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.

Objective To investigate the levels and influencing factors for eye lens dose of interventional radiology workers, and to provide a basis for reasonable and scientific radiation protection. Methods Thermoluminescent eye lens dosimeters were used to monitor the left and right eye lens doses of interventional radiology workers in real time during different surgical positions and varying eye protection conditions. The annual eye lens doses for the operators were estimated based on their yearly workload. The differences in eye lens doses under different conditions were analyzed and the influencing factors were identified. Results For individual interventional operations, the range of personal dose equivalent H_p(3) of the left eye of interventional radiology workers was ( < MDL ~ 418.33) μSv, the median (Q₁, Q₃) was 9.29 ( < MDL, 40.79) μSv, and the mean was 40.79 ± 70.36 μSv. The estimated annual eye lens doses were 4.05 mSv and 17.80 mSv based on the median and mean values of the eye lens dose of a single operation multiplied by average annual frequency of operations per person, respectively. The left eye lens dose was higher than the right eye lens dose of the same operator (Z = −4.24, P < 0.05), and the dose of the right eye lens was strongly positively correlated with that of the left eye lens. The left eye lens dose of the first surgeon was higher than that of the second surgeon in the same operation (Z = −3.10, P < 0.05). The eye lens dose was influenced by operator position (χ² = 9.149, P = 0.002, OR = 8.343), eye protection (χ² = 4.619, P = 0.032, OR = 4.352), and air kerma area product (χ² = 8.032, P = 0.005, OR = 5.488). Conclusion According to the results of this study, a significant portion of interventional operators have eye lens doses that approach or exceed international occupational dose limits. It is recommended to pay attention to the operation frequency of the first operator and the air kerma area product of interventional operation, and strengthen radiation protection and dose monitoring for the eye lens of interventional radiology workers.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Objective:To explore the diagnostic value of first-trimester and mid-trimester ultrasound in screening fetal pentalogy of Cantrell, and to analyze missed and misdiagnosed cases.Methods:The fetal ultrasound image characteristics of pentalogy of Cantrell diagnosed in the Affiliated Suzhou Hospital of Nanjing Medical University from March 2018 to November 2022 were retrospectively analyzed. The necessary sections and key features of ultrasound images for diagnosing the disease in first-trimester and mid-trimester were summarized. The diagnostic value of ultrasound screenings in first-trimester and mid-trimester was analyzed, and the progression of the disease during pregnancy was understood, the missed diagnosis rate and misdiagnosis rate were calculated, and the reasons for missing diagnosis were analyzed. All fetuses were followed up to birth or induction of labor.Pentalogy of Cantrell was divided into types Ⅰ, Ⅱ, and Ⅲ according to Toyama′s research.Results:Among the 120 190 fetuses, 13 cases of pentalogy of Cantrell were diagnosed by ultrasound in first-trimester and mid-trimester. Ultrasound predominantly showed the fetal heart being malpositioned outside the chest and the fetal abdominal contents bulging outside the abdominal cavity, and the sternumal echo was partially or completely missed in some cases. All 13 cases were confirmed by follow-up, including 1 case of type Ⅱ, and 12 cases of type Ⅲ. In addition, 1 missed case of type Ⅱ pentalogy of Cantrell was followed up after birth. The correct diagnostic rates of fetal pentalogy of Cantrell using standard ultrasound sections during the first-trimester and mid-trimester were 99.9% and 100%, the sensitivity were 88.9% and 100%, the specificity were both 100%, the positive predictive values were both 100%, and the negative predictive values were 99.9% and 100%, respectively.Conclusions:First-trimester and mid-trimester ultrasound screenings have high diagnostic accuracy for pentalogy of Cantrell, and early detection and early diagnosis are of great clinical significance for the guidance of pregnancy outcomes.

Objective To assess the efficacy and safety of ascending aorta banding technique combined with typeⅠhybrid aortic arch repair for the aortic arch diseases. Methods The clinical data of patients undergoing ascending aorta banding technique combined with type Ⅰ hybrid arch repair for aortic arch diseases from March 2019 to March 2022 in Beijing Anzhen Hospital were retrospectively analyzed. The technical success, perioperative complications and follow-up results were evaluated. Results A total of 44 patients were collected, including 35 males and 9 females, with a median age of 63.0 (57.5, 64.6) years. The average EuroSCORE Ⅱ score was 8.4%±0.7%. The technical success rate was 100.0%. All patients did not have retrograde type A aortic dissection and endoleaks. One patient died of multiple organ failure 5 days after operation, the in-hospital mortality rate was 2.3%, and the remaining 43 patients survived and were discharged from hospital. The median follow-up period was 14.5 (6-42) months with a follow-up rate of 100.0%. One patient with spinal cord injury died 2 years after hospital discharge. One patient underwent thoracic endovascular aortic repair at postoperative 3 months due to new entry tears near to the distal end of the stent. Conclusion Ascending aorta banding combined with typeⅠhybrid arch repair for the aortic arch diseases does not need cardio-pulmonary bypass. Ascending aorta banding technique strengthens the proximal anchoring area of the stent to avoid risks such as retrograde type A dissection, endoleak and migration. The operation owns small trauma, rapid recovery, low mortality and a low rate of reintervention, which may be considered as a safe and effective choice in the treatment of the elderly, high-risk patients with complex complications.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

This study explored the molecular mechanism of acteoside against hepatoma 22(H22) tumor in mice through c-Jun N-terminal kinase(JNK) signaling pathway. H22 cells were subcutaneously inoculated in 50 male BALB/c mice, and then the model mice were classified into model group, low-dose, medium-dose, and high-dose acteoside groups, and cisplatin group. The administration lasted 2 weeks for each group(5 consecutive days/week). The general conditions of mice in each group, such as mental status, diet intake, water intake, activity, and fur were observed. The body weight, tumor volume, tumor weight, and tumor-inhibiting rate were compared before and after administration. Morphological changes of liver cancer tissues were observed based on hematoxylin and eosin(HE) staining, and the expression of phosphorylated(p)-JNK, JNK, B-cell lymphoma-2(Bcl-2), Beclin-1, and light chain 3(LC3) in each tissue was detected by immunohistochemistry and Western blot. qRT-PCR was performed to detect the mRNA expression of JNK, Bcl-2, Beclin-1, and LC3. The general conditions of mice in model and low-dose acteoside groups were poor, while the general conditions of mice in the remaining three groups were improved. The body weight of mice in medium-dose acteoside group, high-dose acteoside group, and cisplatin group was smaller than that in model group(P<0.01). The tumor volume in model group was insignificantly different from that in low-dose acteoside group, and the volume in cisplatin group showed no significant difference from that in high-dose acteoside group. Tumor volume and weight in medium-dose and high-dose acteoside groups and cisplatin group were lower than those in the model group(P<0.001). The tumor-inhibiting rates were 10.72%, 40.32%, 53.79%, and 56.44% in the low-dose, medium-dose, and high-dose acteoside groups and cisplatin group, respectively. HE staining showed gradual decrease in the count of hepatoma cells and increasing sign of cell necrosis in the acteoside and cisplatin groups, and the necrosis was particularly obvious in the high-dose acteoside group and cisplatin group. Immunohistochemical results suggested that the expression of Beclin-1, LC3, p-JNK, and JNK was up-regulated in acteoside and cisplatin groups(P<0.05). The results of immunohistochemistry, Western blot, and qRT-PCR indicated that the expression of Bcl-2 was down-regulated in the medium-dose and high-dose acteoside groups and cisplatin group(P<0.01). Western blot showed that the expression of Beclin-1, LC3, and p-JNK was up-regulated in acteoside and cisplatin groups(P<0.01), and there was no difference in the expression of JNK among groups. qRT-PCR results showed that the levels of Beclin-1 and LC3 mRNA were up-regulated in the acteoside and cisplatin groups(P<0.05), and the level of JNK mRNA was up-regulated in medium-dose and high-dose acteoside groups and cisplatin group(P<0.001). Acteoside promotes apoptosis and autophagy of H22 cells in mice hepatoma cells by up-regulating the JNK signaling pathway, thus inhibiting tumor growth.
Male ; Animals ; Mice ; Cisplatin/pharmacology* ; Carcinoma, Hepatocellular/genetics* ; MAP Kinase Signaling System ; Beclin-1 ; Apoptosis ; Liver Neoplasms/genetics* ; Necrosis ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; RNA, Messenger/metabolism* ; Autophagy