provide evidence for the condition assessment in paraquat poisoning patients.Methods:In January 2022, The clinical data of paraquat poisoning patients were retrospectively analyzed in the First Affiliated Hospital of Wenzhou Medical University from January 1, 2016 to December 31, 2021. The patients' basic information (age, sex, underlying disease, and occupation) and the ECG within 24 hours were collected, and the data were statistically analyzed by SPSS 22.0. One variable analysis and multivariable logistic regression analysis were used to analyze the risk factors related to prognosis determine in their ECG. The receiver operating characteristic (ROC) curve were used to evaluate the diagnostic value of ECG indexes in patients with paraquat poisoning.Results:A total of 145 patients with paraquat poisoning were finally enrolled in this study, there were 84 patients survived and 60 patients died. One variable analysis revealed that heart rate ( P=0.000) , QTc changes ( P=0.000) , and ST-T changes ( P=0.007) of ECG had statistically significant differences in the prognosis of paraquat poisoning patients between the survival group and the death group. Multifactorial logistic results showed that heart rate ( OR=1.059, 95% CI: 1.033~1.086) and QTc ( OR=1.015, 95% CI: 1.000~1.029) were independent risk factors for death diagnosis of patients with paraquat poisoning ( P<0.05) . ROC curve analysis revealed that the area under the cure (AUC) of the prediction model constructed based on heart rate and QTc was 0.832 (95% CI: 0.765~0.899) , with the best diagnostic efficacy. Conclusion:Heart rate, QTc and the prediction model constructed based on both can be used as prognostic indicators for the diagnosis of patients with paraquat poisoning, and which have reference value for clinical prognosis diagnosis.

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.