Objective:To analyze the expression of tumor-associated transmembrane protein 61 (TMEM61) in cholangiocarcinoma tissues and its influence on prognosis and immune infiltration, as well as the effect on the proliferation of cholangiocarcinoma cells.Methods:In the cholangiocarcinoma gene chip dataset (TCGA-CHOL), differentially expressed genes between cholangiocarcinoma tissues and normal bile duct tissues were screened, and the upregulated TMEM61 gene was selected for further analysis. Based on the TMEM61 expression, cholangiocarcinoma patients higher than the median value were classified as the high-expression group ( n=17), and those lower than the median value were classified as the low-expression group ( n=18). The Kaplan-Meier survival curve was plotted. Functional and pathway enrichment analyses were conducted on differentially expressed genes related to TMEM61, and the correlations between TMEM61 expression and immune cells and immune molecules were respectively analyzed. The expression level of TMEM61 in cholangiocarcinoma tissues was analyzed by immunohistochemistry; The effect of TMEM61 expression on the proliferation of cholangiocarcinoma cells was detected by Western blotting, CCK-8, clone formation assay, etc. Results:Compared with normal tissues, the expression of TMEM61 mRNA in cholangiocarcinoma tissues was significantly upregulated ( t=18.31, P<0.001). The overall survival rate of patients in the high-expression group of TMEM61 was significantly lower than that in the low-expression group, and the difference was statistically significant ( χ2=7.23, P=0.007). The differentially expressed genes related to TMEM61 were involved in cell proliferation, cell cycle and DNA replication, etc. Compared with normal tissues, regulatory T cells ( t=10.21, P<0.001) and M0-type macrophages ( t=5.89, P=0.008) were significantly increased in cholangiocarcinoma tissues. Plasma cells ( t=7.34, P=0.002), γδT cells ( t=9.87, P<0.001), and M2-type macrophages ( t=11.53, P<0.001) were significantly decreased in cholangiocarcinoma tissues. The expression of TMEM61 was correlated with neurociliary protein 1, tumor necrosis factor ligand superfamily member 15 and B7 homologous protein 3 (all P<0.05). The proportion of positive staining area of TMEM61 protein in normal tissues was (10.15±2.27) %, and that in cholangiocarcinoma tissues was (69.43±11.66) %. The difference was statistically significant ( t=14.97, P<0.001). Inhibition of TMEM61 expression led to a decrease in the number of cholangiocarcinoma cell clones and proliferation activity, and the differences were statistically significant (both P<0.01). Conclusion:The expression of TMEM61 is elevated in cholangiocarcinoma tissues and is associated with poor prognosis. The abnormally high expression of TMEM61 affects the infiltration of immune cells and promotes the proliferation of cholangiocarcinoma cells. TMEM61 is expected to become a potential biomarker for the prognosis assessment of cholangiocarcinoma.

Objective To investigate the effects of scribble planar cell polarity protein(SCRIB)on proliferation,apoptosis,and autophagy of glioblastoma(GBM)and elucidate its potential underlying mechanisms.Methods The expression level of SCRIB in GBM tissue was queried through the Biomarker Exploration of Solid Tumors(BEST)database.Lentivirus-mediated shRNA interference was employed to downregulate SCRIB expression in human glioblastoma cell lines U87 and U251,which were divided into negative control group(mock)and SCRIB shRNA interference groups(kd1 and kd2).SCRIB expression levels were detected using Western blotting(WB)and quantitative polymerase chain reaction(qPCR).EdU incorporation and cell apoptosis rates were detected by flow cytometry(FCM).CCK-8 assay was used to detect the proliferation vitality of U87 and U251 cells,and WB was used to detect the expression of proliferation-related proteins.Immunofluorescence(IF)staining was conducted to detect the expression of autophagy-related proteins LC3 and p62,followed by quantitative analysis across multiple fields.WB was also used to detect the expression levels of LC3,p62,and proteins in the JAK-STAT3 signaling pathway.Results Compared with that of normal tissues,SCRIB mRNA expression level was significantly upregulated in GBM tissues(P＜0.05).FCM results showed that EdU incorporation rates were significantly reduced(P＜0.001)while cell apoptosis rates were markedly increased(P＜0.001)in U87 and U251 cells with SCRIB knockdown.CCK-8 results indicated that compared with the mock group,the proliferation vitality of U87 and U251 cells in the SCRIB knockdown group was significantly downregulated(P＜0.001).IF staining showed that LC3 fluorescence aggregation was significantly enhanced(P＜0.001),while p62 fluorescence aggregation was significantly reduced(P＜0.001)in the SCRIB knockdown group.WB results showed that compared with the mock group,the protein expression levels of p27,LC3,p-JAK2 and p-STAT3 were upregulated,while C-Myc,Cyclin D1,MCM,PCNA and p62 were downregulated,with statistically significant differences(P＜0.05).Conclusion Downregulation of SCRIB may induce autophagy and apoptosis in glioblastoma cells by inhibiting the JAK-STAT3 signaling pathway,thereby suppressing cell proliferation.

Objective To investigate the effects of scribble planar cell polarity protein(SCRIB)on proliferation,apoptosis,and autophagy of glioblastoma(GBM)and elucidate its potential underlying mechanisms.Methods The expression level of SCRIB in GBM tissue was queried through the Biomarker Exploration of Solid Tumors(BEST)database.Lentivirus-mediated shRNA interference was employed to downregulate SCRIB expression in human glioblastoma cell lines U87 and U251,which were divided into negative control group(mock)and SCRIB shRNA interference groups(kd1 and kd2).SCRIB expression levels were detected using Western blotting(WB)and quantitative polymerase chain reaction(qPCR).EdU incorporation and cell apoptosis rates were detected by flow cytometry(FCM).CCK-8 assay was used to detect the proliferation vitality of U87 and U251 cells,and WB was used to detect the expression of proliferation-related proteins.Immunofluorescence(IF)staining was conducted to detect the expression of autophagy-related proteins LC3 and p62,followed by quantitative analysis across multiple fields.WB was also used to detect the expression levels of LC3,p62,and proteins in the JAK-STAT3 signaling pathway.Results Compared with that of normal tissues,SCRIB mRNA expression level was significantly upregulated in GBM tissues(P＜0.05).FCM results showed that EdU incorporation rates were significantly reduced(P＜0.001)while cell apoptosis rates were markedly increased(P＜0.001)in U87 and U251 cells with SCRIB knockdown.CCK-8 results indicated that compared with the mock group,the proliferation vitality of U87 and U251 cells in the SCRIB knockdown group was significantly downregulated(P＜0.001).IF staining showed that LC3 fluorescence aggregation was significantly enhanced(P＜0.001),while p62 fluorescence aggregation was significantly reduced(P＜0.001)in the SCRIB knockdown group.WB results showed that compared with the mock group,the protein expression levels of p27,LC3,p-JAK2 and p-STAT3 were upregulated,while C-Myc,Cyclin D1,MCM,PCNA and p62 were downregulated,with statistically significant differences(P＜0.05).Conclusion Downregulation of SCRIB may induce autophagy and apoptosis in glioblastoma cells by inhibiting the JAK-STAT3 signaling pathway,thereby suppressing cell proliferation.

Objective:To analyze the expression of tumor-associated transmembrane protein 61 (TMEM61) in cholangiocarcinoma tissues and its influence on prognosis and immune infiltration, as well as the effect on the proliferation of cholangiocarcinoma cells.Methods:In the cholangiocarcinoma gene chip dataset (TCGA-CHOL), differentially expressed genes between cholangiocarcinoma tissues and normal bile duct tissues were screened, and the upregulated TMEM61 gene was selected for further analysis. Based on the TMEM61 expression, cholangiocarcinoma patients higher than the median value were classified as the high-expression group ( n=17), and those lower than the median value were classified as the low-expression group ( n=18). The Kaplan-Meier survival curve was plotted. Functional and pathway enrichment analyses were conducted on differentially expressed genes related to TMEM61, and the correlations between TMEM61 expression and immune cells and immune molecules were respectively analyzed. The expression level of TMEM61 in cholangiocarcinoma tissues was analyzed by immunohistochemistry; The effect of TMEM61 expression on the proliferation of cholangiocarcinoma cells was detected by Western blotting, CCK-8, clone formation assay, etc. Results:Compared with normal tissues, the expression of TMEM61 mRNA in cholangiocarcinoma tissues was significantly upregulated ( t=18.31, P<0.001). The overall survival rate of patients in the high-expression group of TMEM61 was significantly lower than that in the low-expression group, and the difference was statistically significant ( χ2=7.23, P=0.007). The differentially expressed genes related to TMEM61 were involved in cell proliferation, cell cycle and DNA replication, etc. Compared with normal tissues, regulatory T cells ( t=10.21, P<0.001) and M0-type macrophages ( t=5.89, P=0.008) were significantly increased in cholangiocarcinoma tissues. Plasma cells ( t=7.34, P=0.002), γδT cells ( t=9.87, P<0.001), and M2-type macrophages ( t=11.53, P<0.001) were significantly decreased in cholangiocarcinoma tissues. The expression of TMEM61 was correlated with neurociliary protein 1, tumor necrosis factor ligand superfamily member 15 and B7 homologous protein 3 (all P<0.05). The proportion of positive staining area of TMEM61 protein in normal tissues was (10.15±2.27) %, and that in cholangiocarcinoma tissues was (69.43±11.66) %. The difference was statistically significant ( t=14.97, P<0.001). Inhibition of TMEM61 expression led to a decrease in the number of cholangiocarcinoma cell clones and proliferation activity, and the differences were statistically significant (both P<0.01). Conclusion:The expression of TMEM61 is elevated in cholangiocarcinoma tissues and is associated with poor prognosis. The abnormally high expression of TMEM61 affects the infiltration of immune cells and promotes the proliferation of cholangiocarcinoma cells. TMEM61 is expected to become a potential biomarker for the prognosis assessment of cholangiocarcinoma.

BACKGROUND: Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment, and the concomitant symptoms, including cytokine release syndrome (CRS) or immune-related adverse events (irAEs), are frequently reported. However, clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell (GPBMC) infusion in patients receiving microtransplant (MST) have not yet been well depicted. METHODS: We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison. Clinical symptoms and their correlation with clinical features, laboratory findings, and clinical response were explored. RESULTS: Fever (58.0% [51/88]) and chills (43.2% [38/88]) were the significant early-onset symptoms after GPBMC infusion. Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills (3 [2-5] loci vs. 5 [3-5] loci, P  = 0.043 and 66.7% [12/18] vs. 37.1% [26/70], P  = 0.024). On the other hand, those with decreased CD4 + /CD8 + T-cell ratio developed more fever (0.8 [0.7-1.2] vs. 1.4 [1.1-2.2], P  = 0.007). Multivariable analysis demonstrated that younger patients experienced more fever (odds ratio [OR] = 0.963, 95% confidence interval [CI]: 0.932-0.995, P  = 0.022), while patients with younger donors experienced more chills (OR = 0.915, 95% CI: 0.859-0.975, P  = 0.006). Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion, which indicated mild and transient inflammatory response. Although no predictive value of infusion-related syndrome to leukemia burden change was found, the proportion of host pre-treatment activated T cells was positively correlated with leukemia control. CONCLUSIONS Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes, which were associated with donor- or recipient-derived risk factors, with less safety and tolerance concerns than reported CRS or irAEs.
Humans ; Leukocytes, Mononuclear ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Unrelated Donors ; Granulocyte Colony-Stimulating Factor ; Graft vs Host Disease

Kabuki syndrome (MIM 147920) is an autosomal dominant rare disease featured with multiple malformations and mental retardation. The main clinical manifestations of Kabuki syndrome are characteristic facial features, skeletal abnormalities, dermatoglyphic abnormalities, postpartum growth retardation, mild to moderate mental retardation, as well as other structural and functional abnormalities that may involve multiple systems. The establishment of diagnosis needs to be combined with clinical phenotype and the discovery of pathogenic mutation. Compared with the abundant descriptions and records of genotype-phenotype of postpartum patients, few prenatal diagnosis cases of Kabuki syndrome had been reported, which partially result from lacking the knowledge of its phenotype in fetuses that might suggest the diagnosis. This report performed comprehensive prenatal examinations to identify a fetus's etiology with multiple structural anomalies characterized by ascites, thickening of local skin, and cardiac abnormalities. We ruled out intrauterine infection, thalassemia, and chromosome abnormality by corresponding tests. Finally, trio whole-exome sequencing revealed a de novo heterozygous variation c.15641g > A (p.r5214h) in exon 48 of the KMT2D gene was the fetus's genetic pathogeny causing Kabuki syndrome. This result suggests that Kabuki syndrome should be in the suspected etiology list for prenatal hydrops/ascites. Our study confirmed that prenatal whole-exome sequencing is an efficient tool for diagnosing fetal abnormalities, and a multidisciplinary team is necessary for providing pregnancy guidance to patients.

Kabuki syndrome (MIM 147920) is an autosomal dominant rare disease featured with multiple malformations and mental retardation. The main clinical manifestations of Kabuki syndrome are characteristic facial features, skeletal abnormalities, dermatoglyphic abnormalities, postpartum growth retardation, mild to moderate mental retardation, as well as other structural and functional abnormalities that may involve multiple systems. The establishment of diagnosis needs to be combined with clinical phenotype and the discovery of pathogenic mutation. Compared with the abundant descriptions and records of genotype-phenotype of postpartum patients, few prenatal diagnosis cases of Kabuki syndrome had been reported, which partially result from lacking the knowledge of its phenotype in fetuses that might suggest the diagnosis. This report performed comprehensive prenatal examinations to identify a fetus's etiology with multiple structural anomalies characterized by ascites, thickening of local skin, and cardiac abnormalities. We ruled out intrauterine infection, thalassemia, and chromosome abnormality by corresponding tests. Finally, trio whole-exome sequencing revealed a de novo heterozygous variation c.15641g > A (p.r5214h) in exon 48 of the KMT2D gene was the fetus's genetic pathogeny causing Kabuki syndrome. This result suggests that Kabuki syndrome should be in the suspected etiology list for prenatal hydrops/ascites. Our study confirmed that prenatal whole-exome sequencing is an efficient tool for diagnosing fetal abnormalities, and a multidisciplinary team is necessary for providing pregnancy guidance to patients.

Objective:To construct the concept and its conceptual framework of hospital health literacy(HHL) for exploring the HHL promotion mechanism in the country.Methods:Based on the proceduralised grounded theory, twelve middle or senior managers of hospitals were selected for in-depth interviews and three hospitals were selected for field research from July 2021 to February 2022. Open coding, axial coding, and selective coding were used in data analysis, establishing the concept of HHL and its conceptual framework in China.Results:The conceptual framework of HHL was composed of an internal driver mechanism(hospitals improve their health literacy promotion management system, staff-led health literacy promotion, health literacy promoting physical environment construction), and an external driver mechanism(cooperate with external organizations and institutions to conduct health literacy promotion). The concept of HHL in China was derived as follows: the combination of supportive environments and human resources that health care organizations have in place can improve access and understandability of health information and simplify healthcare services to help patients of different health literacy levels more easily obtain, process, and understand health information as well as to make the most of medical services.Conclusions:Hospital health literacy promotion mechanism in China is a synergy between internal and external driver mechanisms.

Objective:To describe the current situation of health promotion and education in medical and health institutions in China, propose targeted improvement strategies and provide inspiration for medical and health institutions to implement the relevant content of the Health China Action.Methods:We searched China National Knowledge Infrastructure (CNKI) , WanFang Data, VIP China Science and Technology Journal Database, PubMed, Embase, Cochrane Library and so on. The retrieval time limit was from January 1, 2000 to December 30, 2021. The search content was the research on the theme of "health promotion and education in medical and health institutions".Results:A total of 20 articles were included. In the research on health promotion and education of medical and health institutions, the studies involved in "organization management" and "health education" were the most ( n=20) . There were 7 studies (35%) related to "smoke-free hospitals", 4 studies (20%) related to "work effect evaluation", and the studies on "healthy environment" was the least (15%, 3/20) . Conclusions:The work experience of attaching importance to organization management and health education, vigorously promoting the construction of smoke-free hospitals and institutions' health environment, and strengthening the effectiveness evaluation of health promotion and education can provide reference for medical and health institutions to implement the relevant content of health promotion in the Health China Action (2019-2030) .

Cell-Free Nucleic Acids ; blood ; Female ; Humans ; Mosaicism ; Placenta ; Pregnancy