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.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Objective:To evaluate the early outcomes of total hip arthroplasty (THA) and discuss the revisions post THA in the treatment for Kashin-Beck disease (KBD) with severe hip problems.Methods:This retrospective cohort study enrolled 50 patients (64 hips) with a mean age of 52.4±8.7 years, including 25 male patients and 25 female patients (36 left hips and 28 right hips), who were diagnosed as KBD with hip problems and received THA at Arthritis Clinical and Research Centre, Peking University People's Hospital from October 2019 to January 2024. The leg length discrepancy (LLD), femoral offset (FO), abduction angle and anteversion angle were calculated preoperatively and one week post-operation. The postoperative radiological indexes and the functional outcomes in the last follow-up were compared with the preoperative assessment.Results:The surgical duration was 105(80, 120) min and the bleeding amount was 300(200, 400) ml. All the cases were followed up for an average of 37 months (ranging from 21 to 44 months). Significant differences were found on postoperative radiological images, with LLD improving to 0.50±0.78 cm from a preoperative value of -1.36±0.79 cm, and FO increasing to 3.28±1.01 cm from 2.72±0.83 cm ( P<0.05). The mean postoperative abduction angle and anteversion angle were 42.5°±7.7° and 15.1°±5.9°, respectively. A total of 71.8% and 95.3% hips fell within the Lewinnek safe zones of abduction angle and anteversion angle, respectively. In terms of functional outcomes, the average range of motion improved significantly to 185°(173°, 210°) from a preoperative value of 99°(76°, 123°), and the Harris Hip Score increased from 35(26, 43) preoperatively to 70(63, 80) postoperatively ( P<0.05). During the follow-up, there were complications for two cases of femoral stem loosening, one case of periprosthetic femoral fracture, one case of hip dislocation, and one case of acetabular component loosening with hip subluxation. Additionally, seven patients exhibited Trendelenburg gait. A total of five hips required revision surgery due to severe complications, including two cases of femoral stem loosening, one case of periprosthetic femoral fracture, one case of hip dislocation, and one case of acetabular component loosening with subluxation. Conclusions:Patients with KBD demonstrated significant early improvements in both radiological and functional outcomes following THA.

Objective:To evaluate the early outcomes of total hip arthroplasty (THA) and discuss the revisions post THA in the treatment for Kashin-Beck disease (KBD) with severe hip problems.Methods:This retrospective cohort study enrolled 50 patients (64 hips) with a mean age of 52.4±8.7 years, including 25 male patients and 25 female patients (36 left hips and 28 right hips), who were diagnosed as KBD with hip problems and received THA at Arthritis Clinical and Research Centre, Peking University People's Hospital from October 2019 to January 2024. The leg length discrepancy (LLD), femoral offset (FO), abduction angle and anteversion angle were calculated preoperatively and one week post-operation. The postoperative radiological indexes and the functional outcomes in the last follow-up were compared with the preoperative assessment.Results:The surgical duration was 105(80, 120) min and the bleeding amount was 300(200, 400) ml. All the cases were followed up for an average of 37 months (ranging from 21 to 44 months). Significant differences were found on postoperative radiological images, with LLD improving to 0.50±0.78 cm from a preoperative value of -1.36±0.79 cm, and FO increasing to 3.28±1.01 cm from 2.72±0.83 cm ( P<0.05). The mean postoperative abduction angle and anteversion angle were 42.5°±7.7° and 15.1°±5.9°, respectively. A total of 71.8% and 95.3% hips fell within the Lewinnek safe zones of abduction angle and anteversion angle, respectively. In terms of functional outcomes, the average range of motion improved significantly to 185°(173°, 210°) from a preoperative value of 99°(76°, 123°), and the Harris Hip Score increased from 35(26, 43) preoperatively to 70(63, 80) postoperatively ( P<0.05). During the follow-up, there were complications for two cases of femoral stem loosening, one case of periprosthetic femoral fracture, one case of hip dislocation, and one case of acetabular component loosening with hip subluxation. Additionally, seven patients exhibited Trendelenburg gait. A total of five hips required revision surgery due to severe complications, including two cases of femoral stem loosening, one case of periprosthetic femoral fracture, one case of hip dislocation, and one case of acetabular component loosening with subluxation. Conclusions:Patients with KBD demonstrated significant early improvements in both radiological and functional outcomes following THA.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Pulmonary alveolar proteinosis(PAP)is a rare progressive respiratory dysfunction disease of the lung characterized by insidious onset and non-specific clinical manifestations,often leading to misdiagnosed and mistreated.Herein,we reported a case of PAP patient admitted to Jiading District Central Hospital with an atypical appearance of alveolar lavage fluid and whose condition improved significantly after treatment with subcutaneous injection of recombinant human granulocyte-macrophage colony stimulating factor(GM-CSF).Additionally,we have reviewed and summarized the relevant literature to enhance the understanding of the diagnosis and treatment of this disease.

Objective To investigate the role of the GPR120 gene in the progression of sepsis,explore the molecular mechanisms through which GPR120 gene regulates NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)inflammasome activation and macrophage polarization.Methods The blood and pleural fluid samples were collected from the sepsis patients and the control group.The expression of inflammatory factors and the associated proteins were detected by flow cytometry and ELISA.C57BL/6 mice and monocyte-macrophage cell line(Raw264.7)were treated with lipopolysaccharide(LPS)to construct the sepsis models.After the intervention of GPR120 agonist TUG891,the expression of GPR120 gene,NLRP3 inflammasome protein and macrophage polarization protein were detected between the control group and the sepsis group.Results The expression of inflammatory factors,such as IL-1β in the serum of septic patients,significantly increased compared with the control(P<0.001).And the expression of inflammasome proteins such as NLRP3,Caspase-1 and IL-1β in the pleural fluid also increased(all P<0.05).In vivo,LPS could induce severe inflammation in lung tissue,the GPR120 gene expression decreased in lung tissue,and inflammatory factors were up-regulated in mouse serum(P<0.01).The inflammasome-associated protein and M1 type polarization of macrophages were enhanced,the TUG891 could reduce the inflammatory response,inhibit the NLRP3 inflammasome activating,and promote the M2 polarization of macrophages(P<0.01).In vitro,LPS could inhibit the intracellular GPR120 expression.The inflammatory factors secreted more in LPS-induced sepsis cells.TUG891 could promote the up-regulation of GPR120 protein and alleviate the secretion of inflammatory factors(P<0.05).Conclusion In sepsis,GPR120 gene activation could inhibit the NLRP3 inflammasome activation,promote macrophage polarization,and reduce the inflammatory damage,thereby delay the rapid progression of sepsis.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

AIM To investigate the impact of varying dosages of Supplemented Wendan Decoction on the PI3K/Akt/FOXO1 glycolipid metabolic pathway in 3T3-L1 adipocytes.METHODS The CCK-8 assay was used to determine the concentration of Supplemented Wendan Decoction-medicated serum.The mature adipocytes differentiated from 3T3-L1 preadipocytes after induction were further divided into the blank control group,the model group,the rosiglitazone group(10 mg/L),and the Supplemented Wendan Decoction groups(5％,10％,and 20％),followed by the sample collections after 48 hours of treatment.Oil red O staining quantified lipid accumulation in 3T3-L1 adipocytes;extracellular glucose levels were measured using glucose oxidase(GOD)assay;RT-qPCR analyzed mRNA expressions of IRS-1,PI3K,Akt,GLUT4,IL-6,TNF-α and IL-1β;Western blot assessed protein expressions of INSR,IRS-1,PI3K-p85,Akt,FOXO1 and GLUT4.RESULTS No significant changes in cell viability(P＞0.05)were observed in 3T3-L1 preadipocytes exposed to serum containing supplemented Wendan Decoction at different concentrations for 24,48,or 72 hours.The 3T3-L1 preadipocytes held the capacity to differentiate into mature adipocytes within a 14-day induction period.Compared to the model group,all supplemented Wendan Decoction groups exhibited reduced lipid accumulation in adipocytes and downregulated mRNA expression of IRS-1,IL-6,TNF-α and IL-1β(P＜0.01);the low-dose group demonstrated increased mRNA expressions of PI3K and GLUT4(P＜0.05,P＜0.01),alongside elevated protein expressions of INSR,IRS-1,PI3K-p85,Akt and GLUT4(P＜0.05,P＜0.01);the medium-dose group showed enhanced GLUT4 mRNA expression,and upregulated protein expressions of INSR and FOXO1(P＜0.01).After 24 hours intervention,the high-dose Supplemented Wendan Decoction group exhibited increased glucose consumption in adipocytes(P＜0.01),and elevated protein expression of INSR,Akt and FOXO1(P＜0.05,P＜0.01).CONCLUSION Supplemented Wendan Decoction reduces lipid accumulation in adipocytes,regulates glucose and lipid metabolism,and promotes metabolic homeostasis through PI3K/Akt/FOXO1 signaling pathway.