1.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
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.
2.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
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.
3.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
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.
4.Research progress on molecular mechanisms of ginsenosides in alleviating acute lung injury.
Han-Yang ZHAO ; Xun-Jiang WANG ; Qiong-Wen XUE ; Bao-Lian XU ; Xu WANG ; Shu-Sheng LAI ; Ming CHEN ; Li YANG ; Zheng-Tao WANG ; Li-Li DING
China Journal of Chinese Materia Medica 2025;50(16):4451-4470
Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology*
;
Humans
;
Acute Lung Injury/immunology*
;
Animals
;
Panax/chemistry*
;
Drugs, Chinese Herbal
5.Clinical features and sepsis-related factors in 159 patients with necrotizing soft tissue infection.
Hongmin LUO ; Xiaoyan WANG ; Xu MU ; Zeyang YAO ; Chuanwei SUN ; Lianghua MA ; Shaoyi ZHENG ; Huining BIAN ; Wen LAI
Chinese Critical Care Medicine 2025;37(9):817-821
OBJECTIVE:
To explore the clinical features of patients with necrotizing soft tissue infection (NSTI) and the related factors for sepsis, so as to provide a basis for early intervention and improvement of patients' prognosis.
METHODS:
A retrospective case series study was conducted to analyze the clinical data of NSTI patients admitted to the department of burns and wound repair surgery of Guangdong Provincial People's Hospital from October 2021 to December 2024. Demographic information, underlying diseases, infection characteristics, laboratory test results and etiological findings at admission, treatment status, occurrence of complications (including sepsis) and prognosis were collected. Univariate and multivariate Logistic regression analyses were used to identify the associated factors for sepsis in NSTI patients. Receiver operator characteristic curves (ROC curves) were plotted to evaluate the predictive value of individual and combined factors for sepsis.
RESULTS:
A total of 159 NSTI patients were enrolled, mainly middle-aged and elderly males. Most patients had comorbidities, including diabetes mellitus (110 cases, 69.2%) and hypertension (67 cases, 42.1%). The main infection site was the lower extremities (104 cases, 65.4%). Common symptoms included redness (96 cases, 60.4%), swelling (129 cases, 81.1%), local heat (60 cases, 37.7%), pain (100 cases, 62.9%), and skin ulceration or necrosis (9 cases, 5.7%). Imaging findings included soft tissue swelling (66 cases, 57.9%), gas accumulation (41 cases, 36.0%), and abnormal signal/density shadows (50 cases, 43.9%). Staphylococcus aureus was the main pathogenic bacterium [12.0% (31/259)], and drug-resistant Escherichia coli had the highest detection rate among drug-resistant bacteria [35.1% (13/37)]. Regarding debridement and repair, most patients (80 cases, 50.3%) underwent debridement ≥ 72 hours after admission, while only 10.1% (16 cases) received debridement within 6 hours. Most patients underwent multiple debridements, with 2 times of debridements being the most common (68 cases, 42.8%), and the maximum times of debridements reached 6. The largest number of patients received secondary suture (44 cases, 27.7%). In terms of complications, sepsis was the most common (66 cases, 41.51%), followed by acute kidney injury, respiratory failure requiring mechanical ventilation, and multiple organ dysfunction syndrome (MODS), while disseminated intravascular coagulation (DIC) was the least common. During the follow-up period, 9 patients (5.66%) were readmitted within 90 days, and 11 patients died, with a mortality rate of 6.92%. Univariate analysis showed that diabetes, coronary heart disease, gout, body temperature, heart rate, C-reactive protein, platelet count, total bilirubin, albumin, creatinine, out-of-hospital treatment, and out-of-hospital use of antimicrobial agents were significantly associated with sepsis in NSTI patients (all P < 0.05). Multivariate Logistic regression analysis showed that coronary heart disease [odds ratio (OR) = 30.085, 95% confidence interval (95%CI) was 2.105-956.935], C-reactive protein (OR = 1.026, 95%CI was 1.009-1.054), and total bilirubin (OR = 1.436, 95%CI was 1.188-1.948) were independent associated factors for sepsis in NSTI patients (all P < 0.05). ROC curve analysis revealed that the combination of the three predictors yielded the highest AUC for predicting sepsis in NSTI patients compared to any individual predictor [area under the curve (AUC) = 0.799 (95%CI was 0.721-0.878)].
CONCLUSIONS
The clinical features of NSTI patients show certain regularity. Coronary heart disease, C-reactive protein, and total bilirubin are independent associated factors for sepsis in NSTI patients.
Humans
;
Retrospective Studies
;
Male
;
Sepsis
;
Soft Tissue Infections/microbiology*
;
Female
;
Middle Aged
;
Aged
;
Adult
;
Prognosis
;
Risk Factors
;
Necrosis
;
Logistic Models
;
Fasciitis, Necrotizing
6.Investigation and analysis of acute poisoning of organic fluorine mixed gas in a fluorine polymerization plant
Xiawen ZHENG ; Zhen NIE ; Sifeng LIU ; Zhao ZHENG ; Lushan WANG ; Shiming LAI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(3):184-187
In January 2021, an acute chemical poisoning incident occurred at a fluorine polymerization plant. Through the analysis of the occupational health situation of the enterprise, combined with the clinical manifestations of the poisoned patients and the laboratory examination results, it was determined that the incident was an acute poisoning incident caused by the inhalation of organic fluorine mixed gas in the fluorine polymerization plant. Subsequently, it was clarified that the accident was caused by the illegal operation of the employees of the fluorine polymerization plant, which caused the discharge of the organic fluorine mixed gas containing high concentration of octafluoroisobutene, resulting in the poisoning of the on-site construction personnel. In order to avoid the occurrence of similar incidents, enterprises should implement the main responsibility of safety production, regularly organize supervision and inspection, eliminate illegal operations, conduct safety education and training for the staff of the unit and outsourced staff, and improve the emergency rescue ability of sudden poisoning incidents.
7.Establish of the risk predictive model for varicella outbreaks in primary and middle schools
ZHENG Yongtao, YE Chunmei, NI Zuowei, ZHANG Jiani, LAI Fenhua, GAO Yanmin, YANG Dongbo, WANG Yanmei
Chinese Journal of School Health 2024;45(6):873-877
Objective:
To investigate the epidemiological characteristics of varicella outbreaks in primary and middle schools, and to establish a risk predictive model, so as to provide scientific guidance for the prevention of varicella outbreaks in schools.
Methods:
Based on a nested case-control study, primary and middle schools in 4 districts of Shanghai (Yangpu District and Jingan District) and Hangzhou (Xiaoshan District and Linping District) from January to December 2023 were selected to observe the status of varicella outbreaks. Associated factors of varicella outbreaks were investigated and used for establishing the predictive model, which was evaluated by the Hosmer-Lemeshow(H-L) goodness of fit test, receiver operating characteristic (ROC) curve, Calibration curve, decision curve analysis (DCA).
Results:
A total of 98 varicella outbreaks were included, with 195 schools without varicella outbreaks during the same period as controls. Eight factors, including the availability of warm water in restroom, availability of hand soap in restroom, average class size, duration of student attendance at school per day, presence of a fulltime school doctor, hesitancy of the school principal towards varicella vaccination, and rates of first and second doses of varicella vaccination, were identified as potential factors for school varicella outbreaks, with statistically significant differences (χ2/Z=10.01, 20.49, 17.43, 9.74, 32.17, 6.60, 2.20, 3.39, P<0.05). The 8 variables above were employed to construct a risk predictive model, and Hosmer-Lemeshow goodness of fit test yielded a χ2 value of 5.863 (P>0.05); the area under the ROC curve (AUC) was 0.846 (95%CI=0.799-0.893); Calibration curve analysis indicated good consistency between predicted and actual values of the model. DCA demonstrated favorable predictive performance of the model over a wide range.
Conclusions
The predictive model for school varicella outbreaks demonstrates satisfactory accuracy and efficacy. It suggested to make good use of this prediction model and take relevant measures to reduce the risk of varicella transmission in schools.
8.Observation on the outcome of occupational chronic benzene poisoning treated with acupuncture combined with Du-Moxibustion
Ying ZHENG ; Lili LAI ; Xiaofeng DENG ; Chunyue FAN ; Jin WU ; Min OU ; Shufang YAO ; Hailan WANG
China Occupational Medicine 2024;51(2):210-213
ObjectiveTo investigate the effects of acupuncture combined with Du-Moxibustion (ADM) on peripheral blood cell count and levels of immune factors in patients with occupational chronic benzene poisoning. Methods A total of 70 patients with occupational chronic benzene poisoning (leukopenia and neutropenia) were selected as the research subjects by judgement sampling method. They were randomly divided into a control group and an ADM group using a random number table method, with 35 cases in each group. Patients in the control group were treated with conventional Western medicine such as leukocyte boosting and symptomatic treatment. While patients in the ADM group were treated with ADM treatment in addition to treatments of the control group, once per week for five consecutive weeks. Peripheral blood samples of patients were collected before and after treatment from both groups, to detect cell counts and serum levels of immune factors. Results The white blood cell count, red blood cell count, absolute lymphocyte count, absolute neutrophil count, platelet count, and levels of hemoglobin, immunoglobulins (Ig) A, IgM, IgG, complement C3 and complement C4 of patients in both groups improved after treatment compared with those before treatment (all P<0.05). The white blood cell count, levels of IgA, IgM, IgG, complement C3 and complement C4 of patients in the ADM group were higher than those in the control group after treatment (all P<0.05). Conclusion ADM treatment can increase peripheral blood white blood cells and serum levels of immune factor in patients with occupational chronic benzene poisoning (leukopenia, neutropenia), which helps improve patient recovery and can be promoted clinically.
9.Effect of acupoint sticking therapy along meridians on gastrointestinal function recovery in patients after lumbar internal fixation surgery
Peiqian LAI ; Pei HU ; Hongshen WANG ; Yanhua ZHENG ; Meiyan LAN ; Shaohua CHEN
The Journal of Practical Medicine 2024;40(2):267-271
Objective To observe the effect of acupoint sticking therapy along meridians on gastrointestinal function recovery in patients after lumbar internal fixation surgery.Methods From January 2020 to March 2022,125 patients with lumbar degenerative diseases were admitted to our hospital's Department of Orthopaedics and divided into two groups:control(n = 62)and acupoint sticking therapy(n = 63).The control group received standard postoperative care for lumbar internal fixation,while the experimental group received routine care based on acupoint sticking therapy along meridians.The NVAS scores for postoperative nausea and vomiting,abdominal distension and pain,bowel sound,initial exhaust,and defecation time were compared between the two groups.Results Both groups experienced gastrointestinal problems to varied degrees following surgery.The experimental group had signifi-cantly lower rates of nausea,NVAS score,vomiting grade,abdominal distension,return to normal bowel sounds,and time of first exhaust and bowel movement compared to the control group(P<0.05).However,there were no significant differences in abdominal pain and abdominal circumference(P>0.05).There were no adverse reactions in either group.The incidence of postoperative abdominal distension,nausea and vomiting in the observation group was lower than that in the control group,and the difference was statistically significant(P<0.05).Conclusion Acupoint sticking therapy along meridians could accelerate the recovery of gastrointestinal function of patients after lumbar internal fixation,promote rapid recovery after surgery,and improve quality of life.
10.Interaction analysis of mismatch repair protein and adverse clinicopathological features on prognosis of colon cancer
Kexuan LI ; Fuqiang ZHAO ; Qingbin WU ; Junling ZHANG ; Shuangling LUO ; Shidong HU ; Bin WU ; Heli LI ; Guole LIN ; Huizhong QIU ; Junyang LU ; Lai XU ; Zheng WANG ; Xiaohui DU ; Liang KANG ; Xin WANG ; Ziqiang WANG ; Qian LIU ; Yi XIAO
Chinese Journal of Digestive Surgery 2024;23(6):826-835
Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.


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