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.

This article aims to study the processing methods by exploring the main chemical constituents of Aconiti Lateralis Radix Praeparata and the toxicity-attenuating mechanisms. The relevant articles were retrieved from multiple databases with the time interval of 1960-2024, and the chemical constituents of Aconiti Lateralis Radix Praeparata and the toxicity-attenuating mechanisms of its processing methods were summarized. The review revealed that the chemical constituents of Aconiti Lateralis Radix Praeparata included 32 diester-type alkaloids, 36 monoester-type alkaloids, 43 alkanolamine-type alkaloids, and 8 lipid-type alkaloids. At the same time, other chemical constituents such as water-soluble alkaloids were also studied, and their pharmacological activities were summarized. The toxicity-attenuating mechanisms of the processing methods included constituent loss, hydrolysis, ester exchange, and ion-pair action. The processing methods of Aconiti Lateralis Radix Praeparata have developed from being traditional to modern, with simplified operation and increased retention amounts of active constituents, which have improved the efficacy of processed Aconiti Lateralis Radix Praeparata products and have facilitated the industrial production. However, the existing processing methods of Aconiti Lateralis Radix Praeparata cannot completely solve the problem of possible reduction in efficacy during toxicity attenuation. More toxicity-attenuating mechanisms and lipid-type alkaloids of Aconiti Lateralis Radix Praeparata should be explored, which is expected to reduce its toxicity while retaining its efficacy.
Aconitum/toxicity* ; Drugs, Chinese Herbal/isolation & purification* ; Alkaloids/chemistry* ; Animals ; Humans

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective　To assess the diagnostic efficacy of the cell-free Mycobacterium tuberculosis DNA testing (CF-TB) in tuberculous pleurisy. Methods　A total of 71 patients diagnosed with tuberculous pleurisy and 35 patients with non-tuberculous pleurisy were selected from the Fifth People's Hospital of Wuxi between January to December 2022. The standard pleural puncture was conducted to collect pleural effusion, which was then utilized for Mycobacterium tuberculosis culture, GeneXpert Mycobacterium tuberculosis/rifampicin resistance (GeneXpert MTB/RIF), CF-TB, and adenosine deaminase (ADA) testing. Blood samples were subjected to tuberculosis infection T-cell spotting test (T-SPOT.TB) assay. The receiver operator characteristic curve (ROC) was applied to obtain the optimal cut-off value for pleural fluid CF-TB and to compare the diagnostic performance of CF-TB with other methods. Data analysis was conducted using SPSS 22.0 software, with statistical significance defined as P<0.05. Results　The ROC curve analysis determined that the optimal cycle threshold (Ct) value for diagnosing tuberculous pleurisy using CF-TB in pleural fluid was 38.489, with a sensitivity of 91.5% and specificity of 97.1%. In comparison, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of T-SPOT.TB and pleural fluid ADA in diagnosing tuberculous pleurisy were 86.0%, 71.4%, 86.0%, 71.4%, 81.1%, and 55.0%, 91.4%, 92.9%, 50.8%, 67.0%, respectively, all of which were lower than the diagnostic efficiency of CF-TB. Furthermore, the specificity of pleural fluid CF-TB in diagnosing tuberculous pleurisy (97.1%) was not significantly different from GeneXpert MTB/RIF (100%) and Mycobacterium tuberculosis culture (100%), but its sensitivity (91.5%) was significantly higher than both GeneXpert MTB/RIF (19.7%) and Mycobacterium tuberculosis culture (28.2%), with a statistically significant difference (P<0.001). Conclusions　Compared to the conventional gold standard for diagnosing tuberculous pleurisy, CF-TB exhibits a higher sensitivity and its specificity is superior to that of tuberculosis immunological test. Consequently, CF-TB can serve as a valuable complement to other traditional detection methods in aiding the diagnosis of tuberculous pleurisy.

Objective To explore the curative effect of indobufen combined with clopidogrel and its influences on platelet activity and coagulation function in patients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI).Methods According to different treatment methods,patients with AMI were divided into treatment group and control group.The control group was given clopidogrel(75 mg,qd)and aspirin(0.1 g,qd),while treatment group was given clopidogrel(75 mg,qd)and indobufen tablets(0.1 g,bid).All were treated for 1 month.The curative effect,platelet count(PLT),mean platelet volume(MPV),prothrombin time(PT),fibrinogen(FIB)and D-dimer(D-D)before and after treatment,and adverse events within 1 month after medication were compared between the two groups.Results There were 38 cases in treatment group and 43 cases in control group.After treatment,curative effect in treatment group and control group were 97.37％and 86.05％,PLT were(167.89±43.62)× 109·L-1 and(183.73±49.81)× 109·L-1,MPV were(11.86±2.31)and(10.97±2.16)fl,FIB levels were(2.53±0.61)and(2.78±0.72)g·L-1,D-D levels were(0.20±0.06)and(0.22±0.07)mg·L-1,PT were(12.82±2.35)and(12.26±2.28)s,the difference was not statistically significant(all P＞0.05).The incidence of adverse drug reactions in treatment group and control group were 2.63％and 11.63％,and the difference was statistically significant(P＜0.001).Conclusion Indobufen combined with clopidogrel has the comparable curative effect and good anti-platelet aggregation effect as aspirin,and indobufen has higher safety.So it is recommended as the medication regimen for AMI patients after PCI.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To observe the clinical effect of arthroscopic repair with metal suture anchor on type Ⅱ superior labral anterior to posterior(SLAP)lesion of the youth.Methods The clinical data of 32 young patients with type Ⅱ SLAP lesion who underwent arthroscopic repair with metal suture anchor were retrospectively analyzed.The postoperative complications of patients were counted.The visual analogue scale(VAS)score was used to evaluate the pain of patients.Rowe shoulder scoring system,Constant-Murley scoring system and American Shoulder and Elbow Surgeons(ASES)scoring system were used to evaluate the shoulder joint function.Results All the 32 patients successfully completed the operation,and they were followed up for 12 to 27 months,with the mean follow-up time of 15 months.After operation,the symptoms of shoulder pain and limited movement of 32 patients were significantly relieved,without complications such as shoulder joint infection,shoulder joint instability,or neurovascular injury.The postoperative VAS score,Rowe score,Constant-Murley score and ASES score of all patients were better than those before operation(P<0.05).Conclusion Arthroscopic repair with metal suture anchor on type Ⅱ SLAP lesion of the youth can achieve satisfactory clinical outcomes.