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 explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Objective To analyze the risk factors and survival status of Epstein-Barr virus(EBV)infection in pa-tients with aplastic anemia(AA)after haploid allogeneic hematopoietic stem cell transplantation(Haplo-HSCT).Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1,2019 to October 31,2022 were analyzed retrospectively.The occurrence and onset time of EBV viremia,EBV-related diseases(EBV diseases),and post-transplant lymphoproliferative disorders(PTLD)were ob-served,risk factors and survival status were analyzed.Results Among the 78 patients,38 were males and 40 were females,with a median age of 33(9-56)years old;53 patients experienced EBV reactivation,with a total inci-dence of 67.9％,and the median time for EBV reactivation was 33(13,416)days after transplantation.Among pa-tients with EBV reactivation,49 cases(62.8％)were simple EBV viremia,2 cases(2.6％)were possible EBV di-seases,and 2 cases(2.6％)were already confirmed EBV diseases(PTLD).Univariate analysis showed that age 1＜40 years old at the time of transplantation,umbilical cord blood infusion,occurrence of acute graft-versus-host disease(aGVHD)after transplantation,and concurrent cytomegalovirus(CMV)infection were independent risk fac-tors for EBV reactivation in AA patients after Haplo-HSCT.Multivariate analysis showed that concurrent CMV in-fection was an independent risk factor for EBV reactivation in A A patients after Haplo-HSCT(P=0.048).Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation(P＜0.05).The mortality of EBV viremia,EBV diseases,and PTLD alone were 8.2％,50.0％,and 100％,respectively.The 2-year overall survival rate of patients with and without EBV reactivation were 85.3％,and 90.7％,respectively,difference was not statistically significant(P=0.897).However,patients treated with rituximab had 2-year lower survival rate than those who did not use it,with a statistically significant difference(P=0.046).Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT,which affects the prognosis and survival of patients.

Objective:To fabricate the composite scaffolds for bone regeneration with silk fibroin (SF), bacterial cellulose nanofibers (BCNR) and hydroxyapatite (HAp) and evaluate their osteogenic activity.Methods:HAp particles, BCNR and bone morphogenetic protein-2 (BMP2) were added into SF aqueous solution in turn, poured into molds of different sizes after being mixed evenly and processed at -25 ℃ for 24 hours to obtain frozen molds, and the composite scaffolds were frozen-dried by freezing-drying machine. The composite scaffolds with different mass ratios of SF and BCNR were divided into groups A (2∶1), B (4∶1) and C (6∶1), and the inactive composite scaffolds without BMP2 fell into group D. The surface morphology and pore structure of the scaffolds were detected by scanning electron microscopy. The porosity of the scaffolds was measured by mercury intrusion porosimeter. The stress-strain curve was obtained by using the universal material testing machine to compress the scaffolds, with which their compressive strength and Young′s modulus were analyzed. Immortalized mouse embryonic fibroblasts (iMEF) were inoculated on the composite scaffolds of group A, B, C and D. At 4 and 8 days after cell inoculation, the proportion of alive and dead cells in each group was detected by cell survival/death staining; the cell counting kit-8 (CCK-8) was used to detect cell proliferation activity in each group; the positive staining cells were detected in each group by alkaline phosphatase (ALP) staining; the ALP activity was observed in each group with ALP activity detection. A total of 15 female SD rats were selected to establish osteogenesis models with ectopic muscle bag. The composite scaffolds implanted with different SF/BCNR mass ratios and the inactive composite scaffolds without BMP2 fell into group A′ (2∶1), B′ (4∶1), C′ (6∶1) and D′ respectively, and a sham operation group was set at the same time, with 3 rats in each groups. In the sham operation group, the muscle bag and skin were sutured without scaffold implantation after the incision of skin, the blunt separation of the quadriceps muscle, and the formation of muscle bag in the muscle. In the other four groups, the corresponding scaffolds were implanted in the muscle bag and the muscle bag and skin were sutured. X-ray examination was performed at 2 and 4 weeks after operation to observe the osteogenesis in each group. At 4 weeks after operation, the implanted scaffolds and tissue complexes were collected by pathological tissue sectioning, HE staining and Masson staining, and for observing the osteogenesis by in each group. Immunohistochemical staining was also performed on the tissue sections to observe the expression of osteogenic markers type I collagen (COL1) and osteopontin (OPN) in each group.Results:Scanning electron microscopy showed that the lamellar and micropore structures of group B were more regular and uniform than those of groups A and C. The porosity rate analysis showed that the porosity rates of groups B and C were (89.752±1.866)% and (84.257±1.013)% respectively, higher than that of group A [(81.171±1.268)%] ( P<0.05 or 0.01), with the porosity rate of group C lower than that of group B ( P<0.01). The mechanical property test showed that the compressive strengths of groups B and C were (0.373±0.009)MPa and (0.403±0.017)MPa respectively, higher than that of group A [(0.044±0.003)MPa] ( P<0.01), and the Young′s moduli of groups B and C were (7.413±0.094)MPa and (9.515±0.615)MPa respectively, higher than that of group A [(1.881±0.036)MPa] ( P<0.01), with the compressive strength and Young′s modulus of group C higher than those of group B ( P<0.05 or 0.01). The cell survival/death staining showed that the number of dead cells of group B was significantly smaller than that of groups A, C and D at 4 days after cell inoculation, and that group B had the most living cells and the fewest dead cells at 8 days after cell inoculation. The results of CCK-8 experiment showed that at 4 days after cell inoculation, the cell proliferation activity of groups A and B was 0.474±0.009 and 0.545±0.018 respectively, higher than 0.394±0.016 of group D ( P<0.01); the cell proliferation activity of group C was 0.419±0.005, with no significant difference from that of group D ( P>0.05), while the cell proliferation activity of groups A and C were both lower than that of group B ( P<0.01). At 8 days after cell inoculation, the cell proliferation activity of group B was 1.290±0.021, higher than 1.047±0.011 of group D ( P<0.01); the cell proliferation activity of group C was 0.794±0.032, lower than that of group D ( P<0.01); the cell proliferation activity of group A was 1.086±0.020, with no significant difference from that of group D ( P>0.05); the cell proliferation activity of groups A and C was lower than that of group B ( P<0.01). At 4 and 8 days after cell inoculation, ALP staining showed that more positive cells were found in groups A, B and C when compared with group D, and more positive cells were found in group B than in groups A and C. At 4 days after cell inoculation, the ALP activity detection showed that the ALP activity of groups A, B and C was 1.399±0.071, 1.934±0.011 and 1.565±0.034 respectively, higher than 0.082±0.003 of group D ( P<0.01), while the ALP activity of groups A and C was lower than that of group B ( P<0.01). At 8 days after cell inoculation, the cell activity of groups A, B and C was 2.602±0.055, 3.216±0.092 and 2.145±0.170 respectively, higher than 0.101±0.001 of group D ( P<0.01), while the ALP activity of groups A and C was lower than that of group B ( P<0.01). X-ray examination results showed that at 2 weeks after operation, no obvious osteogenesis was observed in the sham operation group, group D′, A′ and C′, while it was observed in group B′. At 4 weeks after operation, obvious osteogenesis was observed in group A′, B′ and C′, with significantly more osteogenesis in group B′ than in the other two groups, while there was no obvious osteogenesis in the sham operation group and group D′. At 4 weeks after operation, the HE staining and Masson staining showed that a large number of uniformly distributed new bone tissue was formed in group B′, while only a small amount of new bone tissue was found locally in groups A′ and C′, and only part of new tissue was found to grow in group D′ with no obvious new bone tissue observed. The maturity of new bone tissue formed in group B′ was higher than that in group A′ and C′. Immunohistochemical staining showed more COL1 and OPN positive staining in group B′ when compared with groups A′ and C′. The expression intensity analysis of COL1 and OPN showed that in groups A′, B′ and C′, the expression intensity of COL1 was 2.822±0.384, 22.810±2.435 and 12.480±0.912 respectively and the expression intensity of OPN was 1.545±0.081, 5.374±0.121 and 2.246±0.116 respectively, with higher expression intensity of COL1 and OPN in groups B′ and C′ than that in group A′ ( P<0.01) and lower expression intensity of COL1 and OPN in group C′ than that in B′ group ( P<0.01). Conclusions:The composite scaffold for bone regeneration is successfully fabricated with SF, BCNR and HAp. The composite scaffold with a mass ratio of SF to BCNR of 4∶1 has uniform pore structure, high porosity, good mechanical properties and biocompatibility, excellent pro-osteogenic properties in vitro, as well as excellent osteo-inductivity and osteo-conductivity.

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.

In this study, the effect of brassinosteroid(BR) on the physiological and biochemical conditions of 2-year-old Panax notoginseng under the cadmium stress was investigated by the pot experiments. The results showed that cadmium treatment at 10 mg·kg~(-1) inhibited the root viability of P. notoginseng, significantly increased the content of H_2O_2 and MDA in the leaves and roots of P. noto-ginseng, caused oxidative damage of P. notoginseng, and reduced the activities of SOD and CAT. Cadmium stress reduced the chlorophyll content of P. notoginseng, increased leaf F_o, reduced F_m, F_v/F_m, and PIABS, and damaged the photosynthesis system of P. notoginseng. Cadmium treatment increased the soluble sugar content of P. notoginseng leaves and roots, inhibited the synthesis of soluble proteins, reduced the fresh weight and dry weight, and inhibited the growth of P. notoginseng. External spray application of 0.1 mg·L~(-1) BR reduced the H_2O_2 and MDA content in P. notoginseng leaves and roots under the cadmium stress, alleviated cadmium-induced oxidative damage to P. notoginseng, improved the antioxidant enzyme activity and root activity of P. notoginseng, increased the content of chlorophyll, reduced the F_o of P. notoginseng leaves, increased F_m, F_v/F_m, and PIABS, alleviated the cadmium-induced damage to the photosynthesis system, and improved the synthesis ability of soluble proteins. In summary, BR can enhance the anti-cadmium stress ability of P. notoginseng by regulating the antioxidant enzyme system and photosynthesis system of P. notoginseng under the cadmium stress. In the context of 0.1 mg·L~(-1) BR, P. notoginseng can better absorb and utilize light energy and synthesize more nutrients, which is more suitable for the growth and development of P. notoginseng.
Cadmium/metabolism* ; Antioxidants/pharmacology* ; Panax notoginseng ; Brassinosteroids/pharmacology* ; Chlorophyll/metabolism* ; Plant Roots/metabolism* ; Stress, Physiological

Neoadjuvant therapy has been widely applied in the treatment of rectal cancer, which can shrink tumor size, lower tumor staging and improve the prognosis. It has been the standard preoperative treatment for patients with locally advanced rectal cancer. The efficacy of neoadjuvant therapy for rectal cancer patients varies between individuals, and the results of tumor regression are obviously different. Some patients with good tumor regression even achieve pathological complete response (pCR). Tumor regression is of great significance for the selection of surgical regimes and the determination of distal resection margin. However, few studies focus on tumor regression patterns. Controversies on the safe distance of distal resection margin after neoadjuvant treatment still exist. Therefore, based on the current research progress, this review summarized the main tumor regression patterns after neoadjuvant therapy for rectal cancer, and classified them into three types: tumor shrinkage, tumor fragmentation, and mucin pool formation. And macroscopic regression and microscopic regression of tumors were compared to describe the phenomenon of non-synchronous regression. Then, the safety of non-surgical treatment for patients with clinical complete response (cCR) was analyzed to elaborate the necessity of surgical treatment. Finally, the review studied the safe surgical resection range to explore the safe distance of distal resection margin.
Humans ; Neoadjuvant Therapy/methods* ; Margins of Excision ; Treatment Outcome ; Rectal Neoplasms/pathology* ; Rectum/pathology* ; Neoplasm Staging ; Retrospective Studies