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 explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU). METHODS: The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed. RESULTS: Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05). CONCLUSIONS The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.
Adolescent ; Infant ; Child, Preschool ; Humans ; Child ; Critical Illness ; Prognosis ; Child, Hospitalized ; Chronic Disease ; Intensive Care Units, Pediatric

Aim To investigate the effect of microinjection of EX527, a selective SIRT1 antagonist, into the ventrolateral orbital cortex (VLO) on morphine-induced conditioned place preference (CPP), and to explore the role of CREB/BDNF in it. Methods The cannulas were implanted bilaterally in the VLO of rats by brain stereotaxis surgery, and the model of morphine-induced CPP was established. The behavioral experiment consisted of four stages:habituation (d 1), pre-test (d 2-4), conditioning training (d 5-14) and test (d 15). At the stage of conditioning training, EX527 (1 μL, 5 g·L

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.

OBJECTIVE: To observe the effect of navel acupuncture on bladder emptying function in patients with urinary retention after stroke based on the conventional treatment. METHODS: A total of 106 patients with urinary retention after stroke were randomly divided into an observation group (53 cases, 3 cases dropped off) and a control group (53 cases, 3 cases dropped off). Patients in the control group were treated with drugs, catheterization and bladder function rehabilitation training. On the basis of the treatment in the control group, the observation group was treated with navel acupuncture, 30 min each time, once every other day, for 4 weeks. The bladder residual urine volume, spontaneous urination volume and catheterization times before and after treatment were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: After treatment, in the two groups, the bladder residual urine volume and catheterization times were lower than those before treatment (P<0.01), and the spontaneous urination volume was higher than that before treatment (P<0.01); the bladder residual urine volume and catheterization times in the observation group were less than those in the control group (P<0.05, P<0.01), and the spontaneous urination volume was higher than that in the control group (P<0.01). The effective rate of the observation group was 90.0 % (45/50), which was higher than 72.0 % (36/50) in the control group (P<0.05). CONCLUSION On the basis of conventional treatment, navel acupuncture can effectively improve the bladder emptying function of patients with urinary retention after stroke.
Humans ; Stroke/therapy* ; Urinary Bladder ; Urinary Retention/therapy*

OBJECTIVES: To evaluate the effect of fluid load on the prognosis of children with sepsis-associated acute kidney injury (AKI) undergoing continuous renal replacement therapy (CRRT). METHODS: A total of 121 children who underwent CRRT for sepsis-associated AKI from August 2018 to March 2021 were enrolled in the retrospective study. According to the fluid load from admission or disease progression to CRRT, they were divided into three groups: low fluid load (fluid load: <5%; n=35), high fluid load (fluid load: 5% - <10%; n=35), and fluid overload (fluid load: ≥10%; n=51). Baseline data and clinical biochemical data before CRRT were collected for comparison and analysis. The Kaplan-Meier survival curve analysis was used for comparison of 28-day survival between groups. The multivariate logistic regression model was used to identify the influencing factors for the prognosis of the children. RESULTS: The survival analysis showed that the fluid overload group had a significantly higher 28-day mortality rate than the low fluid load and high fluid load groups (P<0.05). The multivariate logistic regression analysis showed that an increase in fluid overload volume was a risk factor for increased 28-day mortality in the fluid overload group, while earlier initiation of CRRT was a protective factor (P<0.05). CONCLUSIONS Fluid overload before CRRT may increase the mortality in children with sepsis-associated AKI, and CRRT should be performed for these children as early as possible.
Acute Kidney Injury/therapy* ; Child ; Continuous Renal Replacement Therapy ; Humans ; Prognosis ; Retrospective Studies ; Sepsis/therapy*

OBJECTIVES: To study the clinical characteristics of ultrasound-guided central venous catheterization at various sites in infants with shock, and to explore how to quickly select the site for central venous puncture in infants with shock. METHODS: The medical data of 112 infants who were diagnosed with shock and underwent central venous catheterization in the Pediatric Intensive Care Unit, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from January 2016 to December 2020 were reviewed retrospectively. The patients were divided into an ultrasound group (n=70) and a body surface location group (n=42) according to whether the catheterization was carried out under ultrasound guidance. The application of ultrasound-guided catheterization at various sites in infants was summarized and analyzed, and the success rate of one-time puncture, overall success rate, catheterization time, and complications were compared between these sites. RESULTS: Compared with the body surface location group, the ultrasound group had a significantly higher success rate of one-time puncture, a significantly shorter catheterization time, and a significantly reduced incidence rate of complications in internal jugular vein and femoral vein catheterizations (P<0.05). In the ultrasound group, the proportion of internal jugular vein catheterization was the highest (51%, 36/70), followed by femoral vein catheterization (33%, 23/70), and subclavian vein catheterization (16%, 11/70). For the comparison between different puncture sites under ultrasound guidance, internal jugular vein catheterization showed the shortest time of a successful catheterization [5.5 (5.0, 6.5) minutes] (P<0.05). There was no significant difference in the incidence rate of complications among the different puncture sites groups (P>0.05). CONCLUSIONS In infants with shock, ultrasound-guided internal jugular vein catheterization can be used as the preferred catheterization method for clinicians.
Catheterization, Central Venous/adverse effects* ; Child ; Humans ; Infant ; Jugular Veins/diagnostic imaging* ; Retrospective Studies ; Ultrasonography ; Ultrasonography, Interventional