Autophagy is a cellular self-degradation process that maintains homeostasis and has been shown to promote tumor progression in advanced stages.Pancreatic cancer cells and the surrounding stromal cells exhibit high levels of autophagy.Therefore,targeting au-tophagy has emerged as a promising therapeutic strategy for pancreatic cancer.This review focuses on research targeting autophagy in pancreatic cancer treatment,elaborating on the roles and underlying mechanisms of autophagy in pancreatic cancer cell proliferation,metas-tasis,modulation of the tumor immune microenvironment,and drug resistance.Additional-ly,we summarize preclinical and clinical studies investigating autophagy-targeted therapies both as monotherapy and in combination with other treatments,aiming to provide new theo-retical rationale and therapeutic strategies for pancreatic cancer management.

Autophagy is a cellular self-degradation process that maintains homeostasis and has been shown to promote tumor progression in advanced stages.Pancreatic cancer cells and the surrounding stromal cells exhibit high levels of autophagy.Therefore,targeting au-tophagy has emerged as a promising therapeutic strategy for pancreatic cancer.This review focuses on research targeting autophagy in pancreatic cancer treatment,elaborating on the roles and underlying mechanisms of autophagy in pancreatic cancer cell proliferation,metas-tasis,modulation of the tumor immune microenvironment,and drug resistance.Additional-ly,we summarize preclinical and clinical studies investigating autophagy-targeted therapies both as monotherapy and in combination with other treatments,aiming to provide new theo-retical rationale and therapeutic strategies for pancreatic cancer management.

Objective To investigate the effects of different components of short-chain fatty acids (SCFAs) on depression-like behaviors and intestinal flora in chronic unpredictable mild stress (CUMS)-induced depressive rats. Methods Seventy-six healthy male rats were randomly divided into six groups. Rats in the acetate group (n=12),propionate group (n=15) and butyrate group (n=14) were given intraperitoneal injection (i.p.) of 50 mg/kg sodium acetate,100 mg/kg sodium propionate and 50 mg/kg sodium butyrate,respectively. Rats in the SCFAs group (n=12) were given i.p of 1∶1∶1 sodium acetate,sodium propionate and sodium butyrate mixed solution. Rats in the CUMS group (n=13) were given i.p of 1 mL/100 g saline. Rats in the control group (n=10) did not receive any treatment. Besides the control group,other groups were subjected to CUMS and intraperitoneal injection before stress for 28 days. The depression-like behaviors were assessed by sucrose preference test,forced swimming test,open field test,and then cecal fecal samples were collected to examine the composition of intestinal flora by 16S rRNA sequencing. Results Compared with the control group,the body weight of rats and the sugar preference coefficient decreased and the immobility time increased in the CUMS group (P<0.05). The butyrate group reversed the alterations in change of the sugar preference coefficient and the immobility time (P<0.05). Additionally,the sugar preference coefficient was elevated in the SCFAs group (P<0.05). The community structure of intestinal flora was changed in the CUMS group compared to the control group and was partially improved in the acetate group. The number of unique species reduced in the CUMS group but increased in the acetate group,propionate group,butyrate group and SCFAs group. LEfSe found the enrichment of Bifidobacterium in the propionate group and the enrichment of Collinsella in the SCFAs group. Conclusions Sodium butyrate significantly improves depressive-like behaviors of the CUMS-induced rats. Sodium acetate,sodium propionate,and short-chain fatty acid mixture can influence the composition of intestinal flora. However,their antidepressant effect is not significant. Sodium butyrate may be a better alternative for supplementing short-chain fatty acids in depression.

Vitiligo is an immune memory skin disease.T-cell factor 1(TCF1)is essential for maintaining the memory T-cell pool.There is an urgent need to investigate the characteristics of peripheral memory T-cell profile and TCF1+T-cell frequencies in patients with vitiligo.In this study,31 patients with active vitiligo(AV),22 with stable vitiligo(SV),and 30 healthy controls(HCs)were included.We measured circulating memory and TCF1+T-cell frequencies using flow cytometry.The Spearman's rank test was used to evaluate the correlation between cell frequencies and disease characteristics.Receiver operating characteristic curves(ROC)were constructed to investigate the discriminative power of the cell subpopulations.Circulating CD4+and CD8+terminally differentiated effector memory T-cell(TEMRA)frequencies were significantly higher in the AV group than in HCs(P＜0.05).TCF1+T-cell subpopulations were widespread increased in patients with vitiligo(P＜0.05).After adjusting for potential confounders,CD8+and CD4+central memory(TcM)cells,and CD8+TEMRA were correlated with disease activity(P＜0.05).The combined diagnostic value of the four(naive,effector memory,TcM,and TEMRA)CD8+TCF1+T-cell subsets was relatively high(area under the ROC curve(AUC)=0.804,sensitivity=71.70％,specificity=8334％),and the CD8+T-cell subsets combination per-formed well in discriminating disease activity(AUC=0.849,sensitivity=70.97％,specificity=90.91％).We demonstrated an altered circulating memory T-cell profile and increased TCF1+T-cell percentage in patients with vitiligo.T-cell subpopulations had a strong value for vitiligo diagnosis and activity evaluation.This evidence presents a potential new pharmacological target for inhibiting autoimmunity that leads to vitiligo.

Vitiligo is an immune memory skin disease. T-cell factor 1 (TCF1) is essential for maintaining the memory T-cell pool. There is an urgent need to investigate the characteristics of peripheral memory T-cell profile and TCF1⁺ T-cell frequencies in patients with vitiligo. In this study, 31 patients with active vitiligo (AV), 22 with stable vitiligo (SV), and 30 healthy controls (HCs) were included. We measured circulating memory and TCF1⁺ T-cell frequencies using flow cytometry. The Spearman's rank test was used to evaluate the correlation between cell frequencies and disease characteristics. Receiver operating characteristic curves (ROC) were constructed to investigate the discriminative power of the cell subpopulations. Circulating CD4⁺ and CD8⁺ terminally differentiated effector memory T-cell (T_EMRA) frequencies were significantly higher in the AV group than in HCs (P < 0.05). TCF1⁺ T-cell subpopulations were widespread increased in patients with vitiligo (P < 0.05). After adjusting for potential confounders, CD8⁺ and CD4⁺ central memory (T_CM) cells, and CD8⁺ T_EMRA were correlated with disease activity (P < 0.05). The combined diagnostic value of the four (naïve, effector memory, T_CM, and T_EMRA) CD8⁺TCF1⁺ T-cell subsets was relatively high (area under the ROC curve (AUC) = 0.804, sensitivity = 71.70%, specificity = 83.34%), and the CD8⁺ T-cell subsets combination performed well in discriminating disease activity (AUC = 0.849, sensitivity = 70.97%, specificity = 90.91%). We demonstrated an altered circulating memory T-cell profile and increased TCF1⁺ T-cell percentage in patients with vitiligo. T-cell subpopulations had a strong value for vitiligo diagnosis and activity evaluation. This evidence presents a potential new pharmacological target for inhibiting autoimmunity that leads to vitiligo.

Objective To investigate the effects of different components of short-chain fatty acids (SCFAs) on depression-like behaviors and intestinal flora in chronic unpredictable mild stress (CUMS)-induced depressive rats. Methods Seventy-six healthy male rats were randomly divided into six groups. Rats in the acetate group (n=12),propionate group (n=15) and butyrate group (n=14) were given intraperitoneal injection (i.p.) of 50 mg/kg sodium acetate,100 mg/kg sodium propionate and 50 mg/kg sodium butyrate,respectively. Rats in the SCFAs group (n=12) were given i.p of 1∶1∶1 sodium acetate,sodium propionate and sodium butyrate mixed solution. Rats in the CUMS group (n=13) were given i.p of 1 mL/100 g saline. Rats in the control group (n=10) did not receive any treatment. Besides the control group,other groups were subjected to CUMS and intraperitoneal injection before stress for 28 days. The depression-like behaviors were assessed by sucrose preference test,forced swimming test,open field test,and then cecal fecal samples were collected to examine the composition of intestinal flora by 16S rRNA sequencing. Results Compared with the control group,the body weight of rats and the sugar preference coefficient decreased and the immobility time increased in the CUMS group (P<0.05). The butyrate group reversed the alterations in change of the sugar preference coefficient and the immobility time (P<0.05). Additionally,the sugar preference coefficient was elevated in the SCFAs group (P<0.05). The community structure of intestinal flora was changed in the CUMS group compared to the control group and was partially improved in the acetate group. The number of unique species reduced in the CUMS group but increased in the acetate group,propionate group,butyrate group and SCFAs group. LEfSe found the enrichment of Bifidobacterium in the propionate group and the enrichment of Collinsella in the SCFAs group. Conclusions Sodium butyrate significantly improves depressive-like behaviors of the CUMS-induced rats. Sodium acetate,sodium propionate,and short-chain fatty acid mixture can influence the composition of intestinal flora. However,their antidepressant effect is not significant. Sodium butyrate may be a better alternative for supplementing short-chain fatty acids in depression.

Objective:To retrieve, evaluate and summarize the best evidence of exercise reversal intervention in the elderly with cognitive frailty, and to provide evidence for guiding exercise in elderly patients.Methods:This study was a summary of evidence-based nursing evidence. Based on the PIPOST (P: Population; I: Intervention; P: Professional; O: Outcome; S: Setting; T: Type of evidence) mode, the evidence of exercise reversal intervention in the elderly with cognitive frailty in 25 relevant guideline network and association websites, Chinese and foreign language comprehensive databases such as PubMed, CINAHL, Web of Science, Embase, Chinese Biomedical Database, China National Knowledge Internet and others were searched, extracted and integrated. The retrieval time was from January 1, 2013 to February 14, 2022.Results:A total of 22 articles were included, including 3 guidelines, 2 expert consensuses, 1 clinical decision-making, 1 evidence summary, 9 Meta analysis, and 6 randomized controlled trials. Finally, 28 pieces of the best evidence including 7 dimensions were namely formulate principles,overall assessment, exercise mode, exercise intensity, exercise time and frequency, exercise management, health guidance.Conclusions:This study summarized the best evidence of exercise intervention in the elderly with cognitive frailty, which are systematic, comprehensive, rigorous, and reliable. It can provide references for healthcare administrators to dynamically evaluate patients′cognitive frailty status, formulate personalized exercise programs, and standardize exercise guidance for patients, so as to delay or even reverse cognitive frailty.

Objective:To observe and analyze the morphological characteristic of bone marrow and peripheral blood in patients diagnosed with de novo acute leukemia.Methods:From October 1, 2015 to December 31, 2021, 1151 patients aged 47 (26, 62) years, consisting of 602 males and 549 females with newly diagnosed acute leukemia in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, were collected to preform the morphological analysis in bone marrow and peripheral blood smears. Based on the comprehensive diagnosis results of morphology, immunology, cytogenetics, and molecular biology, comparison between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), AML with RUNX1-RUNXITI gene, AML with CBFβ/MYH11 gene, acute promyelocytic leukemia (APL) with PML/RARA gene, AML with NPM1 gene, the rest of the AML, Ph+ALL and Ph-ALL were performed by Chi-square test along with analysis of the differences in the ratio of wood bundle cells, pseudo-Chediak-Higashi (PCH) inclusions, cytoplasmic small particles, nuclear notches, leukemia cells with cup-like changes (cup cells); as well as the differences in the micromeganuclei, early immature granulocytes, plasma cells, high eosinophils and other accompanying cells and the distribution of "grape-like" aggregation. Finally, the morphological characteristics of acute leukemia cells, the appearance and arrangement of accompanying cells were summarized.Results:Between AML and ALL, there were statistically significant differences in cytoplasmic Auer bodies[(45.5%, 0%), χ 2=211.400, P<0.01], PCH inclusion bodies[(28.9%, 0%), χ 2=114.100, P<0.01], cytoplasmic fine particles[(20.7%, 2.9%), χ 2=53.798, P<0.01], nuclear notches[(0.7%, 6.1%), χ 2=30.906, P<0.01], and goblet cells[(4.9%, 0.3%), χ 2=13.495, P<0.01], micromegakaryus [(22.4%, 0.3%), χ 2=80.398, P<0.01], plasma cells[(87.6%, 10.6%), χ 2=604.241, P<0.01], hyperacidophils[(15.3%, 1.0%), χ 2=46.116, P<0.01] showed significant differences in the "grape-like" aggregation distribution. In AML with RUNX1-RUNXITI gene, the changes of vacuoles and PCH inclusion bodies are more obvious; in AML with CBFβ/MYH11 gene, the increase of hypereosinophils is more obvious; in APL with PML/RARA gene, the increase of woodbundle is more obvious. The morphology of nuclei chromatin, nucleolus, and vacuoles were also different among the groups. Comparison between Ph+ALL and Ph-ALL showed that Ph+ALL was more prone to develop early immature granulocytes and plasma cells (all P<0.05). Conclusion:There are significant differences between AML and ALL in the characteristics of leukemia cells, the regularity of accompanying cells, and the aggregation and distribution patterns. The subtypes of AML with specific genetic abnormalities have their own characteristics in the appearance of vacuoles, PCH inclusions, hypereosinophils, woodbundle cells, and goblet cells. Ph+ALL is more prone to present early immature granulocytes and plasma cells.

Objective: To investigate the expression of CD155/TIGIT in patients with osteosarcoma and its significance Methods : The expression differences of CD155 and TIGIT in tumor tissues of distant metastatic osteosarcoma patients and non⁃metastatic osteosarcoma patients were analyzed by cancer Genome Atlas ( TCGA) database.The surgically removed tissues of osteosarcoma patients were collected to prepare pathological sections and tissue chips , and the tumor tissue and cell morphology were observed by HE staining. Immunohistochemical staining was used to detect the expression of CD155 and TIGIT , and the scores were divided into high expression group and low expression group according to the scores. Chi⁃square test was used to analyze the relationship between CD155/TIG⁃IT expression and clinical features and prognosis. Results : TCGA database data showed higher expression of CD155 and TIGIT in patients with osteosarcoma accompanied by metastasis. HE staining of pathological sections revealed that tumor tissues with high expression of CD155/TIGIT contained more binuclear or multinucleated , hyperchromatic and obviously heteromorphic tumor cells. Immunohistochemical staining and score analysis of tissue chip showed that the expression of CD155 and TIGIT was correlated with clinical stage and distant metastasis ( P < 0. 05) , but not with age , sex , tumor size , pathological type and tumor necrosis rate. Conclusion CD155 and TIGIT may be one of the prognostic indicators of osteosarcoma.

OBJECTIVES: Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. METHODS: Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (e_i) and degree (k_i). RESULTS: Repeated measures 2-factor ANCOVA showed significant main effects on group on the e_i and k_i values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the e_i and k_i values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher e_i and k_i values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher e_i and k_i values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher e_i and k_i values of LSFG (P=0.019 and P=0.026, respectively), and higher e_i value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher e_i values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the e_i and k_i values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the k_i value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. CONCLUSIONS There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high e_i of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased e_i and k_i values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.
Anhedonia ; Antidepressive Agents/therapeutic use* ; Depressive Disorder, Major/drug therapy* ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Prefrontal Cortex