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 analyze the imaging features of primary leiomyosarcoma of the inferior vena cava (PLV).Methods:This study was a case series analysis. The clinical and imaging data of 17 patients with PLV confirmed by pathology who underwent CT, MRI and/or PET-CT examinations in the Second Affiliated Hospital of Zhejiang University School of Medicine from June 2012 to September 2022 were retrospectively collected. The CT or MRI findings, including the number, location, size, shape, margin, density (signal), enhancement characteristics, surrounding invasion, and metastasis of the lesion were analyzed.Results:Among the 17 cases there were 7 males and 10 females, aged 32 to 78 years. All patients had single tumors, the maximum diameter of the mass was 3.8 to 19.0 cm, and in 12 cases it was consistent with the inferior venacava.There were 11 cases of "petal-like" necrosis cystic lesion, and 6 cases of "fissure" necrosis cystic lesion. Collateral circulation was found around the mass in 15 cases. There were 3 cases of intraluminal type, 2 cases of extraluminal type, and 12 cases of junctional type. The tumors of intraluminal type presented as "worm-like" appearance, while the extraluminal and junctional type tumors presented as lobulated shape, with local "umbilical depression sign". The margins were clear in 3 cases and unclear in 14 cases. Vascular invasion by the mass was observed in 7 cases. On CT plain scan, the solid component of PLV presented as isodense or slightly hypodense. On MRI T1-weighted images, the solid component presented as isodense or slightly hypodense, and on fat-suppressed T2-weighted images, it presented as isodense or slightly hyperdense. On MRI diffusion-weighted imaging, 12 cases showed high signal intensity, and the corresponding apparent diffusion coefficient map showed low signal intensity. On CT enhanced scan, 8 cases showed mild to moderate enhancement of the solid part of PLV in the arterial phase and 9 cases showed obvious enhancement. In the venous phase and delayed phase, 10 cases showed continuous enhancement and 7 cases showed progressive enhancement. On MRI enhanced scan, 8 cases showed moderate enhancement and 6 cases showed obvious enhancement of the solid part of PLV in the arterial phase. In the venous phase and delayed phase, continuous progressive enhancement was observed; no enhancement was seen in the necrotic and cystic areas.Conclusion:The imaging characteristics of PLV show that the maximum diameter of the masses are consistent with the direction of inferior vena cava, most masses exhibit a "petal-like" necrotic cyst morphology with collateral circulation, and a localized "umbilical concave sign", and some cases possess hemophilic tube features.

Objective:To analyze the imaging features of primary leiomyosarcoma of the inferior vena cava (PLV).Methods:This study was a case series analysis. The clinical and imaging data of 17 patients with PLV confirmed by pathology who underwent CT, MRI and/or PET-CT examinations in the Second Affiliated Hospital of Zhejiang University School of Medicine from June 2012 to September 2022 were retrospectively collected. The CT or MRI findings, including the number, location, size, shape, margin, density (signal), enhancement characteristics, surrounding invasion, and metastasis of the lesion were analyzed.Results:Among the 17 cases there were 7 males and 10 females, aged 32 to 78 years. All patients had single tumors, the maximum diameter of the mass was 3.8 to 19.0 cm, and in 12 cases it was consistent with the inferior venacava.There were 11 cases of "petal-like" necrosis cystic lesion, and 6 cases of "fissure" necrosis cystic lesion. Collateral circulation was found around the mass in 15 cases. There were 3 cases of intraluminal type, 2 cases of extraluminal type, and 12 cases of junctional type. The tumors of intraluminal type presented as "worm-like" appearance, while the extraluminal and junctional type tumors presented as lobulated shape, with local "umbilical depression sign". The margins were clear in 3 cases and unclear in 14 cases. Vascular invasion by the mass was observed in 7 cases. On CT plain scan, the solid component of PLV presented as isodense or slightly hypodense. On MRI T1-weighted images, the solid component presented as isodense or slightly hypodense, and on fat-suppressed T2-weighted images, it presented as isodense or slightly hyperdense. On MRI diffusion-weighted imaging, 12 cases showed high signal intensity, and the corresponding apparent diffusion coefficient map showed low signal intensity. On CT enhanced scan, 8 cases showed mild to moderate enhancement of the solid part of PLV in the arterial phase and 9 cases showed obvious enhancement. In the venous phase and delayed phase, 10 cases showed continuous enhancement and 7 cases showed progressive enhancement. On MRI enhanced scan, 8 cases showed moderate enhancement and 6 cases showed obvious enhancement of the solid part of PLV in the arterial phase. In the venous phase and delayed phase, continuous progressive enhancement was observed; no enhancement was seen in the necrotic and cystic areas.Conclusion:The imaging characteristics of PLV show that the maximum diameter of the masses are consistent with the direction of inferior vena cava, most masses exhibit a "petal-like" necrotic cyst morphology with collateral circulation, and a localized "umbilical concave sign", and some cases possess hemophilic tube features.

Objective To screen and establish a method for determining the biological activity of anfibatide.Meth-ods Three methods of light transmittance aggregometry(LTA),whole blood electrical impedance aggregometry,and continuous platelet count method were compared and studied.And the constant platelet counting method was chosen and verified to detect the biological activity of anfibatide.Results The RSD values of anfibatide biological activity detected by LTA,whole blood electri-cal impedance aggregometry,and continuous platelet count method were 10.3%,14.0%,and 3.6%,respectively.RSD of repeat-ability of 6 parallel test articles was 11.0%.The RSD of intermediate precision of 12 test articles for different personnel was 9.8%,and the inhibition rate of anfibatide was linear in the range of 0.3-0.5 U.The correlation coefficient was more than 0.990.The ac-tivity of three batches of anfibatide was determined,and the inhibition rate was 49.9%～53.6%.Conclusion The continuous platelet count method for determining anfibatide activity was established and verified,which can be used for quality control for an-fibatide activity since the precision and detection limit of the method met the requirement for activity assay of biological products.

Objective:To evaluate clinical efficacy of adjuvant radiotherapy (RT) for central neurocytoma (CN) after surgical resection.Methods:Clinical data of 136 CN patients admitted to Beijing Tiantan Hospital and Xuanwu Hospital from January 2001 to December 2020 were retrospectively analyzed. Preliminary interventions consisted of craniotomy (gross total resection, subtotal resection and partial resection, the latter two belonging to incomplete resection) and postoperative radiotherapy. Three-dimensional conformal or intensity-modulated radiotherapy was adopted, with a median radiotherapy dose of 54 Gy. Post-recurrence treatment included salvage surgery and radiotherapy. The overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. Univariate analysis was performed by log-rank test to evaluate the effect of each prognostic factor on OS and PFS. The effects of multiple prognostic factors on PFS and OS were assessed by Cox regression model.Results:The median age was 28 years (range: 6-66 years). The median follow-up was 94.5 months (12-237 months). Among all patients, 79 cases underwent total resection, and 68 of them received adjuvant radiotherapy. Thirty-eight patients underwent subtotal resection, and 37 of them were treated with adjuvant radiotherapy. Sixteen patients received partial resection and adjuvant radiotherapy. Three cases received biopsy and postoperative radiotherapy. Among all patients, 3 cases died, including 2 from tumor recurrence and 1 from postoperative complication. Eight patients had recurrences during follow-up. Among them, 7 patients had recurrences at the primary site,1 had tumor dissemination to the spinal cord. The 5- and 10-year OS rates were 98.5% and 96.8%, and the 5- and 10-year PFS rates were 95.3% and 91.6% for the in the entire cohort. In the gross total resection without radiotherapy group, the 5- and 10-year PFS rates were 90.9% and 90.9%, and 96.6% and 96.6% in the gross total resection + radiotherapy group ( P=0.338). The 5- and 10-year OS rates were 100% and 100% in the gross total resection without radiotherapy group, and 98.5% and 98.5% in the gross total resection + radiotherapy group ( P=0.693). The 10-year PFS rates between the gross total resection±radiotherapy group and the incomplete resection+radiotherapy group was 95.8% vs. 90.3% ( P=0.368), and the 10-year OS rate was 98.6% vs. 94.7% ( P=0.436). Multivariate analysis showed that tumor site, degree of surgical resection, adjuvant radiotherapy and age exerted no significant effects on PFS and OS. A total of 81 patients had late neurotoxicities, including 69 cases at grade 1, 9 cases at grade 2, and 3 cases at grade 3. And 64.2% (52/81 cases) of patients suffered from short-term memory impairment. Conclusions:Gross total resection alone yields high efficacy for CN. Postoperative radiotherapy is not required. Incomplete resection combined with postoperative adjuvant radiotherapy can achieve equivalent clinical efficacy to gross total resection.

Objective: To investigate the molecular mechanism and identify potential drugs for subthreshold depression (SD), and elucidate the detalied mechanism of Danzhi Xiaoyao powder (DZXY) in SD. Methods: Using RNA-sequencing, we identified differentially expressed genes (DEGs) in leukocytes of SD compared to healthy controls, deciphered their functions and pathways, and identified the hub genes of SD. We also assessed changes in leukocyte transcription factor activity in patients with SD using the TELiS platform. The Connectivity Map database was retrieved to screen candidate drugs for SD. Based on network pharmacology, we elucidated the “multi-component, multi-target, and multi-pathway” mechanism of DZXY in the treatment of SD. Results: We identified 1080 DEGs (padj <0.05 and |log2 (fold change)| ≥ 1 & protein coding) in the leukocytes of patients with SD. These DEGs, including hub genes, were primarily involved in immune and inflammatory response-related processes. Transcription factor activity analysis revealed similarities between the leukocyte transcriptome profile in SD and the conserved transcriptional response to adversities in immune cells. Connectivity Map analysis identified 28 potential drugs for SD treatment, particularly SB-202190 and TWS-119. Constructing the “Direct Compounds-Direct Targets-Pathways” network for DZXY and SD revealed the curative mechanisms of DZXY in SD, primarily including inflammatory response, lipid metabolism, immune response, and other processes. Conclusion These results provide new insights into the characteristics and functional changes of leukocytes in SD, partially illustrate the pathogenesis of SD, and suggest potential drugs for SD. The curative mechanisms of DZXY in SD are also partially elucidated.

Objective To evaluate the effect of manual massage on complications after endoscopic foam sclerotherapy injection for the treatment of internal hemorrhoids.Methods Consecutive 113 patients with grade Ⅰinternal hemorrhoids were prospectively enrolled and completed endoscopic foam sclerotherapy.The patients were randomly divided into a massage group(n=65)and a control group(n=68).Massage group performed manual perianal massage,Visual analogue scale(VAS)was used to evaluate perianal pain.The postoperative bleeding,short-term and long-term efficacy were also compared.Results The median VAS of 24 h postoperation was 1.0(0.0,3.0)in massage group,which was significantly lower than 2.0(1.0,4.0)in control group,the difference was statistically significant(P=0.014).The no bleeding rate of one week postoperation was 84.6％in massage group,which was significantly higher than 64.7％in control group,the difference was statistically significant(P=0.009).After 12 weeks,6 months and 12 months of follow-up,there were no significant differences in cure rate and remission rate between the two groups(P＞0.05).Conclusion Manual massage after endoscopic sclerosing agent injection is beneficial to relieve postoperative pain of grade Ⅰ internal hemorrhoids and reduce bleeding.

Objective:To evaluate the safety and long-term effectiveness of endoscopic foam sclerotherapy (FS) combined with endoscopic rubber band ligation (ERBL)in the treatment of grade Ⅱ-Ⅲ internal hemorrhoids.Methods:Consecutive patients diagnosed as having grade Ⅱ-Ⅲ internal hemorrhoids in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January to December 2020 were prospectively enrolled in the study, and randomly divided into ERBL group and FS combined with ERBL group. The 24 h visual analogue scale (VAS) for pain and 1-week degree of bleeding were evaluated after the treatment. After follow-up of 6 months, the effectiveness of treatment was evaluated.Results:A total of 84 patients with age of 54.4±7.9 years were enrolled, 57.1% (48/84) males, and 73.8% (62/84)grade Ⅱ internal hemorrhoids. Forty-three patients were assigned to the ERBL group and 41 to the FS combined with ERBL group. There was no significant difference between the two groups in baseline data ( P>0.05). In the FS combined with ERBL group, the mean amount of polidocanol foam was 13.8±2.5 mL, the mean number of injection site was 4.7±1.2, and the median scores of VAS was 0 (0, 3), which was significantly lower than that of ERBL group [2 (0, 4), Z=-2.116, P=0.034]. The bleeding rate 1 week after treatment in the ERBL and FS combined with ERBL group were 20.9% (9/43) and 29.3% (12/41), respectively, and mild bleeding was the main symptom. There was no significant difference between the two groups in the bleeding degree ( U=807.0, P=0.378). After 6 months of follow-up, the total effective rates in the ERBL group and the FS combined with ERBL group were 81.4% (35/43) and 90.2% (37/41), respectively ( U=684.5, P=0.044). Conclusion:FS combined with ERBL can effectively relieve post-treatment perianal pain, and improve the long-term effectiveness.

Objective:To investigate the effect of water-fat separation (Dixon) and spectrally selective attenuated inversion recovery (SPAIR) on fat suppression in the neck.Methods:From June to December 2018, 35 patients, including 16 males and 19 females, aged 23-75 (46±13) years old underwent MRI examinations of cervical vertebrae in Sir Run Run Hospital Affiliated to Nanjing Medical University. The imaging data of Dixon and SPAIR fat suppression scanning were prospectively collected. The scanning sequences included Dixon VIBE-T 1WI, SPAIR VIBE-T 1WI, Dixon TSE-T 2WI and SPAIR TSE-T 2WI. According to the subjective evaluation, the quality of fat suppression was divided into 0-4 grades. The cases with clear depiction of the thyroid tissue on Dixon or SPAIR were counted. Fisher exact test and paired t test or rank sum test were used to compare the noise, SNR and CNR of mandible angle, glottis, thyroid and sternoclavicular joint. Results:There were 29 cases of grade 0, 4 cases of grade 1, 2 cases of grade 2 on Dixon VIBE-T 1WI, 4 cases of grade 3 and 31 cases of grade 4 on SPAIR VIBE-T 1WI group, and the difference was statistically significant ( P<0.05); 28 cases of grade 0, 5 cases of grade 1 and 2 cases of grade 2 on Dixon TSE-T 2WI, 33 cases of grade 3 and 4 on SPAIR TSE-T 2WI, and the difference was statistically significant ( P<0.05). There were 35 cases with clear depiction of the thyroid tissues on DIXON and 4 cases on SPAIR VIBE-T 1WI ( P<0.05); there were 35 cases on DIXON and 3 cases on SPAIR TSE-T 2WI ( P<0.05). At the level of mandible angle, for the SNR of sternocleidomastoid muscle, SNR and CNR of splenius capitis muscle on VIBE-T 1WI, Dixon images were better than those on SPAIR images, and the difference was statistically significant ( P<0.05); the noise, SNR of sternocleidomastoid and splenius capitis muscle on TSE-T 2WI images were more than those in SPAIR images, and the difference was statistically significant ( P<0.05). At the level of glottis, the SNR of sternocleidomastoid muscle and levator scapulae muscle in the sequence of VIBE-T 1WI and Dixon images were significantly higher than those on the images of SPAIR ( P<0.05); the noise and SNR of sternocleidomastoid muscle on Dixon TSE-T 2WI images were significantly higher than those on the images of SPAIR ( P<0.05). At the thyroid level, the noise of Dixon VIBE-T 1WI image was less than that of SPAIR image, the SNR of sternocleidomastoid muscle and levator scapulae muscle on Dixon images was greater than that of SPAIR image, and the difference was statistically significant ( P<0.05); For TSE-T 2WI sequence, the SNR of sternocleidomastoid muscle on Dixon image was greater than that on SPAIR image, and the difference was statistically significant ( P<0.05). At the level of sternoclavicular joint, there were no significant differences for noise, SNR and CNR between the two groups ( P>0.05). Conclusion:Dixon outperforms SPAIR in obtaining better image quality and suppression effect in terms of neck MRI scanning.

Objective: To explore the relationship between split-fat sign and entering and exiting nerve sign on MRI in nerve sheath tumors (NSTs) of extremities. Methods: The MRI data of 141 patients with benign soft tissue NSTs of extremities confirmed by operation and pathology from January 2014 to July 2018 in the Second Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The patients were divided into intramuscular and intermuscular groups according to the location of the tumors. The split-fat sign and entering and exiting nerve sign in the two groups were compared using χ² test. Results: There were 152 NSTs in 141 patients, including 41 intramuscular NSTs and 111 intermuscular NSTs. There were 48 split-fat sign and 14 entering and exiting nerve sign in intramuscular NSTs, while 9 split-fat sign and 190 entering and exiting nerve sign in intermuscular NSTs. Statistical analysis showed that there were statistically significant differences in split-fat sign (χ²=55.545, P<0.001) and entering and exiting nerve sign (χ²=26.969, P<0.001) between the two groups. Conclusion The split-fat sign mostly appeared in intramuscular NSTs, and the entering and exiting nerve sign mostly appeared in intermuscular NSTs.