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.

Tuberculosis （TB） and human immunodeficiency virus infection / acquired immune deficiency syndrome （HIV/AIDS） are both serious global public health threats. Early detection of infected persons and/or patients through TB/HIV bi-directional screening is crucial for prevention and control strategy in China and globally. In recent years， with the promotion and application of new TB and HIV detection technologies worldwide， TB/HIV bi-directional screening technologies and strategies have made remarkable changes. This expert consensus introduces the significance and challenges of TB/HIV bi-directional screening， summarizes important progress of research and applications， and makes recommendations on screening measures and procedures to further strengthen TB/HIV bi-directional screening in China.

Objective To investigate the effect of hedysarum polysacchcaide(HPS)on nuclear transcription factor-κB(NF-κB)/IκB kinase β(IKKβ)signaling pathway in cardiac tissue of db/db mice with diabetic cardiomyopathy(DCM).Methods Altogether 60 7-week-old male db/db mice were randomly divided into model group,control group and experimental-H,-M,-L groups,with 12 mice in each group.In addition,12 db/m mice of the same week age were selected as the normal group.Normal group and model group were given 0.9％NaCl by intragastric administration.Experimental-L,-M,-H groups were given 50,100 and 200 mg·kg-1 HPS suspension by intragastriction,respectively.Control group was given 4 mg·kg-1 rosiglitazone suspension by intragastric administration.Six groups of rats were given the drug once a day for 8 weeks.The contents of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in myocardial tissue were detected by enzyme-linked immunosorbent assay.The mRNA expression levels of NF-κB and IKKβ in myocardial tissue were detected by real-time fluorescence quantitative polymerase chain reaction.The correlation between the expression of NF-κB protein and the content of TNF-α and IL-6 was analyzed.Results The contents of IL-6 in myocardial tissue of normal,model,control and experimental-H groups were(1.24±0.54),(7.72±0.24),(2.90±0.50)and(2.78±0.56)ng·L-1;the contents of TNF-α were(1.96±0.52),(5.25±0.72),(2.84±0.86)and(2.82±0.58)ng·L-1;the mRNA expression levels of NF-κB were I.00±0.00,3.35±0.81,2.05±0.44 and 1.67±0.22;the mRNA expression levels of IKKβ were 1.00±0.00,2.92±0.07,1.51±0.07 and 1.41±0.08,respectively.Compared with the model group,the above indexes of the control and experimental-H groups were statistically significant(P＜0.01,P＜0.05).The expression of NF-κB protein was positively correlated with the content of IL-6 and TNF-α,and the correlation coefficients were 0.866 and 0.740(all P＜0.01).Conclusion HPS can alleviate the damage of myocardial pathology in mice,reduce myocardial collagen deposition and fibrosis,its mechanism may be through regulating the expression of NF-κB/IKKβ signaling pathway to play a role in inhibiting the inflammatory reaction.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

Objective To develop a health-promoting lifestyle scale for women with polycystic ovary syndrome(PCOS),and to test its reliability and validity,and preliminarily apply it.Methods Based on the Pender health promotion model,the item pool of the scale was constructed through literature research,semi-structured interviews and group discussions.After 2 rounds of Delphi expert consultation and pre-survey,the initial scale was formed.From April to July 2022,316 patients with PCOS in the health management center,reproductive medicine center and endocrinology department of a tertiary hospital in Nanjing were selected for item analysis,exploratory factor analysis and reliability test,respectively.From August to October 2022,358 PCOS patients were selected for confirmatory factor analysis.From November 2022 to February 2013,294 PCOS patients were selected,and the scale was used to investigate the status of health-promoting lifestyle in PCOS patients.Results The health-promoting lifestyle scale for PCOS patients included 5 dimensions and 33 items.The total content validity index of the scale was 0.942,and the content validity index of each item was 0.810-1.000.5 common factors were extracted by 2 exploratory factor analyses,and the cumulative variance contribution rate was 62.399％.Confirmatory factor analysis showed that the model fit was good.The Cronbach's a coefficient of the total scale was 0.930;the split-half reliability was 0.842;the test-retest reliability was 0.888.The preliminary application results showed that the total score of health-promoting lifestyle in PCOS patients was(96.925±14.273),and the average score of items was(2.937±0.433),which was at a medium level.Conclusion The health-promoting lifestyle scale for PCOS patients has good reliability and validity,which can be used as a tool for medical staff to assess the level of health-promoting lifestyle of PCOS patients,and can help nurses to quickly identify the level and dimensions of health-promoting lifestyle of patients,so as to formulate individualized precise health management plans.

ObjectiveThis study aimed to observe the impact of sinomenine hydrochloride on the proliferation of fibroblasts and the mRNA expression of related genes in knee joint adhesion and contracture in rabbits. Additionally, we sought to explore its potential mechanisms in combating knee joint adhesion and contracture. MethodsFibroblasts were cultured in vitro, and experimental groups with varying concentrations of sinomenine hydrochloride were established alongside a control group. Cell proliferation was assessed using the CCK-8 assay. Changes in the mRNA expression of fibroblast-related genes following sinomenine hydrochloride treatment were evaluated using RT-qPCR. The impact of the drug on serum levels of inflammatory cytokines was determined using the ELISA method, and the expression of related proteins was assessed using Western blot. ResultsSinomenine hydrochloride was found to inhibit fibroblast viability, with viability decreasing as the concentration of sinomenine hydrochloride increased. The effects of sinomenine hydrochloride in all experimental groups were highly significant (P<0.05). At the mRNA expression level, compared to the control group, sinomenine hydrochloride led to a significant downregulation of inflammatory cytokines in all groups (P<0.05). Additionally, the expression levels of apoptosis-related proteins significantly increased, while Bcl-2 mRNA expression decreased (P<0.05). The mRNA expression levels of the PI3K/mTOR/AKT3 signaling pathway also decreased (P<0.05). At the protein expression level, in comparison to the control group, the levels of inflammatory cytokines IL-6, IL-8, IL-1β, and TGF-β were significantly downregulated in the middle and high-dose sinomenine hydrochloride groups (P<0.05). The expression levels of cleaved-PARP, cleaved caspase-3/7, and Bax increased and were positively correlated with the dose, while the expression levels of the anti-apoptotic protein Bcl-2 and the PI3K/AKT3/mTOR signaling pathway were negatively correlated with the dose. Sinomenine hydrochloride exhibited a significant inhibitory effect on the viability of rabbit knee joint fibroblasts, which may be associated with the downregulation of inflammatory cytokines IL-6, IL-8, and IL-1β, promotion of apoptosis-related proteins cleaved-PARP, cleaved caspase-3/7, and Bax, suppression of Bcl-2 expression, and inhibition of gene expression in the downstream PI3K/AKT3/mTOR signaling pathway. ConclusionSinomenine hydrochloride can inhibit the inflammatory response of fibroblasts in adhesive knee joints and accelerate fibroblast apoptosis. This mechanism may offer a novel approach to improving and treating knee joint adhesion.

OBJECTIVE To explore the material basis of the anti-inflammatory effect of the petroleum ether extract from Melastoma dodecandrum by establishing its fingerprint and combining it with cellular pharmacodynamics experiments. METHODS HPLC method was adopted； the fingerprints of 20 batches of petroleum ether extract from M. dodecandrum were drawn using The Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）； similarity evaluation and common peak identification were carried out. The lipopolysaccharide-induced inflammation model of mice mononuclear macrophages （RAW264.7） was established； the inhibitory rates of nitric oxide （NO） and tumor necrosis factor α （TNF-α） were used as indexes to investigate the anti-inflammatory activity of the petroleum ether extract from M. dodecandrum； grey correlation degree method and partial least square regression analysis were adopted to study the spectrum-effect relationship. Molecular docking was used to validate the binding activity of the anti-inflammatory active ingredients with TNF-α and iNOS protein receptor. RESULTS There were 19 common peaks in the fingerprint of the petroleum ether extract from M. dodecandrum， the similarity of 20 batches of samples ranged from 0.603-0.990， and five components were identified， such as vitexin （peak 5）， isovitexin （peak 6）， ellagic acid （peak 7）， quercetin （peak 9） and luteolin （peak 10）. The grey correlation degree between 19 common peaks of the petroleum ether extract from M. dodecandrum and the inhibition rates of NO and TNF-α were all greater than 0.7； peaks 19， 13， 9 （quercetin）， 12， 5 （vitexin）， 6 （isovitexin）， 8， 7 （ellagic acid）， 18， 1 were positively correlated with NO inhibition rate， and peaks 8， 10 （luteolin）， 13， 15， 3， 19， 17， 7 （ellagic acid）， 18， 1 were positively correlated with inhibition rate of TNF-α. The binding energies of vitexin， isovitexin and quercetin with iNOS protein receptor were less than －5.0 kcal/mol. CONCLUSIONS Vitexin， isovitexin and quercetin may be the basis of the anti-inflammatory effect of the petroleum ether extract from M.dodecandrum.

Background::Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China.Methods::Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed.Results::A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43–0.68; P <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04–13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65–3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38–1.53; P <0.001). Conclusions::In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration::ClinicalTrials.gov, NCT02309398.