Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Background::Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods::Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results::NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions::Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

Coronary artery heavy calcification is always challenging scenarios for interventional cardiologists.Although the treatment strategy guided by intravascular imaging and guaranteed by rotational atherectomy(RA)is recommended by consensus,the application rate of RA in my country is still relatively low.Our center has accumulated a lot of experience in the use of rotational atherectomy to treat severe calcified lesions,especially in complex scenarios such as left main trunk lesions,ostial lesions,and severe vessel tortuosity.Here is a case of interventional treatment of severe eccentric stenosis caused by a huge calcified plaque at the right coronary artery ostium.The method and strategy of plaque modification and partial ablation by intravascular ultrasound-guided RA are discussed.

Objective:To investigate the effects of dexmedetomidine(DEX)on the malignant biological behavior of gastric cancer(GC)cells through the immune regulation mechanism mediated by cyclic GMP-AMP synthase-stimulator of interferon gene(cGAS-STING)pathway.Methods:GC cell line MGC-803 was randomly divided into Control group(blank medium treatment),DEX low concentration group(DEX-L group,1 ng/ml),DEX medium concentration group(DEX-M group,10 ng/ml),DEX high concentra-tion group(DEX-H group,100 ng/ml)and DEX high concentration+cGAS inhibitor RU.521 group(DEX-H+RU.521 group,100 ng/ml DEX+1.0 μmol/L RU.521).Cell proliferation was detected by CCK-8 method.Cell scratch test was used to detect the migration ability of cells in each group.Transwell test was used to detect the invasive ability of cells in each group.The apoptosis rate was detected by flow cytometry.The levels of IL-2,interferon gamma(IFN-γ)and tumor necrosis factor alpha(TNF-α)in cells were detected by ELISA.Real time-fluorescent quantitative PCR(RT-qPCR)was applied to detect the expression levels of cGAS,STING and interferon typeⅠ(IFN-Ⅰ)mRNA.Western blot was used to detect the expressions of cGAS,STING,Bax,CyclinD1,matrix metalloproteinase 9(MMP9),N-cadherin,Vimentin,E-cadherin,Caspase3,Caspase8 and their shear type and phosphorylation level of TANK-binding kinase 1(TBK1)and interferon regulatory factor 3(IRF3).Results:Compared with Control group,the cell migration rate,number of cell invasions,TNF-α level,CyclinD1,MMP9,N-cadherin,Vimentin protein expressions in MGC-803 cells in DEX-M and DEX-H groups were decreased obviously(P<0.05),the growth inhibition rate(48 h,72 h),apoptosis rate,IL-2,IFN-γ,Bax,E-cadherin,Cleaved Caspase3,Cleaved Caspase8 protein expression levels,cGAS,STING,IFN-Ⅰ mRNA levels and protein expression levels and phosphorylation levels of TBK1 and IRF3 were increased obviously(P<0.05).RU.521 weakened the inhibitory effects of DEX on the proliferation,migration and invasion of GC cells and the ability to induce apoptosis,and alleviated the improvement on immune function.Conclusion:DEX may inhibit the proliferation,migration and invasion of GC cells and induce apoptosis of GC cells by acti-vating cGAS-STING pathway mediated immune regulation.

Giardia duodenalis is a zoonotic intestinal parasitic protozoan that can severely harm human and animal health,and causes substantial economic losses to humans and animal husbandry annually.Currently,no effective drugs and vaccines a-gainst giardiasis are available.With the development of bioinformatics and sequencing techniques,genomic sequencing of the Giardia genome and comparative genomics analysis have advanced understanding of the molecular characteristics of Giardia.This article reviews the current status of genome sequencing,structural genomics,comparative genomics,and functional ge-nomics for Giardia duodenalis,to provide new ideas for understanding the origins,evolution and pathogenic mechanisms of Giardia,to aid in the diagnosis,design of new veterinary drugs,and development of vaccines for giardiasis.

Objective:To analyze the clinical and ultrasonographic characteristics of ductal carcinoma in situ(DCIS)and intraductal papilloma(IDP),and to construct a nomogram predictive model for DCIS and IDP.Methods:We selected data from 156 cases(212 nodules)of DCIS and 158 cases(238 nodules)of IDP confirmed by pathology.Through univariate and multivariate analy-ses,we evaluated the influencing factors of ultrasonic diagnosis of DCIS and established a diagnos-tic model to clarify the value of each ultrasonographic sign in diagnosis.Results:The univariate analysis showed statistically significant differences between the two groups in terms of age,medi-cal history,nodule long diameter,volume,margin,posterior echo,calcification,color Doppler flow imaging(CDFI),and resistance index(R/)(P＜0.05).The multivariate logistic regression analysis showed that the absence of abnormal ducts around the nodule,posterior echo attenuation,pres-ence of microcalcifications,and RI≥0.70,tend to indicate DCIS,while simple dilation or lack of blood supply of the duct around the nodule tend to indicate IDP.These indicators were included in the nomogram model,which showed high predictive performance,calibration,and clinical value in both the training and validation sets.Conclusion:The nomogram model based on sonographic fea-tures can easily distinguish DCIS from IDP.The presence of abnormal ducts around the nodule,posterior echo attenuation,presence of microcalcifications,and RI＞0.70 should raise suspicion for DCIS.