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.

To introduce the general thinking, guidelines, work objectives and elaboration process of the general technical requirements adopted by volume Ⅳ of the Chinese Pharmacopoeia 2025 Edition, and to summarize and figure out the main characteristics on dosage forms, physico-chemical testing, microbial and biological testing, reference standards and guidelines The newly revised general chapters of pharmacopoeia give full play to the normative and guiding role of the Chinese Pharmacopoeia standard, track the frontier dynamics of international drug regulatory science and the elaboration of monographs, expand the application of state-of-the-art technologies, and steadily promote the harmonization and unification with the ICH guidelines； further enhance the overall capacity of TCM quality control, actively implement the 3 R principles on animal experiments, and practice the concept of environmental-friendly； replace and/or reduce the use of toxic and hazardous reagents, strengthen the requirements of drug safety control This paper aims to provide a full-view perspective for the comprehensive, correct understanding and accurate implementation of general technical requirements included in the Chinese Pharmacopoeia 2025 Edition.

Objective: To explore the bidirectional causal relationship between 731 immune cell phenotypes and recurrent aphthous ulcers (RAU) using Mendelian randomization (MR). Methods: A two-sample bidirectional MR study was conducted using publicly available genome-wide association study (GWAS) summary statistics for 731 immune cell phenotypes and the RAU GWAS summary data from the FinnGen consortium. The inverse-variance weighted (IVW) method was used as the primary analysis tool, with supplementary analyses including the weighted median (WM) method, MR-Egger regression, weighted mode, and simple mode. Sensitivity analyses were conducted using Cochran’s Q test, the mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method for detecting pleiotropy and outliers, and leave-one-out cross-validation. Furthermore, differential analysis was performed using a clinical cohort dataset from the Gene Expression Omnibus (GEO) to further validate the MR results. Results: In the forward MR analysis, 731 immune cell phenotypes were considered as exposures and RAU as the outcome. Among them, 52 immune cell phenotypes showed a significant causal effect on RAU (P<0.05). After false discovery rate (FDR) correction, two immune phenotypes remained significantly associated with RAU risk: with increased monocyte-derived myeloid suppressor cells (M-MDSC) (OR = 1.06; 95% CI: 1.03-1.09) and CD33 on granulocytic myeloid-derived suppressor cells (G-MDSC) (OR = 1.06; 95% CI: 1.03-1.09), the risk of RAU also increased. In reverse MR, RAU was found to have a significant causal effect on two immune cell phenotypes (P<0.05), but no significant effects were found after FDR correction. Sensitivity analysis showed no significant heterogeneity between SNPs (P>0.05). Differential analysis of the GEO dataset revealed that the characteristic genes of myeloid-derived suppressor cells (MDSC) (CTBS, IPMK, and UBA3) were significantly upregulated in RAU (P<0.05). Conclusion The MR results of 731 immune cell phenotypes suggest that M-MDSC and CD33 molecules on G-MDSC may be risk factors for RAU development. The clinical GEO dataset further validated that MDSC may play a role in RAU, while RAU did not show a significant causal association with the 731 immune cell phenotypes.

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.

Aim To investigate the promotional effects of neutrophil extracellular traps(NETs)on renal tissue damage and intestinal flora disruption induced by dia-betic kidney disease(DKD)and the potential mecha-nisms.Methods C57BL/6 mice were divided into:control group(NC),DNase Ⅰ control group(DNase Ⅰ)diabetic nephropathy group(DKD),and DNase Ⅰ treated group(DKD+DNase Ⅰ).The pathological changes of mouse kidney were observed by PAS,MAS-SON,and HE staining.The expression and distribu-tion of the relevant proteins of NETs in renal tissue of the mice in each group were observed by immunohisto-chemistry.The expression and distribution of coke-death-related proteins in the kidney tissues of mice in each group were observed by immunohistochemistry.The protein expression of NETs-related indexes,focal death-related indexes and NF-κB signaling pathway-re-lated indexes in kidney tissue of mice in each group were detected by immunoblotting.Results The ex-pression of indicators related to NETs was elevated in the DKD group,and their expression decreased after degradation of NETs by DNase Ⅰ(P＜0.01).Patho-logical staining results showed that the kidneys of DKD mice were structurally abnormal,and the structure was improved after degradation of NETs by DNase Ⅰ.The results of immunohistochemical staining and immunob-lotting showed that the expression of pyroptosis-related proteins in kidney tissues of mice in the DKD group was elevated compared with that in the control group(P＜0.01).NF-κB-related signaling pathway protein expression profile expression rose,and its expression decreased after degradation of NETs by DNase Ⅰ(P＜0.01)Conclusions NETs are generated in diabetic nephropathy and promote the onset of renal focal death and activation of the NF-κB signaling pathway,thereby exacerbating diabetes-induced kidney injury.

Objective To investigate the effect of erector spinae plane block on postoperative delirium and cognitive function in elderly patients with lung cancer undergoing thoracoscopic radical surgery.Methods A total of 90 elderly patients with lung cancer underwent thoracoscopic radical surgery were selected and randomly divided into the control group and the observation group,with 45 cases in each group.The patients in the control group were given general anesthesia,while the patients in the observation group were given erector spinae plane block before general anesthesia.The vital signs at different time points,opioid dosage,number of analgesic pump compressions,incision pain visual analogue scale(VAS)score,cognitive function and postoperative delirium of patients between the two groups were compared.Results At the end of anesthesia,the mean arterial pressure(MAP)and heart rate of patients in the observation group were significantly lower than those in the control group(P<0.05).The dosage of remifentanil during operation,sufentanil during perioperative period and number of analgesia pumps compressions of patients in the observation group were significantly less than those in the control group(P<0.05).The incision pain VAS scores 6 hours,12 hours,24 hours and 48 hours after surgery of patients in the observation group were significantly lower than those in the control group(P<0.05).The scores of cognitive function 6 hours and 24 hours after surgery of patients in the observation group were significantly higher than those in the control group(P<0.05);and the incidence of delirium 6 hours and 24 hours after surgery in the control group was significantly higher than those in the observation group(P<0.05).Conclusion Erector spinae plane block can significantly relieve the perioperative pain of elderly patients with lung cancer undergoing thoracoscopic radical surgery,reduce the dosage of opioids and the incidence of postoperative delirium,improve the postoperative cognitive function of patients,which provides a new idea for reducing the incidence of postoperative mental diseases.

Objective To investigate the effect of subanesthetic dose of esketamine for postoperative analgesia on early recovery in elderly patients undergoing laparoscopic radical resection of rectal cancer.Methods Elderly patients undergoing laparoscopic radical resection of rectal cancer were included,and they were divided into the AS group(61 cases received esketamine for intravenous self-controlled analgesia)and the SF group(60 cases received sufentanil for intravenous self-controlled analgesia)by random number table method.The operation time,intraoperative infusion volume,urine output,intraoperative blood loss,postoperative rescue analgesia,tramadol dosage and the number of patient controlled intravenous analgesia(PCIA)compressions within 48 hours after surgery,postoperative visual analogue scale(VAS)score,Ramsay sedation score,first ambulation time after surgery,first gas passage time after surgery,and first feeding time after surgery were compared between the two groups.The occurrence of adverse reactions in the two groups was recorded.The levels of interleukin-6(IL-6)and C-reactive protein(CRP)immediately after surgery,24 hours and 72 hours after surgery in the two groups were detected by ELISA.The scores of anxiety and depression 3 days,1 week and 1 month after surgery were compared between the two groups.Results There was no significant difference in the operation time,intraoperative infusion volume,urine output,intraoperative blood loss,postoperative rescue analgesia,tramadol dosage or PCIA compressions within 48 hours after surgery between the two groups(P＞0.05).The levels of IL-6 and CRP gradually increased immediately after surgery and 24 hours and 72 hours after surgery in the two groups(P＜0.05),and the levels of IL-6 and CRP 24 hours and 72 hours after surgery in the AS group were significantly lower than those in the SF group(P＜0.05).The first ambulation time after surgery,first gas passage time after surgery,and first feeding time after surgery in the AS group were earlier than those in the SF group(P＜0.05).The incidences of nausea,vomiting and dizziness in the AS group were significantly lower than those in the SF group(P＜0.05).The levels of IL-6 and CRP 24 hours and 72 hours after surgery in the AS group were significantly lower than those in the SF group(P＜0.05).The scores of anxiety and depression 3 days and 1 week after surgery in the AS group were significantly lower than those in the SF group(P＜0.05).Conclusion Subanesthetic dose of esketamine for postoperative analgesia can alleviate short-term postoperative anxiety and depression in elderly patients undergoing laparoscopic radical resection of rectal cancer,relieve postoperative pain and inflammatory responses and have a low incidence of adverse reactions,which contribute to early recovery of patients.

The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Objective:To explore and analyze the clinical features and prognostic factors of secondary intestinal diffuse large B-cell lymphoma(SI-DLBCL),in order to provide reference for the basic research and clinical diagnosis and treatment of secondary lymphoma of rare sites in the field of hematology.Methods:The clinical data of 138 patients with SI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were collected and sorted,the clinical and pathological features,diagnosis,treatment and prognosis were analyzed.Cox regression risk model was used to conduct univariate and multivariate analysis on the prognostic risk factors.Results:Among the 138 patients with SI-DLBCL included in this study,85(61.59％)were male,53(38.41％)were female,the median age of onset was 59.5(16-84)years,the clinical manifestations lacked specificity,the first-line treatment regimen was mainly chemotherapy(67.39％),94 cases(68.12％)received chemotherapy alone,40 cases(28.98％)were treated with chemotherapy combined with surgery,and 4 cases(2.90％)were treated with surgery alone.The median follow-up time was 72(1-148)months.Among the 138 patients with SI-DLBCL,79(57.25％)survived,34(24.64％)died,25 cases(18.12％)lost to follow-up,the PFS rates of 1-year,3-year and 5-year were 57.97％,49.28％and 32.61％,and the OS rates of 1-year,3-year and 5-year were 60.14％,54.35％and 34.06％,respectively.The results of univariate Cox regression analysis showed that age,Lugano stage and IPI score were the influencing factors of OS in SI-DLBCL patients,and age,Lugano stage and IPI score were the influencing factors of PFS in SI-DLBCL patients.The results of multivariate Cox analysis showed that Lugano stage was an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.Conclusion:Patients with SI-DLBCL are more common in middle-aged and elderly men,and the early clinical manifestations lack specificity,and the first-line treatment regimen is mainly R-CHOP chemotherapy,and Lugano stage is an independent prognostic factor affecting OS and PFS in SI-DLBCL patients.