High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatograph...High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatography. Sometimesonly an unclear duct shows in magnetic resonance cholangiopancreatographywith no focal strictures and upstream dilatation of the main pancreatic duct. Serialpancreatic juice cytology is valuable in diagnosis of those patients.展开更多
Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature ...Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.展开更多
BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects.The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy(H...BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects.The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy(HIPEC)has been shown to increase survival rates in these patients.Despite these advancements,debates persist regarding the magnitude of survival improvement attributed to this treatment modality.The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis,and it took a comparative analysis of patients exhibiting positive and negative cytological findings.Between April 2013 and March 2020,84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts:HIPEC(20 patients with peritoneal metastasis),cytology-positive(23 patients without peritoneal nodules but with positive wash cytology),and cytology-negative(41 patients with advanced gastric cancer,no peritoneal nodules,and negative wash cytology).The HIPEC cohort underwent gastrectomy with HIPEC,while the cytology-positive and cytology-negative groups received gastrectomy alone.The demographic,pat-hological,and survival data of the groups were compared.RESULTS The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss.Nevertheless,the complication rates were consistent across all three groups.Median survival in the HIPEC group was 20.00±4.89 months,with 1-year,2-year,and 3-year overall survival rates of 73.90%,28.70%,and 9.60%,respectively.These figures paralleled the survival rates of the cytology-positive group(52.20%at 1 year,28.50%at 2 years,and 19.00%at 3 years).Notably,47%of patients experienced peritoneal recurrence.CONCLUSION HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis,mirroring the outcomes in cytology-positive patients.However,peritoneal recurrence remained high.展开更多
目的Rausch and Schiller(1954)在美国阿拉斯加白令海峡St.Lawrence岛从北极狐(Alopex lagopus)和雪撬狗(sledge dogs)发现西伯利亚棘球绦虫新种(Echinococcus sibiricensis sp.nov.),但诸多学者认为E.sibiricensis Rausch et Schiller,...目的Rausch and Schiller(1954)在美国阿拉斯加白令海峡St.Lawrence岛从北极狐(Alopex lagopus)和雪撬狗(sledge dogs)发现西伯利亚棘球绦虫新种(Echinococcus sibiricensis sp.nov.),但诸多学者认为E.sibiricensis Rausch et Schiller,1954是欧洲的多房棘球绦虫(Echinococcus multilocularis Leuckart,1863)的地理株(或亚种)(Vogel,1957;Skrjabin and Abuladze,1964;Kumaratilake and Thompson,1982;Meyajaki,1991等)。于1985-2002年间,作者在我国内蒙古大兴安岭北麓草场多年进行泡状棘球蚴(alveolar Echinococcus)病原的野外调查和实验室鼠类的人工感染试验,结果发现该地区同地点存在有北美西伯利亚棘球绦虫、欧洲多房棘球绦虫及苏俄多房棘球绦虫三种不同"地理株",而且三种成虫常混合感染于同一终宿主沙狐(Vulpes corsac)的体内,它们的幼虫期也存在于当地的布氏田鼠(Microtus brandti)。2001年,作者再次检查当地沙狐151只,从中检出19只感染有泡状棘球绦虫成虫。含成熟虫体的13只阳性沙狐中,感染西伯利亚棘球绦虫有11只,其中2只单独感染此虫种,另9只还混合感染了欧洲多房棘球绦虫及苏俄多房棘球绦虫三虫种。在呼伦贝尔草原的泡状棘球蚴病原中,西伯利亚棘球绦虫是优势种,它在终宿主沙狐和中间宿主的感染率都高过其他虫种。本文着重介绍西伯利亚棘球绦虫的成虫子宫结构和它幼虫期在野外布氏田鼠及人工感染实验鼠体内的发育情况。展开更多
Objective To investigate the protective immunity against Echinococcus granulosus in mice immunized with rEg14-3-3. Methods ICR mice were subcutaneously immunized three times with rEg14-3-3, followed by the challenge w...Objective To investigate the protective immunity against Echinococcus granulosus in mice immunized with rEg14-3-3. Methods ICR mice were subcutaneously immunized three times with rEg14-3-3, followed by the challenge with Echinococcus granulosus protoscoleces intraperitoneally and then sacrificed after six months of post-challenge to detect the proliferation of splenocytes by MTT assay, and to measure the secretion of IL-2, IL-4, IL-20, and IFN -y by ELISA. The rate of reduced hydatid cyst and the levels of IgE, igG and IgG subclasses in sera were examined. Results Mice vaccinated with rEg14-3-3 and challenged with protoscoleces revealed significant protective immunity of 84.47%. ELISA analysis indicated that the immunized mice generated specific high levels of IgG and the prevailing isotypes of IgG were IgG1 and IgG2a. Splenocytes from mice immunized with rEg14-3-3 showed a significant proliferation response. The secretion of IFN-V and IL-2 increased significantly in the vaccinated mice whereas there was no significant difference in IL-4 and IL-20 levels between vaccinated and control mice. Conclusion The results indicate that the rEg24-3-3 vaccine could induce a high level of protective immunity as a promising vaccine candidate to prevent cystic echinococcosis.展开更多
BACKGROUND: A previous report has identified a significantly higher sensitivity of cancer detection for dedicated grasping basket than brushing at endoscopic retrograde cholangiopancreato- graphy (ERCP). This study...BACKGROUND: A previous report has identified a significantly higher sensitivity of cancer detection for dedicated grasping basket than brushing at endoscopic retrograde cholangiopancreato- graphy (ERCP). This study aimed to compare the diagnostic accuracy of Geenen brush and Dormia basket cytology in the differential diagnosis of bile duct stricture. METHOD: The current study enrolled one hundred and fourteen patients who underwent ERCP with both Geenen brush and Dormia basket cytology for the differential diagnosis of bile duct stricture at our institution between January 2008 and December 2012. RESULTS: We adopted sequential performances of cytologic samplings by using initial Geenen brush and subsequent Dormia basket cytology in 59 patients and initial Dormia basket and subsequent Geenen brush cytology in 55 patients. Presampling balloon dilatations and biliary stentings for the stricture were performed in 17 (14.9%) and 107 patients (93.9%), respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Geenen brush cytology for the diagnosis of malignant bile duct stricture were 75.0%, 100.0%, 100.0%, 66.7% and 83.3%, respectively, and those of Dormia basket cytology were 64.5%, 100.0%, 100.0%, 58.5% and 76.3%, respectively (P=0.347 and 0.827 for sensitivity and accuracy, respectively). The good and excellent cellular yields (≥grade 2) were obtained by Geenen brush and Dormia basket cytology in 88 (77.2%) and 79 (69.3%) patients, respectively.CONCLUSION: The sensitivity, specificity and accuracy of biliary sampling with a Dormia basket are comparable to those with conventional Geenen brush cytology in the detection of malignant bile duct stricture.展开更多
Objective To establish and optimize the proteomic analysis of protoscoleces-specific antigens from Echinococcus granulosus. To provide a foundation for identifying specific antigens in the soluble proteins of E. granu...Objective To establish and optimize the proteomic analysis of protoscoleces-specific antigens from Echinococcus granulosus. To provide a foundation for identifying specific antigens in the soluble proteins of E. granulosus protoscoleces for further research. Methods Brood capsules were collected aseptically from fertile E. granulosus cysts from the livers of an infected patient. The fertile E. granulosus cysts were fractured, and protoscoleces were collected by centrifugation. The soluble proteins of protoscoleces were acquired using the 2D Quant kit according to the manufacturer's instructions. We employed two-dimensional electrophoresis (2-DE) combined with immunoblot assay (Western blot) to analyze the soluble components of E. granulosus protoscoleces antigens. The 2-DE and immunoblot maps obtained were analyzed with PDQuest 8.0 image analysis software. Results About 233 soluble protein spots were identified with Coomassie-stained gels. Most of the proteins had a molecular weight of 16 000 Da to 117 000 Da, and an isoelectric point value of 3.0 to 10.0. 2-DE immunoblot was conducted and 57 specific antigen spots were observed, among which 23 spots were identified. Conclusion 2-DE combined with Western blot is the key to successful proteomic analysis and presents a new possibility for searching the specific E. granulosus protoscoleces antigens.展开更多
Objective: To investigate new scolicidal agent from natural resources to cope with the side effects associated with synthetic drugs in Echinococcosis. Methods: The scolicidal potential of methanolic fruit powder extra...Objective: To investigate new scolicidal agent from natural resources to cope with the side effects associated with synthetic drugs in Echinococcosis. Methods: The scolicidal potential of methanolic fruit powder extract (10 and 20 mg/mL) of Mallotus philippinensis ( M. philippinensis ) was investigated. Viability of protoscoleces was confirmed by trypan blue exclusion method, where mortality was observed at concentration of 10 and 20 mg/mL in 60 min treatment against Echinococcus granulosus ( E. granulosus ), under in-vitro conditions with reference to the known standard drug Praziquantel . Results: At concentration 10 and 20 mg/mL, the mortality rate was observed 97% and 99% respectively for 60 min treatment; while up to 93% mortality was observed with 20 mg/mL for only 10 min treatment. The concentration above 20 mg/mL for above 2 h showed 100% mortality, irrespective of further incubation. Conclusions: As compared with the standard anti-parasitic drug Praziquantel our extract has significant scolicidal activity with almost no associated side effects.展开更多
Objective:To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus(E. granulosus). Methods:We analysed EG95 polymorphism by collecting tota...Objective:To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus(E. granulosus). Methods:We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1(DNASTAR Inc.,Madison,WI),and the phylogenetic analysis was performed by using MEGA5.1(CEMI,Tempe,AZ,USA). In addition,linear and conformational epitopes were analysed,including secondary structure,NXT/S glycosylation,fibronectin type ecoⅢ(Fnndary Ⅲ) domain and glycosylphosphatidylinositol anchor signal(GPIanchor). The s structure was predicted by PSIPRED method. Results:Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence,X90928. However,EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates,respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine,X90928,and they belonged to Subgroup 1. However,in comparison to X90928,several amino acid mutations occurred in most isolates besides oncosphere,which potentially altered the immunodominant linear epitopes,glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. Conclusions:This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates,and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.展开更多
Objective:To identify full length cDNA sequence of lactate dehydrogenase(LDH) from adult Echinococcus granulosus(E.granulosus) and to predict the structure and function of its encoding protein using bioinformatics met...Objective:To identify full length cDNA sequence of lactate dehydrogenase(LDH) from adult Echinococcus granulosus(E.granulosus) and to predict the structure and function of its encoding protein using bioinformatics methods.Methods:With the help of NCBI,EMBI, Expasy and other online sites,the open reading frame(ORF),conserved domain,physical and chemical parameters,signal peptide,epitope,topological structures of the protein sequences were predicted and a homology tertiary structure model was created:Vector NT1 software was used for sequence alignment,phylogenetic tree construction and tertiary structure prediction. Results:The target sequence was 1 233 bp length with a 996 bp biggest ORF encoding 331 amino acids protein with typical L-LDH conserved domain.It was confirmed as full length cDNA of LDH from E.granulosus and named as EgLDH(GenBank accession number:HM748917).The predicted molecular weight and isoelectric point of the deduced protein were 3 5516.2Da and 6.32 respectively.Compared with LDHs from Taenia solium,Taenia saginata asiatica,Spirometra erinaceieuropaei.Schistosoma japonicum,Clonorchis sinensis and human,it showed similarity of 86% ,85% ,55% ,58% ,58% and 53% ,respectively.EgLDH contained 3 putative transmembrane regions and 4 major epitopes(54aa-59aa.81aa-87aa,97aa-102aa,307aa-313aa),the latter were significant different from the corresponding regions of human LDH.In addition,some NAD and substrate binding sites located on epitopes 54aa-59aa and 97aa-102aa,respectively.Tertiary structure prediction showed that 3 key catalytic residues 105R,165D and 192H forming a catalytic center near the epitope 97aa-102aa,most NAD and substrate binding sites located around the center.Conclusions:The full length cDNA sequences of EgLDH were identified.It encoded a putative transmembrane protein which might be an ideal target molecule for vaccine and drugs.展开更多
Aim: To compare the results of bladder tumor associated antigen (BTA TRAK), nuclear matrix protein 22 (NMP 22) and voided urine cytology (VUC) in detecting bladder cancer. Methods: A total of 135 elderly male ...Aim: To compare the results of bladder tumor associated antigen (BTA TRAK), nuclear matrix protein 22 (NMP 22) and voided urine cytology (VUC) in detecting bladder cancer. Methods: A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups: (i) 93 patients with bladder cancer; (ii) 42 patients with urinary benign conditions; and (iii) 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results: The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion: The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.展开更多
AIM: To explore the effect of Echinococcusmultilocularis on the activation of mitogen-activated protein kinase (MAPK) signaling pathways and on livercell proliferation.METHODS: Changes in the phosphorylation of MA...AIM: To explore the effect of Echinococcusmultilocularis on the activation of mitogen-activated protein kinase (MAPK) signaling pathways and on livercell proliferation.METHODS: Changes in the phosphorylation of MAPKs and proliferating cell nuclear antigen (PCNA)expression were measured in the liver of patients withalveolar echinococcosis (AE). MAPKs, MEK1/2 [MAPK/extracellular signal-regulated protein kinase (ERK)kinase] and ribosomal S6 kinase (RSK) phosphorylationwere detected in primary cultures of rat hepatocytesin contact in vitro with (1) E. multilocu/aris vesicle fluid(EmF), (2)E. multilocularis-conditioned medium (EmCM).RESULTS: In the liver of AE patients, ERK 1/2 andp38 MAPK were activated and PCNA expression wasincreased, especially in the vicinity of the metacestode.Upon exposure to EmF, p38, c-Jun N-terminal kinase(JNK) and ERK1/2 were also activated in hepatocytesin vitro, as well as MEK1/2 and RSK, in the absenceof any toxic effect. Upon exposure to EmCM, only JNKwas up-regulated.CONCLUSION: Previous studies have demonstratedan influence of the host on the MAPK cascade inE. multilocularis. Our data suggest that the reverse,i.e. parasite-derived signals efficiently acting onMAPK signaling pathways in host liver ceils, is actuallyoperating.展开更多
BACKGROUND: Telomerase activity is reported to be specific and frequent in human pancreatic cancer. We conducted this study to assess the usefulness of monitoring telomerase activity in exfoliated cells obtained by pa...BACKGROUND: Telomerase activity is reported to be specific and frequent in human pancreatic cancer. We conducted this study to assess the usefulness of monitoring telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of pancreatic cancer. METHODS: Exfoliated cells obtained by pancreatic duct brushing during ERCP from 21 patients (18 with pancreatic cancer, 3 with chronic pancreatitis) were examined. Telomerase activity was detected by polymerase chain reaction and telomeric repeat amplification protocol assay (PCR-TRAP-ELISA). RESULTS: D450 values of telomerase activity were 0.446 +/- 0.2700 in pancreatic cancer and 0.041 +/- 0.0111 in chronic pancreatitis. 77.8% (14/18) of patients with pancreatic cancer had cells with telomerase activity. None of the samples from patients with chronic pancreatitis showed telomerase activity, when the cutoff value of telomerase activity was set at 2.0. Cytological examination showed cancer cells in 66.7% (12/18) of the patients. CONCLUSIONS: Telomerase activity may be an early malignant event in pancreatic cancer development. Cytology and telomerase activity in cells obtained by pancreatic duct brushing may complement each other for the diagnosis of pancreatic cancer.展开更多
BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic le- sions. Nonetheless, the diagnostic valu...BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic le- sions. Nonetheless, the diagnostic value of this procedure may be limited by low cellularity of the specimen, contamination of intestinal cells and unfeasibility of ancillary immunocy- tochemical procedures. The present study was to evaluate its usefulness in the diagnosis of neoplastic lesions.展开更多
We describe the clinical, imaging and cytopathological features of solid pseudopapillary tumor of the pancreas (SPTP) diagnosed by endoscopic ultrasound- guided (EUS-guided) fine-needle aspiration (FNA). A 17-year-old...We describe the clinical, imaging and cytopathological features of solid pseudopapillary tumor of the pancreas (SPTP) diagnosed by endoscopic ultrasound- guided (EUS-guided) fine-needle aspiration (FNA). A 17-year-old woman was admitted to our hospital with complaints of an unexplained episodic abdominal pain for 2 mo and a short history of hypertension in the endocrinology clinic. Clinical laboratory examinations revealed polycystic ovary syndrome, splenomegaly and low serum amylase and carcinoembryonic antigen (CEA) levels. Computed tomography (CT) analysis revealed a mass of the pancreatic tail with solid and cystic consistency. EUS confirmed the mass, both in body and tail of the pancreas, with distinct borders, which caused dilation of the peripheral part of the pancreatic duct (major diameter 3.7 mm). The patient underwent EUS-FNA. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform malignant cells, forming microadenoid structures, branching, papillary clusters with delicate fibrovascular cores and nuclear overlapping. Naked capillaries were also seen. The nuclei of malignant cells were round or oval, eccentric with fine granular chromatin, small nucleoli and nuclear grooves in some of them. The malignant cells were periodic acid Schiff (PAS)-Alcian blue (+) and immunocytochemically they were vimentin (+), CA 19.9 (+), synaptophysin (+), chromogranin (-), neuro-specific enolase (-), a1- antitrypsin and a1-antichymotrypsin focal positive. Cytologic findings were strongly suggestive of SPTP. Biopsy confirmed the above cytologic diagnosis. EUS- guided FNA diagnosis of SPTP is accurate. EUS findings,cytomorphologic features and immunostains of cell block help distinguish SPTP from pancreatic endocrine tumors, acinar cell carcinoma and papillary mucinous carcinoma.展开更多
AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with s...AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.展开更多
文摘High-grade pancreatic intraepithelial neoplasia is a challenging diagnosis and itdoes not exhibit mass lesions. It is suspected based on changes in the mainpancreatic duct in magnetic resonance cholangiopancreatography. Sometimesonly an unclear duct shows in magnetic resonance cholangiopancreatographywith no focal strictures and upstream dilatation of the main pancreatic duct. Serialpancreatic juice cytology is valuable in diagnosis of those patients.
基金supported by the National Natural Science Foundation of China (No. U20A20371)the National Key Technology Research and Development Program of the Ministry of Science and Technology of China (No. D171100006517004)+2 种基金Beijing Municipal Administration of Hospitals’ Youth Program (QML20191103)Clinical Medicine Plus X-Young Scholars Project, Peking Universitythe Fundamental Research Funds for the Central Universities and the Science Foundation of Peking University Cancer Hospital。
文摘Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.
文摘BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects.The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy(HIPEC)has been shown to increase survival rates in these patients.Despite these advancements,debates persist regarding the magnitude of survival improvement attributed to this treatment modality.The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis,and it took a comparative analysis of patients exhibiting positive and negative cytological findings.Between April 2013 and March 2020,84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts:HIPEC(20 patients with peritoneal metastasis),cytology-positive(23 patients without peritoneal nodules but with positive wash cytology),and cytology-negative(41 patients with advanced gastric cancer,no peritoneal nodules,and negative wash cytology).The HIPEC cohort underwent gastrectomy with HIPEC,while the cytology-positive and cytology-negative groups received gastrectomy alone.The demographic,pat-hological,and survival data of the groups were compared.RESULTS The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss.Nevertheless,the complication rates were consistent across all three groups.Median survival in the HIPEC group was 20.00±4.89 months,with 1-year,2-year,and 3-year overall survival rates of 73.90%,28.70%,and 9.60%,respectively.These figures paralleled the survival rates of the cytology-positive group(52.20%at 1 year,28.50%at 2 years,and 19.00%at 3 years).Notably,47%of patients experienced peritoneal recurrence.CONCLUSION HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis,mirroring the outcomes in cytology-positive patients.However,peritoneal recurrence remained high.
文摘目的Rausch and Schiller(1954)在美国阿拉斯加白令海峡St.Lawrence岛从北极狐(Alopex lagopus)和雪撬狗(sledge dogs)发现西伯利亚棘球绦虫新种(Echinococcus sibiricensis sp.nov.),但诸多学者认为E.sibiricensis Rausch et Schiller,1954是欧洲的多房棘球绦虫(Echinococcus multilocularis Leuckart,1863)的地理株(或亚种)(Vogel,1957;Skrjabin and Abuladze,1964;Kumaratilake and Thompson,1982;Meyajaki,1991等)。于1985-2002年间,作者在我国内蒙古大兴安岭北麓草场多年进行泡状棘球蚴(alveolar Echinococcus)病原的野外调查和实验室鼠类的人工感染试验,结果发现该地区同地点存在有北美西伯利亚棘球绦虫、欧洲多房棘球绦虫及苏俄多房棘球绦虫三种不同"地理株",而且三种成虫常混合感染于同一终宿主沙狐(Vulpes corsac)的体内,它们的幼虫期也存在于当地的布氏田鼠(Microtus brandti)。2001年,作者再次检查当地沙狐151只,从中检出19只感染有泡状棘球绦虫成虫。含成熟虫体的13只阳性沙狐中,感染西伯利亚棘球绦虫有11只,其中2只单独感染此虫种,另9只还混合感染了欧洲多房棘球绦虫及苏俄多房棘球绦虫三虫种。在呼伦贝尔草原的泡状棘球蚴病原中,西伯利亚棘球绦虫是优势种,它在终宿主沙狐和中间宿主的感染率都高过其他虫种。本文着重介绍西伯利亚棘球绦虫的成虫子宫结构和它幼虫期在野外布氏田鼠及人工感染实验鼠体内的发育情况。
基金supported by National Natural Science Foundation of China (No.30260105 and No.30660176)
文摘Objective To investigate the protective immunity against Echinococcus granulosus in mice immunized with rEg14-3-3. Methods ICR mice were subcutaneously immunized three times with rEg14-3-3, followed by the challenge with Echinococcus granulosus protoscoleces intraperitoneally and then sacrificed after six months of post-challenge to detect the proliferation of splenocytes by MTT assay, and to measure the secretion of IL-2, IL-4, IL-20, and IFN -y by ELISA. The rate of reduced hydatid cyst and the levels of IgE, igG and IgG subclasses in sera were examined. Results Mice vaccinated with rEg14-3-3 and challenged with protoscoleces revealed significant protective immunity of 84.47%. ELISA analysis indicated that the immunized mice generated specific high levels of IgG and the prevailing isotypes of IgG were IgG1 and IgG2a. Splenocytes from mice immunized with rEg14-3-3 showed a significant proliferation response. The secretion of IFN-V and IL-2 increased significantly in the vaccinated mice whereas there was no significant difference in IL-4 and IL-20 levels between vaccinated and control mice. Conclusion The results indicate that the rEg24-3-3 vaccine could induce a high level of protective immunity as a promising vaccine candidate to prevent cystic echinococcosis.
基金supported by a grant from JEIL Pharmaceuticals (Seoul, Korea)
文摘BACKGROUND: A previous report has identified a significantly higher sensitivity of cancer detection for dedicated grasping basket than brushing at endoscopic retrograde cholangiopancreato- graphy (ERCP). This study aimed to compare the diagnostic accuracy of Geenen brush and Dormia basket cytology in the differential diagnosis of bile duct stricture. METHOD: The current study enrolled one hundred and fourteen patients who underwent ERCP with both Geenen brush and Dormia basket cytology for the differential diagnosis of bile duct stricture at our institution between January 2008 and December 2012. RESULTS: We adopted sequential performances of cytologic samplings by using initial Geenen brush and subsequent Dormia basket cytology in 59 patients and initial Dormia basket and subsequent Geenen brush cytology in 55 patients. Presampling balloon dilatations and biliary stentings for the stricture were performed in 17 (14.9%) and 107 patients (93.9%), respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Geenen brush cytology for the diagnosis of malignant bile duct stricture were 75.0%, 100.0%, 100.0%, 66.7% and 83.3%, respectively, and those of Dormia basket cytology were 64.5%, 100.0%, 100.0%, 58.5% and 76.3%, respectively (P=0.347 and 0.827 for sensitivity and accuracy, respectively). The good and excellent cellular yields (≥grade 2) were obtained by Geenen brush and Dormia basket cytology in 88 (77.2%) and 79 (69.3%) patients, respectively.CONCLUSION: The sensitivity, specificity and accuracy of biliary sampling with a Dormia basket are comparable to those with conventional Geenen brush cytology in the detection of malignant bile duct stricture.
基金supported by the National Natural Science Foundation of China (Nos. 30260105 and 30660176)the Natural Science Foundation of Ningxia Hui Autonomous Region (NZ10192)the Doctor’s Subject Science Foundation of Ningxia Medical University (KF2010-33)
文摘Objective To establish and optimize the proteomic analysis of protoscoleces-specific antigens from Echinococcus granulosus. To provide a foundation for identifying specific antigens in the soluble proteins of E. granulosus protoscoleces for further research. Methods Brood capsules were collected aseptically from fertile E. granulosus cysts from the livers of an infected patient. The fertile E. granulosus cysts were fractured, and protoscoleces were collected by centrifugation. The soluble proteins of protoscoleces were acquired using the 2D Quant kit according to the manufacturer's instructions. We employed two-dimensional electrophoresis (2-DE) combined with immunoblot assay (Western blot) to analyze the soluble components of E. granulosus protoscoleces antigens. The 2-DE and immunoblot maps obtained were analyzed with PDQuest 8.0 image analysis software. Results About 233 soluble protein spots were identified with Coomassie-stained gels. Most of the proteins had a molecular weight of 16 000 Da to 117 000 Da, and an isoelectric point value of 3.0 to 10.0. 2-DE immunoblot was conducted and 57 specific antigen spots were observed, among which 23 spots were identified. Conclusion 2-DE combined with Western blot is the key to successful proteomic analysis and presents a new possibility for searching the specific E. granulosus protoscoleces antigens.
基金support provided by Department of Science and Technology,Government of India, New Delhi, in the form of project grant(vide file no.SR/SO/HS-0062/2009)
文摘Objective: To investigate new scolicidal agent from natural resources to cope with the side effects associated with synthetic drugs in Echinococcosis. Methods: The scolicidal potential of methanolic fruit powder extract (10 and 20 mg/mL) of Mallotus philippinensis ( M. philippinensis ) was investigated. Viability of protoscoleces was confirmed by trypan blue exclusion method, where mortality was observed at concentration of 10 and 20 mg/mL in 60 min treatment against Echinococcus granulosus ( E. granulosus ), under in-vitro conditions with reference to the known standard drug Praziquantel . Results: At concentration 10 and 20 mg/mL, the mortality rate was observed 97% and 99% respectively for 60 min treatment; while up to 93% mortality was observed with 20 mg/mL for only 10 min treatment. The concentration above 20 mg/mL for above 2 h showed 100% mortality, irrespective of further incubation. Conclusions: As compared with the standard anti-parasitic drug Praziquantel our extract has significant scolicidal activity with almost no associated side effects.
基金supported by the grants from the National Natural Science Foundation of China (No. 81501762)the Talents Scientific Research Foundation of Xuzhou Medical University (No. D2015004)+4 种基金the Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (PPZY2015B161)the Training Programs of Innovation and Entrepreneurship for College Students in Jiangsu Province (No. 201510313017Z)the Jiangsu Planned Projects for Postdoctoral Research Funds (No. 1501061A)the China Postdoctoral Science Foundation funded project (No. 2015M581864)the Jiangsu Qing Lan Project
文摘Objective:To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus(E. granulosus). Methods:We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1(DNASTAR Inc.,Madison,WI),and the phylogenetic analysis was performed by using MEGA5.1(CEMI,Tempe,AZ,USA). In addition,linear and conformational epitopes were analysed,including secondary structure,NXT/S glycosylation,fibronectin type ecoⅢ(Fnndary Ⅲ) domain and glycosylphosphatidylinositol anchor signal(GPIanchor). The s structure was predicted by PSIPRED method. Results:Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence,X90928. However,EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates,respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine,X90928,and they belonged to Subgroup 1. However,in comparison to X90928,several amino acid mutations occurred in most isolates besides oncosphere,which potentially altered the immunodominant linear epitopes,glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. Conclusions:This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates,and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.
基金Supported by National Nature Science Foundation of China(No:30860070)
文摘Objective:To identify full length cDNA sequence of lactate dehydrogenase(LDH) from adult Echinococcus granulosus(E.granulosus) and to predict the structure and function of its encoding protein using bioinformatics methods.Methods:With the help of NCBI,EMBI, Expasy and other online sites,the open reading frame(ORF),conserved domain,physical and chemical parameters,signal peptide,epitope,topological structures of the protein sequences were predicted and a homology tertiary structure model was created:Vector NT1 software was used for sequence alignment,phylogenetic tree construction and tertiary structure prediction. Results:The target sequence was 1 233 bp length with a 996 bp biggest ORF encoding 331 amino acids protein with typical L-LDH conserved domain.It was confirmed as full length cDNA of LDH from E.granulosus and named as EgLDH(GenBank accession number:HM748917).The predicted molecular weight and isoelectric point of the deduced protein were 3 5516.2Da and 6.32 respectively.Compared with LDHs from Taenia solium,Taenia saginata asiatica,Spirometra erinaceieuropaei.Schistosoma japonicum,Clonorchis sinensis and human,it showed similarity of 86% ,85% ,55% ,58% ,58% and 53% ,respectively.EgLDH contained 3 putative transmembrane regions and 4 major epitopes(54aa-59aa.81aa-87aa,97aa-102aa,307aa-313aa),the latter were significant different from the corresponding regions of human LDH.In addition,some NAD and substrate binding sites located on epitopes 54aa-59aa and 97aa-102aa,respectively.Tertiary structure prediction showed that 3 key catalytic residues 105R,165D and 192H forming a catalytic center near the epitope 97aa-102aa,most NAD and substrate binding sites located around the center.Conclusions:The full length cDNA sequences of EgLDH were identified.It encoded a putative transmembrane protein which might be an ideal target molecule for vaccine and drugs.
文摘Aim: To compare the results of bladder tumor associated antigen (BTA TRAK), nuclear matrix protein 22 (NMP 22) and voided urine cytology (VUC) in detecting bladder cancer. Methods: A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups: (i) 93 patients with bladder cancer; (ii) 42 patients with urinary benign conditions; and (iii) 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results: The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion: The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.
基金Supported by A PhD grant from the French Ministry of Foreign Affairs (French Embassy in Beijing) to Ren-Yong Linby a project grant from the "Foundation Transplantation" (2005-2006)+1 种基金by a grant from NSFC, No. 30860253 and 30760239by the Xinjiang Key-Lab project grants on Echinococcosis, No. XJDX0202-2005-01 and XJDX0202-2007-04
文摘AIM: To explore the effect of Echinococcusmultilocularis on the activation of mitogen-activated protein kinase (MAPK) signaling pathways and on livercell proliferation.METHODS: Changes in the phosphorylation of MAPKs and proliferating cell nuclear antigen (PCNA)expression were measured in the liver of patients withalveolar echinococcosis (AE). MAPKs, MEK1/2 [MAPK/extracellular signal-regulated protein kinase (ERK)kinase] and ribosomal S6 kinase (RSK) phosphorylationwere detected in primary cultures of rat hepatocytesin contact in vitro with (1) E. multilocu/aris vesicle fluid(EmF), (2)E. multilocularis-conditioned medium (EmCM).RESULTS: In the liver of AE patients, ERK 1/2 andp38 MAPK were activated and PCNA expression wasincreased, especially in the vicinity of the metacestode.Upon exposure to EmF, p38, c-Jun N-terminal kinase(JNK) and ERK1/2 were also activated in hepatocytesin vitro, as well as MEK1/2 and RSK, in the absenceof any toxic effect. Upon exposure to EmCM, only JNKwas up-regulated.CONCLUSION: Previous studies have demonstratedan influence of the host on the MAPK cascade inE. multilocularis. Our data suggest that the reverse,i.e. parasite-derived signals efficiently acting onMAPK signaling pathways in host liver ceils, is actuallyoperating.
文摘BACKGROUND: Telomerase activity is reported to be specific and frequent in human pancreatic cancer. We conducted this study to assess the usefulness of monitoring telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of pancreatic cancer. METHODS: Exfoliated cells obtained by pancreatic duct brushing during ERCP from 21 patients (18 with pancreatic cancer, 3 with chronic pancreatitis) were examined. Telomerase activity was detected by polymerase chain reaction and telomeric repeat amplification protocol assay (PCR-TRAP-ELISA). RESULTS: D450 values of telomerase activity were 0.446 +/- 0.2700 in pancreatic cancer and 0.041 +/- 0.0111 in chronic pancreatitis. 77.8% (14/18) of patients with pancreatic cancer had cells with telomerase activity. None of the samples from patients with chronic pancreatitis showed telomerase activity, when the cutoff value of telomerase activity was set at 2.0. Cytological examination showed cancer cells in 66.7% (12/18) of the patients. CONCLUSIONS: Telomerase activity may be an early malignant event in pancreatic cancer development. Cytology and telomerase activity in cells obtained by pancreatic duct brushing may complement each other for the diagnosis of pancreatic cancer.
文摘BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic le- sions. Nonetheless, the diagnostic value of this procedure may be limited by low cellularity of the specimen, contamination of intestinal cells and unfeasibility of ancillary immunocy- tochemical procedures. The present study was to evaluate its usefulness in the diagnosis of neoplastic lesions.
文摘We describe the clinical, imaging and cytopathological features of solid pseudopapillary tumor of the pancreas (SPTP) diagnosed by endoscopic ultrasound- guided (EUS-guided) fine-needle aspiration (FNA). A 17-year-old woman was admitted to our hospital with complaints of an unexplained episodic abdominal pain for 2 mo and a short history of hypertension in the endocrinology clinic. Clinical laboratory examinations revealed polycystic ovary syndrome, splenomegaly and low serum amylase and carcinoembryonic antigen (CEA) levels. Computed tomography (CT) analysis revealed a mass of the pancreatic tail with solid and cystic consistency. EUS confirmed the mass, both in body and tail of the pancreas, with distinct borders, which caused dilation of the peripheral part of the pancreatic duct (major diameter 3.7 mm). The patient underwent EUS-FNA. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform malignant cells, forming microadenoid structures, branching, papillary clusters with delicate fibrovascular cores and nuclear overlapping. Naked capillaries were also seen. The nuclei of malignant cells were round or oval, eccentric with fine granular chromatin, small nucleoli and nuclear grooves in some of them. The malignant cells were periodic acid Schiff (PAS)-Alcian blue (+) and immunocytochemically they were vimentin (+), CA 19.9 (+), synaptophysin (+), chromogranin (-), neuro-specific enolase (-), a1- antitrypsin and a1-antichymotrypsin focal positive. Cytologic findings were strongly suggestive of SPTP. Biopsy confirmed the above cytologic diagnosis. EUS- guided FNA diagnosis of SPTP is accurate. EUS findings,cytomorphologic features and immunostains of cell block help distinguish SPTP from pancreatic endocrine tumors, acinar cell carcinoma and papillary mucinous carcinoma.
文摘AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.