Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective To investigate the short- and long-term prognoses and the risk factors affecting “textbook outcome” (TO) after laparoscopic pancreaticoduodenectomy (LPD) for pancreatic ductal adenocarcinoma (PDAC). Methods The clinical and follow-up data of patients diagnosed with PDAC and treated with LPD from January 2019 to December 2022 were retrospectively analyzed. The prognosis was compared between TO and non-TO groups, and univariate and multivariate logistic regression analyses were used to identify independent prognostic factors for TO. Results A total of 284 patients were enrolled in this study, including 185 cases in the TO group and 99 cases in the non-TO group. The 1-, 3- and 5-year overall survival (OS) rates of the TO and non-TO groups with PDAC were 87.3% vs. 85.9%, 52.5% vs. 38.4%, and 18.0% vs. 4.5%, respectively (P=0.020); the recurrence-free survival (RFS) rates were 74.1% vs. 65.7%, 27.1% vs. 21.0%, and 10.0% vs. 0%, respectively (P=0.042). Multivariate logistic regression analysis showed that operation time >360 min (OR=0.561, 95%CI: 0.321-0.979, P=0.042), intraoperative blood loss >400 ml (OR=0.392, 95%CI: 0.175-0.879, P=0.023), hard or tough texture of pancreas (OR=2.240, 95%CI: 1.247-4.022, P=0.007), and main pancreatic duct diameter >3 mm (OR=1.931, 95%CI: 1.126-3.312, P=0.017) were independent prognostic factors for TO. Conclusion After the learning curve, more than 60% of patients with PDAC can achieve TO after LPD. The chances of achieving TO are significantly reduced when the operation time >360 min, the intraoperative blood loss >400 ml, the texture of pancreas was soft, and the diameter of the main pancreatic duct >3 mm.

ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.

ObjectiveTo investigate the effects of Pinelliae Rhizoma Praeparatum （PRP） on lung tissue， gut microbiota， and short-chain fatty acid （SCFA） metabolism in a model of mice with cold fluid retention in the lung and explore its mechanism of action in resolving dampness and phlegm based on the interconnection between the lung and large intestine. MethodsFifty female ICR mice were randomly divided into a normal group， model group， positive control group （Xiaoqinglong granules， 6.5 g·kg^-1）， and high-dose and low-dose PRP decoction groups （3.0， 1.5 g·kg^-1）， with 10 mice in each group. A model of mice with cold fluid retention in the lung was established using ovalbumin （OVA） sensitization combined with cold-water immersion. Drug interventions were conducted from day 18 to day 33 for 15 consecutive days. The airway resistance value of the mice was measured using a non-invasive pulmonary function analyzer. Phlegm-resolving effects were evaluated via a microplate reader. Eosinophil and neutrophil counts in bronchoalveolar lavage fluid （BALF） were analyzed using an automated hematology analyzer. Serum levels of total immunoglobulin E （IgE）， interferon-γ （IFN-γ）， interleukin-4 （IL-4）， and BALF levels of interleukin-6 （IL-6） and interleukin-8 （IL-8） were quantified by enzyme-linked immunosorbent assay （ELISA）. Lung histopathology was assessed using hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） was employed to detect mucin 5AC （MUC5AC） and aquaporin 5 （AQP5） protein expression in lung tissue. Gut microbiota composition was analyzed via agarose gel electrophoresis， and fecal SCFA levels were measured by gas chromatography-mass spectrometry （GC-MS）. ResultsCompared with the normal group， the model group exhibited significantly increased airway resistance value （RI） （P<0.05）， elevated eosinophil and neutrophil counts and IL-6 and IL-8 levels in BALF （P<0.05）， increased serum IgE and IL-4 levels （P<0.05）， with reduced IFN-γ levels （P<0.05）. It also showed thickened bronchial walls， widened alveolar septa， narrowed lumens， and mucus plugs in lung tissue， upregulated MUC5AC protein expression and downregulated AQP5 protein expression （P<0.05）， decreased relative abundance of beneficial gut microbiota （Firmicutes， Clostridia， Clostridiales， Lactobacillaceae， and Lactobacillus）， and increased abundance of harmful microbiota （Bacteroidetes， Bacteroidia， Bacteroidales， Muribaculaceae， and Muribaculum）. In addition， the model group presented reduced fecal SCFA levels （acetate， propionate， and butyrate） （P<0.05）. After the intervention of PRP decoction， compared to the model group， all drug administration groups showed decreased RI （P<0.05）， increased phenol red excretion， declined eosinophil and neutrophil counts and IL-6， IL-8， IgE， and IL-4 levels （P<0.05）， and improved IFN-γ levels （P<0.05） and lung pathology improved. The MUC5AC protein expression decreased （P<0.05）， and the AQP5 protein expression increased （P<0.05）. The disorder of gut microbiota was improved， and the diversity of gut microbiota was restored， with a significantly increased relative abundance ratio of beneficial microbiota （P<0.05） and a significantly reduced relative abundance ratio of harmful microbiota （P<0.05）. The SCFA levels （acetate， propionate， and butyrate） increased （P<0.05）. The efficacy indicators of serum inflammatory factors （IgE， IL-4， and IFN-γ）， phlegm-resolving effect， airway resistance， total pathological score， and the protein expression of MUC5AC and AQP5 were correlated with gut microbiota and SCFAs. ConclusionPRP decoction alleviates cold-phlegm syndrome by modulating the gut-lung axis， promoting beneficial gut microbiota， enhancing SCFA production， restoring the balance of gut microbiota， and suppressing respiratory inflammation. This study provides novel insights into the TCM theory of interconnection between the lung and large intestine.

ObjectiveTo investigate the effects of Pinelliae Rhizoma Praeparatum （PRP） on lung tissue， gut microbiota， and short-chain fatty acid （SCFA） metabolism in a model of mice with cold fluid retention in the lung and explore its mechanism of action in resolving dampness and phlegm based on the interconnection between the lung and large intestine. MethodsFifty female ICR mice were randomly divided into a normal group， model group， positive control group （Xiaoqinglong granules， 6.5 g·kg^-1）， and high-dose and low-dose PRP decoction groups （3.0， 1.5 g·kg^-1）， with 10 mice in each group. A model of mice with cold fluid retention in the lung was established using ovalbumin （OVA） sensitization combined with cold-water immersion. Drug interventions were conducted from day 18 to day 33 for 15 consecutive days. The airway resistance value of the mice was measured using a non-invasive pulmonary function analyzer. Phlegm-resolving effects were evaluated via a microplate reader. Eosinophil and neutrophil counts in bronchoalveolar lavage fluid （BALF） were analyzed using an automated hematology analyzer. Serum levels of total immunoglobulin E （IgE）， interferon-γ （IFN-γ）， interleukin-4 （IL-4）， and BALF levels of interleukin-6 （IL-6） and interleukin-8 （IL-8） were quantified by enzyme-linked immunosorbent assay （ELISA）. Lung histopathology was assessed using hematoxylin-eosin （HE） staining. Immunohistochemistry （IHC） was employed to detect mucin 5AC （MUC5AC） and aquaporin 5 （AQP5） protein expression in lung tissue. Gut microbiota composition was analyzed via agarose gel electrophoresis， and fecal SCFA levels were measured by gas chromatography-mass spectrometry （GC-MS）. ResultsCompared with the normal group， the model group exhibited significantly increased airway resistance value （RI） （P<0.05）， elevated eosinophil and neutrophil counts and IL-6 and IL-8 levels in BALF （P<0.05）， increased serum IgE and IL-4 levels （P<0.05）， with reduced IFN-γ levels （P<0.05）. It also showed thickened bronchial walls， widened alveolar septa， narrowed lumens， and mucus plugs in lung tissue， upregulated MUC5AC protein expression and downregulated AQP5 protein expression （P<0.05）， decreased relative abundance of beneficial gut microbiota （Firmicutes， Clostridia， Clostridiales， Lactobacillaceae， and Lactobacillus）， and increased abundance of harmful microbiota （Bacteroidetes， Bacteroidia， Bacteroidales， Muribaculaceae， and Muribaculum）. In addition， the model group presented reduced fecal SCFA levels （acetate， propionate， and butyrate） （P<0.05）. After the intervention of PRP decoction， compared to the model group， all drug administration groups showed decreased RI （P<0.05）， increased phenol red excretion， declined eosinophil and neutrophil counts and IL-6， IL-8， IgE， and IL-4 levels （P<0.05）， and improved IFN-γ levels （P<0.05） and lung pathology improved. The MUC5AC protein expression decreased （P<0.05）， and the AQP5 protein expression increased （P<0.05）. The disorder of gut microbiota was improved， and the diversity of gut microbiota was restored， with a significantly increased relative abundance ratio of beneficial microbiota （P<0.05） and a significantly reduced relative abundance ratio of harmful microbiota （P<0.05）. The SCFA levels （acetate， propionate， and butyrate） increased （P<0.05）. The efficacy indicators of serum inflammatory factors （IgE， IL-4， and IFN-γ）， phlegm-resolving effect， airway resistance， total pathological score， and the protein expression of MUC5AC and AQP5 were correlated with gut microbiota and SCFAs. ConclusionPRP decoction alleviates cold-phlegm syndrome by modulating the gut-lung axis， promoting beneficial gut microbiota， enhancing SCFA production， restoring the balance of gut microbiota， and suppressing respiratory inflammation. This study provides novel insights into the TCM theory of interconnection between the lung and large intestine.

OBJECTIVE: To explore clinical characteristics, lesion sites and correlation differences of different types of diabetic foot gangrene, and to provide evidence-based basis for clinical classification of diabetic foot gangrene. METHODS: A retrospective analysis was conducted on 266 patients with newly diagnosed diabetic foot gangrene who were admitted from January 2018 to December 2018, including 183 males and 83 females, aged from 35 to 92 years old with an average of (69.55±10.84) years old, and they were divided into wet gangrene group and dry gangrene group according to the different natures of gangrene. There were 139 patients in wet gangrene group, including 98 males and 41 females, aged from 35 to 90 years old with an average of (68.95±10.93) years old. There were 127 patients in dry gangrene group, including 85 males and 42 females, aged from 38 to 92 years old with an average of (70.21±10.75) years old. Body mass index (BMI), waist-to-hip ratio (WHR), body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, and Wagner grade between two groups were recorded to evaluate symptoms and signs. The white blood cell count (WBC), neutrophil percentage (NEUT%), and C-reactive protein (C-reactive protein), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) in peripheral blood between two groups were detected and compared to evaluate the infection status;the severity of diabetic peripheral neuropathy (DPN) was evaluated by using Toronto Clinical Scoring System (TCSS);the degree of pain in patients with diabetic foot gangrene was evaluated by numerical rating scale (NRS); ankle-brachial index (ABI) and popliteal artery blood flow velocity were used to evaluate the degree of arterial lesions. Spearman correlation analysis was used to analyze the correlations between gangrene TCSS, ABI and age, BMI, WHR, body temperature, calf skin temperature difference, WBC, NEUT%, CRP, ESR, PCT, IL-6, NRS, and Wagner classification indicators. RESULTS: The body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, Wagner grade, WBC, NEUT%, CRP, ESR, PCT, IL-6, TCSS score, ABI, and popliteal artery blood flow velocity in wet gangrene group were higher than those in dry gangrene group (P<0.01), and BMI, WHR, and NRS score in dry gangrene group were higher than those in wet gangrene group;the differences were all statistically significant (P<0.01). The results of Spearman correlation analysis showed TCSS score of gangrene patients was correlated with body temperature (r=0.214), calf skin temperature difference (r=0.364), WBC (r=0.240), NEUT% (r=0.291), CRP (r=0.347), ESR (r=0.167), PCT (r=0.241), IL-6 (r=0.316), and popliteal fossa arterial blood flow velocity (r=0.261) and Wagner grade (r=0.273) were positively correlated, and the differences were statistically significant (P<0.01). ABI was negatively correlated with age (r=-0.183), BMI (r=-0.252), WHR (r=-0.288), and NRS score (r=-0.354), and the differences were statistically significant (P<0.01). CONCLUSION Diabetic foot gangrene is an extremely difficult and critical disease. Wet gangrene has a significant synergic effect with infection and neuropathy, while dry gangrene is closely related to vascular occlusion. The main contradiction of gangrene could be revealed through blood vessels, nerves and infection, providing evidence-based basis for the selection of debridement timing, anti-infection strategies and revascularization, with the aim of reducing the risk of amputation.
Humans ; Male ; Female ; Aged ; Middle Aged ; Diabetic Foot/diagnosis* ; Aged, 80 and over ; Adult ; Retrospective Studies ; Gangrene/physiopathology* ; C-Reactive Protein

OBJECTIVE: To explore the current research status and hotspots in the field of biomechanics of diabetic foot by bibliometric analysis methods. METHODS: Literatures related to biomechanics of diabetic foot published in the Web of Scienc Core Collection (WoSCC) from 1981 to 2024 were searched. CiteSpace software and R language bibliometrics plugin were used to conduct a visual analysis of annual publication volume of the literature, including publication volume of each country and region, the publication situation of authors and institutions, the citation situation of individual literature, and the co-occurrence network of keywords. RESULTS: Totally 996 literatures were included, and the number of published papers increased steadily. The United States (261 papers) and China (89 papers) were the top two countries in terms of the number of published papers. The mediating centrality of the United States was 0.94, and that of China was 0.01. Scholars such as Cavanagh and institutions like the Cleveland Clinic were at the core of research in this field. High-frequency keywords include plantar pressure (plantar pressure), diabetic foot (diabetic foot), ulceration (ulcer), etc. The research focuses on plantar pressure, ulcer formation and prevention, etc. CONCLUSION Biomechanical research on diabetic foot mainly focuses on the pressure distribution on the sole of the foot, callus formation, mechanical analysis of soft tissues on the sole of the foot, and the study of plantar decompression caused by Achilles tendon elongation. The research trend has gradually shifted from focusing on joint range of motion to gait and the design of braces and assistive devices, and has begun to pay attention to muscle strength, gait imbalance and proprioception abnormalities.
Humans ; Diabetic Foot/physiopathology* ; Biomechanical Phenomena ; Bibliometrics

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective:To evaluate the feasibility, safety, and short-term efficacy of robot-assisted unilateral axillary approach for partial or total thyroidectomy without inflation. Methods:A retrospective analysis was performed on the clinical data of 98 patients who underwent gasless unilateral axillary approach robot-assisted resection of bilateral thyroid lesions at Sun Yat-sen University Cancer Center between October 2022 and October 2024. Perioperative indicators were recorded and compared among patients undergoing different surgical approaches（total thyroidectomy vs. bilateral partial thyroidectomy） and with different body mass index（BMI） values, including operative time, intraoperative blood loss, number of lymph nodes dissected, incidence of postoperative hoarseness, incidence of postoperative hypocalcemia, and other postoperative complications. Results:A total of 98 patients were included, of whom 78.57% were female, with a median age of 39 years（interquartile range[IQR]: 35-49） and a median BMI of 24.08 kg/m²（IQR: 21.43-25.98）. The median intraoperative blood loss was 32.14 mL（IQR: 20.00-50.00）, the median operative time was 130.0 minutes（IQR: 104.80-150.30）, and the median hospital stay was 2.01 days（IQR: 1.00-2.00）. The most common postoperative complication was transient hypocalcemia, with an incidence of 16.32%. There were no cases of permanent recurrent laryngeal nerve palsy or conversion to open surgery. Compared with the non-total thyroidectomy group, the total thyroidectomy group had a significantly longer operative time（135.10±33.28 min vs 120.30±30.53 min, P=0.033）. Subgroup analysis based on BMI showed no statistically significant differences in operative time, hospital stay, drainage volume, or incidence of hypocalcemia between patients with BMI≥25 kg/m² and those with BMI<25 kg/m². Conclusion:The gasless unilateral axillary approach for robot-assisted partial or total thyroidectomy demonstrates favorable safety, cosmetic outcomes, and feasibility. Appropriate selection of surgical techniques and meticulous protection of critical structures during the procedure can further reduce the risk of complications and optimize therapeutic outcomes.
Humans ; Thyroidectomy/methods* ; Retrospective Studies ; Female ; Robotic Surgical Procedures/methods* ; Male ; Adult ; Middle Aged ; Axilla/surgery* ; Operative Time ; Postoperative Complications ; Thyroid Neoplasms/surgery* ; Thyroid Gland/surgery* ; Lymph Node Excision

In recent years, robot-assisted thyroid surgery has gained widespread adoption in major hospitals worldwide, offering advantages such as a shorter learning curve and superior cosmetic outcomes while overcoming the limitations of endoscopic surgery. Currently, the main surgical approaches include the transaxillary, bilateral axillo-breast（BABA）, retroauricular, and transoral vestibular routes. However, the widespread adoption of robotic thyroidectomy still faces several challenges, including technical complexity, prolonged operative time, a higher complication rate during the learning curve, and high costs. Nevertheless, when performed by experienced surgeons on carefully selected patients, robotic thyroidectomy can achieve outcomes comparable to those of conventional open transcervical thyroidectomy. This article provides a systematic review of the development and latest advances in robotic thyroid surgery.
Humans ; Robotic Surgical Procedures/methods* ; Thyroidectomy/methods* ; Thyroid Gland/surgery*