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.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

Objective:To explore the effect of the defect area and volume of intra-articular impacted fragments (IAIF) on the contact stress of the ankle joint surface.Methods:A 23-year-old male volunteer, 168 cm in height and 60 kg in weight, with no history of trauma or anatomic abnormality of the ankle, was selected. On the basis of a normal ankle finite-element model, IAIF-defect finite-element models were established. The first group consisted of IAIF-defect models with identical area but different volumes: on the distal tibial articular surface the defect area was 4 mm × 5 mm (20 mm 2), and the heights were 2 mm, 3 mm, 4 mm, 5 mm and 6 mm. The second group consisted of IAIF-defect models with identical defect volume but different areas. The defect volume was 90 mm 3, while the defect areas on the distal tibial articular surface were 2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm, and 5 mm×6 mm, with corresponding heights of 15 mm, 10 mm, 6 mm, 5 mm, and 3 mm. Under a 600 N vertical load the contact stress of the ankle joint was calculated, and the finite-element data were recorded and analyzed. Pearson correlation analysis was used to analyze, separately for the two groups, the correlation between IAIF defect and the maximum contact stress (MCS) of the distal tibial articular surface, and simple linear regression analysis was performed to obtain regression equations. Equivalence zero testing was used to verify the correlations and to compare their differences. Results:For IAIF defects with the same area but different volumes, including 4 mm×5 mm×2 mm, 4 mm×5 mm×3 mm, 4 mm×5 mm×4 mm, 4 mm×5 mm×5 mm, and 4 mm× 5 mm×6 mm, the corresponding maximum contact stress (MCS) on the distal tibial joint surface were 3.846 MPa, 3.839 MPa, 3.835 MPa, 3.833 MPa, and 3.831 MPa, respectively, with an average of 3.837 MPa. The mean ±1% range is from 3.799 MPa to 3.875 MPa. The correlation analysis showed that the IAIF defects with the same area but different volumes were negatively correlated with contact stress ( r=-0.956, P=0.011). The linear regression equation was MCS=-0.0002×VI+3.851, where VI denotes IAIF volume. Equivalence zero testing confirmed that all measured values lay within the predefined ±1 % margin, satisfying the equivalence null hypothesis. For IAIF defects of identical volume (90 mm 3) but varying articular surface areas—2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm and 5 mm×6 mm—the corresponding MCS values were 2.147 MPa, 2.812 MPa, 3.622 MPa, 4.476 MPa and 6.186 MPa, respectively (mean 3.849 MPa; equivalence band 3.811-3.887 MPa at ±1% of the mean). Correlation analysis demonstrated a strong positive relationship between identical-volume varying-area IAIF defects and contact stress ( r=0.996, P<0.001). The linear regression equation was MCS=0.168×AI+1.236, where AI denotes IAIF area. Equivalence zero testing indicated that none of the measured values fell within the predefined ±1% margin, failing to satisfy the equivalence null hypothesis. Conclusion:In posterior ankle fractures, the volume change of IAIF defects has no clinical significance in relation to MCS, showing a small negative correlation. However, the area change of IAIF defects is clinically significant in relation to MCS, demonstrating a larger positive correlation.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

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.

Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P＜0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P＜0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.

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 analyze the clinical characteristics of children with moyamoya disease and the influence of Chinese medicine identification and acupuncture treatment plan on their prognosis.Methods A retrospective analysis was conducted on the diagnosis and treatment of children diagnosed with moyamoya disease who underwent surgery and were treated with acupuncture at Tianjin Children's Hospital on July 10,2023.The main acupuncture points were as follows:Points on head and face:shangxing,yintang,touwei,middle line of vertex,anterior oblique line of vertex-temporal(the upper 1/5 section),lateral line 1 of vertex,anterior temporal line,renzhong,shanglianquan,sibai,yingxiang,quanliao,xiaguan,and dicang;Points on upper extremities:jiquan,chize,neiguan(quick stabbing without leaving needles),jianyu,jianliao,quchi,waiguan,yangxi,houxi,hegu;Points on lower extremities:weizhong,weiyang(quick stabbing without leaving needles),biguan,xuehai,liangqiu,zusanli,qiuxu,sanyinjiao,and taichong),the needles were performed once a day,and continuous treatment for 5 days each week,and the general conditions of the children were observed after 2 weeks of treatment,and the Fugl-Meyer assessment(FMA),the Barthel index(BI),and the simple test for evaluating hand function(STEF)were used,to assess left upper limb motor function;neurophysiologic techniques were used to examine motor nerve conduction in the left limb.Results The child was an 8-year-old male admitted to the hospital on July 10,2023.①Complaint:unfavorable movement of the left limb for more than 1 month.②History:the child had an abnormal seizure during waking hours 2 years before admission,which lasted for about 1 minute and then resolved on its own,and he could recall the course of the seizure afterward.Attended at the department of neurology of our hospital and diagnosed with moyamoya disease after being discharged from the hospital,the child was found at home to have weakness of the left limbs,unable to lift the upper limbs and unable to walk on the lower limbs.Attended at the department of neurosurgery of a certain hospital and was diagnosed with acute cerebral infarction and underwent cranio-cerebral vascular anastomosis.After the operation,the child's left limb activity is unfavorable,the right limb has no motor disorder and sensory abnormality,speech expression is unclear,to further improve the motor function of the child's limbs,the patient was referred to the rehabilitation department of our hospital,the initial diagnosis of moyamoya disease disease recovery(left hemiplegia),according to the specific conditions of the adjustment of the acupuncture program,2 weeks after the treatment,the patient's facial lines were basically symmetrical,crying and laughing,the corner of the mouth does not droop.After 4 weeks of treatment,the child was able to walk on the ground independently,but hemiplegic gait,left lower limb muscle tone basically relieved,proximal muscle strength grade Ⅲ-Ⅳ,distal muscle strength grade Ⅱ-Ⅲ.After 6 weeks of treatment,the child's hemiplegic gait was improved,proximal muscle strength was grade Ⅳ,distal muscle strength was grade Ⅲ-Ⅳ,the left hand could hold objects for a few minutes,left thumb flexor strength was grade Ⅲ,dorsal extensor strength was grade Ⅱ,and the rest of the four fingers flexor and dorsal extensor strength was grade Ⅳ.The proximal muscle strength was grade Ⅴ and distal muscle strength was grade Ⅳ.The left wrist could move freely,the left interphalangeal joint could extend and hold objects,and the motor function of the left upper limb was basically established,and the condition was stabilized.FMA,BI and STEF scores all increased with the prolongation of the treatment time,and the latency and nerve conduction velocity of the median nerve,peroneal nerve and tibial nerve tended to normal after treatment.Conclusion The efficacy of traditional acupuncture in treating pediatric moyamoya disease after cerebral infarction surgery rehabilitation is remarkable,which can significantly improve the clinical symptoms of children recovering from moyamoya disease.

BACKGROUND:The reduction of contact area,edge load,and stress increase of adjacent cartilage caused by knee cartilage defect are considered to easily cause degenerative changes in this tissue,which may develop into knee osteoarthritis.Growth factors are considered to be a treatment method to promote the healing of damaged cartilage and delay the progression of degenerative arthritis.OBJECTIVE:To analyze the hotspots and prospects of growth factor-promoted knee cartilage regeneration research by bibliometric methods.METHODS:The first author retrieved 321 articles related to growth factor-promoted knee cartilage regeneration research from the Web of Science core set database.VOSviewer 1.6.19 software was used to analyze the publication volume,country,institution,keyword,and literature citation status of the articles,and investigate the research hotspots.RESULTS AND CONCLUSION:(1)From 2000 to 2024,the annual number of publications in the field of growth factor-promoted knee cartilage regeneration showed an overall upward trend,with the highest number of publications in 2021.Harvard University in the United States published the most papers.(2)Keyword analysis showed that the frequency of keywords such as growth factor,cartilage,cartilage repair,platelet-rich plasma,and cartilage regeneration was high.In addition,the keyword co-occurrence network diagram showed that growth factor was closely related to keywords such as cartilage repair and cartilage regeneration,indicating that growth factor research plays an important role in the field of cartilage regeneration.(3)The results of literature citation analysis showed that the combination of platelet-rich plasma and muscle-derived stem cells may provide a new and effective treatment strategy for patients with osteoarthritis,which can deepen the understanding of cartilage repair mechanisms by promoting stem cell proliferation and cartilage formation.Fibroblast growth factor 2,fibroblast growth factor 18,and insulin growth factor 1 play a key role in cartilage repair and can promote chondrocyte proliferation and matrix synthesis.In particular,fibroblast growth factor 18 can promote the repair of damaged cartilage,thereby alleviating patients'pain and dysfunction,which deserves further in-depth study in the future.The latest research has developed a new Polyhedrin Delivery System(PODS)that can continuously release growth factors such as bone morphogenetic protein 2 and 7,significantly promoting chondrocyte proliferation and cartilage repair.This system provides a new perspective and potential therapy for the treatment of osteoarthritis.(4)Therefore,bone morphogenetic protein 2,7,insulin growth factor 1,and recombinant human fibroblast growth factor 18 are promising growth factor therapies for promoting cartilage regeneration.In the future,further in-depth research on the mechanism of action of growth factors,optimization of treatment strategies,and strengthening of long-term efficacy and safety evaluation are needed.

Objective:To explore the effect of the defect area and volume of intra-articular impacted fragments (IAIF) on the contact stress of the ankle joint surface.Methods:A 23-year-old male volunteer, 168 cm in height and 60 kg in weight, with no history of trauma or anatomic abnormality of the ankle, was selected. On the basis of a normal ankle finite-element model, IAIF-defect finite-element models were established. The first group consisted of IAIF-defect models with identical area but different volumes: on the distal tibial articular surface the defect area was 4 mm × 5 mm (20 mm 2), and the heights were 2 mm, 3 mm, 4 mm, 5 mm and 6 mm. The second group consisted of IAIF-defect models with identical defect volume but different areas. The defect volume was 90 mm 3, while the defect areas on the distal tibial articular surface were 2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm, and 5 mm×6 mm, with corresponding heights of 15 mm, 10 mm, 6 mm, 5 mm, and 3 mm. Under a 600 N vertical load the contact stress of the ankle joint was calculated, and the finite-element data were recorded and analyzed. Pearson correlation analysis was used to analyze, separately for the two groups, the correlation between IAIF defect and the maximum contact stress (MCS) of the distal tibial articular surface, and simple linear regression analysis was performed to obtain regression equations. Equivalence zero testing was used to verify the correlations and to compare their differences. Results:For IAIF defects with the same area but different volumes, including 4 mm×5 mm×2 mm, 4 mm×5 mm×3 mm, 4 mm×5 mm×4 mm, 4 mm×5 mm×5 mm, and 4 mm× 5 mm×6 mm, the corresponding maximum contact stress (MCS) on the distal tibial joint surface were 3.846 MPa, 3.839 MPa, 3.835 MPa, 3.833 MPa, and 3.831 MPa, respectively, with an average of 3.837 MPa. The mean ±1% range is from 3.799 MPa to 3.875 MPa. The correlation analysis showed that the IAIF defects with the same area but different volumes were negatively correlated with contact stress ( r=-0.956, P=0.011). The linear regression equation was MCS=-0.0002×VI+3.851, where VI denotes IAIF volume. Equivalence zero testing confirmed that all measured values lay within the predefined ±1 % margin, satisfying the equivalence null hypothesis. For IAIF defects of identical volume (90 mm 3) but varying articular surface areas—2 mm×3 mm, 3 mm×3 mm, 3 mm×5 mm, 3 mm×6 mm and 5 mm×6 mm—the corresponding MCS values were 2.147 MPa, 2.812 MPa, 3.622 MPa, 4.476 MPa and 6.186 MPa, respectively (mean 3.849 MPa; equivalence band 3.811-3.887 MPa at ±1% of the mean). Correlation analysis demonstrated a strong positive relationship between identical-volume varying-area IAIF defects and contact stress ( r=0.996, P<0.001). The linear regression equation was MCS=0.168×AI+1.236, where AI denotes IAIF area. Equivalence zero testing indicated that none of the measured values fell within the predefined ±1% margin, failing to satisfy the equivalence null hypothesis. Conclusion:In posterior ankle fractures, the volume change of IAIF defects has no clinical significance in relation to MCS, showing a small negative correlation. However, the area change of IAIF defects is clinically significant in relation to MCS, demonstrating a larger positive correlation.