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 clinical characteristics of vaccine-associated immune thrombocytopenia(VA-ITP)based on the US Vaccine Adverse Event Reporting System(VAERS), and to provide a reference for vaccine safety monitoring, vaccination prevention, and clinical diagnosis and treatment.Methods Data from VAERS on all reported cases of immune thrombocytopenia(ITP) after vaccination since the establishment of the database in 1990 to the data lock point of 7th November 2023 were analyzed retrospectively for information on such as sex, age, vaccine type, vaccine dose, and occurrence time of ITP.Results Among the 877 cases of VA-ITP, there were 868 cases of effective statistical vaccine types, involving 43 vaccine types. The top 10 vaccine types were COVID-19 vaccine(434 cases, 50%), MMR vaccine(82 cases, 9. 4%),HEPA vaccine(48 cases, 5. 5%), FLU3 vaccine(41 cases, 4. 7%), FLU4 vaccine(32 cases, 3. 7%), HPV4 vaccine(30 cases,3. 5%), DTAP vaccine(29 cases, 3. 3%), MMRV vaccine(32 cases, 3. 7%), VARZOS vaccine(17 cases, 2. 0%) and HPV9vaccine(13 cases, 1. 5%). Among the 877 reported cases, 843 cases with definite sex were counted, including 374 males and469 females, with a male-to-female ratio of 1∶1. 25. The 377 cases of patients were under 18 years of age, accounting for about 44. 7% of the total, and there was significant difference in the composition ratio of sexes among patients with VA-ITP at different ages(χ~2= 10. 029, P < 0. 05). The incidence of ITP within 8 days after vaccination, with a total of 336 cases, was39.9%, and there was no significant difference in the occurrence time composition ratio of ITP between different sexes(χ~2=3. 296, P > 0. 05). The 54. 9% of ITP occurred after the first dose of vaccine, and there was no significant difference in the composition ratio of different vaccination doses between male and female recipients(χ~2= 5. 323, P > 0. 05), but there was significant difference in the composition ratio of vaccination doses among different age groups(χ~2= 30. 591, P < 0. 01).Conclusion By analyzing the summary data from VAERS database, the adverse reaction of VA-ITP was fully recognized.After clinical vaccination, attention should be focused on the platelet status of minors and the elderly, as well as those who were vaccinated within 8 days, and the continuous vaccine safety monitoring should be carried out, which is helpful to reduce the missed diagnosis of vaccine adverse events(AE) and improve the efficiency of clinical diagnosis and treatment.

Purpose: Leptin interacts not only with leptin receptor (LEPR) but also engages with other receptors. While the pro-oncogenic effects of the adrenergic receptor β2 (ADRB2) are well-established, the role of leptin in activating ADRB2 in triple-negative breast cancer (TNBC) remains unclear. Materials and Methods: The pro-carcinogenic effects of LEPR were investigated using murine TNBC cell lines, 4T1 and EMT6, and a tumor-bearing mouse model. Expression levels of LEPR, NADPH oxidase 4 (NOX4), and ADRB2 in TNBC cells and tumor tissues were analyzed via western blot and quantitative real-time polymerase chain reaction. Changes in reactive oxygen species (ROS) levels were assessed using flow cytometry and MitoSox staining, while immunofluorescence double-staining confirmed the co-localization of LEPR and ADRB2. Results: LEPR activation promoted NOX4-derived ROS and mitochondrial ROS production, facilitating TNBC cell proliferation and migration, effects which were mitigated by the LEPR inhibitor Allo-aca. Co-expression of LEPR and ADRB2 was observed on cell membranes, and bioinformatics data revealed a positive correlation between the two receptors. Leptin activated both LEPR and ADRB2, enhancing intracellular ROS generation and promoting tumor progression, which was effectively countered by a specific ADRB2 inhibitor ICI118551. In vivo, leptin injection accelerated tumor growth and lung metastases without affecting appetite, while treatments with Allo-aca or ICI118551 mitigated these effects. Conclusion This study demonstrates that leptin stimulates the growth and metastasis of TNBC through the activation of both LEPR and ADRB2, resulting in increased ROS production. These findings highlight LEPR and ADRB2 as potential biomarkers and therapeutic targets in TNBC.

Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.

Objective:To analyze the utilization of pre-exposure prophylaxis (PrEP) service against HIV and related factors in young men who have sex with men (MSM) in Hangzhou.Methods:A cross-sectional study design was used in this questionnaire survey in young MSM recurited through local MSM social organization in Hangzhou from September 2022 to March 2023. The estimated sample size was 242. The information about the social-demographic characteristics, behavioral characteristics, utilization of the post exposure prophylaxis (PEP) service, awareness and utilization of PrEP service of the young MSM were collected. Logistic regression model was used to analyze the related factors of the PrEP utilization.Results:A total of 273 young MSM aged 16- 24 years were surveyed in the study. A total for 20.1% (55/273) of them had used PrEP service. Multivariate logistic regression analysis showed that the factors related to PrEP service utilization included age 16-20 years (a OR=3.03, 95% CI:1.12-8.20), education level of senior high school or below (a OR=2.83, 95% CI:1.09-7.35), full-time/part-time work (a OR=3.25, 95% CI: 1.26-8.38), homosexual activity in the past 6 months (a OR=6.71, 95% CI:1.84-24.55), inquiring medical staff about PrEP (a OR=4.71, 95% CI:1.99-11.13) and PEP service use (a OR=6.09, 95% CI:2.69-13.81). Conclusions:The utilization rate of PrEP service was low in young MSM in Hangzhou. It is necessary to strengthen the health education about PrEP and improve the undertanding of PrEP and service capability of medical staff to promote the utilization of PrEP service in young MSM.

Objective:To analyze the utilization of pre-exposure prophylaxis (PrEP) service against HIV and related factors in young men who have sex with men (MSM) in Hangzhou.Methods:A cross-sectional study design was used in this questionnaire survey in young MSM recurited through local MSM social organization in Hangzhou from September 2022 to March 2023. The estimated sample size was 242. The information about the social-demographic characteristics, behavioral characteristics, utilization of the post exposure prophylaxis (PEP) service, awareness and utilization of PrEP service of the young MSM were collected. Logistic regression model was used to analyze the related factors of the PrEP utilization.Results:A total of 273 young MSM aged 16- 24 years were surveyed in the study. A total for 20.1% (55/273) of them had used PrEP service. Multivariate logistic regression analysis showed that the factors related to PrEP service utilization included age 16-20 years (a OR=3.03, 95% CI:1.12-8.20), education level of senior high school or below (a OR=2.83, 95% CI:1.09-7.35), full-time/part-time work (a OR=3.25, 95% CI: 1.26-8.38), homosexual activity in the past 6 months (a OR=6.71, 95% CI:1.84-24.55), inquiring medical staff about PrEP (a OR=4.71, 95% CI:1.99-11.13) and PEP service use (a OR=6.09, 95% CI:2.69-13.81). Conclusions:The utilization rate of PrEP service was low in young MSM in Hangzhou. It is necessary to strengthen the health education about PrEP and improve the undertanding of PrEP and service capability of medical staff to promote the utilization of PrEP service in young MSM.

Objective:To observe the safety and short-term efficacy of using an autologous fascia lata sling (AFLS) for tension-free mid-urethral sling (MUS) in the treatment of stress urinary incontinence (SUI).Methods:Between February 2022 and December 2023, 11 patients with SUI underwent AFLS-MUS. Preoperative data were recorded, including basic patient information and completion of urinary distress inventory 6 (UDI-6). During surgery, AFLS was harvested through a small incision using a tendon extractor, and used as a sling for transobturator or retropubic MUS. Perioperative indicators were recorded, including surgical approach, operation time, intraoperative blood loss, postoperative hospital stay, duration of catheterization, perioperative complications (Clavien-Dindo classification), and surgical costs. Follow-ups included outpatient physical examination at 2 months postoperatively, and telephone follow-up at 6 months, 1 year, and annually thereafter. Follow-up content included the presence or absence of urinary leakage symptoms, UDI-6, satisfaction, patient global impression of improvement (PGI-I), and complications.Results:The age of the 11 patients was (54.8±10.9) years (range: 41-72 years), with body mass index of (23.9±1.8) kg/m2 (range: 21.4-27.3 kg/m2). All patients experienced urinary leakage after coughing, sneezing and physical activity, with positive SUI provocation tests. The preoperative UDI-6 was 50.0±21.6 (range: 16.7-79.2), the result of 1-hour pad test was (18.9±12.0) g (range: 2.5-71.2 g). Four cases underwent MUS only, with operation time of (98.0±13.3) minutes (range: 86-117 minutes), and intraoperative blood loss of (17.5±5.0) ml (range: 10-20 ml); 7 cases also underwent pelvic floor repair simultaneously. The postoperative hospital stay was (3.5±2.0) days (range: 2-9 days). The duration of catheterization was (4.5±3.8) days (range: 2-11 days), with postoperative urinary retention in three cases, one of which underwent sling release surgery due to severe postoperative voiding difficulty 1 week after MUS, with no other complications of Clavien-Dindo grade 2 or above. The cost of AFLS harvest plus MUS was (2 762±293) yuan. At the 2-month outpatient follow-up, all patients were free of urinary leakage symptoms, with UDI-6 of 2.3±1.9 (range: 0-8.3); satisfaction was "very satisfied" in 10 cases and "fairly satisfied" in 1 case, with PGI-I all being "much better", and pelvic examinations were normal. Telephone follow-up showed one case lost to follow-up, and the remaining 10 cases had follow-up time of (18.6±4.9) months (range: 7-26 months), all without urinary leakage, with UDI-6 of 2.7±2.6, satisfaction rated as "very satisfied", and PGI-I all "much better".Conclusion:This modified AFLS-MUS for the treatment of SUI shows good short-term efficacy and high safety in harvest site, with the need for more data accumulation and long-term follow-up.

Objective:To evaluate the effect of short-chain fatty acid(SCFA) on perioperative cognitive dysfunction in aged rats through mitogen-activated protein kinase p38(p38 MAPK)/nuclear factor-κB p65(NF-κB p65) pathway.Methods:According to random number table method, 32 healthy SPF-grade male SD rats, aged 16 months and weighing 520~620 g, were divided into control group, short-chain fatty acid group (SCFA group), perioperative cognitive dysfunction group (PCD group) and perioperative cognitive dysfunction+ short-chain fatty acid group (SCFA+ PCD group), with 8 rats in each group. The perioperative cognitive dysfunction model was established by sevoflurane anesthesia plus internal fixation of tibial fractures. Rats in SCFA group and SCFA+ PCD group freely drank water added with SCFA for 28 days. On the 29th day, rats in SCFA+ FCD group underwent tibial fracture internal fixation surgery. Morris water maze test was performed on the 7th day after surgery to evaluate the cognitive function of rats. The Nissl bodies of hippocampus were observed by Nissl's staining. The hippocampus tissue was collected to analyze the expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), p38 MAPK, phosphorylated p38 MAPK, NF-κB p65 and phosphorylated NF-κB p65 by Western blot.The SPSS 27.0 software was used for statistical analysis. One-way ANOVA was used for comparison among multiple groups, and LSD- t test was used for further pairwise comparison. Results:(1) The results of Morris water maze test showed that the times of crossing the original platform, the escape latency and the residence time in the original platform quadrant were statistically significant among the four groups on the 7th day after surgery ( F=13.80, 47.80, 6.46, all P<0.05). The escape latencies of the SCFA+ PCD group and PCD group were both longer than that in the control group (both P<0.05). The times of crossing the original platform in SCFA+ PCD group and PCD group were less than that of control group (both P<0.05). The residence time in the original platform quadrant in SCFA+ PCD group and PCD group was shorter than that of control group (both P<0.05).Compared with PCD group, the escape latency was shorter, the times of crossing the original platform were more and the residence time in the original platform quadrant was longer in SCFA+ PCD group (all P<0.05). (2) The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were statistically significant among the four groups ( F=184.28, 139.27, 19.40, 58.47, all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were higher in SCFA+ PCD group (0.49±0.10, 0.60±0.05, 0.489±0.012, 0.435±0.005) and PCD group (0.85±0.05, 1.12±0.08, 0.519±0.028, 0.473±0.008) than those in control group (0.13±0.02, 0.42±0.10, 0.437±0.010, 0.362±0.013)(all P<0.05). The expression levels of IL-1β, IL-6, phosphorylated p38 MAPK and phosphorylated NF-κB p65 were lower in SCFA+ PCD group than PCD group (all P<0.05). (3) The average gray value of Nissl bodies was statistically significant different among the four groups ( F=14.65, P<0.05). The average gray value of Nissl bodies was lower in SCFA+ PCD group (193.2±8.1) and PCD group (160.5±14.1) than that of control group (221.2±14.8) (both P<0.05). The average gray value of Nissl bodies was higher in SCFA+ PCD group than that in PCD group( P<0.05). Conclusion:Short-chain fatty acid attenuates cognitive dysfunction, which may be related with inhibiting p38 MAPK/NF-κB p65 pathway and reducing the neuroinflammation.

Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine（CHO-HepB）26 years post-vaccination in the rural China.Methods:Zhengding county，Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires，and hepatitis B virus（HBV）serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants（mean time since vaccination：26.2 years），the seroprevalence rates were 0.6% for HBsAg（95% CI：0.0%-1.6%），64.6% for anti-HBs（95% CI：57.6%-71.6%），and 1.1% for anti-HBc（95% CI：0.0%-2.7%）. Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age，the estimated vaccine protection rate was 95%. Two notable cases were identified：one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity，suggestive of transient HBV exposure（1999—2009）without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys（2005，2009，2013，and 2017）revealed no significant upward trends in HBsAg and anti-HBc positivity（both P>0.05）over 26 years，while anti-HBs seropositivity declined significantly（ P<0.05）from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.

Objective:To observe the safety and short-term efficacy of using an autologous fascia lata sling (AFLS) for tension-free mid-urethral sling (MUS) in the treatment of stress urinary incontinence (SUI).Methods:Between February 2022 and December 2023, 11 patients with SUI underwent AFLS-MUS. Preoperative data were recorded, including basic patient information and completion of urinary distress inventory 6 (UDI-6). During surgery, AFLS was harvested through a small incision using a tendon extractor, and used as a sling for transobturator or retropubic MUS. Perioperative indicators were recorded, including surgical approach, operation time, intraoperative blood loss, postoperative hospital stay, duration of catheterization, perioperative complications (Clavien-Dindo classification), and surgical costs. Follow-ups included outpatient physical examination at 2 months postoperatively, and telephone follow-up at 6 months, 1 year, and annually thereafter. Follow-up content included the presence or absence of urinary leakage symptoms, UDI-6, satisfaction, patient global impression of improvement (PGI-I), and complications.Results:The age of the 11 patients was (54.8±10.9) years (range: 41-72 years), with body mass index of (23.9±1.8) kg/m2 (range: 21.4-27.3 kg/m2). All patients experienced urinary leakage after coughing, sneezing and physical activity, with positive SUI provocation tests. The preoperative UDI-6 was 50.0±21.6 (range: 16.7-79.2), the result of 1-hour pad test was (18.9±12.0) g (range: 2.5-71.2 g). Four cases underwent MUS only, with operation time of (98.0±13.3) minutes (range: 86-117 minutes), and intraoperative blood loss of (17.5±5.0) ml (range: 10-20 ml); 7 cases also underwent pelvic floor repair simultaneously. The postoperative hospital stay was (3.5±2.0) days (range: 2-9 days). The duration of catheterization was (4.5±3.8) days (range: 2-11 days), with postoperative urinary retention in three cases, one of which underwent sling release surgery due to severe postoperative voiding difficulty 1 week after MUS, with no other complications of Clavien-Dindo grade 2 or above. The cost of AFLS harvest plus MUS was (2 762±293) yuan. At the 2-month outpatient follow-up, all patients were free of urinary leakage symptoms, with UDI-6 of 2.3±1.9 (range: 0-8.3); satisfaction was "very satisfied" in 10 cases and "fairly satisfied" in 1 case, with PGI-I all being "much better", and pelvic examinations were normal. Telephone follow-up showed one case lost to follow-up, and the remaining 10 cases had follow-up time of (18.6±4.9) months (range: 7-26 months), all without urinary leakage, with UDI-6 of 2.7±2.6, satisfaction rated as "very satisfied", and PGI-I all "much better".Conclusion:This modified AFLS-MUS for the treatment of SUI shows good short-term efficacy and high safety in harvest site, with the need for more data accumulation and long-term follow-up.