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
The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is...The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is a new national policy for the management of people living with HIV with the administration of dolutegravir (DTG)-based fixed-dose combination. The aim of our study was to evaluate HIV-1 resistance to antiretrovirals (ARVs) in infected adult subjects in Cte d’Ivoire in the context of a systematic switch to a DTG-based combination. Between February 2022 and October 2023, a cross-sectional survey with random sampling was conducted in 06 services caring for people living with HIV. A total of 139 participants were included in the study. Adults with a viral load ≥ 1000 copies/mL were tested for HIV-1 ARV resistance mutations. Molecular analyses were performed using protocol of ANRS-MIE (National Agency for Research on AIDS and emerging infectious diseases). The interpretation is performed by HIVGRAD (https://www.hiv-grade.de/cms/grade/). The frequencies of HIV-1 resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (IINTs) and protease inhibitors (PIs) were 82%, 73%, 19% and 11% respectively. The main mutations observed in the different classes were K103N (45%), M184V (64%), E157Q (19%) and L10V/M46I/A71V/I54V (6%) respectively. This study reveals the emergence of resistance to DTG-based fixed-dose combinations, favored by high rates of resistance to NRTIs and NNRTIs. This finding underlines the need for enhanced viral load monitoring and HIV-1 genotyping tests to guide the choice of NRTIs for combination therapy. In addition, monitoring for mutations to second-generation NRTIs is essential, given the scale-up of DTG-based regimens currently underway in Cte d’Ivoire.展开更多
Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-st...Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-strand breaks of DNA,causing insertional mutation.The random insertional mutant library constructed using this method has become a method of forward genetics for gene cloning.However,the establishment of a random insertional mutant library requires a high transformation efficiency of exogenous genes.Many microalgal species show a low transformation efficiency,making constructing random insertional mutant libraries difficult.In this study,we established a highly efficient transformation method for constructing a random insertional mutant library of Nannochloropsis oceanica,and tentatively tried to isolate its genes to prove the feasibility of the method.A gene that may control the growth rate and cell size was identified.This method will facilitate the genetic studies of N.oceanica,which should also be a reference for other microalgal species.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
<b><span>Background:</span></b><span> Liquid-based cytology (LBC) is a method of manufacturing cyto-diagnostic specimens. Improved accuracy is expected from standardizing specim...<b><span>Background:</span></b><span> Liquid-based cytology (LBC) is a method of manufacturing cyto-diagnostic specimens. Improved accuracy is expected from standardizing specimen production and use of this method is rapidly spreading in oral cytology. On the other hand, LBC reportedly requires training to show peculiar cell findings compared to those of conventional smear cytology (CVC). Few studies have compared detailed cell findings for oral CVC and LBC.</span><span> </span><b><span>Objec</span></b><b><span>tives:</span></b><span> The aim of this study was to compare cytological findings between CVC </span><span>and LBC using cytomorphological image analysis.</span><span> </span><b><span>Materials and Methods:</span></b><span> Cytological specimens were collected from 20 patients (negative for squamous neoplasia in 10, dysplasia in 5, squamous cell carcinoma in 5) and 5 controls of the tongue between January 2017 and December 2018. Two different preparation techniques were investigated cytomorphologically for CVC and LBC (BD Cytorich</span><sup><span style="vertical-align:super;">TM</span></sup><span>).</span><span> </span><b><span>Results:</span></b><span> LBC showed significantly higher cell numbers tha</span><span>n CVC for all lesions. LBC-to-CVC ratio ranged from 9.52 (hyp</span><span>erkeratosis) to 1.87 (deep cells in oral squamous cell carcinoma (OSCC)). Nuclear area of </span><span>normal, hyperkeratosis, and inflammation were significantly higher in LBC tha</span><span>n those of CVC. Hyperchromasia was significantly more frequent with </span><span>CVC than with LBC for hyperkeratosis, inflammation, dysplasia and OSCC. There was no significant difference in circularity between CVC and LBC </span><span>among all lesions. </span><b><span>Conclusion:</span></b><span> Only one cytomorphological disadvantage was </span><span>se</span><span>en with LBC, in the form of decreased hyperchromasia. Further </span><span>clarification of the advantages and disadvantages of LBC is needed, including management of precision and screening practices.展开更多
BACKGROUND Both squamous cell carcinoma(SCC)and papillary thyroid carcinoma(PTC)are common malignant tumors in the neck.However,seldom has SCC of the thyroid been diagnosed.Further,cytological features of SCC and PTC ...BACKGROUND Both squamous cell carcinoma(SCC)and papillary thyroid carcinoma(PTC)are common malignant tumors in the neck.However,seldom has SCC of the thyroid been diagnosed.Further,cytological features of SCC and PTC have rarely been reported.The significance of fine-needle aspiration cytology(FNAC)in the diagnosis of neck masses has been established.Herein,we present an exceedingly rare case of an intrathyroidal SCC diagnosed using FNAC,along with its cytological features.CASE SUMMARY A 66-year-old man presented with a left-sided neck mass.Ultrasound examination showed an ill-defined nodule.The appearance was hypoechoic with a few hyperechoic spots.FNAC of the left thyroid nodule was performed.A cellular smear was obtained,and it showed a large number of neoplastic cells with rich cytoplasm and poor cell adhesion.Tumor cell nuclei showed coarse nuclear chromatin and a few enlarged prominent nucleoli.An increased nuclear/cytoplasm ratio was observed.Thus,malignancy was diagnosed without a confirmed tumor type.Percutaneous tumor biopsy was performed to make a definite diagnosis.The tumor cells showed typical squamous cell characteristics.CONCLUSION Head and neck SCC and PTC have different cytologies.Measures are needed to ensure accurate diagnosis using FNAC.展开更多
The strawberry species Fragaria nilgerrensis Schlechtendal ex J.Gay,renowned for its distinctive white,fragrant peach-like fruits and strong disease resistance,is an exceptional research material.In a previous study,a...The strawberry species Fragaria nilgerrensis Schlechtendal ex J.Gay,renowned for its distinctive white,fragrant peach-like fruits and strong disease resistance,is an exceptional research material.In a previous study,an ethyl methane sulfonate(EMS)mutant library was established for this species,resulting in various yellow leaf mutants.Leaf yellowing materials are not only the ideal materials for basic studies on photosynthesis mechanism,chloroplast development,and molecular regulation of various pigments,but also have important utilization value in ornamental plants breeding.The present study focused on four distinct yellow leaf mutants:mottled yellow leaf(MO),yellow green leaf(YG),light green leaf(LG),and buddha light leaf(BU).The results revealed that the flavonoid content and carotenoid-to-chlorophyll ratio exhibited a significant increase among these mutants,while experiencing a significant decrease in chlorophyll and carotenoid contents compared to the wild type(WT).To clarify the regulatory mechanisms and network relationships underlying these mutants,the RNA-seq and weighted gene coexpression network(WGCNA)analyses were employed.The results showed flavonoid metabolism pathway was enriched both in MO and YG mutants,while the chlorophyll biosynthesis pathway and carotenoid degradation pathway were only enriched in MO and YG mutants,respectively.Subsequently,key structural genes and transcription factors were identified on metabolic pathways of three pigments through correlation analyses and quantitative experiments.Furthermore,a R2R3-MYB transcription factor,FnMYB4,was confirmed to be positively correlated with flavonoid synthesis through transient overexpression,virus-induced gene silencing(VIGS),and RNA interference(RNAi),accompanying by reoccurrence and attenuation of mutant phenotype.Finally,dual-luciferase(LUC)and yeast one-hybrid assays confirmed the binding of FnMYB4 to the FnFLS and FnF3H promoters,indicating that FnMYB4 positively regulates flavonoid synthesis.In addition,correlation analyses suggested that FnMYB4 also might be involved in chlorophyll and carotenoid metabolisms.These findings demonstrated the pivotal regulatory role of FnMYB4 in strawberry leaf coloration.展开更多
A green-revertible albino mutant-Qiufeng M was found from the japonica rice (Oryza sativa L. ssp. japonica) Qiufeng in the field. The first three leaves of the mutant were albino with some green. The leaf color beca...A green-revertible albino mutant-Qiufeng M was found from the japonica rice (Oryza sativa L. ssp. japonica) Qiufeng in the field. The first three leaves of the mutant were albino with some green. The leaf color became pale green since the fourth leaf and the glume had the same phenomenon as the first three leaves. The measuring data of the pigment content confirmed the visually observed results. It truly had a remarkable changing process in the leaf color in Qiufeng M. Comparison of the main agronomic characters between Qiufeng and Qiufeng M indicated that the neck length and grain weight showed significant difference at the 1% level, and other characters were not different. Genetic analysis showed that the green-revertible albino trait was controlled by a single recessive nucleic gene. Using 209 recessive mutant individuals in the F2 population derived from the cross Pei'ai 64S × Qiufeng M, a gene, tentatively named gra(t), was located between the SSR markers of RM475 and RM2-22 on the long arm of chromosome 2. The genetic distance were 17.3 cM and 2.9 cM respectively.展开更多
[Objective] The aim was to improve the genetic property of peppers, the mutant population of Capsicum annuum L cultivar "6421" was constructed. [Method] The seeds of "6421" were treated with 0.2% to 1.2% ethyl met...[Objective] The aim was to improve the genetic property of peppers, the mutant population of Capsicum annuum L cultivar "6421" was constructed. [Method] The seeds of "6421" were treated with 0.2% to 1.2% ethyl methane sulfonate to identified LD50, and then 10 000 LD^o of treated seeds were sowed to construct mutant population. The agronomic characters and genetic regularity of dwarf mutants in M4 generation were analyzed. [Result] Our results showed that GR and SSR were 45.2% and 40.2% respectively at 1.0% EMS, close to LD50, with GI (17.6) and seed Ⅵ (19.7) being half of that of control; 562 M4 mutants were identified in 2015, and the mutation could be characterized according 11 major categories and 32 subcategories; Simultaneously, we found that plant height, plant width, diameter of mainstem, length of main-stem, the number of main-stem nodes and branch of lines E29, E58, E142 and E312 were all significantly different from that of the control. The mutation of lines E29, E58 and E312 was all controlled by a single recessive gene. [Conclusionl The study first created a pepper mutant population, which provides not only the germplasm resources for further breeding but also direct and effective materials for genomic study of the pepper.展开更多
A mutant with abnormal hull was first discovered from a twin-seedling strain W2555 in rice (Oryza sativa L.). The mutant had sparse branches and decreased number of florets from the base to the peak. Frequently, the...A mutant with abnormal hull was first discovered from a twin-seedling strain W2555 in rice (Oryza sativa L.). The mutant had sparse branches and decreased number of florets from the base to the peak. Frequently, the florets at the top of the panicle did not develop completely. The underdeveloped florets often showed slender and white in their life cycle. Genetic analysis indicated that the mutant traits were controlled by a single recessive gene (temporarily designated as ah). ah gene controlled the development of inflorescence meristem and the flower organ. The florets of mutant showed degenerated lemma and palea. Stamens and lodicules were homeoticly transformed into pistils and palea/lemma-like structures, respectively. It seemed that ah mutant phenotypes of the homeotic conversions in lodicules and stamens were very similar to that of the B loss-of-function spwl gene reported previously in rice.展开更多
[Objective] The aim was to explore the relevance between decreased 1 000-grain weight and grain-filling characteristics of rice giant embryo mutant.[Method] Richards equation was used to describe grain filling process...[Objective] The aim was to explore the relevance between decreased 1 000-grain weight and grain-filling characteristics of rice giant embryo mutant.[Method] Richards equation was used to describe grain filling processes of giant embryo mutant MH-ge1 and its corresponding wild type so as to analyze the parameters of grain-filling characteristics of materials.[Result] The initial filling power of mutant MH-ge1 was higher than the wild type MH86,however,the maximum filling rate,the mean filling rate and the final increment of mutant MH-ge1 was lower than those of MH86.[Conclusion] The grain-filling characteristics of mutant MH-ge1 were poorer than the wild type MH86,thus resulting in the decrease of the grain weight of the giant embryo rice.展开更多
[Objective] This study was conducted to detect the variation induction ability of ethyl methanesulfonate (EMS), to construct a mutant population. [Method] 0.6%, 1.2% and 2.4% EMS solutions were used for inducing 2 4...[Objective] This study was conducted to detect the variation induction ability of ethyl methanesulfonate (EMS), to construct a mutant population. [Method] 0.6%, 1.2% and 2.4% EMS solutions were used for inducing 2 400 stem segments of test-tube plantlets of tetraploid potato Longshu 7, and an asexual mutant population including leaf, plant type, stem, stolon, glandular hair traits was constructed. [Result] Twenty two mutation types, i.e. etiolated plantlet, albino plantlet, leaf-color gradient, etiolated vein, wrapped bud, lobed leaf, crinkled leaf, deformed compound leaf, cluster, branch, top enlargement, top bifurcation, succulent, stolon distortion, stolon shift, early tuberization, hair stolon, stem enlargement, vine stem, foliage stem, glandular hair and whorled leaf types were observed in total. There were 52 mutant single plants in total, with a mutation rate of 21.67‰. [Conclusion] The glandular hair, clustered short-stem, branched stem and early tuberization types of mutants have higher application value, and are anticipated to be used in potato functional genome research, gene improvement and germplasm innovation.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
Comparative studies of absorption spectra of phycobiliproteins of Gracilaria lemaneiformis Greville and its pigmental mutants were conducted in this study. The results showed that the absorption spectra of phycoerythr...Comparative studies of absorption spectra of phycobiliproteins of Gracilaria lemaneiformis Greville and its pigmental mutants were conducted in this study. The results showed that the absorption spectra of phycoerythrins ( PE) from different material changed significantly, while those of phycocyanins (PC) and allophycocyanins (APC) were basically similar. In order to disclose the essence of die difference, partial sequences of die subunit genes of PE of Qingdao strain of G. lemaneiformis (qd) and its pigmental mutants were determined. The amino acid sequences were deduced and used to explain spectral shifts of PE from the pigmental mutants. The amino acid sequences of PE resembled each other, and several residues changed among qd and its pigmental mutants. Residue substitutions were found in a region consisting of amino acids which determined are secondary structure and subunits interactions, thus might influence the confirmation and interaction of subunits, and further caused spectral deviation.展开更多
AIM: To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METH...AIM: To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METHODS: The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA (HBV DNA) level and hepatitis B e antigen (HBeAg) were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development. RESULTS: During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio: 95.74 (12.13-891.31), P 〈 0.0001], male sex [odds ratio: 7.61 (2.20-47.95); P = 0.006], and higher Iogzo HBV DNA [odds ratio: 4.69 (1.16-20.43); P 〈 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio: 26.51 (2.36-381.47); P = 0.007], presence of precore mutants [odds ratio: 4.23 (1.53-19.58), P = 0.02] and presence of basal core promoter mutants [odds ratio: 2.93 (1.24-7.57); P = 0.02] were independent predictors for progression to hepatocellular carcinoma. CONCLUSION: Our results show that high levels of baseline serum HBV DNA are associated with non- hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.展开更多
A high_CO 2_requiring mutant of Synechococcus sp. PCC7942 has been isolated after chemical mutagenesis of ethyl methane sulphonate (EMS). It was able to grow at 4% CO 2, but not under ambient CO 2. The initial s...A high_CO 2_requiring mutant of Synechococcus sp. PCC7942 has been isolated after chemical mutagenesis of ethyl methane sulphonate (EMS). It was able to grow at 4% CO 2, but not under ambient CO 2. The initial screening of the mutant showed that the genetic reversion rate was about 10 -7 and death occurred 2-3 days after being transferred from 4% CO 2 to the ambient air. Its photosynthetic dependence on external dissolved inorganic carbon was higher than that of the wild type cells, but its carbonic anhydrase activity was comparatively low. In the ultrastructural level, various types of aberrant carboxysomes appeared in the mutant cells: rod_shaped carboxysomes, irregular carboxysomes and the “empty_inclusion carboxysomes" with increasing number of glycogen granules surrounding the thylakoids. All these alterations indicated that the mutant was defective in utilizing the external CO 2. The induction of carboxysomes by lower levels of CO 2 and the biogenesis of carboxysomes are herein discussed.展开更多
TP53 is a tumor suppressor gene that is mutated in most cancer types and has been extensively studied in cancer research.p53 plays a critical role in regulating the expression of target genes and is involved in key pr...TP53 is a tumor suppressor gene that is mutated in most cancer types and has been extensively studied in cancer research.p53 plays a critical role in regulating the expression of target genes and is involved in key processes such as apoptosis,cell cycle regulation,and genomic stability,earning it the title“guardian of the genome.”Numerous studies have demonstrated p53’s influence on and regulation of autophagy,ferroptosis,the tumor microenvironment,and cell metabolism,all of which contribute to tumor suppression.Alterations in p53,specifically mutant p53(mutp53),not only impair its tumor-suppressing functions but also enhance oncogenic characteristics.Recent data indicate that mutp53 is strongly associated with poor prognosis and advanced cancers,making it an ideal target for the development of novel cancer therapies.This review summarizes the post-translational modifications of p53,the mechanisms of mutp53 accumulation,and its gain-of-function,based on previous findings.Additionally,this review discusses its impact on metabolic homeostasis,ferroptosis,genomic instability,the tumor microenvironment,and cancer stem cells,and highlights recent advancements in mutp53 research.展开更多
BACKGROUND Smear cytology(SC)using endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)is the established and traditional choice for diagnosing pancreatic lesions.Liquid-based cytology(LBC)is a novel alternati...BACKGROUND Smear cytology(SC)using endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)is the established and traditional choice for diagnosing pancreatic lesions.Liquid-based cytology(LBC)is a novel alternative cytological method,however,the comparative diagnostic efficacy of LBC remains inconclusive.AIM To examine the diagnostic efficacy of LBC and SC for pancreatic specimens obtained through EUS-FNA via a systematic review and meta-analysis.METHODS A systematic literature search was performed using PubMed,EMBASE,the Cochrane Library,and Web of Science.The numbers of true positives,false positives,true negatives,and false negatives for each cytological test(LBC and CS)were extracted from the included studies.The pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve(AUC)were calculated,and the AUC was compared by Tukey's multiple comparisons test.The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies II tool.RESULTS A total of 1656 patients in eight studies were included.The pooled sensitivity and specificity and the AUC for LBC were 0.76(95%CI:0.72-0.79),1.00(95%CI:0.98-1.00),and 0.9174,respectively,for diagnosing pancreatic lesions.The pooled estimates for SC were as follows:Sensitivity,0.68(95%CI:0.64-0.71);specificity,0.99(95%CI:0.96-100.00);and AUC,0.9714.Similarly,the corresponding values for LBC combined with SC were 0.87(95%CI:0.84-0.90),0.99(95%CI:0.96-1.00),and 0.9894.Tukey’s multiple comparisons test was used to compare the sensitivities and AUCs of the three diagnostic methods;statistically significant differences were found between the three methods,and LBC combined with SC was superior to both LBC(P<0.05)and SC(P<0.05).The pooled sensitivity and AUC did not change significantly in the sensitivity analysis.CONCLUSION LBC may be sensitive than SC in the cytological diagnosis of pancreatic lesions,however,the superior diagnostic performance of their combination emphasizes their integrated usage in the clinical evaluation of pancreatic lesions.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The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is a new national policy for the management of people living with HIV with the administration of dolutegravir (DTG)-based fixed-dose combination. The aim of our study was to evaluate HIV-1 resistance to antiretrovirals (ARVs) in infected adult subjects in Cte d’Ivoire in the context of a systematic switch to a DTG-based combination. Between February 2022 and October 2023, a cross-sectional survey with random sampling was conducted in 06 services caring for people living with HIV. A total of 139 participants were included in the study. Adults with a viral load ≥ 1000 copies/mL were tested for HIV-1 ARV resistance mutations. Molecular analyses were performed using protocol of ANRS-MIE (National Agency for Research on AIDS and emerging infectious diseases). The interpretation is performed by HIVGRAD (https://www.hiv-grade.de/cms/grade/). The frequencies of HIV-1 resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (IINTs) and protease inhibitors (PIs) were 82%, 73%, 19% and 11% respectively. The main mutations observed in the different classes were K103N (45%), M184V (64%), E157Q (19%) and L10V/M46I/A71V/I54V (6%) respectively. This study reveals the emergence of resistance to DTG-based fixed-dose combinations, favored by high rates of resistance to NRTIs and NNRTIs. This finding underlines the need for enhanced viral load monitoring and HIV-1 genotyping tests to guide the choice of NRTIs for combination therapy. In addition, monitoring for mutations to second-generation NRTIs is essential, given the scale-up of DTG-based regimens currently underway in Cte d’Ivoire.
基金the National Key R&D Program of China(Nos.2018YFD0901506,2018YFD0900305)the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(No.2018 SDKJ0406-3)。
文摘Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-strand breaks of DNA,causing insertional mutation.The random insertional mutant library constructed using this method has become a method of forward genetics for gene cloning.However,the establishment of a random insertional mutant library requires a high transformation efficiency of exogenous genes.Many microalgal species show a low transformation efficiency,making constructing random insertional mutant libraries difficult.In this study,we established a highly efficient transformation method for constructing a random insertional mutant library of Nannochloropsis oceanica,and tentatively tried to isolate its genes to prove the feasibility of the method.A gene that may control the growth rate and cell size was identified.This method will facilitate the genetic studies of N.oceanica,which should also be a reference for other microalgal species.
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<b><span>Background:</span></b><span> Liquid-based cytology (LBC) is a method of manufacturing cyto-diagnostic specimens. Improved accuracy is expected from standardizing specimen production and use of this method is rapidly spreading in oral cytology. On the other hand, LBC reportedly requires training to show peculiar cell findings compared to those of conventional smear cytology (CVC). Few studies have compared detailed cell findings for oral CVC and LBC.</span><span> </span><b><span>Objec</span></b><b><span>tives:</span></b><span> The aim of this study was to compare cytological findings between CVC </span><span>and LBC using cytomorphological image analysis.</span><span> </span><b><span>Materials and Methods:</span></b><span> Cytological specimens were collected from 20 patients (negative for squamous neoplasia in 10, dysplasia in 5, squamous cell carcinoma in 5) and 5 controls of the tongue between January 2017 and December 2018. Two different preparation techniques were investigated cytomorphologically for CVC and LBC (BD Cytorich</span><sup><span style="vertical-align:super;">TM</span></sup><span>).</span><span> </span><b><span>Results:</span></b><span> LBC showed significantly higher cell numbers tha</span><span>n CVC for all lesions. LBC-to-CVC ratio ranged from 9.52 (hyp</span><span>erkeratosis) to 1.87 (deep cells in oral squamous cell carcinoma (OSCC)). Nuclear area of </span><span>normal, hyperkeratosis, and inflammation were significantly higher in LBC tha</span><span>n those of CVC. Hyperchromasia was significantly more frequent with </span><span>CVC than with LBC for hyperkeratosis, inflammation, dysplasia and OSCC. There was no significant difference in circularity between CVC and LBC </span><span>among all lesions. </span><b><span>Conclusion:</span></b><span> Only one cytomorphological disadvantage was </span><span>se</span><span>en with LBC, in the form of decreased hyperchromasia. Further </span><span>clarification of the advantages and disadvantages of LBC is needed, including management of precision and screening practices.
基金by National Natural Science Foundation of China,No.81601692Program of Liaoning Province Department of Education,JCZR2020013 and 345 Talent Program of Shengjing Hospital.
文摘BACKGROUND Both squamous cell carcinoma(SCC)and papillary thyroid carcinoma(PTC)are common malignant tumors in the neck.However,seldom has SCC of the thyroid been diagnosed.Further,cytological features of SCC and PTC have rarely been reported.The significance of fine-needle aspiration cytology(FNAC)in the diagnosis of neck masses has been established.Herein,we present an exceedingly rare case of an intrathyroidal SCC diagnosed using FNAC,along with its cytological features.CASE SUMMARY A 66-year-old man presented with a left-sided neck mass.Ultrasound examination showed an ill-defined nodule.The appearance was hypoechoic with a few hyperechoic spots.FNAC of the left thyroid nodule was performed.A cellular smear was obtained,and it showed a large number of neoplastic cells with rich cytoplasm and poor cell adhesion.Tumor cell nuclei showed coarse nuclear chromatin and a few enlarged prominent nucleoli.An increased nuclear/cytoplasm ratio was observed.Thus,malignancy was diagnosed without a confirmed tumor type.Percutaneous tumor biopsy was performed to make a definite diagnosis.The tumor cells showed typical squamous cell characteristics.CONCLUSION Head and neck SCC and PTC have different cytologies.Measures are needed to ensure accurate diagnosis using FNAC.
基金the National Natural Science Foundation of China(Grant No.32372652)the Liaoning Provincial Science and Technology Project of‘Jiebangguashuai’(Grant No.2022JH1/10400016)the Shenyang Academician and Expert Workstation Project(Grant No.2022-15).
文摘The strawberry species Fragaria nilgerrensis Schlechtendal ex J.Gay,renowned for its distinctive white,fragrant peach-like fruits and strong disease resistance,is an exceptional research material.In a previous study,an ethyl methane sulfonate(EMS)mutant library was established for this species,resulting in various yellow leaf mutants.Leaf yellowing materials are not only the ideal materials for basic studies on photosynthesis mechanism,chloroplast development,and molecular regulation of various pigments,but also have important utilization value in ornamental plants breeding.The present study focused on four distinct yellow leaf mutants:mottled yellow leaf(MO),yellow green leaf(YG),light green leaf(LG),and buddha light leaf(BU).The results revealed that the flavonoid content and carotenoid-to-chlorophyll ratio exhibited a significant increase among these mutants,while experiencing a significant decrease in chlorophyll and carotenoid contents compared to the wild type(WT).To clarify the regulatory mechanisms and network relationships underlying these mutants,the RNA-seq and weighted gene coexpression network(WGCNA)analyses were employed.The results showed flavonoid metabolism pathway was enriched both in MO and YG mutants,while the chlorophyll biosynthesis pathway and carotenoid degradation pathway were only enriched in MO and YG mutants,respectively.Subsequently,key structural genes and transcription factors were identified on metabolic pathways of three pigments through correlation analyses and quantitative experiments.Furthermore,a R2R3-MYB transcription factor,FnMYB4,was confirmed to be positively correlated with flavonoid synthesis through transient overexpression,virus-induced gene silencing(VIGS),and RNA interference(RNAi),accompanying by reoccurrence and attenuation of mutant phenotype.Finally,dual-luciferase(LUC)and yeast one-hybrid assays confirmed the binding of FnMYB4 to the FnFLS and FnF3H promoters,indicating that FnMYB4 positively regulates flavonoid synthesis.In addition,correlation analyses suggested that FnMYB4 also might be involved in chlorophyll and carotenoid metabolisms.These findings demonstrated the pivotal regulatory role of FnMYB4 in strawberry leaf coloration.
基金This work was supported by the Major Research Program on Technology of Agricultural Structure Adjustment (No. 05-01-05B)Jiangsu High Technology Program (No. BG2004301, BG2004304, and BG2005301).
文摘A green-revertible albino mutant-Qiufeng M was found from the japonica rice (Oryza sativa L. ssp. japonica) Qiufeng in the field. The first three leaves of the mutant were albino with some green. The leaf color became pale green since the fourth leaf and the glume had the same phenomenon as the first three leaves. The measuring data of the pigment content confirmed the visually observed results. It truly had a remarkable changing process in the leaf color in Qiufeng M. Comparison of the main agronomic characters between Qiufeng and Qiufeng M indicated that the neck length and grain weight showed significant difference at the 1% level, and other characters were not different. Genetic analysis showed that the green-revertible albino trait was controlled by a single recessive nucleic gene. Using 209 recessive mutant individuals in the F2 population derived from the cross Pei'ai 64S × Qiufeng M, a gene, tentatively named gra(t), was located between the SSR markers of RM475 and RM2-22 on the long arm of chromosome 2. The genetic distance were 17.3 cM and 2.9 cM respectively.
基金Supported by Natural Science Foundation of Hunan(2016JJ6064)China Agriculture Research System(CARS-25-A-8)~~
文摘[Objective] The aim was to improve the genetic property of peppers, the mutant population of Capsicum annuum L cultivar "6421" was constructed. [Method] The seeds of "6421" were treated with 0.2% to 1.2% ethyl methane sulfonate to identified LD50, and then 10 000 LD^o of treated seeds were sowed to construct mutant population. The agronomic characters and genetic regularity of dwarf mutants in M4 generation were analyzed. [Result] Our results showed that GR and SSR were 45.2% and 40.2% respectively at 1.0% EMS, close to LD50, with GI (17.6) and seed Ⅵ (19.7) being half of that of control; 562 M4 mutants were identified in 2015, and the mutation could be characterized according 11 major categories and 32 subcategories; Simultaneously, we found that plant height, plant width, diameter of mainstem, length of main-stem, the number of main-stem nodes and branch of lines E29, E58, E142 and E312 were all significantly different from that of the control. The mutation of lines E29, E58 and E312 was all controlled by a single recessive gene. [Conclusionl The study first created a pepper mutant population, which provides not only the germplasm resources for further breeding but also direct and effective materials for genomic study of the pepper.
基金This work was supported by the Program for Changjiang Scholars and Innovative Research Team in University(No.IRTO453).
文摘A mutant with abnormal hull was first discovered from a twin-seedling strain W2555 in rice (Oryza sativa L.). The mutant had sparse branches and decreased number of florets from the base to the peak. Frequently, the florets at the top of the panicle did not develop completely. The underdeveloped florets often showed slender and white in their life cycle. Genetic analysis indicated that the mutant traits were controlled by a single recessive gene (temporarily designated as ah). ah gene controlled the development of inflorescence meristem and the flower organ. The florets of mutant showed degenerated lemma and palea. Stamens and lodicules were homeoticly transformed into pistils and palea/lemma-like structures, respectively. It seemed that ah mutant phenotypes of the homeotic conversions in lodicules and stamens were very similar to that of the B loss-of-function spwl gene reported previously in rice.
基金Supported by International Atomic Energy Agency(120609/R0)Scientific and Research Development Foundation of Zhejiang Agriculture and Forest University(2351000977)~~
文摘[Objective] The aim was to explore the relevance between decreased 1 000-grain weight and grain-filling characteristics of rice giant embryo mutant.[Method] Richards equation was used to describe grain filling processes of giant embryo mutant MH-ge1 and its corresponding wild type so as to analyze the parameters of grain-filling characteristics of materials.[Result] The initial filling power of mutant MH-ge1 was higher than the wild type MH86,however,the maximum filling rate,the mean filling rate and the final increment of mutant MH-ge1 was lower than those of MH86.[Conclusion] The grain-filling characteristics of mutant MH-ge1 were poorer than the wild type MH86,thus resulting in the decrease of the grain weight of the giant embryo rice.
文摘[Objective] This study was conducted to detect the variation induction ability of ethyl methanesulfonate (EMS), to construct a mutant population. [Method] 0.6%, 1.2% and 2.4% EMS solutions were used for inducing 2 400 stem segments of test-tube plantlets of tetraploid potato Longshu 7, and an asexual mutant population including leaf, plant type, stem, stolon, glandular hair traits was constructed. [Result] Twenty two mutation types, i.e. etiolated plantlet, albino plantlet, leaf-color gradient, etiolated vein, wrapped bud, lobed leaf, crinkled leaf, deformed compound leaf, cluster, branch, top enlargement, top bifurcation, succulent, stolon distortion, stolon shift, early tuberization, hair stolon, stem enlargement, vine stem, foliage stem, glandular hair and whorled leaf types were observed in total. There were 52 mutant single plants in total, with a mutation rate of 21.67‰. [Conclusion] The glandular hair, clustered short-stem, branched stem and early tuberization types of mutants have higher application value, and are anticipated to be used in potato functional genome research, gene improvement and germplasm innovation.
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.
文摘Comparative studies of absorption spectra of phycobiliproteins of Gracilaria lemaneiformis Greville and its pigmental mutants were conducted in this study. The results showed that the absorption spectra of phycoerythrins ( PE) from different material changed significantly, while those of phycocyanins (PC) and allophycocyanins (APC) were basically similar. In order to disclose the essence of die difference, partial sequences of die subunit genes of PE of Qingdao strain of G. lemaneiformis (qd) and its pigmental mutants were determined. The amino acid sequences were deduced and used to explain spectral shifts of PE from the pigmental mutants. The amino acid sequences of PE resembled each other, and several residues changed among qd and its pigmental mutants. Residue substitutions were found in a region consisting of amino acids which determined are secondary structure and subunits interactions, thus might influence the confirmation and interaction of subunits, and further caused spectral deviation.
文摘AIM: To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma. METHODS: The mean follow-up time was 83.6 ± 39.6 mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes, hepatitis B viral DNA (HBV DNA) level and hepatitis B e antigen (HBeAg) were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development. RESULTS: During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio: 95.74 (12.13-891.31), P 〈 0.0001], male sex [odds ratio: 7.61 (2.20-47.95); P = 0.006], and higher Iogzo HBV DNA [odds ratio: 4.69 (1.16-20.43); P 〈 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio: 26.51 (2.36-381.47); P = 0.007], presence of precore mutants [odds ratio: 4.23 (1.53-19.58), P = 0.02] and presence of basal core promoter mutants [odds ratio: 2.93 (1.24-7.57); P = 0.02] were independent predictors for progression to hepatocellular carcinoma. CONCLUSION: Our results show that high levels of baseline serum HBV DNA are associated with non- hepatocellular carcinoma-related deaths of liver failure, while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.
文摘A high_CO 2_requiring mutant of Synechococcus sp. PCC7942 has been isolated after chemical mutagenesis of ethyl methane sulphonate (EMS). It was able to grow at 4% CO 2, but not under ambient CO 2. The initial screening of the mutant showed that the genetic reversion rate was about 10 -7 and death occurred 2-3 days after being transferred from 4% CO 2 to the ambient air. Its photosynthetic dependence on external dissolved inorganic carbon was higher than that of the wild type cells, but its carbonic anhydrase activity was comparatively low. In the ultrastructural level, various types of aberrant carboxysomes appeared in the mutant cells: rod_shaped carboxysomes, irregular carboxysomes and the “empty_inclusion carboxysomes" with increasing number of glycogen granules surrounding the thylakoids. All these alterations indicated that the mutant was defective in utilizing the external CO 2. The induction of carboxysomes by lower levels of CO 2 and the biogenesis of carboxysomes are herein discussed.
文摘TP53 is a tumor suppressor gene that is mutated in most cancer types and has been extensively studied in cancer research.p53 plays a critical role in regulating the expression of target genes and is involved in key processes such as apoptosis,cell cycle regulation,and genomic stability,earning it the title“guardian of the genome.”Numerous studies have demonstrated p53’s influence on and regulation of autophagy,ferroptosis,the tumor microenvironment,and cell metabolism,all of which contribute to tumor suppression.Alterations in p53,specifically mutant p53(mutp53),not only impair its tumor-suppressing functions but also enhance oncogenic characteristics.Recent data indicate that mutp53 is strongly associated with poor prognosis and advanced cancers,making it an ideal target for the development of novel cancer therapies.This review summarizes the post-translational modifications of p53,the mechanisms of mutp53 accumulation,and its gain-of-function,based on previous findings.Additionally,this review discusses its impact on metabolic homeostasis,ferroptosis,genomic instability,the tumor microenvironment,and cancer stem cells,and highlights recent advancements in mutp53 research.
基金the Natural Science Foundation of Zhejiang Province,No.LQ20H160061Medical Health Science and Technology Project of Zhejiang Provincial Health Commission,No.2018255969.
文摘BACKGROUND Smear cytology(SC)using endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)is the established and traditional choice for diagnosing pancreatic lesions.Liquid-based cytology(LBC)is a novel alternative cytological method,however,the comparative diagnostic efficacy of LBC remains inconclusive.AIM To examine the diagnostic efficacy of LBC and SC for pancreatic specimens obtained through EUS-FNA via a systematic review and meta-analysis.METHODS A systematic literature search was performed using PubMed,EMBASE,the Cochrane Library,and Web of Science.The numbers of true positives,false positives,true negatives,and false negatives for each cytological test(LBC and CS)were extracted from the included studies.The pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve(AUC)were calculated,and the AUC was compared by Tukey's multiple comparisons test.The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies II tool.RESULTS A total of 1656 patients in eight studies were included.The pooled sensitivity and specificity and the AUC for LBC were 0.76(95%CI:0.72-0.79),1.00(95%CI:0.98-1.00),and 0.9174,respectively,for diagnosing pancreatic lesions.The pooled estimates for SC were as follows:Sensitivity,0.68(95%CI:0.64-0.71);specificity,0.99(95%CI:0.96-100.00);and AUC,0.9714.Similarly,the corresponding values for LBC combined with SC were 0.87(95%CI:0.84-0.90),0.99(95%CI:0.96-1.00),and 0.9894.Tukey’s multiple comparisons test was used to compare the sensitivities and AUCs of the three diagnostic methods;statistically significant differences were found between the three methods,and LBC combined with SC was superior to both LBC(P<0.05)and SC(P<0.05).The pooled sensitivity and AUC did not change significantly in the sensitivity analysis.CONCLUSION LBC may be sensitive than SC in the cytological diagnosis of pancreatic lesions,however,the superior diagnostic performance of their combination emphasizes their integrated usage in the clinical evaluation of pancreatic lesions.