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.

OBJECTIVES: To develop and validate a preoperative clinical-radiomics model for predicting overall survival (OS) and disease-free survival (DFS) in patients with extrahepatic cholangiocarcinoma (eCCA) undergoing radical resection. METHODS: In this retrospective study, consecutive patients with pathologically-confirmed eCCA who underwent radical resection at our institution from 2015 to 2022 were included. The patients were divided into a training cohort and a validation cohort according to the chronological order of their CT examinations. Least absolute shrinkage and selection operator (LASSO)-Cox regression was employed to select predictive radiomic features and clinical variables. The selected features and variables were incorporated into a Cox regression model. Model performance for 1-year OS and DFS prediction was assessed using calibration curves, area under receiver operating characteristic curve (AUC), and concordance index (C-index). RESULTS: This study included 123 patients (mean age 64.0 ± 8.4 years, 85 males/38 females), with 86 in the training cohort and 37 in the validation cohort. The OS-predicting model included four clinical variables and four radiomic features. It achieved a training cohort AUC of 0.858 (C-index = 0.800) and a validation cohort AUC of 0.649 (C-index = 0.605). The DFS-predicting model included four clinical variables and four other radiomic features. It achieved a training cohort AUC of 0.830 (C-index = 0.760) and a validation cohort AUC of 0.717 (C-index = 0.616). CONCLUSIONS The preoperative clinical-radiomics models show promise as a tool for predicting 1-year OS and DFS in eCCA patients after radical surgery.
Humans ; Male ; Female ; Retrospective Studies ; Middle Aged ; Cholangiocarcinoma/mortality* ; Prognosis ; Bile Duct Neoplasms/mortality* ; Tomography, X-Ray Computed/methods* ; Aged ; Radiomics

Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.

Band 3 protein is an important channel protein in the erythrocyte membrane which mediates the anion transport process inside and outside the cell membrane,as well as contributes to the maintenance of erythrocyte morphology,and has important physiological functions.However,the distribution state of this protein in the primary cell membrane is not known.Cryo-scanning electron microscopy enables imaging of the surface morphology of biological samples in a near-physiological state.In order to investigate the distribution of band 3 protein on erythrocyte membranes under physiological conditions,the present study utilized 5-nm gold nanoparticles modified with the antibodies to specifically bind to the band 3 protein on human blood erythrocyte membranes and imaged them by cryo-scanning electron microscopy,to obtain distribution of band 3 protein on human blood erythrocyte membranes.The results showed that the membrane proteins on the erythrocyte membranes tended to be clustered and distributed to form ″protein islands″,and band 3 proteins were mainly distributed in these protein islands,which were tightly connected with each other to form several functional microregions to play their respective roles.

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 observe the therapeutic effect of acupuncture combined with western conventional therapy on type Ⅱ respiratory failure of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and evaluate the effect of acupuncture on diaphragmatic function and prognosis by bedside ultrasound. METHODS: A total of 111 patients with AECOPD type Ⅱ respiratory failure were randomized into an acupuncture group, a conventional treatment group and a non-acupoint acupuncture group, 37 cases in each one. The routine AECOPD nursing care and treatment with western medicine were provided in the 3 groups. Additionally, in the acupuncture group, acupuncture was applied at Dingchuan (EX-B 1), Feishu (BL 13), Taiyuan (LU 9), Danzhong (CV 17) and Zhongwan (CV 12), etc. In the non-acupoint acupuncture group, acupuncture was given at the points 5 to 10 mm lateral to each of the acupoints selected in the acupuncture group. Acupuncture was given once every day, 30 min each time, consecutively for 10 days in the above two groups. Separately, before treatment, on day 3, 7 and 10 of treatment, arterial partial pressure of oxygen (PaO RESULTS: On day 3, 7 and 10 of treatment, PaO CONCLUSION Acupuncture as adjunctive therapy achieves significant therapeutic effect on AECOPD type Ⅱ respiratory failure. It improves diaphragmatic function, promotes oxygenation and relieves carbon dioxide retention of artery, alleviates clinical symptoms and reduces the time of mechanic ventilation and hospitalization. Besides, the bedside ultrasound detection can objectively reflect the effect of acupuncture on diaphragmatic function in the patients with AECOPD complicated with typeⅡrespiratory failure.
Acupuncture Points ; Acupuncture Therapy ; Diaphragm ; Humans ; Pulmonary Disease, Chronic Obstructive/therapy* ; Respiratory Insufficiency/therapy*

OBJECTIVE: To observe the analgesic and sedative effects of acupuncture in elderly patients with severe pneumonia during invasive mechanical ventilation. METHODS: A total of 188 elderly patients with severe pneumonia were randomly divided into an observation group and a control group, 94 cases in each group. Both groups were treated with routine nursing and treatment of severe pneumonia such as invasive mechanical ventilation, analgesia and sedation. Based on these, the observation group was treated with acupuncture at Neiguan (PC 6), Hegu (LI 4), Yintang (GV 29) and Baihui (GV 20), twice a day until the mechanical ventilation was offline. The critical care pain observation tool (CPOT) score and Richmond agitation-sedation score (RASS) were observed before treatment and 0.5 h after analgesia and sedation; the average time of reaching the standard, the reaching standard rate of shallow sedation and analgesia within 0.5 h and 72 h as well as the dosage of analgesic and sedative drugs and compilations were compared between the two groups. The mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR) and blood oxygen saturation (SpO RESULTS: At the time point of 0.5 h after treatment, the CPOT and RASS scores in the two groups were lower than those before treatment ( CONCLUSION Acupuncture has analgesic and sedative effect in elderly patients with severe pneumonia during invasive mechanical ventilation, which could reduce the dosage of sedative and analgesic drugs and the occurrence of complications, improve blood oxygen, and has good safety.
Acupuncture Therapy ; Aged ; Analgesia ; Humans ; Intensive Care Units ; Pain ; Pneumonia ; Respiration, Artificial

Background: Previous studies demonstrate that eccrine sweat glands are innervated by both cholinergic and adrenergic nerves. However, it is still unknown whether the secretory coils and ducts of eccrine sweat glands are equally innervated by the sympathetic nerve fibers. To well understand the mechanisms on sweat secretion and reabsorption, the differential innervation of secretory coils and ducts in human eccrine sweat glands was investigated in the study. Methods: From June 2016 to June 2017, six human skins were fixed, paraffin-embedded, and cut into 5 μm-thick sections, followed by costaining for nerve fiber markers protein gene product 9.5 (PGP 9.5), tyrosine hydroxylase (TH) and vasoactive intestinal peptide (VIP), and eccrine sweat gland markers K7, S100P, and K14 by combining standard immunofluorescence with tyramide signal amplification (IF-TSA). Stained sections were observed under the microscope, photographed, and analyzed. Results: The fluorescent signals of PGP 9.5, TH, and VIP were easily visualized, by IF-TSA, as circular patterns surrounding eccrine sweat glands, but only PGP 9.5 could be observed by standard IF. The IF-TSA method is more sensitivity than standard IF in detecting antigens expressed at low levels. PGP 9.5, TH, and VIP appeared primarily surrounding the secretory coils and sparsely surrounding the sweat ducts. Conclusion Sweat secretion is mainly controlled by autonomic nerves whereas sweat reabsorption is less affected by nerve activity.
Eccrine Glands ; innervation ; Fluorescent Antibody Technique ; Humans ; Nerve Fibers ; Sweat Glands ; innervation ; Vasoactive Intestinal Peptide ; analysis