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.

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

OBJECTIVE: To investigate the effectiveness of Xuanshen Yishen Decoction (XYD) in the treatment of hypertension. METHODS: Hospital electronic medical records from 2019-2023 were utilized to emulate a randomized pragmatic clinical trial. Hypertensive participants were eligible if they were aged ⩾40 years with baseline systolic blood pressure (BP) ⩾140 mm Hg. Patients treated with XYD plus antihypertensive regimen were assigned to the treatment group, whereas those who followed only antihypertensive regimen were assigned to the control group. The primary outcome assessed was the attainment rate of intensive BP control at discharge, with the secondary outcome focusing on the 6-month all-cause readmission rate. RESULTS: The study included 3,302 patients, comprising 2,943 individuals in the control group and 359 in the treatment group. Compared with the control group, a higher proportion in the treatment group achieved the target BP for intensive BP control [8.09% vs. 17.5%; odds ratio (OR)=2.29, 95% confidence interval (CI)=1.68 to 3.13; P<0.001], particularly in individuals with high homocysteine levels (OR=3.13; 95% CI=1.72 to 5.71; P<0.001; P for interaction=0.041). Furthermore, the 6-month all-cause readmission rate in the treatment group was lower than in the control group (hazard ratio=0.58; 95% CI=0.36 to 0.91; P=0.019), and the robustness of the results was confirmed by sensitivity analyse. CONCLUSIONS XYD could be a complementary therapy for intensive BP control. Our study offers real-world evidence and guides the choice of complementary and alternative therapies. (Registration No. ChiCTR2400086589).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Antihypertensive Agents/pharmacology* ; Blood Pressure/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Hypertension/physiopathology* ; Patient Readmission ; Treatment Outcome

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.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Objective: To compare the differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all cause death, thromboembolic events, major bleeding events and composite endpoint in patients with nonvalvular atrial fibrillation. Methods: This is a retrospective cohort study. From the China Atrial Fibrillation Registry cohort study, the patients with atrial fibrillation who were>18 years old were randomly divided into CAS risk score group and CHA₂DS₂-VASc risk score group respectively. According to the anticoagulant status at baseline and follow-up, patients in the 2 groups who complied with the scoring specifications for anticoagulation were selected for inclusion in this study. Baseline information such as age and gender in the two groups were collected and compared. Follow-up was performed periodically to collect information on anticoagulant therapy and endpoints. The endpoints were all-cause death, thromboembolism events and major bleeding, the composite endpoint events were all-cause death and thromboembolism events. The incidence of endpoints in CAS group and CHA₂DS₂-VASc group was analyzed, and multivariate Cox proportional risk model was used to analyze whether the incidence of the endpoints was statistically different between the two groups. Results: A total of 5 206 patients with AF were enrolled, average aged (63.6±12.2) years, and 2092 (40.2%) women. There were 2 447 cases (47.0%) in CAS risk score group and 2 759 cases (53.0%) in CHA₂DS₂-VASc risk score group. In the clinical baseline data of the two groups, the proportion of left ventricular ejection fraction<55%, non-paroxysmal atrial fibrillation, oral warfarin and HAS BLED score in the CAS group were lower than those in the CHA₂DS₂-VASc group, while the proportion of previous diabetes history and history of antiplatelet drugs in the CAS group was higher than that in the CHA₂DS₂-VASc group, and there was no statistical difference in other baseline data. Patients were followed up for (82.8±40.8) months. In CAS risk score group, 225(9.2%) had all-cause death, 186 (7.6%) had thromboembolic events, 81(3.3%) had major bleeding, and 368 (15.0%) had composite endpoint. In CHA₂DS₂-VASc risk score group, 261(9.5%) had all-cause death 209(7.6%) had thromboembolic events, 112(4.1%) had major bleeding, and 424 (15.4%) had composite endpoint. There were no significant differences in the occurrence of all-cause death, thromboembolic events, major bleeding and composite endpoint between anticoagulation in CAS risk score group and anticoagulation in CHA₂DS₂-VASc risk score group (log-rank P =0.643, 0.904, 0.126, 0.599, respectively). Compared with CAS risk score, multivariable Cox proportional hazards regression models showed no significant differences for all-cause death, thromboembolic events, major bleeding and composite endpoint between the two groups with HR(95%CI) 0.95(0.80-1.14), 1.00(0.82-1.22), 0.83(0.62-1.10), 0.96(0.84-1.11), respectively. All P>0.05. Conclusions: There were no significant differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all-cause death, thromboembolic events, and major bleeding events in Chinese patients with non-valvular atrial fibrillation.
Adolescent ; Anticoagulants ; Atrial Fibrillation/drug therapy* ; Cohort Studies ; Female ; Hemorrhage/complications* ; Humans ; Male ; Retrospective Studies ; Risk Assessment ; Stroke/epidemiology* ; Stroke Volume ; Thromboembolism/etiology* ; Ventricular Function, Left

OBJECTIVE: To assess the trends in characteristics, treatments, and outcomes of acute myocardial infarction (AMI) patients in tertiary Chinese medicine (CM) hospitals in China between 2006 and 2013. METHODS: This retrospective study was based on two nationwide epidemiological surveys of AMI in tertiary CM hospitals during 2 years (2006 and 2013). Patients admitted to the hospital for AMI were enrolled. Hospital records were used as the data source. Case data were derived regarding baseline characteristics, treatments, and outcomes of patients to assess changes from 2006 to 2013. Logistic regression was used to analyze the relationship between prognosis, general influencing factors of disease, and various treatment measures. RESULTS: Totally 26 tertiary CM hospitals in 2006 and 29 tertiary CM hospitals in 2013 (18 were repetitive) were surveyed. A total of 2,311 patients with AMI were enrolled (1,094 cases in 2006 and 1,217 cases in 2013). From 2006 to 2013, the mean age did not significantly change, but the proportion of patients younger than 65 years increased. The prevalence of risk factors such as hypertension, diabetes, and hyperlipidemia also increased. Significant increases were observed in primary percutaneous coronary intervention [20.48% (2006) vs. 24.90% (2013)] and revascularization [36.11% (2006) vs. 52.42% (2013)]. In-hospital mortality decreased from 11.15% in 2006 to 10.60% in 2013. A mortality logistic regression analysis identified reperfusion therapy [odds ratio (OR), 0.222; 95% confidence interval (CI), 0.106-0.464], Chinese patent medicines (OR, 0.394; 95% CI, 0.213-0.727), and CM decoctions (OR, 0.196; 95% CI, 0.109-0.353) as protective factors. CONCLUSION Reperfusion and revascularization capabilities of tertiary CM hospitals have improved significantly, but in-hospital mortality has not significantly decreased. Efforts are needed to improve medical awareness of AMI and expand the use of CM to reduce in-hospital mortality in China.

In recent years， with the change in life style， social environment， and national childbearing policy， the proportion of high-risk pregnant women has increased significantly， triggering the spectrum of obstetric diseases to constantly change， which has brought new challenges to the diagnosis and treatment of obstetrics. Traditional Chinese medicine （TCM） has been proved effective in dealing with a variety of obstetric diseases， and various treatment methods are available， which can serve as alternative means for solving refractory obstetric diseases. However， most obstetric clinicians are currently less aware of the therapeutic effects of TCM， which has significantly hindered its participation in clinical treatment. Therefore， the China Association of Chinese Medicine （CACM） organized the outstanding young obstetricians of TCM and western medicine to discuss 15 obstetric diseases responding specifically to TCM or integrated TCM and western medicine， including hyperemesis gravidarum， threatened abortion， ectopic gestation， cough during pregnancy， pregnancy-induced hypertension syndrome， maternal-fetal ABO incompatibility， postpartum hypogalactia， residual pregnancy tissue in uterine cavity， puerperal infection， pantalgia after childbirth， hematoma/undesirable healing after caesarean section， postpartum urinary retention， ileus after cesarean section， pelvic floor dysfunction， and postnatal depression. The suggestions for their treatment with TCM or integrated TCM and western medicine were also proposed， aiming to provide patients with effective and personalized treatments in clinical practice and improve the diagnosis and treatment effects of obstetric diseases， thus benefiting the public. At the same time， more obstetrical clinicians are expected to understand the therapeutic effects and advantages of TCM and draw on the strengths of both TCM and western， thereby promoting the establishment of an obstetric diagnosis and treatment system with Chinese characteristics.