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.

Objective:To investigate the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) versus functional electrical stimulation (FES) in the treatment of post-stroke complex regional pain syndrome. Methods:The randomized controlled study included 60 patients with post-stroke complex regional pain syndrome who received treatment at the Wenzhou TCM Hospital of Zhejiang Chinese Medical University from July 2021 to February 2023. These patients were divided into an rTMS group ( n = 30) and an FES group ( n = 30) using a random number table method. Patients in the rTMS group were treated with rTMS, while those in the FES group were treated with FES. All treatments were performed once daily for 8 consecutive weeks. The clinical efficacy, total active movement score of the fingers, Fugl-Meyer assessment scale score, Activity of Daily Living score, modified Barthel Index score, shoulder joint range of motion, and safety were compared between the two groups. Results:The total response rate in the FES group was 86.7% (26/30), which was significantly higher than 83.3% (25/30) in the rTMS group ( Z = 0.09, P = 0.93). After treatment, there were no significant differences between the two groups in terms of total active movement score of the fingers and Fugl-Meyer assessment scale score ( P = 0.244, 0.262). No significant differences were found between the two groups in MBI score and ADL score (both P > 0.05). There was also no significant difference in shoulder joint range of motion between the two groups ( P > 0.05). Conclusion:Both rTMS and FES are highly effective for post-stroke complex regional pain syndrome. They can improve upper limb function, enhance daily living abilities, and remodel neurological functions of the brain.

Objective:To describe the epidemiological distribution of hemorrhoids in a physical exami-nation population in China,which could provide evidence for precision prevention and early intervention of hemorrhoids.Methods:Chinese subjects over 18 years of age who underwent a physical examination in a nationwide chain of physical examination centers in 2018 were studied in a cross-sectional design,which collected information by a questionnaire and physical examination results from each subject.The epidemiological distribution of hemorrhoids was described using Logistic models.The gender-,age-,and region-detection rates of hemorrhoids were standardized to the Sixth National Population Census of the People's Republic of China(2010).Results:A total of 2 940 295 adult subjects were included in the study,of whom the average age was(41.7±14.0)years,and 52.6％were females.The standardized detection rate of hemorrhoids was higher for females(43.7％)than that for males(17.7％;P＜0.001)in this study.In the females,the age distribution of hemorrhoids was inverted U-shaped,with the highest standardized detection rate of hemorrhoids in the age group of 30-39 years(63.5％).In the males,the standardized detection rate of hemorrhoids increased along with age,with the highest percentage of 17.2％in the age group of 50-59 years,and the standardized detection rate of hemorrhoids in the age group of 60 and above decreased slightly(P＜0.001 for trend test).The participants with hypertension had a higher standardized detection rate of hemorrhoids than those with normal blood pressure in both males and females(P＜0.001).The standardized detection rate of hemorrhoids showed a positive corre-lation with body mass index(P＜0.001 for trend test in males).Conclusion:The detection rate of hemorrhoids varied to gender,age,obesity,and hypertension status,which could help to identify the risk factors and the high-risk sub-groups,and hence to strengthen health education and early detection accordingly,which could eventually reduce the incidence of hemorrhoids and improve the quality of life and health in the Chinese population.This study was conducted in a physical examination population,and the conclusions of this study should be extrapolated with caution.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Objective To investigate the effect of chaperone-mediated autophagy(CMA)on the damage of mouse microglial BV2 cells induce by unconjugated bilirubin(UCB).Methods The BV2 cell experiments were divided into two parts.(1)For the CMA activation experiment:control group(treated with an equal volume of dimethyl sulfoxide),QX77 group(treated with 20 μmol/L QX77 for 24 hours),UCB group(treated with 40 μmol/L UCB for 24 hours),and UCB+QX77 group(treated with both 20 μmol/L QX77 and 40 μmol/L UCB for 24 hours).(2)For the cell transfection experiment:LAMP2A silencing control group(treated with an equal volume of dimethyl sulfoxide),LAMP2A silencing control+UCB group(treated with 40 μmol/L UCB for 24 hours),LAMP2A silencing group(treated with an equal volume of dimethyl sulfoxide),and LAMP2A silencing+UCB group(treated with 40 μmol/L UCB for 24 hours).The cell viability was assessed using the modified MTT method.The expression levels of p65,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),and cysteinyl aspartate specific proteinase-1(caspase-1)were detected by Western blot.The relative mRNA expression levels of the inflammatory cytokines interleukin(IL)-l β,IL-6,and tumor necrosis factor-α(TNF-α)were determined by real-time quantitative polymerase chain reaction.Levels of IL-6 and TNF-α in the cell culture supernatant were measured using ELISA.The co-localization of heat shock cognate protein 70 with p65 and NLRP3 was detected by immunofluorescence.Results Compared to the UCB group,the cell viability in the UCB+QX77 group increased,and the expression levels of inflammation-related proteins p65,NLRP3,and caspase-1,as well as the mRNA relative expression levels of IL-1β,IL-6,and TNF-α and levels of IL-6 and TNF-αdecreased(P＜0.05).Compared to the control group,there was co-localization of heat shock cognate protein 70 with p65 and NLRP3 in both the UCB and UCB+QX77 groups.After silencing the LAMP2A gene,compared to the LAMP2A silencing control+UCB group,the LAMP2A silencing+UCB group showed increased expression levels of inflammation-related proteins p65,NLRP3,and caspase-1,as well as increased mRNA relative expression levels of IL-1 β,IL-6,and TNF-α and levels of IL-6 and TNF-α(P＜0.05).Conclusions CMA is inhibited in UCB-induced BV2 cell damage,and activating CMA may reduce p65 and NLRP3 protein levels,suppress inflammatory responses,and counteract bilirubin neurotoxicity.[Chinese Journal of Contemporary Pediatrics,2024,26(4):385-393]

This is the first reported case of a female with monkeypox infection in Kunming City,Yunnan Province.An epi-demiological investigation was conducted to provide a scientific basis for the prevention and control of monkeypox epidemics in China,especially for early detection in females in accordance with the"Monkeypox prevention and control program(2023 ver-sion)".Diagnosis was performed as described in the"Monkeypox Diagnosis and Treatment Guidelines(2022 version)".Speci-mens were collected for laboratory testing.The epidemiological investigation determined that the female patient had sexual in-tercourse with her newly married husband once before disease onset and the husband hid his history of male homosexual sex.The laboratory test results of the woman and her husband were positive for the nucleic acid of the monkeypox virus.Both had typical clinical symptoms,including rash.The epidemiological investigation,clinical symptoms,laboratory test results,and previous epidemic data of monkeypox in Yunnan province confirmed the woman as the first female infected with monkeypox in Yunnan Province and her husband was the presumed source of infection.

Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.