Objective To explore the feasibility and clinical experience of the middle hepatic vein splitting-reconstruction technique in split liver transplantation from low-age donor livers. Methods A retrospective analysis was conducted on the cases of two low-age donor livers that underwent middle hepatic vein splitting-reconstruction, which were transplanted into four child recipients at the Liver Transplantation Center of the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to July 2023. The surgical and postoperative conditions were summarized and analyzed. Results Donor 1 was a 6-year-old and 4-month-old girl with a body weight of 21 kg, and the obtained donor liver weighed 496 g. After splitting, the left and right liver weights were 201 g and 280 g, and transplanted into a 9-month-old boy weighing 6.5 kg and a 9-month-old boy weighing 7.5 kg, respectively. The graft to recipient weight ratio (GRWR) was 3.09% and 3.73%, respectively. Donor 2 was a 5-year-old and 8-month-old boy with a body weight of 19 kg, and the donor liver weighed 673 g. After splitting, the left and right liver weights were 230 g and 400 g, and transplanted into a 13-month-old girl weighing 9.5 kg and a 15-month-old boy weighing 12 kg. The GRWR was 2.42% and 3.33%, respectively. Both donor livers were split ex vivo, with the middle hepatic vein being completely split in the middle and reconstructed using allogeneic iliac vein and iliac artery vascular patches. According to GRWR, none of the 4 transplant livers were reduced in volume. Among the 4 recipients, one died due to postoperative portal vein thrombosis and non-function of the transplant liver, while the other three cases recovered smoothly without early or late complications. Regular follow-up was conducted until July 31, 2023, and liver function recovered well. Conclusions Under the premise of detailed assessment of the donor liver and meticulous intraoperative operation, as well as matching with suitable child recipients, low-age donor livers may be selected for splitting. The complete splitting and reconstruction of the middle hepatic vein in the middle may effectively ensure the adequate venous return of the left and right liver and provide sufficient functional liver volume.

ObjectiveThe rapid advancement of bioanalytical technologies has heightened the demand for high-throughput, label-free, and real-time cellular analysis. Electrochemical impedance spectroscopy (EIS) operating in the GHz frequency range (GHz-EIS) has emerged as a promising tool for characterizing cell suspensions due to its ability to rapidly and non-invasively capture the dielectric properties of cells and their microenvironment. Although GHz-EIS enables rapid and label-free detection of cell suspensions, significant challenges remain in interpreting GHz impedance data for complex samples, limiting the broader application of this technique in cellular research. To address these challenges, this study presents a novel method that integrates GHz-EIS with deep learning algorithms, aiming to improve the precision of cell suspension concentration identification and quantification. This method provides a more efficient and accurate solution for the analysis of GHz impedance data. MethodsThe proposed method comprises two key components: dielectric property dataset construction and backpropagation (BP) neural network modeling. Yeast cell suspensions at varying concentrations were prepared and separately introduced into a coaxial sensor for impedance measurement. The dielectric properties of these suspensions were extracted using a GHz-EIS dielectric property extraction method applied to the measured impedance data. A dielectric properties dataset incorporating concentration labels was subsequently established and divided into training and testing subsets. A BP neural network model employing specific activation functions (ReLU and Leaky ReLU) was then designed. The model was trained and tested using the constructed dataset, and optimal model parameters were obtained through this process. This BP neural network enables automated extraction and analytical processing of dielectric properties, facilitating precise recognition of cell suspension concentrations through data-driven training. ResultsThrough comparative analysis with conventional centrifugal methods, the recognized concentration values of cell suspensions showed high consistency, with relative errors consistently below 5%. Notably, high-concentration samples exhibited even smaller deviations, further validating the precision and reliability of the proposed methodology. To benchmark the recognition performance against different algorithms, two typical approaches—support vector machines (SVM) and K-nearest neighbor (KNN)—were selected for comparison. The proposed method demonstrated superior performance in quantifying cell concentrations. Specifically, the BP neural network achieved a mean absolute percentage error (MAPE) of 2.06% and an R² value of 0.997 across the entire concentration range, demonstrating both high predictive accuracy and excellent model fit. ConclusionThis study demonstrates that the proposed method enables accurate and rapid determination of unknown sample concentrations. By combining GHz-EIS with BP neural network algorithms, efficient identification of cell concentrations is achieved, laying the foundation for the development of a convenient online cell analysis platform and showing significant application prospects. Compared to typical recognition approaches, the proposed method exhibits superior capabilities in recognizing cell suspension concentrations. Furthermore, this methodology not only accelerates research in cell biology and precision medicine but also paves the way for future EIS biosensors capable of intelligent, adaptive analysis in dynamic biological research.

Objective To investigate the effect of diosgenin on the proliferation and apoptosis of breast cancer cells and its potential molecular mechanism. Methods The breast cancer cell line MCF-7 was treated with low, medium, and high doses of diosgenin, and cell proliferation was detected through the MMT method. Flow cytometry was used to detect cell apoptosis. Nuclear-cytoplasmic-protein separation method was applied to detect the subcellular localization of death associated protein (DAXX). qRT-PCR and Western blot were used to detect the expressions of DAXX and c-Jun N-terminal kinase pathway (JNK)-related proteins. Results Diosgenin considerably inhibited the proliferation of MCF-7 cells and promoted cell apoptosis in a concentration-dependent manner. Diosgenin can promote the movement of DAXX from nucleus into the cytoplasm. Diosgenin upregulated the expression of cell surface death receptor (Fas), increased the phosphorylation levels of JNK and mitogen activated protein kinase (p38), and activated the JNK/p38 signaling pathway with concentration dependence. Conclusion Diosgenin inhibits the proliferation and promotes the apoptosis of the breast cancer cell line MCF-7, whose mechanism may be related to the regulation of DAXX subcellular localization and the activation of JNK/p38 signaling pathway.

Background/Aims: Reflux symptoms frequently present in patients diagnosed with functional dyspepsia (FD). This investigation sought to elucidate the contribution of gastroesophageal reflux in the overlap relationship. Methods: Consecutive patients presenting with reflux symptoms and/or FD symptoms were prospectively included. Comprehensive assessments, including symptoms evaluation, endoscopy, esophageal functional examinations (high-resolution manometry and reflux monitoring), and proton pump inhibitor (PPI) treatment efficacy evaluation, were conducted in these patients. Results: The study enrolled 315 patients, 43.2% of which had concurrent FD symptoms and overlapping reflux symptoms. Notably, a mere 28.7% of patients in the overlap symptoms group had objective gastroesophageal reflux disease evidences (the grade of esophagitis≥ B or the acid exposure time ≥ 4.2%). Functional heartburn was demonstrated to be the main cause of overlapping reflux symptoms(55.1%). Reflux parameters analysis revealed that the reflux burden in the overlap symptoms group paralleled that of the FD symptoms group, with both registering lower levels than the reflux symptoms group (P < 0.05). Furthermore, PPI response rates were notably diminished in the overlap symptoms group (P < 0.001), even for those with objective gastroesophageal reflux disease evidences. Conclusions The study illuminated that overlapping reflux symptoms in FD was common. Strikingly, these symptoms primarily diverged from reflux etiology and exhibited suboptimal responses to PPI intervention. These findings challenge prevailing paradigms and accentuate the imperative for nuanced therapeutic approaches tailored to the distinctive characteristics of overlapping reflux symptoms in the context of FD.

Background: Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort. Methods: This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed. Results: During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders. Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

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.

Metabolites produced as intermediaries or end-products of microbial metabolism provide crucial signals for health and diseases, such as metabolic dysfunction-associated steatotic liver disease (MASLD). These metabolites include products of the bacterial metabolism of dietary substrates, modification of host molecules (such as bile acids [BAs], trimethylamine-N-oxide, and short-chain fatty acids), or products directly derived from bacteria. Recent studies have provided new insights into the association between MASLD and the risk of developing chronic kidney disease (CKD). Furthermore, alterations in microbiota composition and metabolite profiles, notably altered BAs, have been described in studies investigating the association between MASLD and the risk of CKD. This narrative review discusses alterations of specific classes of metabolites, BAs, fructose, vitamin D, and microbiota composition that may be implicated in the link between MASLD and CKD.

Background: Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort. Methods: This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed. Results: During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders. Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

Background: Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort. Methods: This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed. Results: During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders. Conclusion High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.