Through network pharmacology and molecular docking technology, combined with in vitro experiment verification, we explored the mechanism of action of Porana racemosa Roxb. (PRA) in the treatment of rheumatoid arthritis (RA), and provided a modern pharmacological basis for the treatment of RA by PRA. The potential target of chemical components in the analyzed moth rattan was predicted by Swiss Target Prediction database; OMIM, GeneCards, TTD and Disgenet databases were used to search the disease targets of RA; the protein interaction (PPI) network and medicine-composition-target network were constructed using STRING database and Cytoscape software; GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis were carried out using DAVID database, and molecular docking software was used to dock the potentially active ingredients of PRA and core targets; finally, MH7A cells were selected for cell viability, scratch healing and mRNA expression level analysis of key genes to explore the effects of PRA and their potentially active ingredients on the proliferation, migration and apoptosis of MH7A cells. In this study, a total of 628 potentially active ingredient targets, 1 890 RA targets and 235 intersection targets were identified. It was screened that the potentially active ingredients of RA treatment by PRA were ethylcaffeate, N-p-coumaroyltyramine, 9,12,15-octadecatrienoic acid, methyl ester and so on, and the core targets involved tumor necrosis factor (TNF), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2) and so on. 1 200 GO entries and 166 KEGG pathway entries were obtained from the enrichment analysis; molecular docking results showed that N-p-coumaroyltyramine and ethylcaffeate had good binding activity with TNF, MMP9, cysteine-aspartate protease 3 (CASP3), PTGS2, B-cell lymphoma 2 (BCL2) proteins. In vitro experiments showed that PRA, ethylcaffeate and N-p-coumaroyltyramine could inhibit the proliferation, migration and invasion of MH7A cells, up-regulate the expression of apoptosis-related gene CASP3 mRNA, and down-regulate the expression of MMP9, PTGS2 and BCL2 mRNA, and it can also down-regulate the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) mRNA and PI3K and p-AKT proteins. This study preliminarily revealed that the treatment of RA by PRA may be related to proliferation, migration, invasion, apoptosis and regulation of PI3K/AKT signaling pathway.

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.

Lung cancer is one of the most common and deadliest cancers globally, with its incidence and mortality rates rising each year. Therefore, finding new, safe, and effective alternative therapies poses a significant research challenge in this field. Programmed cell death refers to the process by which cells actively self-destruct in response to specific stimuli, regulated by genetic mechanisms. Modern research indicates that dysregulation of programmed cell death is widespread in the occurrence and progression of lung cancer, allowing cancer cells to evade death while continuing to proliferate and metastasize. Thus, inducing the death of lung cancer cells can be considered a novel therapeutic strategy for treating the disease. In recent years, research on traditional Chinese medicine(TCM) in the field of oncology has gained widespread attention, becoming a focal point. An increasing number of studies have demonstrated that TCM can inhibit the progression of lung cancer and exert anti-cancer effects by inducing apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis. This paper provided a comprehensive review of the molecular mechanisms of programmed cell death in lung cancer, along with the potential mechanisms and research advancements related to the regulation of these processes by TCM, so as to establish a theoretical foundation and direction for future basic and clinical research on lung cancer.
Humans ; Lung Neoplasms/pathology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Apoptosis/drug effects* ; Animals ; Autophagy/drug effects*

Objective To investigate the effects of peripheral blood neutrophil infiltration on the polarization regulation of cerebral resident microglia under a permanent ischemic stroke model.Methods Fifty-eight C57BL/6 mice were divided into two groups.One group was sham group,and the other group of mice was subjected to permanent middle cerebral artery occlusion surgery.Mice were euthanized 48 hours,7 days,14 days,and 30 days after surgery for tissue collection.Western blotting was used to detect expression levels of M1 microglia markers CD 16,M2 microglia marker arginase 1(Arg1),inflammatory cytokine interleukin-1 β(IL-1β),and neutrophil marker myeloperoxidase(MPO)in brain tissue.Immunofluorescence histochemical staining was used to assess neutrophil infiltration and M2 microglial distribution around the infarct area in brain sections.In vitro,purified neutrophils were co-cultured with BV2 microglial cells.After lipopolysaccharide stimulation,the phagocytosis of neutrophils by BV2 cells was observed,and the expression levels of CD16 and Arg1 proteins in BV2 cells were detected.Results Western blotting showed that the levels of CD16(P＜0.05),IL-1β(P＜0.001),and MPO(P＜0.05)in brain tissue increased significantly 48 hours and 7 days after surgery,then decreased,with MPO expression returning to normal levels 30 days after surgery.Immunofluorescence showed a significant increase of MPO-positive cells around the infarct area of the mouse cerebral cortex 48 hours after surgery(P＜0.001),followed by a decrease(P＜0.05).The number of ionized calcium binding adapter molecule 1(Iba1)and MPO double-positive cells gradually increased after surgery,and reached their peak at 14 days(P＜0.05).Iba1 and Arg1 double-positive cells also increased significantly 7 days(P＜0.05)and 14 days(P＜0.01)after surgery.In vitro,co-culture experiments showed that after BV2 phagocytosing neutrophils,CD 16(P＜0.05)significantly decreased and Arg1 significantly upregulated(P＜0.05).Conclusion In a permanent ischemic stroke model,microglia transition from M1 to M2 type after phagocytosing neutrophils,and the injured brain area changes from pro-inflammatory state to anti-inflammatory state.

Objective To explore the correlation of traditional Chinese medicine(TCM)syndrome types with endoscopic features and pathological types of gastric polyps.Methods A total of 1 746 patients with gastric polyps admitted to the Department of Spleen and Stomach Diseases,Dongguan Hospital of Guangzhou University of Chinese Medicine were enrolled.The clinical data of the patients were collected,including gender,age,information obtained by four diagnostic methods of TCM,and pathological types and predilection sites of gastric polyps as well as their number and size.The distribution of TCM syndromes in the patients with gastric polyps and their correlation with endoscopic features and pathological types of the polyps were analyzed.Results(1)Of the 1 746 patients,1 107(63.40%)were female and 639(36.60%)were male,with the male to female ratio being 1∶1.73.The incidence of gastric polyps was positively correlated with the age(P＜0.01):the older the age,the higher the incidence rate.The middle-aged and elderly people were the predilection population for gastric polyps,and the patients aged over 40 years old accounted for 87.40%.(2)The TCM syndrome types of patients with gastric polyps were predominated by spleen-stomach qi deficiency syndrome(418 cases,23.94%),and then came cold-damp obstruction syndrome(394 cases,22.57%),damp-heat in the spleen and stomach syndrome(353 cases,20.22%),qi stagnation and phlegm obstruction syndrome(311 cases,17.81%)and phlegm blended with blood stasis syndrome(70 cases,15.46%).(3)There was a statistically significant difference in the distribution of TCM syndromes between the genders(P＜0.01):spleen-stomach qi deficiency syndrome,cold-damp obstruction syndrome,qi stagnation and phlegm obstruction syndrome and phlegm blended with blood stasis syndrome were more common in the female,while damp-heat in the spleen and stomach syndrome was more common in the male.The distribution of TCM syndromes varied in different age groups(P＜0.01):patients aged over 30 years old were more likely to suffer spleen-stomach qi deficiency syndrome,patients aged 30-39 and 40-49 years old were more likely to suffer damp-heat in the spleen and stomach syndrome,patients aged 50-59 years old were more likely to suffer qi stagnation and phlegm obstruction syndrome,and patients aged 60 years old or above were more likely to suffer cold-damp obstruction syndrome.(4)The pathological types of gastric polyps were predominated by fundus gland polyps(1 327 cases,76.00%),followed by hyperplastic polyps(266 cases,15.23%),inflammatory polyps(146 cases,8.36%),and adenomatous polyps(7 cases,0.40%).There was a statistically significant difference in the distribution of TCM syndromes among various pathological types(P＜0.01):fundus gland polyps were common in the patients with spleen-stomach qi deficiency syndrome,hyperplastic polyps were common in the patients with qi stagnation and phlegm obstruction syndrome,inflammatory polyps were common in the patients with cold-damp obstruction syndrome,and adenomatous polyps were common in the patients with phlegm blended with blood stasis syndrome.(5)Gastric polyps were characterized by multiple polyps(1 120 cases,64.15%),single polyp was rare(626 cases,35.85%).The distribution of TCM syndromes varied in the patients with different number of polyps(P＜0.05):patients with multiple polyps were predominated by spleen-stomach qi deficiency syndrome(25.45%),patients with single polyp were predominated by damp-heat in the spleen and stomach syndrome(24.28%).(6)Gastric polyps frequently appeared in the gastric body and gastric fundus,with the diameter being or less than 0.5 cm.And the differences of the distribution of TCM syndromes in the patients with various favored sites and polyp size were not statistically significant(P＞0.05).Conclusion TCM syndrome types of patients with gastric polyps are correlated with gender and age of the patients and with the pathological types and number of gastric polyps.The incidence is positively correlated with the age,and middle-aged and elderly people are the predilection population of gastric polyps.The female incidence is significantly higher than that of the male,and damp-heat in the spleen and stomach syndrome is more common in the male while the rest of syndrome types are more common in the female.The patients with gastric fundus gland polyps usually suffer spleen-stomach qi deficiency syndrome,patients with hyperplastic polyps usually suffer qi stagnation and phlegm obstruction syndrome,patients with inflammatory polyps usually suffer cold-damp obstruction syndrome,and patients with adenomatous polyps usually suffer phlegm blended with blood stasis syndrome.

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.

Objective: To explore the development of the pancreatic surgeon technique in a high-volume center. Methods: A total of 284 cases receiving pancreatic surgery by a single surgeon from June 2015 to December 2020 were retrospectively included in this study. The clinical characteristics and perioperative medical history were extracted from the medical record system of Zhongshan Hospital,Fudan University. Among these patients,there were 140 males and 144 females with an age (M (IQR)) of 61.0 (16.8) years(range: 15 to 85 years). The "back-to-back" pancreatic- jejunal anastomosis procedure was used to anastomose the end of the pancreas stump and the jejunal wall. Thirty days after discharge,the patients were followed by outpatient follow-up or telephone interviews. The difference between categorical variables was analyzed by the Chi-square test or the CMH chi-square test. The statistical differences for the quantitative data were analyzed using one-way analysis of variance or Kruskal-Wallis H test and further analyzed using the LSD test or the Nemenyi test,respectively. Results: Intraoperative blood loss in pancreaticoduodenectomy between 2015 and 2020 were 300,100(100),100(100),100(0),100(200) and 150 (200) ml,respectively. Intraoperative blood loss in distal pancreatectomy was 250 (375),100 (50),50 (65), 50 (80),50 (50),and 50 (100) ml,respectively. Intraoperative blood loss did not show statistical differences in the same operative procedure between each year. The operative time for pancreaticoduodenectomy was respectively 4.5,5.0(2.0),5.5(0.8),5.0(1.3),5.0(3.3) and 5.0(1.0) hours in each year from 2015 to 2020,no statistical differences were found between each group. The operating time of the distal pancreatectomy was 3.8 (0.9),3.0 (1.5),3.0 (1.8),2.0 (1.1),2.0 (1.5) and 3.0(2.0) hours in each year,the operating time was obviously shorter in 2018 compared to 2015 (P=0.026) and 2020 (P=0.041). The median hospital stay in 2020 for distal pancreatectomy was 3 days shorter than that in 2019. The overall incidence of postoperative pancreatic fistula gradually decreased,with a incident rate of 50.0%,36.8%,31.0%,25.9%,21.1% and 14.8% in each year. During this period,in a total of 3,6,4,2,0 and 20 cases received laparoscopic operations in each year. The incidence of clinically relevant pancreatic fistula (grade B and C) gradually decreased,the incident rates were 0,4.8%,7.1%,3.4%,4.3% and 1.4%,respectively. Two cases had postoperative abdominal bleeding and received unscheduled reoperation. The overall rate of unscheduled reoperation was 0.7%. A patient died within 30 days after the operation and the overall perioperative mortality was 0.4%. Conclusion: The surgical training of a high-volume center can ensure a high starting point in the initial stage and steady progress of pancreatic surgeons,to ensure the safety of pancreatic surgery.
Male ; Female ; Humans ; Pancreatic Fistula/surgery* ; Retrospective Studies ; Blood Loss, Surgical ; Pancreatectomy/methods* ; Pancreaticoduodenectomy ; Postoperative Complications ; Surgeons ; Postoperative Hemorrhage ; Pancreatic Neoplasms/surgery*

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.