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.

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.

Objectives: To analyze the influencing factors of No. 253 lymph node metastasis in descending colon cancer, sigmoid colon cancer, and rectal cancer, and to investigate the prognosis of No. 253 lymph node-positive patients by propensity score matching analysis. Methods: A retrospective analysis was performed on clinical data from patients with descending colon cancer, sigmoid colon cancer, rectosigmoid junction cancer, and rectal cancer who underwent surgery between January 2015 and December 2019 from the Cancer Hospital of the Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Peking Union Medical College Hospital, General Hospital of the Chinese People's Liberation Army, and Peking University Cancer Hospital. A total of 3 016 patients were included according to inclusion and exclusion criteria, comprising 1 848 males and 1 168 females, with 1 675 patients aged≥60 years and 1 341 patients aged<60 years. Clinical and pathological factors from single center data were subjected to univariate analysis to determine influencing factors of No. 253 lymph node metastasis, using a binary Logistic regression model. Based on the results of the multivariate analysis, a nomogram was constructed. External validation was performed using data from other multicenter sources, evaluating the effectiveness through the area under the receiver operating characteristic curve and the calibration curve. Using data from a single center, the No. 253 lymph node-positive group was matched with the negative group in a 1∶2 ratio (caliper value=0.05). Survival analysis was performed using the Kaplan-Meier method and Log-rank test. The Cox proportional hazards model was used to determine independent prognostic factors. Results: (1) The tumor diameter≥5 cm (OR=4.496,95%CI:1.344 to 15.035, P=0.015) T stage (T4 vs. T1: OR=11.284, 95%CI:7.122 to 15.646, P<0.01), N stage (N2 vs. N0: OR=60.554, 95%CI:7.813 to 469.055, P=0.043), tumor differentiation (moderate vs. well differentiated: OR=1.044, 95%CI:1.009 to 1.203, P=0.044; poor vs. well differentiated: OR=1.013, 95%CI:1.002 to 1.081, P=0.013), tumor location (sigmoid colon vs. descending colon: OR=9.307, 95%CI:2.236 to 38.740, P=0.002), pathological type (mucinous adenocarcinoma vs. adenocarcinoma: OR=79.923, 95%CI:15.113 to 422.654, P<0.01; signet ring cell carcinoma vs. adenocarcinoma: OR=27.309, 95%CI:4.191 to 177.944, P<0.01), and positive vascular invasion (OR=3.490, 95%CI:1.033 to 11.793, P=0.044) were independent influencing factors of No. 253 lymph node metastasis. (2) The area under the curve of the nomogram prediction model was 0.912 (95%CI: 0.869 to 0.955) for the training set and 0.921 (95%CI: 0.903 to 0.937) for the external validation set. The calibration curve demonstrated good consistency between the predicted outcomes and the actual observations. (3) After propensity score matching, the No. 253 lymph node-negative group did not reach the median overall survival time, while the positive group had a median overall survival of 20 months. The 1-, 3- and 5-year overall survival rates were 83.9%, 61.3% and 51.6% in the negative group, and 63.2%, 36.8% and 15.8% in the positive group, respectively. Multivariate Cox analysis revealed that the T4 stage (HR=3.067, 95%CI: 2.357 to 3.990, P<0.01), the N2 stage (HR=1.221, 95%CI: 0.979 to 1.523, P=0.043), and No. 253 lymph node positivity (HR=2.902, 95%CI:1.987 to 4.237, P<0.01) were independent adverse prognostic factors. Conclusions: Tumor diameter ≥5 cm, T4 stage, N2 stage, tumor location in the sigmoid colon, adverse pathological type, poor differentiation, and vascular invasion are influencing factors of No. 253 lymph node metastasis. No. 253 lymph node positivity indicates a poorer prognosis. Therefore, strict dissection for No. 253 lymph node should be performed for colorectal cancer patients with these high-risk factors.

Aim To study the effect of salidroside (SAL) on cerebral vascular endothelial cells of rats with ischemic brain injury and its mechanism of action. Methods Twenty-four healthy adult SD male rats were prepared by bolt plugging method to prepare MCAO models,and randomly divided into sham surgery group ( Sham ) , model group ( MCAO ) , and SAL administration group (MCAO + SAL) ,and the concentration of SAL was 50 mg • kg ~ , with a continuous administration for six days. Western blot was used to detect the protein expression of ICAM-1, VCAM-1 , E-se-lectin,and P-selectin in injured brain tissue of rats. In vitro cell experiments using HUVECs were subjected to different concentrations of salidroside (0. 1,1,10 jjunol • L ) and LPS (100 ^g • L ) intervened for 24 hours,and CCK-8 was employed to detect the effects of SAL and LPS on the survival of HUVECs. In vitro an-giogenesis experiments, LPS group ( 100 (jLg • L~ ) and SAL administration group ( LPS + Sal) intervened in HUVECs for 24 hours,and the concentrations of SAL administration were 0. 1,1, and 10 jjunol • L , then the effects of LPS and SAL on their angiogenesis were observed. The protein expressions of ICAM-1, VCAM-1 ,E-selectin,and P-selectin in HUVECs were detected by Western blot. Results SAL could reduce the expression of ICAM-1, VCAM-1, E-selectin, and P-selectin in ischemic brain tissue of MCAO rats. In vitro experimental studies found that salidroside had no effect on the survival of HUVECs. LPS inhibited the angiogenesis of HUVECs, and after the action of SAL, SAL (1,10 jjimol • L ) reversed the effect of LPS and promoted its angiogenesis. Compared with the control group,the expressions of ICAM-1, VCAM-1, E-selectin and P-selectin of HUVECs after LPS stimulation increased, while the expressions of ICAM-1, VCAM-1 , E-selectin and P-selectin were significantly reduced after the addition of SAL, which promoted the angiogenesis ability of HUVECs. Conclusions SAL can improve the ability of cell regeneration in rats with ischemic brain injury and promote the ability of blood vessel formation.

Humans ; Mpox (monkeypox) ; China

Since the end of 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has swept the world,bringing great harm to human society and significantly increasing the health burden.Due to stron-ger infectivity,faster transmission,and higher reinfection rate of the Omicron variant,it has now replaced the Delta variant as the main epidemic strain for both imported and local outbreaks in China.Chinese Diagnosis and treatment protocol for SARS-CoV-2 infection(10th trial version)emphasizes"strengthening the protection of key popula-tions,"which includes the increasing number of immunocompromised population.These people have a high inci-dence of severe diseases and a high fatality rate after infected with SARS-CoV-2,and belong to the high-risk popula-tions of severe or critical diseases.Moreover,due to underlying diseases,these people take immunosuppressants and other related drugs chronically.The interactions between anti-SARS-CoV-2 infection treatment drugs and origi-nal drugs are complicated,thus bring significant challenges to the treatment after the SARS-CoV-2 infection.Cur-rently,there is a lack of guidelines or consensus on the diagnosis and treatment of SARS-CoV-2 infection among im-munocompromised population.Therefore,the Guangzhou Institute of Respiratory Health and National Center for Respiratory Medicine organized experts from multiple disciplines(respiratory and critical care medicine,organ transplantation,rheumatology and immunology,hematology,infection,critical care medicine,etc.)in China.Af-ter multiple rounds of discussions,13 items of recommendations are made as the reference for peers based on evi-dence-based medical evidence,so as to provide a theoretical and practical reference for the diagnosis and treatment strategies of this population.

Through consulting the ancient herbs， medical books and modern literature， this paper made textual research on the name， origin， producing area， quality evaluation， collection and processing of medicinal materials of Sang （Mori Folium， Mori Cortex， Mori Ramulus， Mori Fructus） in famous classical formulas， in order to provide a basis for the development of famous classical formulas containing medicinal materials of Sang. According to the research， Mori Folium and Mori Cortex were first used as medicines in Shengnong Bencaojing ， Mori Ramulus was first used as medicine in Jinxiaofang， and Mori Fructus was first used as medicine in Xinxiu Bencao. Before the Tang dynasty， there were Nyusang and Shansang. Since Tang dynasty， there were many sources of medicinal materials of Sang， including Baisang （Morus alba）， Jisang （M. australis）， Shansang （M. mongolica）， etc. According to textual research， the mainstream varieties were M. australis， M. alba and their cultivated varieties. In modern times， according to the relevant information and the Chinese Pharmacopoeia， M. alba is the original base. In ancient times， the origin of mulberry changed with the development of sericulture， mulberry has been widely planted since the Song dynasty. In the Ming and Qing dynasties， mulberry has been planted most in Jiangsu and Zhejiang. In modern times， they are mainly produced in Jiangsu， Zhejiang， Anhui， Hunan and other places. In recent years， due to the related policies and strategies such as "moving silkworms from east to west"， the center of silkworm breeding has gradually transferred to the west. As for the quality evaluation and harvesting and processing of mulberry medicinal materials， Most of the ancient and modern records of Mori Folium are the same. They are harvested after frost， and dried after removing impurities. The quality is better when the leaves are large and thick， yellowish green， holding prickly hands and undergoing frost. The harvesting period of Mori Cortex is slightly different in ancient and modern records. Ancient books record that it can be harvested all the year round， but in modern times， it is mostly harvested from late autumn to the next spring. The processing methods include removing soil and fibrous roots， scraping off yellow-brown rough skin， peeling off white skin and drying in the sun. The quality is better when they are white， thick， flexible， free of rough skin and full of powder. There are few records about the collection， processing and quality evaluation of Mori Ramulus and Mori Fructus in ancient Chinese herbal books. According to modern literature， Mori Ramulus is usually collected in late spring and early summer， with leaves removed， slightly dried， sliced while fresh， and dried in the sun. The best quality of Mori Ramulus is fine and tender with the yellow and white section. Mori Fructus is harvested from April to June when the fruit turns red， and dried in the sun， or slightly steamed and dried in the sun， and it is better to be big， dark purple， oily and thick. There are many processing methods of mulberry medicinal materials. Ancient books record stir frying， baking， burning and steaming of Mori Folium， in modern times， there is honey-roasted method， but most of them are used as raw products. In ancient materia medica， Mori Cortex has firing method， baking method， stir-frying method， honey-fried method， etc. In modern times， there are stir-fried and honey-fried methods， and most of them are used as raw products. Ancient books record that Mori Ramulus has cutting and frying methods， while modern ones have cutting， frying， wine-processed and bran-processed methods. Processing methods of Mori Fructus are consistent in ancient and modern times， and they are mostly dried after being cleaned or steamed. Based on the research results， it is suggested that M. alba should be selected as mulberry medicinal materials in the famous classical formulas， and appropriate medicinal parts and processing methods can be selected according to the indications of the famous classical formulas.

In order to provide the basis for the development of famous classical formulas containing Myrrha， the name， origin， quality evaluation， harvest and processing of Myrrha were systematically researched by consulting the ancient herbal and medical books， combining with the modern related literature. According to textual research， the results showed that Commiphora myrrha was the main base in ancient times， which was produced in Somalia， Ethiopia and northern Kenya. In addition， raw and fried products of Myrrha were the commonly used specifications in ancient herbal medicine， which are still used today. Nowadays， Myrrha， fried Myrrha and vinegar-processed Myrrha were the commonly used specifications. Among the three specifications， Myrrha is the raw products after cleaning， fried Myrrha is a kind of processed products， which has relevant records in ancient materia medica and is still used today. Vinegar-processed Myrrha is a new processing specification in modern times. Based on the research results， it is suggested that Myrrha in Shentong Zhuyutang should be the purified raw Myrrha in accordance with the 2020 edition of Chinese Pharmacopoeia.