OBJECTIVE To investigate the effects of L-mimosine on the proliferation and apoptosis of melanoma cells and its molecular mechanisms.METHODS The effects of different concentrations of L-mimosine on the viability of melanoma A375 and B16 cells were examined by the MTT assay.The ability of L-Mimosine to affect colony formation was assessed by the plate colony for-mation assay.The effects of L-mimosine on cell apoptosis,reactive oxygen species(ROS),and mitochondrial membrane potential were analyzed by flow cytometry.The changes in the expression levels of intracellular proteins such as Bcl-2,Bax,Cyt C,Cleaved Caspase-3,Cleaved Caspase-9,Bim-EL,Bad,p-JNK,p-c-Jun,p-MKK4,and p-ASK1 were detected by Western blot.The tumor-bearing mouse model was subjected to histological and TUNEL staining analysis of tumor tissues after treatment with normal saline,L-mimosine alone,and L-mimosine in combination with N-acetylcysteine(NAC).RESULTS L-mimosine significantly inhibited the prolifera-tion of A375 and B16 cells and significantly promoted cell apoptosis.Western blot analysis showed that L-mimosine could significantly increase the content of Apaf-1 and Cyt C in the cytoplasm,up-regulate the expression of Cleaved PARP,Cleaved Caspase-3,Cleaved Caspase-9,Bax,Bim-EL and Bad,and down-regulate the expression of anti-apoptotic protein Bcl-2.Further experiments showed that L-mimosine significantly induced the accumulation of ROS in A375 cells and activated the JNK/c-Jun signaling pathway,which was manifested by the significant increase of p-JNK,p-c-Jun,p-MKK4 and p-ASK1.Additionally,the antioxidant NAC could significantly antagonize the ROS accumulation induced by L-mimosine,thereby reversing the pro-apoptotic effects of L-mi-mosine on melanoma cells.In vivo experiments,NAC also significantly antagonized the tumor growth inhibition induced by L-mi-mosine,as evidenced by increased tumor volume and reversed expression levels of apoptosis-related proteins.CONCLUSION L-mi-mosine induces apoptosis in melanoma cells by increasing ROS levels and activating the JNK/c-Jun signaling pathway.

Objective:To understand the incidence rate of herpes zoster (HZ) and postherpetic neuralgia (PHN) in Beijing, and analyze the incidence trend of HZ and PHN from 2015 to 2022.Methods:Cases of HZ and PHN from 2015 to 2022 were retrieved from the Hospital Information Systems (HIS) of all primary and above hospitals/clinics in three districts representing the urban, inner suburban, and outer suburban areas of Beijing. After duplication screening, the first visit cases were screened, and the incidence characteristics were described. The incidence rate of HZ and PHN in each year by sex and age group and the age-standardized incidence rate were calculated. The annual percentage increase (APC) of incidence rate was calculated using the Joint regression model, and the change trend was analyzed.Results:The age-standardized incidence rate of HZ in Beijing from 2015 to 2022 ranged from 7.44‰ to 10.05‰, with an average annual incidence rate of 8.95 ‰, significantly increasing with age ( P<0.001). The Joinpoint regression model showed that the overall age-standardized incidence of HZ remained relatively stable, with no significant difference (APC=2.28%, t=1.56, P=0.170). However, the incidence rate among the 0-19-year-old group exhibited a trend of decrease (APC=-10.70%, t=-6.29, P<0.001). For PHN, the age-standardized incidence in Beijing ranged from 0.77‰ to 2.67‰, with an average annual incidence rate of 1.59‰ and a proportion of 9.48% to 26.86% among HZ cases. Both the incidence of PHN and its proportion among HZ cases increased with age ( P<0.001). The age-standardized incidence of PHN increased annually (APC=18.56%, t=9.02, P<0.001). Conclusion:The incidence rate of HZ and PHN in Beijing continues to be at a high level, and PHN shows an increasing trend over time.

OBJECTIVE To investigate the effects of L-mimosine on the proliferation and apoptosis of melanoma cells and its molecular mechanisms.METHODS The effects of different concentrations of L-mimosine on the viability of melanoma A375 and B16 cells were examined by the MTT assay.The ability of L-Mimosine to affect colony formation was assessed by the plate colony for-mation assay.The effects of L-mimosine on cell apoptosis,reactive oxygen species(ROS),and mitochondrial membrane potential were analyzed by flow cytometry.The changes in the expression levels of intracellular proteins such as Bcl-2,Bax,Cyt C,Cleaved Caspase-3,Cleaved Caspase-9,Bim-EL,Bad,p-JNK,p-c-Jun,p-MKK4,and p-ASK1 were detected by Western blot.The tumor-bearing mouse model was subjected to histological and TUNEL staining analysis of tumor tissues after treatment with normal saline,L-mimosine alone,and L-mimosine in combination with N-acetylcysteine(NAC).RESULTS L-mimosine significantly inhibited the prolifera-tion of A375 and B16 cells and significantly promoted cell apoptosis.Western blot analysis showed that L-mimosine could significantly increase the content of Apaf-1 and Cyt C in the cytoplasm,up-regulate the expression of Cleaved PARP,Cleaved Caspase-3,Cleaved Caspase-9,Bax,Bim-EL and Bad,and down-regulate the expression of anti-apoptotic protein Bcl-2.Further experiments showed that L-mimosine significantly induced the accumulation of ROS in A375 cells and activated the JNK/c-Jun signaling pathway,which was manifested by the significant increase of p-JNK,p-c-Jun,p-MKK4 and p-ASK1.Additionally,the antioxidant NAC could significantly antagonize the ROS accumulation induced by L-mimosine,thereby reversing the pro-apoptotic effects of L-mi-mosine on melanoma cells.In vivo experiments,NAC also significantly antagonized the tumor growth inhibition induced by L-mi-mosine,as evidenced by increased tumor volume and reversed expression levels of apoptosis-related proteins.CONCLUSION L-mi-mosine induces apoptosis in melanoma cells by increasing ROS levels and activating the JNK/c-Jun signaling pathway.

Objective:To analyze the epidemiological characteristics and trend of hospitalization of the patients with herpes zoster in Beijing from 2017 to 2022.Methods:In this retrospective study, the information of hospitalization of herpes zoster patients were collected from all medical institutions at the first level and above in Xicheng, Changping, and Miyun districts of Beijing. The age and gender specific hospitalization rates and age-standardized hospitalization rates were calculated. Joinpoint regression model was used to explore the trend of the hospitalization rates, and the influencing factors of the hospital stay length and complications were analyzed.Results:The age-standardized hospitalization rate of the patients with herpes zoster was 10.82/100 000-18.43/100 000 in Beijing from 2017 to 2022 [annual percent change (APC) =5.86%, 95% CI: -2.80%-15.98%]. The age-standardized hospitalization rate of the cases with herpes zoster as the main diagnosis showed an upward trend (APC=11.35%, 95% CI: 7.21%-16.23%). The age-standardized hospitalization rate showed an upward trend in women (APC=14.34%, 95% CI: 7.95%-22.37%). The hospitalization rate showed a downward trend in age group 30-39 years (APC=-24.92%, 95% CI: -48.56% - -1.85%) and showed upward trends in age group 70-79 years and 80-109 years (APC=23.18%, 95% CI: 13.53%-35.58%; APC=4.90%, 95% CI: 1.18%-9.19%). Complications occurred in 66.28% (680/1 026) of the patients. The median hospital stay length was 9 (5,15) days, and the patients with high age (≥80 years) and two or more complications had longer hospital stay, which were 12 (6, 23) and 14 (7, 27) days respectively ( P<0.001). Conclusions:The hospitalization rate in women and the elderly aged ≥70 years with herpes zoster as the main diagnosis showed upward trends in Beijing in recent years. The elderly aged ≥80 years usually had longer hospital stay, showing a relatively disease burden level. More attention should be paid to development of intervention strategies, such as vaccine, for this population.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To understand the incidence rate of herpes zoster (HZ) and postherpetic neuralgia (PHN) in Beijing, and analyze the incidence trend of HZ and PHN from 2015 to 2022.Methods:Cases of HZ and PHN from 2015 to 2022 were retrieved from the Hospital Information Systems (HIS) of all primary and above hospitals/clinics in three districts representing the urban, inner suburban, and outer suburban areas of Beijing. After duplication screening, the first visit cases were screened, and the incidence characteristics were described. The incidence rate of HZ and PHN in each year by sex and age group and the age-standardized incidence rate were calculated. The annual percentage increase (APC) of incidence rate was calculated using the Joint regression model, and the change trend was analyzed.Results:The age-standardized incidence rate of HZ in Beijing from 2015 to 2022 ranged from 7.44‰ to 10.05‰, with an average annual incidence rate of 8.95 ‰, significantly increasing with age ( P<0.001). The Joinpoint regression model showed that the overall age-standardized incidence of HZ remained relatively stable, with no significant difference (APC=2.28%, t=1.56, P=0.170). However, the incidence rate among the 0-19-year-old group exhibited a trend of decrease (APC=-10.70%, t=-6.29, P<0.001). For PHN, the age-standardized incidence in Beijing ranged from 0.77‰ to 2.67‰, with an average annual incidence rate of 1.59‰ and a proportion of 9.48% to 26.86% among HZ cases. Both the incidence of PHN and its proportion among HZ cases increased with age ( P<0.001). The age-standardized incidence of PHN increased annually (APC=18.56%, t=9.02, P<0.001). Conclusion:The incidence rate of HZ and PHN in Beijing continues to be at a high level, and PHN shows an increasing trend over time.

Objective:To analyze the epidemiological characteristics and trend of hospitalization of the patients with herpes zoster in Beijing from 2017 to 2022.Methods:In this retrospective study, the information of hospitalization of herpes zoster patients were collected from all medical institutions at the first level and above in Xicheng, Changping, and Miyun districts of Beijing. The age and gender specific hospitalization rates and age-standardized hospitalization rates were calculated. Joinpoint regression model was used to explore the trend of the hospitalization rates, and the influencing factors of the hospital stay length and complications were analyzed.Results:The age-standardized hospitalization rate of the patients with herpes zoster was 10.82/100 000-18.43/100 000 in Beijing from 2017 to 2022 [annual percent change (APC) =5.86%, 95% CI: -2.80%-15.98%]. The age-standardized hospitalization rate of the cases with herpes zoster as the main diagnosis showed an upward trend (APC=11.35%, 95% CI: 7.21%-16.23%). The age-standardized hospitalization rate showed an upward trend in women (APC=14.34%, 95% CI: 7.95%-22.37%). The hospitalization rate showed a downward trend in age group 30-39 years (APC=-24.92%, 95% CI: -48.56% - -1.85%) and showed upward trends in age group 70-79 years and 80-109 years (APC=23.18%, 95% CI: 13.53%-35.58%; APC=4.90%, 95% CI: 1.18%-9.19%). Complications occurred in 66.28% (680/1 026) of the patients. The median hospital stay length was 9 (5,15) days, and the patients with high age (≥80 years) and two or more complications had longer hospital stay, which were 12 (6, 23) and 14 (7, 27) days respectively ( P<0.001). Conclusions:The hospitalization rate in women and the elderly aged ≥70 years with herpes zoster as the main diagnosis showed upward trends in Beijing in recent years. The elderly aged ≥80 years usually had longer hospital stay, showing a relatively disease burden level. More attention should be paid to development of intervention strategies, such as vaccine, for this population.

Granulocytic myeloid-derived suppressor cells(G-MDSCs)are one of the main subgroups of MD-SCs,which are widely enriched in most cancers.It can inhibit the killing function of T-lymphocyte through the expression of arginase-1(Arg-1)and reactive oxygen species(ROS),reshape the tumor immune microenvironment,and promote the oc-currence and development of tumors.In recent years,more and more studies have found that G-MDSCs are significantly cor-related with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer,and the use of drugs specifi-cally targeting the recruitment,differentiation and function of G-MDSCs can effectively inhibit tumor progression.This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs.

Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P＜0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P＜0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P＜0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P＜0.001; ρ=0.28, P＜0.001; ρ=0.32, P＜0.001; ρ=0.21, P=0.004; ρ=0.32, P＜0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P＜0.001; r=0.231, P=0.002; r=0.258, P＜0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P＜0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.

Objective:To analyze the expression of FAT1 gene in pancreatic adenocarcinoma and its relationship with clinicopathological features, prognosis, and immunotherapy for pancreatic adenocarcinoma.Methods:(1) Bioinformatics analysis: based on FAT1 mRNA expression and clinical data of 179 cases of pancreatic adenocarcinoma in the TCGA database, and FAT1 mRNA expression data of 328 cases of normal pancreatic tissues in the GTEx database. We analyzed the differences in FAT1 mRNA expression in pancreatic adenocarcinoma and normal pancreatic tissues and the relationship between FAT1 mRNA expression and the degree of differentiation, clinical stage, prognosis, immune cell infiltration, and immune checkpoint-associated genes in pancreatic adenocarcinoma. FAT1-related differentially expressed genes were analyzed by applying Limma 3.40.2 software package, and GO and KEGG enrichment analysis was performed on the differentially expressed genes. Immunohistochemical (IHC) of FAT1 in pancreatic adenocarcinoma and normal pancreatic tissues was analyzed by HPA database. (2) Validation of own tissue samples: tissue samples and clinical and prognostic data of 192 patients with pancreatic ductal adenocarcinoma admitted to Zhejiang Cancer Hospital from March 8, 2010 to September 30, 2020 were collected. IHC was performed on the tissue samples to verify the protein expression of FAT1 in pancreatic adenocarcinoma and its relationship with immune-related proteins, the degree of differentiation of pancreatic adenocarcinoma, clinical staging, and prognosis.Results:(1) Bioinformatics analysis: the FAT1 mRNA expression of 179 pancreatic adenocarcinoma tissues from the TCGA database was 5.55±1.04, which was higher than that of 328 normal pancreatic tissues with FAT1 mRNA from the GTEx database (2.95±0.53, P＜0.001). FAT1-specific IHC images showed that FAT1 expression was generally high in pancreatic adenocarcinoma tissues, and FAT1 expression shifted from the cell membrane to the cytoplasm. The FAT1 mRNA expression in the highly differentiated group (31 cases), the moderately differentiated group (96 cases), and the lowly differentiated group (52 cases) were 4.99±1.46, 5.51±0.80, and 5.68±1.08, the expression of pancreatic adenocarcinoma tissues were all higher than that of normal pancreatic tissues (all P＜0.001), and the FAT1 mRNA expression of the moderately differentiated group and the poorly differentiated group were all higher than that of the highly differentiated group (all P＜0.001). The median progression-free survival time (PFS) and median overall survival time (OS) of the 90 patients in the FAT1 mRNA low-expression group were 16.5 and 24 months, respectively, which were longer than those of the 89 patients in the FAT1 mRNA high-expression group (median PFS and OS were 13 and 18 months, respectively; P-values were 0.011 and 0.005, respectively). Multifactorial Cox regression analysis showed that FAT1 mRNA expression level was an independent influencing factor for OS in pancreatic adenocarcinoma patients ( HR=1.47, 95% CI: 1.09-1.99). Correlation analysis showed that FAT1 mRNA expression in pancreatic adenocarcinoma was positively correlated with B-cell infiltration, CD8+ T-cell infiltration, neutrophil infiltration, macrophage infiltration, and myeloid dendritic cell infiltration ( ρ=0.27, P＜0.001; ρ=0.28, P＜0.001; ρ=0.32, P＜0.001; ρ=0.21, P=0.004; ρ=0.32, P＜0.001), and also positively correlated with mRNA expression of CD274, HAVCR2, and PDCD1LG2 ( r=0.327, P＜0.001; r=0.231, P=0.002; r=0.258, P＜0.001). GO and KEGG enrichment analyses showed that FAT1 mRNA expression levels were associated with activation of the Wnt signaling pathway ( P=0.029), the PI3K/Akt pathway ( P<0.001), and other tumor microenvironment-related pathways. (2) Validation of own tissue samples: among 192 pancreatic adenocarcinoma tissues, FAT1 was highly expressed in 58 cases (30.21%), and the proportion of FAT1-expressing positive tumor cells was positively correlated with the combined positive score of PD-L1 and the number of CD3+ T-cells infiltration ( r=0.154, P=0.032; r=0.287, P＜0.001), and the protein expression of FAT1 had no correlation with the differentiation degree of pancreatic adenocarcinoma ( ρ=0.082, P=0.254). The median OS of 58 patients in the FAT1 high-expression group and 134 patients in the FAT1 low-expression group were 18.89 and 25.84 months, respectively, and the difference was not statistically significant (χ2=1.93, P=0.165). Conclusion:FAT1 gene is highly expressed in pancreatic adenocarcinoma tissues, may play an oncogenic role in pancreatic adenocarcinoma, may be an adverse influence on overall survival and progression-free survival of patients; FAT1 gene may be involved in multiple immune-related pathways and promote tumor immune escape.