Objective:To investigate the clinical characteristics, therapeutic efficacy and prognosis of patients with human immunodeficiency virus (HIV)-associated Hodgkin lymphoma.Methods:A retrospective case series study was conducted. The clinical data of 22 HIV-associated Hodgkin lymphoma patients in Chongqing University Cancer Hospital from December 2013 to June 2022 were retrospectively analyzed. Their clinical features, laboratory results, treatment, and prognosis were analyzed. Kaplan-Meier method was used to perform survival analysis.Results:The age [ M ( Q1, Q3)] of 22 patients was 44 years old (36 years old, 53 years old); 18 cases were male, 4 cases were female; clinical staging was stage Ⅲ in 5 patients and stage Ⅱ in 17 patients. All 22 patients were infected with HIV through sexual transmission, with 10 cases transmitted through man sex with man and 12 cases transmitted through heterosexual transmission. Nine patients were found to be infected with HIV at the time of diagnosis of lymphoma, and 13 patients presented with lymphoma at 22.2 months (12.3 months, 38.4 months) after diagnosis of HIV infection. Of the 22 patients, 3 abandoned treatment; 19 patients were treated with antiretroviral therapy combined with ABVD regimen chemotherapy, 9 patients had complete remission, and 10 patients had partial remission. After follow-up of 46.8 months (24.8 months, 64.5 months), the 5-year progression-free survival rate was 83.9%, and the 5-year overall survival rate was 89.5%. Conclusions:HIV-associated Hodgkin lymphoma exhibits an invasive process in clinical practice, and standardized antiretroviral therapy combined with ABVD regimen chemotherapy can lead to long-term survival for patients.

Objective To generate mice with whole-body overexpression of human METRNL gene.Methods Based on Cre-loxP system,Dppa3-Cre mice were mated with Rosa26-LSL-METRNL knock-in mice(R26-LSL-METRNL+/-)to generate R26-L-METRNL+/-mice.The genotypes of the offsprings were identified,and tissues of the blood,heart,liver,spleen,lung,kidney,brain,white adipose and muscle were collected.The expression of human METRNL gene in mice was investigated by quantitative real-time PCR,western blot and enzyme linked immunosorbent assay.Results Compared with wild type control mice,human METRNL in R26-L-METRNL+/-mice significantly expressed at both mRNA and protein levels in tissues,with abundant METRNL protein in blood.Conclusion The mouse model overexpressing human METRNL gene(R26-L-METRNL+/-mouse)was successfully constructed.

Objective To study the effect of MT-1207 on blood glucose,blood lipids and atherosclerosis in mice.Methods The apolipoprotein E knockout(ApoE-/-)mice were fed with normal feed,drug feed containing losartan and drug feed containing MT-1207 at a dosage of 30 mg/kg.The body weight,blood glucose and blood lipids were detected,and the plaque area of atherosclerotic was evaluated.8-week-old male C57 mice were fed a high fat diet and given intragastric administration of MT-1207 and losartan at a dose of 30 mg/kg per day.The body weight,blood glucose and lipids levels were also examined to further evaluate the effects of MT-1207 on blood glucose and lipids levels.Results ApoE-/-mice treated with MT-1207 and losartan gained weight faster.There was no significant improvement in blood glucose and lipid levels,and no significant change in atherosclerotic plaque area.MT-1207 and losartan had no significant improvement effect on blood glucose and blood lipids of C57 mice.Conclusion MT-1207 and losartan couldn't improve the levels of blood glucose,blood lipids and atherosclerosis,and couldn't aggravate atherosclerosis.

Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

Growth arrest and DNA damage-inducible 45b(GADD45b)was initially discovered to be involved in processes such as cell cycle arrest,differentiation and apoptosis.It is an important signal regulatory molecule in cells,responsible for signal transduction under various physiological or environmental stimuli.The GADD45b gene belongs to the GADD45 gene family.This gene is commonly expressed in human and fetal tissues,but the expression is tissue-specific,with high expression in the liver and bone marrow.The GADD45b protein is a small,evolutionarily conserved acidic protein distributed in both the cytoplasm and nucleus.Research has shown that GADD45b is closely associated with signaling pathways such as p38/MAPK and TGFβ/Smad3,and it has functions including improving tissue fibrosis and inflammation progression,inhibiting cell autophagy,and enhancing neural function recovery.GADD45b plays a significant role in tumors,innate immunity,neurological diseases,and disorders of hepatic glucose and lipid metabolism.The incidence of non-alcoholic fatty liver disease(NAFLD)is increasing year by year in China and has become a serious public health issue in the country.Disorders in hepatic glucose and lipid metabolism are major causes of NAFLD.Multiple studies have shown that GADD45b gene and protein exhibit abnormal expression in liver diseases with hepatic glucose and lipid metabolism disorders.Previous research has found that GADD45b can increase the stability of the FoxO1 protein in hepatocytes,and enhance the expression of PGC1a,thereby promoting hepatic gluconeogenesis.Additionally,GADD45b can inhibit fatty acid transport in hepatocytes by binding to FABP1 and reduce hepatic steatosis by interacting with HSP72 protein.Therefore,the roles of GADD45b in promoting hepatic gluconeogenesis,inhibiting fatty acid transport,and reducing steatosis may form the basis for research into treatments for hepatic glucose and lipid metabolism disorders and liver diseases.This paper reviews the characteristics and functions of the GADD45b protein,as well as recent advances in the study of hepatic glucose and lipid metabolism and liver diseases,aiming to provide reference for further GADD45b research.

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.

Objective To investigate the mechanism by which Liraglutide improves the inflammatory response in metabolic associated fatty liver disease(MAFLD)by regulating the interferon gene stimulating factor(STING)signaling pathway.Methods 20 male C57BL/6J mice were randomly divided into normal diet group(NC),Liraglutide intervention group(NC+Lir group),high fat diet group(HFD group)and Liraglutide intervention high fat diet group(HFD+Lir group),with 5 in each group.Mouse primary hepato-cytes(MPHs)were divided into normal control(Con)group,Liraglutide intervention group(Con+Lir group),palmitic acid group(PA group)and Liraglutide intervention PA group(PA+Lir group).The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in serum and triglyceride(TG)contents in liver were detected.HE and oil red O staining were used to observe the pathological changes in the liver and to calculate the MAFLD activity score(NAS).The mRNA expression levels of STING,IL-1β and TNF-α in tissues and cells were detected by qRT-PCR.The protein expression levels of STING,p-IRF3 and IFN-β were detected by Western blot.Results Body weight,liver tissue weight,serum ALT,AST,liver TG,steatosis,lobular inflammation and balloon-like NAS in HFD group were higher than those in NC group(P＜0.05 or P＜0.01).Body weight,liver tissue weight,serum ALT,AST,liver TG,steatosis,lobular inflammation and balloon-like NAS in HFD+Lir group were lower than those in HFD group(P＜0.05 or P＜0.01).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in liver of HFD group were higher than those of NC group(P＜0.05).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in HFD+ Lir group were lower than those in HFD+ Lir group(P＜0.05).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in PA group were higher than those in Con group(P＜0.01).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in PA+Lir group were lower than those in PA group(P＜0.05 or P＜0.01).Conclusion Liraglutide ameliorates the high-fat-induced inflammation responses in MAFLD by regulating the STING signaling pathways.

Liver transplantation is an effective method for the treatment of hepatocellular carcinoma (HCC). In order to reduce the high recurrence rate of tumor after liver transplantation for HCC, some scholars put forward the famous Milan criteria. Since the Milan criteria are too strict, some HCC patients with relatively “good biological behavior” and large lesions or multiple nodules are excluded from the waiting list for liver transplantation, and thus a large number of “expanded versions of the Milan criteria” appeared around the world. As for the histopathology of HCC, microvascular invasion (MVI) and poorly differentiated tumor tissue are significantly associated with the high recurrence rate after liver transplantation for HCC. This article reviews and summarizes the articles on the application of 18F-FDG PET/CT in liver transplantation for HCC in China and foreign countries and points out that the uptake of 18F-FDG in HCC lesions reflects the difference in the biological behavior (i.e., invasion) of tumor tissue. The intense uptake of 18F-FDG is positively correlated with MVI and poor differentiation of HCC. In addition, 18F-FDG can detect extrahepatic metastatic lesions sensitively and accurately. Preoperative 18F-FDG PET/CT findings have a high value in predicting the prognosis of liver transplantation for HCC, and it is a trend to incorporate such findings into the criteria for liver transplantation in HCC. It is also expected to unify the various expanded versions of the Milan criteria. The new criteria for liver transplantation may be defined as follows: the Milan criteria should be followed in general; as for the patients who do not meet the Milan criteria, liver transplantation can be performed for those who have lesions with negative 18F-FDG PET/CT results, without the involvement of major blood vessels or extrahepatic metastasis.

OBJECTIVE：To study the regulatory effects of stilbene glucosid e（TSG）on c-Jun N-terminal kinase （JNK）and protein phosphortase 2B（PP2B）in APP/PS1/Tau transgenic dementia （3×Tg-AD）mice，and to explore its potential mechanism of anti-Alzheimer’s disease （AD）. METHODS ：Totally 45 male 3×Tg-AD mice were randomly divided into model group ，positive control group （huperzine A ，0.15 mg/kg），TSG low-dose ，medium-dose and high-dose groups （0.033，0.1，0.3 g/kg），with 9 mice in each group. Another 9 normal male C 57BL/6J mice were included into normal control group. Administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 60 d. Normal control group and model group were given constant volume of normal saline intragastrically. After medication ，Morris water maze experiment was used to test the spatial learning and memory ability of mice in each group ；Nissl staining was used to observe the changes of Nissl bodies in cerebral cortex and hippocampus ；mRNA and protein expressions of JNK and PP 2B were detected by qRT-PCR and Western blotting assay. RESULTS：Compared with normal control group ，the escape latency was significantly prolonged （P＜0.01），the retention time of the original platform quadrant was significantly shortened （P＜ and the times of crossing the platform was significantly reduced in model group （P＜0.01）；the number of Nissl bodies in cerebral cortex and hippocampus was significantly 729011126@qq.com reduced，the staining was slight ；the relative expressions of JNK mRNA and protein were significantly increased （P＜ 0.01），and the relative expressi ons of PP 2B mRNA and protein were significantly decreased （P＜0.01）. Compared with model group ，the escape latency was significantly shortened in positive control group and TSG groups （P＜0.01）；the retention time of the original platform quadrant was significantly prolonged （P＜0.01）；the times of crossing the platform was significantly increased （P＜0.01）；the number of Nissl bodies in cerebral cortex and hippocampus was increased significantly ，the staining was heavy ；the relative expression of JNK protein was significantly decreased（P＜0.05 or P＜0.01），the relative expressions of PP 2B mRNA and protein were significantly increased （P＜0.01）， while the relative expression of JNK mRNA was significantly decreased in TSG high-dose group （P＜0.05）. CONCLUSIONS ：TSG can improve the learning and memory ability and neuronal damage of 3 × Tg-AD mice. The mechanism may be related to down-regulating the transcription and expression of protein kinase JNK ，up-regulating the transcription and expression of protein phosphatase PP 2B.