BACKGROUND Liver hepatocellular carcinoma(LIHC)is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment(TME)and immune evasion.Regulatory T cells(Tregs)play a critical role in tumor ...BACKGROUND Liver hepatocellular carcinoma(LIHC)is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment(TME)and immune evasion.Regulatory T cells(Tregs)play a critical role in tumor progression.Suppressor of cytokine signaling 2(SOCS2),a key immune regulator,may modulate Treg activity and impact LIHC growth and metastasis.AIM To explore how the SOCS2 affects Treg activity in LIHC and its impact on tumor growth and metastasis.METHODS LIHC transcriptome data from The Cancer Genome Atlas database were analyzed using Gene Set Enrichment Analysis,Estimation of Stromal and Immune Cells in Malignant Tumors Using Expression Data,and Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts to evaluate immune pathways and Treg infiltration.Key prognostic genes were identified using Weighted Gene Coexpression Network Analysis and machine learning.In vitro,co-culture experiments,migration assays,apoptosis detection,and enzyme-linked immunosorbent assay were conducted.In vivo,tumor growth,metastasis,and apoptosis were assessed using subcutaneous and lung metastasis mouse models with hematoxylin and eosin staining,Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling,and immunohistochemistry analyses.RESULTS SOCS2 overexpression inhibited Treg cell activity,reducing LIHC cell migration and invasion while increasing apoptosis.In vivo,SOCS2 suppressed tumor growth and metastasis,confirming its therapeutic potential.CONCLUSION SOCS2 modulates CD4+T function in the TME,contributing to LIHC progression.Targeting SOCS2 presents a potential therapeutic strategy for treating LIHC.展开更多
Secondary aluminum dross(SAD),a by-product of aluminum extraction from primary aluminum dross,contains metallic aluminum particles coated with dense oxidized films,complicating the recovery of metallic aluminum using ...Secondary aluminum dross(SAD),a by-product of aluminum extraction from primary aluminum dross,contains metallic aluminum particles coated with dense oxidized films,complicating the recovery of metallic aluminum using traditional methods.Ball-milling was employed to break and alter the structure of these oxidized films.The results indicated that the films became thinner and stripped away,exposing the aluminum surface.Based on the in-situ observation of the structure evolution of milled SAD particles with temperature,the metallic aluminum liquid was efficiently recovered from SAD at 680℃via supergravity-enhanced separation,where the recovery ratio and mass fraction of Al in the separated aluminum phase were up to 95.72%and 99.10 wt.%,respectively.Moreover,the tailings can be harmlessly utilized in refractory,cement and ceramic fields with subsequent treatment,such as denitrification,dechlorination,and fluoride fixation.展开更多
Monoclonal antibodies(MAbs) are important tools for the study of proteins′ function and structure. But there has been no report on the preparation of MAbs against human KIAA0100 protein up to date. Here, first, we ge...Monoclonal antibodies(MAbs) are important tools for the study of proteins′ function and structure. But there has been no report on the preparation of MAbs against human KIAA0100 protein up to date. Here, first, we generated the mouse MAb against human KIAA0100 protein using purified recombinant 6×Histidinc(6×His)-tagged human KIAA0100 protein segment(1557–2234) as an antigen; then, the m RNA expression of human KIAA0100 gene was detected in U937 cells using Northern blot analysis. The results showed that the mouse MAb against human KIAA0100 protein could sensitively recognize the human KIAA0100 protein using Western blot analysis and immunocytochemistry analysis. Besides, Western blot analysis revealed that human KIAA0100 gene possibly encoded two different protein products(254 k Da and < 250 k Da) in U937 cells. Moreover,Northern blot analysis confirmed that human KIAA0100 gene might produced two different m RNA products(6000–10000 bp and 5000–6000 bp) in U937 cells. The results provide a basis for large-scale production of the MAb against human KIAA0100 protein, which will be useful for the study of human KIAA0100 protein′s function/structure and MAb-targeted drugs in the future.展开更多
Three pairs of specific primers were designed to amplify the F2-1, F2-2 and XF2-2 truncated sequences of ORF2 which encodes the capsid protein of porcine circovirus type 2 (PCV-2). The F2-1 sequence had most of the ...Three pairs of specific primers were designed to amplify the F2-1, F2-2 and XF2-2 truncated sequences of ORF2 which encodes the capsid protein of porcine circovirus type 2 (PCV-2). The F2-1 sequence had most of the NLS region of ORF2, but the F2-2 and XF2-2 genes had the NLS region deleted. Truncated genes were subcloned into pET-32a(+) vectors to construct recombinant fusion expression vectors. The vectors were then transformed into Rosetta(DE3) E. coli and expressed by induction of IPTG. Expressed proteins were detected by western blotting and ELISA. The protein with best immunoreactivity was confirmed and selected, then utilized to inoculate SPF rabbits to prepare polyclonal antibodies. The protein and prepared polyclonal antibody were utilized to detect sera samples against PCV-2 from Shandong province and PCV-2 particles in PK-15 cells. In our study, three recombinant fusion proteins were successfully obtained, and the molecular weights of fusion proteins were 35.9 kDa, 33.6 kDa and 38.6 kDa respectively detected by SDS-PAGE. All of the proteins showed positive reaction with anti-PCV-2 antisera, and His-XF2-2 showed better immunoreactivity than the others. The protein of His-XF2-2 was coated as antigen in ELISA to detect the seroprevalence of PCV-2 in certain districts of Shandong province, the seropositivity rate was 27.7 % (73/264). Specific fluorescence and positive signals for PCV-2 could be detected in PK-15 cells inoculated with PCV-2 with the participation of prepared antibodies against His-XF2-2 in IFA and IPMA. Experimental results indicated that the truncated PCV-20RF2 gene containing most of the NLS region was successfully expressed in E. coli, and His-XF2-2 was demonstrated to have better immunoreactivity with anti-PCV-2 antisera than the other two fusion proteins. His-XF2-2 and prepared polyclonal antibodies against it had a satisfactory capability in detecting PCV-2 infection.展开更多
The structure genes spike(S) ,nucleocapsid(N) ,membrane(M) ,small membrane(sM) of a porcine epidemic diarrhea virus(PEDV) strain DX isolated in Gansu province,North-west of China,were cloned,sequenced and compared wit...The structure genes spike(S) ,nucleocapsid(N) ,membrane(M) ,small membrane(sM) of a porcine epidemic diarrhea virus(PEDV) strain DX isolated in Gansu province,North-west of China,were cloned,sequenced and compared with published sequences of PEDV strains. The nucleotide sequences encoding the entire S,sM,M and N genes open reading frame(ORF) of DX were 4 152,231,681 and 1 326 bases long respectively. There were transcription regulatory sequences(TRSs) upstream of the initiator ATG of the S,N and M genes. The amino acids sequences of S,M and N contained 30,3 and 7 potential asparagine(N) -linked glycosylation sites. Homologous analysis and phylogenetic trees showed that DX had the closest relationship with strains LJB/06,JS-2004-2Z and CH/HLJH/06 that were also isolated from China and indicated the prevalence of some PEDV isolates in China were widespread since the JS-2004-2Z strain originated from the south of the China,and LJB/06 and CH/HLJH/06 were isolated from northeast China. The N gene was cloned using two primers which contained Nco I and BamH I restriction enzyme sites and subcloned into expression vector pET30a. The recombinant plasmid was then transformed into E.coli Rossta. SDS-PAGE showed there was a protein of about 55kDa as expected and Western blot indicated the N protein had biological activity.展开更多
The complete genome sequence of transmissible Gastroenteritis virus (TGEV) strain TS, previously isolated from Gansu province, was cloned and compared with published sequence data from other TGEV strains. Phylogenetic...The complete genome sequence of transmissible Gastroenteritis virus (TGEV) strain TS, previously isolated from Gansu province, was cloned and compared with published sequence data from other TGEV strains. Phylogenetic tree analysis based on the amino acid and nucleotide sequences of the S gene showed that the TGEV strains were divided into 3 clusters. TGEV TS showed a close evolutionary relationship to the American Miller cluster but had a 5' non-translated region (NTR) sequence closely related to the American Purdue cluster. Continued culture in different cell types indicated that TGEV TS virulence could be attenuated after fifty passages in Porcine kidney (PK-15) cells, and that the Porcine kidney cell line IB-RS-2 (IBRS) was not suitable for culture of the TGEV strain TS.展开更多
Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. He...Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online softwares; Secondly, Human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system in U937 cells. Cell proliferation and apoptosis were next evaluated in KIAA0100-knockdown U937 cells. The bioinformatic prediction showed that human KIAA0100 gene was located on 17q11.2, and human KIAA0100 protein was located in the secretory pathway. Besides, human KIAA0100 protein contained a signalpeptide, a transmembrane region, three types of secondary structures (alpha helix, extended strand, and random coil) , and four domains from mitochondrial protein 27 (FMP27). The observation on functional characterization of human KIAA0100 gene revealed that its downregulation inhibited cell proliferation, and promoted cell apoptosis in U937 cells. To summarize, these results suggest human KIAA0100 gene possibly comes within mitochondrial genome; moreover, it is a novel anti-apoptotic factor related to carcinogenesis or progression in acute monocytic leukemia, and may be a potential target for immunotherapy against acute monocytic leukemia.展开更多
BACKGROUND The results of intensive statin pretreatment before percutaneous coronary intervention(PCI)is inconsistent between Chinese and Western populations,and there are no corresponding meta-analyses involving hard...BACKGROUND The results of intensive statin pretreatment before percutaneous coronary intervention(PCI)is inconsistent between Chinese and Western populations,and there are no corresponding meta-analyses involving hard clinical endpoints in the available published literature.AIM To evaluate the efficacy and safety of high-dose statin loading before PCI in Chinese patients through a meta-analysis.METHODS Relevant studies were identified by searching the electronic databases of PubMed,Embase and Cochrane’s Library to December 2019.The outcomes included an assessment of major adverse cardiovascular event(MACE),non-fatal myocardial infarction(MI),cardiac death,target vessel revascularization(TVR),myalgia/myasthenia and abnormal alanine aminotransferase(ALT)in all enrolled patients.Random effect model and fixed effect model were applied to combine the data,which were further analyzed byχ2 test and I2 test.The main outcomes were then analyzed through the use of relative risks(RR)and its 95%confidence interval(95%CI).RESULTS Eleven studies involving 3123 individuals were included.Compared with patients receiving placebo or no statin treatment before surgery,intensive statin treatment was associated with a clear reduction of risk of MACE(RR=0.44,95%CI:0.31-0.61,P<0.00001).However,compared with the patients receiving moderateintensity statin before surgery,no advantage to intensive statin treatment was seen(RR=1.04,95%CI:0.82-1.31,P=0.74).In addition,no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR(RR=0.43,95%CI:0.18-1.02,P=0.06),myalgia/myasthenia(RR=1.35,95%CI:0.30-5.95,P=0.69)and abnormal alanine aminotransferase(RR=1.47,95%CI:0.54-4.02,P=0.45)except non-fatal MI(RR=0.54,95%CI:0.33-0.88,P=0.01).CONCLUSION Compared with placebo or no statin pretreatment,intensive statin before PCI displayed reduced incidence of MACE.However,there was no significant benefit between high and moderate-intensity statin.In addition,no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR,myalgia/myasthenia and abnormal alanine aminotransferase except non-fatal MI.展开更多
BACKGROUND Liver interventional surgery is a relatively safe and minimally invasive surgery.However,for patients who have undergone Whipple surgery,the probability of developing a liver abscess after liver interventio...BACKGROUND Liver interventional surgery is a relatively safe and minimally invasive surgery.However,for patients who have undergone Whipple surgery,the probability of developing a liver abscess after liver interventional surgery is very high.Fungal liver abscess has a high mortality rate,especially when complicated with malignant tumors,diabetes,coronavirus disease 2019(COVID-19)and other complications.Fungal liver abscess is rare,and there are no guidelines or expert consensus on the course of antifungal therapy.CASE SUMMARY A 54-year-old woman with pancreatic head cancer received albumin-bound paclitaxel in combination with gemcitabine chemotherapy after laparoscopic pancreaticoduodenectomy.Liver metastasis was found 1 mo after completion of 8 cycles of chemotherapy,followed by ablation of the liver metastasis.After half a month of liver metastasis ablation,the patient experienced fever after chemotherapy and was diagnosed with liver abscess complicated with COVID-19 by contrast-enhanced abdominal computed tomography and real-time polymerase chain reaction detection.The results of pus culture showed Candida albicans,which was sensitive to fluconazole.The patient underwent percutaneous catheter drainage,antifungal therapy with fluconazole,and antiviral therapy with azvudine.During antifungal therapy,the patient showed a significant increase in liver enzyme levels and was discharged after liver protection therapy.Oral fluconazole was continued for 1 wk outside the hospital,and fluconazole was used for a total of 5 wk.The patient recovered well and received 4 cycles of fluorouracil,leucovorin,oxaliplatin,and irinotecan after 2 mo of antifungal therapy.CONCLUSION Effective treatment of Candida albicans liver abscess requires early detection,percutaneous catheter drainage,and 5 wk of antifungal therapy.Meanwhile,complications such as COVID-19 should be actively managed and nutritional support should be provided.展开更多
Platelet-derived growth subunit A(PDGFA)plays critical roles in development of glioblastoma(GBM)with substantial evidence from TCGA database analyses and in vivo mouse models.So far,only platelet-derived growth recept...Platelet-derived growth subunit A(PDGFA)plays critical roles in development of glioblastoma(GBM)with substantial evidence from TCGA database analyses and in vivo mouse models.So far,only platelet-derived growth receptor a(PDGFRA)has been identified as receptor for PDGFA.However,PDGFA and PDGFRA are categorized into different molecular subtypes of GBM in TCGA_GBM database.展开更多
Medulloblastoma(MB)is one of the most common childhood malignant brain tumors(WHO grade IV),traditionally divided into WNT,SHH,Group 3,and Group 4 subgroups based on the transcription profiles,somatic DNA alterations,...Medulloblastoma(MB)is one of the most common childhood malignant brain tumors(WHO grade IV),traditionally divided into WNT,SHH,Group 3,and Group 4 subgroups based on the transcription profiles,somatic DNA alterations,and clinical outcomes.Unlike WNT and SHH subgroup MBs,Group 3 and Group 4 MBs have similar transcriptomes and lack clearly specific drivers and targeted therapeutic options.The recently revised WHO Classification of CNS Tumors has assigned Group 3 and 4 to a provisional non-WNT/SHH entity.In the present study,we demonstrate that Kir2.1,an inwardly-rectifying potassium channel,is highly expressed in non-WNT/SHH MBs,which promotes tumor cell invasion and metastasis by recruiting Adam10 to enhance S2 cleavage of Notch2 thereby activating the Notch2 signaling pathway.Disruption of the Notch2 pathway markedly inhibited the growth and metastasis of Kir2.1-overexpressing MB cell-derived xenograft tumors in mice.Moreover,Kir2.1^(high)/nuclear N2ICD^(high)MBs are associated with the significantly shorter lifespan of the patients.Thus,Kir2.1^(high)/nuclear N2ICD^(high)can be used as a biomarker to define a novel subtype of non-WNT/SHH MBs.Our findings are important for the modification of treatment regimens and the development of novel-targeted therapies for non-WNT/SHH MBs.展开更多
基金Supported by Wu Jieping Medical Foundation,No.320.6750.2021-06-30Guangdong Basic and Applied Basic Research Foundation,No.2019A1515110120National Natural Science Foundation of China,No.82002974。
文摘BACKGROUND Liver hepatocellular carcinoma(LIHC)is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment(TME)and immune evasion.Regulatory T cells(Tregs)play a critical role in tumor progression.Suppressor of cytokine signaling 2(SOCS2),a key immune regulator,may modulate Treg activity and impact LIHC growth and metastasis.AIM To explore how the SOCS2 affects Treg activity in LIHC and its impact on tumor growth and metastasis.METHODS LIHC transcriptome data from The Cancer Genome Atlas database were analyzed using Gene Set Enrichment Analysis,Estimation of Stromal and Immune Cells in Malignant Tumors Using Expression Data,and Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts to evaluate immune pathways and Treg infiltration.Key prognostic genes were identified using Weighted Gene Coexpression Network Analysis and machine learning.In vitro,co-culture experiments,migration assays,apoptosis detection,and enzyme-linked immunosorbent assay were conducted.In vivo,tumor growth,metastasis,and apoptosis were assessed using subcutaneous and lung metastasis mouse models with hematoxylin and eosin staining,Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling,and immunohistochemistry analyses.RESULTS SOCS2 overexpression inhibited Treg cell activity,reducing LIHC cell migration and invasion while increasing apoptosis.In vivo,SOCS2 suppressed tumor growth and metastasis,confirming its therapeutic potential.CONCLUSION SOCS2 modulates CD4+T function in the TME,contributing to LIHC progression.Targeting SOCS2 presents a potential therapeutic strategy for treating LIHC.
基金supported by the National Natural Science Foundation of China(Nos.52304342,52174275,51774037)the China Postdoctoral Science Foundation(No.2021M700393)。
文摘Secondary aluminum dross(SAD),a by-product of aluminum extraction from primary aluminum dross,contains metallic aluminum particles coated with dense oxidized films,complicating the recovery of metallic aluminum using traditional methods.Ball-milling was employed to break and alter the structure of these oxidized films.The results indicated that the films became thinner and stripped away,exposing the aluminum surface.Based on the in-situ observation of the structure evolution of milled SAD particles with temperature,the metallic aluminum liquid was efficiently recovered from SAD at 680℃via supergravity-enhanced separation,where the recovery ratio and mass fraction of Al in the separated aluminum phase were up to 95.72%and 99.10 wt.%,respectively.Moreover,the tailings can be harmlessly utilized in refractory,cement and ceramic fields with subsequent treatment,such as denitrification,dechlorination,and fluoride fixation.
基金financial support from the National Natural Science Foundation of China (81270596)
文摘Monoclonal antibodies(MAbs) are important tools for the study of proteins′ function and structure. But there has been no report on the preparation of MAbs against human KIAA0100 protein up to date. Here, first, we generated the mouse MAb against human KIAA0100 protein using purified recombinant 6×Histidinc(6×His)-tagged human KIAA0100 protein segment(1557–2234) as an antigen; then, the m RNA expression of human KIAA0100 gene was detected in U937 cells using Northern blot analysis. The results showed that the mouse MAb against human KIAA0100 protein could sensitively recognize the human KIAA0100 protein using Western blot analysis and immunocytochemistry analysis. Besides, Western blot analysis revealed that human KIAA0100 gene possibly encoded two different protein products(254 k Da and < 250 k Da) in U937 cells. Moreover,Northern blot analysis confirmed that human KIAA0100 gene might produced two different m RNA products(6000–10000 bp and 5000–6000 bp) in U937 cells. The results provide a basis for large-scale production of the MAb against human KIAA0100 protein, which will be useful for the study of human KIAA0100 protein′s function/structure and MAb-targeted drugs in the future.
基金supported by the special studies for social welfare researches in institutes (2005DIB4J041)
文摘Three pairs of specific primers were designed to amplify the F2-1, F2-2 and XF2-2 truncated sequences of ORF2 which encodes the capsid protein of porcine circovirus type 2 (PCV-2). The F2-1 sequence had most of the NLS region of ORF2, but the F2-2 and XF2-2 genes had the NLS region deleted. Truncated genes were subcloned into pET-32a(+) vectors to construct recombinant fusion expression vectors. The vectors were then transformed into Rosetta(DE3) E. coli and expressed by induction of IPTG. Expressed proteins were detected by western blotting and ELISA. The protein with best immunoreactivity was confirmed and selected, then utilized to inoculate SPF rabbits to prepare polyclonal antibodies. The protein and prepared polyclonal antibody were utilized to detect sera samples against PCV-2 from Shandong province and PCV-2 particles in PK-15 cells. In our study, three recombinant fusion proteins were successfully obtained, and the molecular weights of fusion proteins were 35.9 kDa, 33.6 kDa and 38.6 kDa respectively detected by SDS-PAGE. All of the proteins showed positive reaction with anti-PCV-2 antisera, and His-XF2-2 showed better immunoreactivity than the others. The protein of His-XF2-2 was coated as antigen in ELISA to detect the seroprevalence of PCV-2 in certain districts of Shandong province, the seropositivity rate was 27.7 % (73/264). Specific fluorescence and positive signals for PCV-2 could be detected in PK-15 cells inoculated with PCV-2 with the participation of prepared antibodies against His-XF2-2 in IFA and IPMA. Experimental results indicated that the truncated PCV-20RF2 gene containing most of the NLS region was successfully expressed in E. coli, and His-XF2-2 was demonstrated to have better immunoreactivity with anti-PCV-2 antisera than the other two fusion proteins. His-XF2-2 and prepared polyclonal antibodies against it had a satisfactory capability in detecting PCV-2 infection.
基金National Basic Research Program (2004CCA00500)National High-tech Development Research Program of China (2006AA02Z440)
文摘The structure genes spike(S) ,nucleocapsid(N) ,membrane(M) ,small membrane(sM) of a porcine epidemic diarrhea virus(PEDV) strain DX isolated in Gansu province,North-west of China,were cloned,sequenced and compared with published sequences of PEDV strains. The nucleotide sequences encoding the entire S,sM,M and N genes open reading frame(ORF) of DX were 4 152,231,681 and 1 326 bases long respectively. There were transcription regulatory sequences(TRSs) upstream of the initiator ATG of the S,N and M genes. The amino acids sequences of S,M and N contained 30,3 and 7 potential asparagine(N) -linked glycosylation sites. Homologous analysis and phylogenetic trees showed that DX had the closest relationship with strains LJB/06,JS-2004-2Z and CH/HLJH/06 that were also isolated from China and indicated the prevalence of some PEDV isolates in China were widespread since the JS-2004-2Z strain originated from the south of the China,and LJB/06 and CH/HLJH/06 were isolated from northeast China. The N gene was cloned using two primers which contained Nco I and BamH I restriction enzyme sites and subcloned into expression vector pET30a. The recombinant plasmid was then transformed into E.coli Rossta. SDS-PAGE showed there was a protein of about 55kDa as expected and Western blot indicated the N protein had biological activity.
基金National Basic Research Program(2004CCA00500)National High-tech Development Research Program of China (2006AA02Z440)
文摘The complete genome sequence of transmissible Gastroenteritis virus (TGEV) strain TS, previously isolated from Gansu province, was cloned and compared with published sequence data from other TGEV strains. Phylogenetic tree analysis based on the amino acid and nucleotide sequences of the S gene showed that the TGEV strains were divided into 3 clusters. TGEV TS showed a close evolutionary relationship to the American Miller cluster but had a 5' non-translated region (NTR) sequence closely related to the American Purdue cluster. Continued culture in different cell types indicated that TGEV TS virulence could be attenuated after fifty passages in Porcine kidney (PK-15) cells, and that the Porcine kidney cell line IB-RS-2 (IBRS) was not suitable for culture of the TGEV strain TS.
基金financial support from the National Natural Science Foundation of China (No. 081718110232)
文摘Our previous study demonstrated that human KIAA0100 gene was a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online softwares; Secondly, Human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system in U937 cells. Cell proliferation and apoptosis were next evaluated in KIAA0100-knockdown U937 cells. The bioinformatic prediction showed that human KIAA0100 gene was located on 17q11.2, and human KIAA0100 protein was located in the secretory pathway. Besides, human KIAA0100 protein contained a signalpeptide, a transmembrane region, three types of secondary structures (alpha helix, extended strand, and random coil) , and four domains from mitochondrial protein 27 (FMP27). The observation on functional characterization of human KIAA0100 gene revealed that its downregulation inhibited cell proliferation, and promoted cell apoptosis in U937 cells. To summarize, these results suggest human KIAA0100 gene possibly comes within mitochondrial genome; moreover, it is a novel anti-apoptotic factor related to carcinogenesis or progression in acute monocytic leukemia, and may be a potential target for immunotherapy against acute monocytic leukemia.
基金Supported by the Scientific Research Project of Nanjing Clinical Medical Centre,No.1 Ning Health Science Education[2020].
文摘BACKGROUND The results of intensive statin pretreatment before percutaneous coronary intervention(PCI)is inconsistent between Chinese and Western populations,and there are no corresponding meta-analyses involving hard clinical endpoints in the available published literature.AIM To evaluate the efficacy and safety of high-dose statin loading before PCI in Chinese patients through a meta-analysis.METHODS Relevant studies were identified by searching the electronic databases of PubMed,Embase and Cochrane’s Library to December 2019.The outcomes included an assessment of major adverse cardiovascular event(MACE),non-fatal myocardial infarction(MI),cardiac death,target vessel revascularization(TVR),myalgia/myasthenia and abnormal alanine aminotransferase(ALT)in all enrolled patients.Random effect model and fixed effect model were applied to combine the data,which were further analyzed byχ2 test and I2 test.The main outcomes were then analyzed through the use of relative risks(RR)and its 95%confidence interval(95%CI).RESULTS Eleven studies involving 3123 individuals were included.Compared with patients receiving placebo or no statin treatment before surgery,intensive statin treatment was associated with a clear reduction of risk of MACE(RR=0.44,95%CI:0.31-0.61,P<0.00001).However,compared with the patients receiving moderateintensity statin before surgery,no advantage to intensive statin treatment was seen(RR=1.04,95%CI:0.82-1.31,P=0.74).In addition,no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR(RR=0.43,95%CI:0.18-1.02,P=0.06),myalgia/myasthenia(RR=1.35,95%CI:0.30-5.95,P=0.69)and abnormal alanine aminotransferase(RR=1.47,95%CI:0.54-4.02,P=0.45)except non-fatal MI(RR=0.54,95%CI:0.33-0.88,P=0.01).CONCLUSION Compared with placebo or no statin pretreatment,intensive statin before PCI displayed reduced incidence of MACE.However,there was no significant benefit between high and moderate-intensity statin.In addition,no significant difference was observed between intensive statin therapy and non-intensive statin therapy on the incidence of TVR,myalgia/myasthenia and abnormal alanine aminotransferase except non-fatal MI.
文摘BACKGROUND Liver interventional surgery is a relatively safe and minimally invasive surgery.However,for patients who have undergone Whipple surgery,the probability of developing a liver abscess after liver interventional surgery is very high.Fungal liver abscess has a high mortality rate,especially when complicated with malignant tumors,diabetes,coronavirus disease 2019(COVID-19)and other complications.Fungal liver abscess is rare,and there are no guidelines or expert consensus on the course of antifungal therapy.CASE SUMMARY A 54-year-old woman with pancreatic head cancer received albumin-bound paclitaxel in combination with gemcitabine chemotherapy after laparoscopic pancreaticoduodenectomy.Liver metastasis was found 1 mo after completion of 8 cycles of chemotherapy,followed by ablation of the liver metastasis.After half a month of liver metastasis ablation,the patient experienced fever after chemotherapy and was diagnosed with liver abscess complicated with COVID-19 by contrast-enhanced abdominal computed tomography and real-time polymerase chain reaction detection.The results of pus culture showed Candida albicans,which was sensitive to fluconazole.The patient underwent percutaneous catheter drainage,antifungal therapy with fluconazole,and antiviral therapy with azvudine.During antifungal therapy,the patient showed a significant increase in liver enzyme levels and was discharged after liver protection therapy.Oral fluconazole was continued for 1 wk outside the hospital,and fluconazole was used for a total of 5 wk.The patient recovered well and received 4 cycles of fluorouracil,leucovorin,oxaliplatin,and irinotecan after 2 mo of antifungal therapy.CONCLUSION Effective treatment of Candida albicans liver abscess requires early detection,percutaneous catheter drainage,and 5 wk of antifungal therapy.Meanwhile,complications such as COVID-19 should be actively managed and nutritional support should be provided.
基金This work was supported by:The National Key Research and Development Program of China(2017YFC1309004 to Y.W.)The National Natural Science Foundation of China(81972365 to Y.W.,81821003 to X.-W.B.,81602006 to F.-L.C.,and 81922056 to Y.S.)Chongqing Academician Program(cstc2019yszx-jcyjX0008 to Y.W.and cstc2018jcyj-yszxX0008 to X.-H.Y.).
文摘Platelet-derived growth subunit A(PDGFA)plays critical roles in development of glioblastoma(GBM)with substantial evidence from TCGA database analyses and in vivo mouse models.So far,only platelet-derived growth receptor a(PDGFRA)has been identified as receptor for PDGFA.However,PDGFA and PDGFRA are categorized into different molecular subtypes of GBM in TCGA_GBM database.
基金the National Key Research and Development Program of China(2016YFA0101203 to XW Bian and 2017YFC1309004 to Y Wang)the National Natural Science Foundation of China(31991172,81821003 to X.-W.Bian,81402080 to Y.-X.Wang)Chongqing Basic and Frontier Research Project(cstc2018jcyjAX0406 to Y.-X.Wang and cstc2018jcyjAX0168 to S.-Q.Lv).
文摘Medulloblastoma(MB)is one of the most common childhood malignant brain tumors(WHO grade IV),traditionally divided into WNT,SHH,Group 3,and Group 4 subgroups based on the transcription profiles,somatic DNA alterations,and clinical outcomes.Unlike WNT and SHH subgroup MBs,Group 3 and Group 4 MBs have similar transcriptomes and lack clearly specific drivers and targeted therapeutic options.The recently revised WHO Classification of CNS Tumors has assigned Group 3 and 4 to a provisional non-WNT/SHH entity.In the present study,we demonstrate that Kir2.1,an inwardly-rectifying potassium channel,is highly expressed in non-WNT/SHH MBs,which promotes tumor cell invasion and metastasis by recruiting Adam10 to enhance S2 cleavage of Notch2 thereby activating the Notch2 signaling pathway.Disruption of the Notch2 pathway markedly inhibited the growth and metastasis of Kir2.1-overexpressing MB cell-derived xenograft tumors in mice.Moreover,Kir2.1^(high)/nuclear N2ICD^(high)MBs are associated with the significantly shorter lifespan of the patients.Thus,Kir2.1^(high)/nuclear N2ICD^(high)can be used as a biomarker to define a novel subtype of non-WNT/SHH MBs.Our findings are important for the modification of treatment regimens and the development of novel-targeted therapies for non-WNT/SHH MBs.