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 compare clinical efficacy of robot-assisted(RA)and remote sensing navigation alignment(RSNA)system-assisted total knee arthroplasty(TKA).Methods From March 2023 to June 2023,60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis(KOA)were admitted and divided into RSNA group and RA group according to different treatment methods,with 30 patients in each group.There were 5 males and 25 females in RSNA group,aged from 56 to 81 years old with an average of(66.33±7.16)years old;body mass index(BM1)ranged from 19.87 to 38.54 kg·m-2 with an average of(28.40±6.18)kg·m-2;the courses of disease ranged from 5 to 36 months with an average of(18.20±8.98)months;RSNA system was used to assist the positioning of osteotomy.There were 7 males and 23 females in RA group,aged from 55 to 82 years old with an average of(67.83±8.61)years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an aver-age of(28.01±4.89)kg·m-2;the courses of disease ranged from 3 to 33 months with an average of(17.93±9.20)months;RA was performed.Operation time,incision length,latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups.Hip-knee ankle angle(HKAA),HKAA deviation,lateral distal femoral angle(LDFA),medial proximal tibial angle(MPTA)and posterior tibial slope(PTS)were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index(WOMAC)and Knee Society score(KSS)were used to evaluate functional recovery before operation,3 and 6 months after operation.Results The operation was performed successfully in both groups,and there were no serious complications such as vascular and nerve injury during operation.The wound healed well at stage Ⅰafter operation,and the follow-up time was 6 months.The operation time,latent blood loss at 2 weeks after operation and inci-sion length in RSNA group were(94.35±5.75)min,(130.54±17.53)mland(14.73±2.14)cm,respectively;while(102.57±6.88)min,(146.33±19.47)ml and(16.78±2.32)cm in RA group,respectively.RSNA group was better than RA group(P＜0.05).No deep vein thrombosis occurred in both groups at 2 weeks after operation,5 patients occurred intermuscular vein throm-bosisin in RSNA group and 8 patients in RA group,the difference was not statistically significant(P＞0.05).In RSNA group,HKAA,LDFA and MPTA were(173.00±5.54)°,(86.96±3.45)°,(82.79±3.35)° before operation,and(178.34±1.85)°,(89.92±0.42)°,(89.84±0.73)° at 1 week after operation,respectively.In RA group,HKAA,LDFA and MPTA were(173.31±6.48)°,(87.15±3.40)° and(82.99±3.05)° before operation,and(178.52±1.79)°,(90.03±0.39)° and(90.15±0.47)° at 1 week after operation,respectively.HKAA,LDFA and MPTA were significantly improved in both groups at 1 week after oper-ation(P＜0.05).There were no significant difference in HKAA,LDFA,MPTA and PTS between two groups before operation and 1 week after operation(P＞0.05).There was no significant difference in deviation distribution of HKAA at 1 week after op-eration(x2=2.61 1,P=0.456).There were no significant difference in WOMAC and KSS between two groups before operation,3 and 6 months after operation(P＞0.05),and postoperative WOMAC and KSS at 3 and 6 months between two groups were im-proved compared with those before operation(P＜0.05).Conclusion Both RA and RSNA system assisted TKA could obtain ac-curate osteotomy,RA has higher surgical accuracy,RSNA system assisted operation has less trauma,and operation is simpler.

Objective To explore clinical accuracy of remote sensing navigation alignment(RSNA)system in total knee arthroplasty(TKA)and its influence on postoperative clinical efficacy.Methods From May 2021 to May 2022,60 knee os-teoarthritis(KOA)patients with Kellgren-Lawrence(K-L)grade Ⅲ to Ⅳ treated by unilateral primary TKA were selected and divided into RSNA group and traditional operation group according to treatment methods,and 30 patients in each group.There were 6 males and 24 females in RSNA group,aged from 55 to 86 years old with an average of(68.06±8.23)years old;body mass index(BMI)ranged from 22.15 to 34.58 kg·m-2 with an average of(28.20±3.01)kg·m-2;the courses of disease ranged from 2 to 60 months with an average of(18.80±14.80)months;13 patients with grade Ⅲ and 17 patients with grade Ⅳaccording to K-L grading.In traditional operation group,there were 8 males and 22 females,aged from 57 to 85 years old with an average of(67.26±6.32)years old;BMI ranged from 23.94 to 34.55 kg·m-2 with an average of(27.49±2.32)kg·m-2;the courses of disease ranged from 3 to 60 months with an average of(21.30±16.44)months;14 patients with grade Ⅲ and 16 pa-tients with grade Ⅳ according to K-L grading.Western Ontario and McMaster Universities(WOMAC)osteoarthritis index and Knee Society score(KSS)were used to evaluate functional recovery of patients.Hip-knee-ankle angle(HKAA),distal femoral valgus angle(FVA)and distal fermoral flexion angle(DFFA)were measured before operation.HKAA and HKAA deviation angle were measured at 1 week after operation,and defective rate of lower limb force line,femur prosthesis valgus angle(FP-VA)and femoral prosthesis flexion angle(FPFA),respectively,were calculated.Results There were no serious complications such as vascular and nerve injury during operation,and wound healed at stage Ⅰ.Both groups were followed up for 6 months.There were no significant difference in WOMAC index,KSS,HKAA,FVA and DFFA between two groups before operation(P＞0.05).The force line defect rate,HKAA,HKAA deviation angle,FPVA deviation angle and FPFA of RSNA group were 6.7％,(178.74±1.56)°,(1.25±1.56)°,(1.84±0.16)° and(4.85±2.46)°,respectively;while in traditional operation group were 20％,(176.73±3.46)°,(3.27±3.46)°,(2.44±0.26)°,(6.60±1.86)°;the difference between two groups were statistically sig-nificant(P＜0.05).There were no significant difference in WOMAC index and KSS between two groups at 3 and 6 months after operation(P＞0.05).Conclusion RSNA system could reduce defective rate of lower limb force line,FPVA deviation angle and FPFA after TKA,which is more accurate and easy to operate than traditional intramedullary localization surgery while ensuring postoperative efficacy.

Objective:To compare the aortic remodeling of the Fabulous stent system and standard thoracic aortic endovascular repair (TEVAR) on distal aorta type B aortic dissection (TBAD). Methods:The prospective data collected between Dec 2017 and Oct 2019 from 134 patients with type B aortic dissection (TBAD) who underwent treatment with the "Fabulous" stent system, and retrospective data from 159 TBAD patients receiving standard TEVAR from corresponding multicenter. By using propensity score matching analysis, we compared the prognosis and aortic remodeling outcomes in patients undergoing Fabulous and standard TEVAR treatments during a 1-year postoperative follow-up.Results:In this study, 62 patients in Fabulous group and 62 patients in standard TEVAR were included.There were no significant statistical differences in baseline characteristics between the two groups. In terms of aortic remodeling in bare stent region, Fabulous group had better change trends of diameter of true lumen [10.6 (4.4, 14.5) mm vs. 4.7 (0.9, 10.7) mm, P=0.001] and false lumen [-24.2 (-30.5, -4.9) mm vs. 0.7 (-11.8, 2.3) mm, P<0.001] than those in the standard TEVAR group. The rate of complete false lumen thrombosis was also higher in the Fabulous group (62.9% vs. 37.1%, P=0.042). Conclusion:The Fabulous stent system, when compared to standard TEVAR surgery, demonstrates good aortic remodeling outcomes in the distal aorta.

The lymphatic system, as well as pathological changes of the lymphatic system, underlies the progress of an array of diseases and conditions, including cancer, inflammation and autoimmune disorders, infectious diseases and metabolic syndrome. A variety of biological targets in the lymphatic system can be employed to modulate these high-burden diseases, and the pharmacokinetics and drug delivery strategies in the context of lymphatics are of critical importance to optimise drug exposure to lymphatic-related targets. As such, research and drug development in this field has gained increasing attention in recent years. This article aims to provide an overview of pharmaceutical research with a focus on the lymphatic system and therapeutic targets within the lymphatics, followed by lymphatic drug delivery approaches, which may be of interest for researchers in academia, pharmaceutical industry and regulatory sciences.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective To observe the inhibitory effect of Guiqi Yiyuan ointment on tumor growth in mice with Lewis lung cancer,and to explore the molecular mechanism of Guiqi Yiyuan ointment combined with cisplatin through phosphoinositide 3-kinase/protein kinase B/mammalian rapamycin target protein(PI3K/Akt/mTOR)signal pathway.Methods Sixty C57BL/6 mice were randomly divided into 6 groups with 10 mice in each group.Except for the blank group(0.9％NaCl),Lewis lung cancer-bearing mice were randomly divided into model group(0.9％NaCl),control group(0.9％NaCl,cisplatin 5 mg·kg-1)and low,medium,high dose experimental groups(Guiqi Yiyuan ointment 1.6,3.3,6.6 g·kg-1,cisplatin 5 mg·kg-1).Flow cytometry was used to detect bone marrow-derived suppressor cells(MDSCs);the expression of related proteins in tumor tissues was detected by Western blot.Results The tumor inhibition rates in control group and low,medium,high dose experimental groups were(39.87±4.45)％,(45.74±14.97)％,(57.78±4.70)％and(69.82±11.05)％.The proportion of MDSCs in bone marrow of in blank group,model group,control group and low,medium,high dose experimental groups were(36.13±1.08)％,(68.63±2.94)％,(58.93±2.02)％,(58.00±1.50)％,(50.93±5.06)％and(43.07±2.41)％.The protein expressions of p-PI3K/PI3K in model group,control group and low,medium and high experimental groups were 0.97±0.03,0.77±0.02,0.72±0.01,0.68±0.03 and 0.53±0.02;PTEN were 0.21±0.07,0.65±0.07,0.74±0.06,0.99±0.13,1.11±0.13;p-Akt/Akt were 1.01±0.02,0.82±0.02,0.77±0.00,0.72±0.03 and 0.52±0.04;p-mTOR/mTOR were 1.01±0.01,0.76±0.05,0.69±0.07,0.59±0.06 and 0.47±0.06.There were significant differences between low,medium,high experimental groups and control group(all P＜0.05).Conclusion Guiqi Yiyuan ointment combined with cisplatin can significantly improve the quality of life and inhibit tumor growth in mice.The mechanism may be the inhibition of PI3K/Akt/mTOR signal pathway and the enhancement of tumor cell apoptosis and autophagy.

Objective To observe the effects of traditional Chinese medicine compound Platycodon grandiflorum Bai powder on the growth of subcutaneously implanted tumor and the expression of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),cysteinyl aspartate specific proteinase(caspase)-3 and caspase-9 in subcutaneously implanted tumor of Lewis lung cancer mice.Methods The model of transplanted tumor of Lewis lung cancer in mice was established.Seventy SPF male C57BL/6 mice were randomly divided into blank group,model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combined group.Blank group and model group were given 0.9％NaCl 0.2 mL by gavage;control group was given 0.9％NaCl by gavage and 25 mg·kg-1cisplatin intraperitoneally;high,medium,low dose experimental groups were given 193,96,48 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,respectively;combined group was given 96 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,and 25 mg·kg-1 cisplatin intraperitoneally,once every other day.The myelogenous suppressor cells(MDSCs)of mouse bone marrow were detected by flow cytometry,and the expressions of Bel-2,Bax,caspase-3 and caspase-9 in tumor cells were detected by immunofluorescence.Results The percentage of MDSCs in bone marrow of mice in blank group,model group,low dose experimental,medium,high dose experimental group,control group and combination group were(32.50±2.76)％,(63.13±3.14)％,(48.43±2.23)％,(42.53±1.28)％,(32.93±3.56)％,(51.30±4.25)％and(19.90±6.21)％,respectively.The fluorescence intensities of Bax in model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combination group were 10.42±0.68,12.40±1.23,15.14±0.65,22.95±1.76,27.18±1.62 and 31.61±1.28;Bel-2 were 36.85±0.80,33.92±4.20,28.88±1.01,20.04±2.21,15.69±2.36 and 6.05±0.73;caspase-3 were 5.28±0.44,7.63±0.55,9.66±0.85,14.73±1.18,17.95±1.29 and 22.92±1.95;caspase-9 were 9.48±0.90,11.57±0.72,13.45±0.93,15.73±1.44,19.20±0.96 and 23.21±1.51.There were significant differences between medium,high dose experimental groups and model group(all P＜0.05),and there were significant differences between combined group and control group(all P＜0.05).Conclusion Platycodon grandiflorum Bai powder can up-regulating the expression of Bax,caspase-3 and caspase-9,down-regulating the expression of Bel-2,inhibiting MDSCs,promoting tumor cell apoptosis and inhibiting tumor growth.