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 create a prediction model for stroke risk among middle-aged and elderly populations, so as to provide a basis for early identification of high-risk population for stroke. Methods: From October to December 2023, residents aged ≥45 years in Chongchuan District, Nantong City, Jiangsu Province were selected using a multi-stage stratified random sampling method. The demographic information, life behavior, and chronic disease data were collected through a questionnaire survey. The standardized prevalence of stroke was calculated using data from the seventh National Population Census. The subjects were randomly divided into the training set and the internal validation set according to the ratio of 8∶2. The basic demographic information, life behavior, and chronic diseases of residents aged ≥45 years in Rugao City were collected from July to August 2023 as the external validation set. Predictive factors were selected using multivariable logistic regression model, and a nomogram for stroke among residents aged ≥45 years was established. The prediction effect was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and Hosmer-Lemeshow goodness of fit test. Results: A total of 6 290 residents aged ≥45 years were included, including 2 975 males (47.30%) and 3 315 females (52.70%). The average age was (61.90±10.20) years. The prevalence of stroke was 3.80%, and the standardized prevalence was 3.36%. The multivariable logistic regression showed that age, smoking, hypertension, and hyperlipidemia were predictors of stroke risk among residents aged ≥45 years, and the prediction model was ln[p/(1-p)]=-4.619+0.046×age+0.383×smoking+0.887×hypertension+0.678×hyperlipidemia. The AUC values of the training set, internal validation set, and external validation set were 0.748, 0.755, and 0.738, respectively. The consistency indexes were 0.748, 0.755, and 0.738, respectively. The Hosmer-Lemeshow goodness of fit test showed a good fitting effect (P>0.05). Conclusion The prediction model based on age, smoking, hypertension, and hyperlipidemia has good discrimination and calibration, and can be used to predict the risk of stroke among middle-aged and elderly populations aged ≥45 years.

Bronchiectasis(BE) is the third major chronic airway disease, and its incidence rate shows a continuously increasing trend. Bronchiectasis is a highly heterogeneous chronic airway disease. Due to structural alterations, airflow limitation, and mucus hypersecretion, clinical treatment faces many challenges. Particularly, problems including Pseudomonas aeruginosa-dominant drug-resistant bacterial colonization, recurrent infections, airway mucus hypersecretion, and impaired lung function are the most urgent, requiring long-term and personalized treatment and management integrating traditional Chinese and western medicine to prevent the recurrence and continuous progression of the disease. In recent years, both traditional Chinese medicine and western medicine have made certain progress in pathogenesis theories, clinical studies, and basic research regarding the therapeutic challenges of bronchiectasis. Therefore, this paper summarized relevant research from the past 10 years and explored future directions and potential advantages of integrated traditional Chinese and western medicine treatment, providing references for optimizing the clinical management strategies for bronchiectasis.
Bronchiectasis/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional/methods* ; Animals

OBJECTIVE: To evaluate the impact of sutureless approach to the dorsal venous complex (DVC) combined with robotic-assisted laparoscopic prostatectomy on sexual function of patients with prostatic cancer. METHODS: This study included 114 prostate cancer patients who underwent robot-assisted laparoscopic radical prostatectomy at our hospital from January 2021 to January 2024. The patients were randomly divided into a control group (n=57) and an observation group (n=57). The control group received conventional "figure-of-eight" suture ligation of the dorsal venous complex (DVC), while the observation group underwent direct DVC transection using monopolar electrocautery scissors after increasing pneumoperitoneum pressure.Surgical duration, intraoperative blood loss, positive surgical margin rates, and positive apical margin rates were recorded. The continence rates and rates of morning erections at 1, 3 and 6 months after the operation were compared between groups. Sexual function was assessed pre-operatively and at 6 months post-operation by using the IIEF-5 and PEDT. RESULTS: The operative time in the observation group was significantly longer than that in the control group (［115.71 ± 19.42］ min vs ［103.42 ± 12.78］ min， P<0.05). While no significant differences were observed in intraoperative blood loss, positive surgical margin rate, or positive apical margin rate between the two groups (P>0.05). At 3 and 6 months after the operation, the observation group exhibited higher urinary continence rates and morning erection recovery rates compared to the control group （P<0.05). Furthermore, at 6 months postoperatively, the observation group demonstrated significantly higher IIEF-5 scores and lower PEDT scores than those of control group(P<0.05). CONCLUSION The use of a sutureless DVC technique in robotic-assisted laparoscopic radical prostatectomy protects the post-operative sexual function in patients.
Humans ; Male ; Prostatectomy/methods* ; Laparoscopy/methods* ; Prostatic Neoplasms/surgery* ; Robotic Surgical Procedures/methods* ; Middle Aged ; Operative Time ; Aged

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Background With the rapid development of the food delivery industry, take-away deliverymen become an essential component of urban logistics. However, high labor intensity, unstable income, and extended working hours place them at considerable risk of occupational burnout. Available studies have paid insufficient attention to the mental health of this population, and effective predictive or preventive approaches remain limited. Objective To understand the status of occupational burnout among take-away deliverymen, identify influencing factors based on restricted cubic spline analysis, and develop a predictive model to provide a theoretical basis for improving their mental health. Methods A cross-sectional survey was conducted among full-time take-away deliverymen registered to the "Ele.me" and "Meituan" platforms in Hangzhou between September 1 and November 30, 2024, using both online and offline approaches. A questionnaire covered sociodemographic, household, and occupational information, and the Maslach Burnout Inventory–General Survey were used in this survey. Univariate analyses and logistic regression were used to identify factors associated with burnout and to construct a predictive model. Model performance was evaluated using receiver operating characteristic (ROC) curve and calibration curve. Furthermore, restricted cubic spline was used to further explore the relationship between age, working hours, and occupational burnout. Results Among the 1192 participants, 735 (61.66%) experienced occupational burnout. The logistic regression model indicated that older age (OR=1.021, P=0.010), educational attainment of college level or above compared to junior high school or below, (OR=2.837, P<0.001), and longer daily working hours (OR=1.081, P=0.001) were positively associated with occupational burnout. In contrast, work experience of 3−5 years (OR=0.666, P=0.016) and more than 5 years (OR=0.382, P<0.001) compared to those with <3 years, as well as providing three social insurances (OR=0.655, P=0.006) or five social insurances (OR=0.478, P<0.001) compared to those without any social insurances coverage, were negatively associated with occupational burnout. The predictive model based on these variables achieved an area under the curve (AUC) of 0.783 (95% CI: 0.756~0.809), and good agreement between calibration curves. The restricted cubic spline analysis revealed that the risk of occupational burnout was highest among delivery workers aged 33−46 years. Those with daily working hours between 3.5 and 8.1 h had a lower risk, while the risk significantly increased when working hours exceeded 8.1 h per day. Conclusion The prevalence of reporting occupational burnout among take-away deliverymen in Hangzhou is high. The developed predictive model provides valuable insights for the prevention and control of burnout in this population. Measures such as optimizing social security systems, rational work schedule allocation, and enhancing psychological support may help reduce occupational burnout among take-away deliverymen.

O-acetyl-L-homoserine (OAH) is a promising platform compound for the production of L-methionine and other valuable compounds, while its low yield and low conversion rate limit the industrial application. To solve these problems, we constructed a strain for high OAH production with the previously constructed L-homoserine producer Escherichia coli HS33 as the chassis by systematic metabolic engineering. Firstly, PEP accumulation, pyruvate utilization, and OAH synthesis pathway (overexpressing aspB, aspA, and thrA^C1034T) were enhanced to obtain an initial strain accumulating 13.37 g/L OAH. Subsequently, the co-factor synthesis genes were integrated to supply reducing power and energy, which increased the yield to 15.79 g/L. The OAH yield of the engineered strain OAH28 was further increased to 17.49 g/L by strengthening the acetic acid reuse pathway, improving the supply of acetyl-CoA, and regulating the expression of MetX from different sources. Finally, in a 5 L fermenter, OAH28 achieved an OAH titer of 47.12 g/L, with a glucose conversion rate of 32% and productivity of 0.59 g/(L·h). The results lay a foundation for increasing the OAH production by metabolic engineering and give insights into the industrial production of OAH.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Homoserine/biosynthesis* ; Fermentation