Objective To observe the effects of a stepped early activity program combined with lower limb joint rehabilitation devices in mechanically ventilated patients in the intensive care unit(ICU).Methods Sixty mechanically ventilated patients admitted to the ICU of Tianjin First Central Hospital from October 2022 to June 2023 were selected as study subjects and randomly divided into an intervention group(n=30)and a control group(n=30)using a random number table.The control group received routine rehabilitation nursing combined with lower limb joint rehabilitation devices,while the intervention group was additionally treated with the stepped early activity program.The duration of mechanical ventilation,length of ICU stay,incidence of delirium,Medical Research Council(MRC)muscle strength scores,phase angle(PA),and skeletal muscle mass index(SMI)were compared between the two groups.Results The intervention group showed significantly shorter durations of mechanical ventilation and the length of ICU stay compared to the control group[mechanical ventilation time(days):9.20±4.51 vs.11.73±4.59,the length of ICU stay(days):10.73±5.37 vs.14.00±6.03,both P<0.05].Post-intervention MRC muscle strength scores,PA,and SMI significantly increased in both groups,with greater improvements observed in the intervention group[MRC muscle strength score:54.17±2.10 vs.50.17±3.51;PA(°):5.80±0.60 vs.5.49±0.54;SMI(kg/m2):6.87±0.46 vs.6.62±0.45,all P<0.05].No statistically significant difference was found in delirium incidence between the two groups[26.7%(8/30)vs.33.3%(10/30),P>0.05].Conclusion The combination of a stepped early activity program and lower limb joint rehabilitation devices effectively shortens mechanical ventilation time and the length of ICU stay,restores muscle strength,and promotes recovery in mechanically ventilated ICU patients,demonstrating significant clinical value.

Objective:To systematically summarize, describe, and evaluate the evidence related to convex baseplates use in adult ostomy patients through an evidence map, in order to identify research gaps and future directions.Methods:A systematic search was conducted in Chinese and English databases, including China National Knowledge Infrastructure, Wanfang Data, VIP, and PubMed, and others, from database inception to September 2024. Randomized controlled trials and quasi-experimental studies on convex baseplates use in adult ostomy patients were included. Literature quality was assessed using the Cochrane Handbook 5.1.0 bias risk assessment tool and the critical appraisal tool for quasi-experimental studies from the Joanna Briggs Institute Centre for Evidence-Based Healthcare. Based on the PICO principle [participant (P) , intervention (I) , comparison (C) , outcome (O) ] , an evidence mapping coding system was extracted and developed by integrating relevant guidelines and consensus. Data extraction and coding were performed using EPPI-Reviewer software, and key evidence characteristics and literature quality were presented using bubble charts.Results:A total of eight randomized controlled trials and six quasi-experimental studies were included. Most of the 14 studies had a high risk of bias. The target populations for interventions were divided into two categories: prevention and treatment. The main complications involved stoma skin-mucosal separation, stoma peristomal dermatitis, and stoma height issues. The main outcome measures included baseplate seal integrity, wound healing, complication rates, clinical symptoms, adverse events, patient acceptance, and quality of life.Conclusions:Most of the studies on convex baseplates has focused on enterostomy patients. The majority of studies have a high risk of bias, and the number of studies is limited. Further clarification is needed on the selection criteria for convex baseplates with different characteristics, and the clinical application effects of convex baseplates urgently need further evaluation.

Tujia ethnic group medicine Xuetong is derived from Kadsura heteroclita, the stem of which has the medicinal value for anti-rheumatoid arthritis, liver protection, anti-tumor, anti-oxidation effects, and has been widely used in Hunan and Guangdong in China. The selection of reliable and stable reference genes is the basis for subsequent molecular research on K. heteroclita. In this study, GAPDH, TUA, Actin, UBQ, EF-1α, 18S-rRNA, CYP, UBC, TUB, H2A, and RPL were selected as candidate reference genes in Kadsura heteroclita. The gene expression levels of the 11 candidate reference genes of K. heteroclita in its 6 different parts(stem-inside of the cambium, stem-outside of the cambium, fruit, flower, root, and leaf) and under different intervention conditions [drought stress, salt stress, and methyl jasmonate(MeJA) treatment] were detected by quantitative real-time polymerase chain reaction(qRT-PCR). The expression stability of the 11 candidate reference genes was comprehensively analyzed and evaluated by geNorm, NormFinder, ΔCT algorithm, and RefFinder software. The results showed that the expression of UBC and RPL was relatively stable in 6 different parts, and UBC and GAPDH genes were relatively stable under different intervention conditions. To verify the reliability of reference genes for K. heteroclita, this study further examined the relative expression levels of KhFPS, KhIDI, KhCAS, KhSQE, KhSQS, KhSQS-2, KhHMGS, KhHMGR, KhMVD, KhMVK, KhDXR, KhDXS, KhPMVK, and KhGGPS in different parts and under different intervention conditions, which might relate to the synthesis of the main component(Xuetongsu) of K. heteroclita. The results showed that with UBC and RPL or UBC and GAPDH as the reference genes, the expression trends of these 14 genes were basically consistent in different parts or under different intervention conditions for K. heteroclita. In conclusion, UBC can be used as a reference gene of K. heteroclita for its different parts and different intervention conditions, which lays a foundation for further research on the biosynthetic pathway of main components in K. heteroclita.
Real-Time Polymerase Chain Reaction/methods* ; Reference Standards ; Gene Expression Regulation, Plant ; Gene Expression Profiling ; Plant Proteins/metabolism* ; Drugs, Chinese Herbal

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

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 observe the effects of a stepped early activity program combined with lower limb joint rehabilitation devices in mechanically ventilated patients in the intensive care unit(ICU).Methods Sixty mechanically ventilated patients admitted to the ICU of Tianjin First Central Hospital from October 2022 to June 2023 were selected as study subjects and randomly divided into an intervention group(n=30)and a control group(n=30)using a random number table.The control group received routine rehabilitation nursing combined with lower limb joint rehabilitation devices,while the intervention group was additionally treated with the stepped early activity program.The duration of mechanical ventilation,length of ICU stay,incidence of delirium,Medical Research Council(MRC)muscle strength scores,phase angle(PA),and skeletal muscle mass index(SMI)were compared between the two groups.Results The intervention group showed significantly shorter durations of mechanical ventilation and the length of ICU stay compared to the control group[mechanical ventilation time(days):9.20±4.51 vs.11.73±4.59,the length of ICU stay(days):10.73±5.37 vs.14.00±6.03,both P<0.05].Post-intervention MRC muscle strength scores,PA,and SMI significantly increased in both groups,with greater improvements observed in the intervention group[MRC muscle strength score:54.17±2.10 vs.50.17±3.51;PA(°):5.80±0.60 vs.5.49±0.54;SMI(kg/m2):6.87±0.46 vs.6.62±0.45,all P<0.05].No statistically significant difference was found in delirium incidence between the two groups[26.7%(8/30)vs.33.3%(10/30),P>0.05].Conclusion The combination of a stepped early activity program and lower limb joint rehabilitation devices effectively shortens mechanical ventilation time and the length of ICU stay,restores muscle strength,and promotes recovery in mechanically ventilated ICU patients,demonstrating significant clinical value.

Aim To explore the effects of Kui Jie Kang(KJK)on modulating the farnesoid X receptor(FXR)pathway in the gut microbiota and bile acid metabolism in mice with ulcerative colitis(UC).Methods Mice were subjected to DSS-induced UC and randomly as-signed to the control(CON),model(MOD),and two KJK-dosed groups(KJK.H at 12.8 g·kg-1,KJK.L at 3.2 g·kg-1).Mouse body weight was recorded,and disease activity index(DAI)was scored.The his-topathological changes in colonic tissue were observed via HE staining,and the number of goblet cells and mucosal layer repair were assessed using PAS and Al-cian blue staining.Bile acid content in feces was measured using LC-MS/MS,gut microbiota composition was analyzed by 16S rRNA gene sequencing,and the expression of FXR target genes and related proteins was detected by RT-qPCR and Western blot.Results KJK significantly ameliorated colonic shortening,de-creased disease activity index in UC mice,reduced his-topathological scores,increased the number of goblet cells and mucus secretion,altered the levels of primary and secondary bile acids,and increased the relative a-bundance of beneficial bacteria such as Lactobacillus.Additionally,it significantly upregulated the expression of FXR and FGF15 mRNA and protein in colonic tissue and downregulated the expression of hepatic CYP7A1 mRNA,and the correlation analysis in this study clearly revealed a significant correlation between bile acid me-tabolism disorders and gut microbiota imbalance in UC.Conclusion KJK activates the intestinal FXR-FGF15-CYP7A1 pathway,thereby regulating bile acid metabolism and restoring gut microbiota balance,which may be key to its improvement of UC.

Aim To explore the effects of Kui Jie Kang(KJK)on modulating the farnesoid X receptor(FXR)pathway in the gut microbiota and bile acid metabolism in mice with ulcerative colitis(UC).Methods Mice were subjected to DSS-induced UC and randomly as-signed to the control(CON),model(MOD),and two KJK-dosed groups(KJK.H at 12.8 g·kg-1,KJK.L at 3.2 g·kg-1).Mouse body weight was recorded,and disease activity index(DAI)was scored.The his-topathological changes in colonic tissue were observed via HE staining,and the number of goblet cells and mucosal layer repair were assessed using PAS and Al-cian blue staining.Bile acid content in feces was measured using LC-MS/MS,gut microbiota composition was analyzed by 16S rRNA gene sequencing,and the expression of FXR target genes and related proteins was detected by RT-qPCR and Western blot.Results KJK significantly ameliorated colonic shortening,de-creased disease activity index in UC mice,reduced his-topathological scores,increased the number of goblet cells and mucus secretion,altered the levels of primary and secondary bile acids,and increased the relative a-bundance of beneficial bacteria such as Lactobacillus.Additionally,it significantly upregulated the expression of FXR and FGF15 mRNA and protein in colonic tissue and downregulated the expression of hepatic CYP7A1 mRNA,and the correlation analysis in this study clearly revealed a significant correlation between bile acid me-tabolism disorders and gut microbiota imbalance in UC.Conclusion KJK activates the intestinal FXR-FGF15-CYP7A1 pathway,thereby regulating bile acid metabolism and restoring gut microbiota balance,which may be key to its improvement of UC.