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.

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

Objective To explore the correlation between blood biochemical indexes and blood pressure levels among college students in Kunming City.Methods In November 2021,a cluster sampling method was used to survey 4,781 college students at a university in Yunnan Province.Data collected included height,weight and blood pressure,and blood samples were collected for blood biochemical testing.The Mann-Whitney U test and Kruskal-Wallis H test were used to compare the distribution differences of hypertension among college students with different demographic characteristics,while a generalized linear model was used to analyze the correlation between blood biochemical indicators and blood pressure levels.Results The prevalence rate of hypertension among college students was 8.45%(404/4 781).After adjusting confounding variables,blood glucose(GLU,β=1.48,95%CI:0.75～2.20)and serum Total Protein(TP,β=0.25,95%CI:0.19～0.32)were found to be correlated with systolic blood pressure(SBP)levels(all P<0.05);blood glucose(GLU,β=1.25,95%CI:0.64～1.86)and serum total protein(TP,β=0.28,95%CI:0.23～0.34)were correlated with diastolic blood pressure(DBP)level(P<0.05).Stratified group analysis by sex showed that,after controlling for confounding factors,TP(β=0.32,95%CI:0.18～0.45)was correlated with SBP levels in male students;TP(β=0.32,95%CI:0.21～0.43)was correlated with DBP levels in male students(P<0.05).GLU(β=2.18,95%CI:1.29～3.07)and TP(β=0.23,95%CI:0.15～0.31)were correlated with SBP levels in female students;GLU(β=1.48,95%CI:0.73～2.24)and TP(β=0.26,95%CI:0.20～0.33)were correlated with DBP levels in female students(all P<0.05).Conclusion Our findings suggest that blood glucose and serum total protein level are correlated with blood pressure levels in female college students,while serum total protein level are correlated with blood pressure levels in male college students.

Objective To investigate the epidemiological characteristics of dengue fever in Shenzhen City in 2024, so as to provide insights into formulation of the preventive and control measures for dengue fever. Methods The epidemiological data of dengue cases reported in Shenzhen City in 2024 were extracted from the China Disease Prevention and Control Information System and field epidemiological survey data of dengue fever in Shenzhen City, and the temporal, regional and population distributions of dengue fever cases, source of acquire dengue virus infections, disease diagnosis and treatment and outbreaks were analyzed. The dengue virus nucleic acid was tested and the serotypes of dengue virus were characterized using real-time quantitative reverse transcription PCR (RT-qPCR) assay, and the dengue virus gene was sequenced using next-generation sequencing (NGS). In addition, the surveillance on the density of Aedes albopictus was performed using Breteau index (BI) and mosquito oviposition index (MOI). Results A total of 1 735 dengue fever cases were reported in Shenzhen City in 2024, including 952 local cases and 783 imported cases. Most imported dengue fever cases acquired infections from eight cities of Foshan, Guangzhou, Zhongshan, Jiangmen, Dongguan, Zhaoqing, Huizhou, and Zhuhai in the Pearl River Delta region (664 cases, 84.8% of total imported cases) into Baoan, Longgang, and Nanshan districts. The epidemic exhibited an early onset and rapid progression, peaking during the period between September and November (1 632 cases, 94.1% of total cases), and dengue fever cases were distributed across 73 subdistricts in 10 districts, with most cases reported in densely populated central and western regions. The dengue fever cases had a male-to-female ratio of 1.9∶1.0, and a median age of 37 (21) years, with a higher median age among local cases than among imported cases [40 (20) years vs. 33(15) years; Z = -10.30, P < 0.05]. Housework, unemployment, workers, and business service were predominant occupations (1 405 cases, 81.0% of total cases), and there was a significant difference in the constituent ratio of occupations between local and imported cases (χ² = 92.30, P < 0.05). Among the 1 735 dengue fever cases, the median duration from onset to definitive diagnosis was 3.3 (2.9) days, and 1 686 cases (97.2%) were identified in healthcare facilities, with a low rate of hospitalization and isolation seen in 1 701 inpatients with available epidemiological data (485 cases, 28.5% of total inpatients). A total of 29 outbreaks of dengue fever occurred in Shenzhen City across 2024, which primarily in construction sites (27 outbreaks, 93.1% of total). Dengue virus type I was the dominant serotype causing dengue fever in Shenzhen City in 2024. Sequencing showed that the genomes of dengue virus from multiple dengue fever cases in Shenzhen City shared a high sequence homology with those from cities neighboring Shenzhen City, and there might be intra-city transmission of dengue virus among multiple construction sites in Shenzhen City. The Aedes albopictus density was significantly higher in Shenzhen City in 2024 than in 2023, peaking from May to September. The annual MOI values ranged from 0.9 to 14.0, and the BI values ranged from 0.6 to 6.0. Conclusions The overall epidemic of dengue fever was severe in Shenzhen City in 2024, which was greatly affected by case importation from neighboring cities, construction sites-centered local transmission, and the effectives of routine mosquito vector control was not satisfactory. Integrated dengue fever control measures should be implemented, focusing on regional joint prevention and control mechanisms, capacity building for mosquito vector control, addressing challenges in epidemic containment at construction sites, and strengthening case detection and management systems.

Objective To investigate the epidemiological characteristics and effectiveness of emergency responses to epidemic foci in Guangzhou City in 2024, so as to optimization of the dengue fever control strategy in Guangzhou City. Methods All data pertaining to dengue fever cases in Guangzhou City in 2024 were collected from the National Notifiable Infectious Disease Surveillance Information Reporting System. The temporal, spatial and population distributions of dengue fever cases and sources of infections were descriptively analyzed, and the effectiveness of emergency responses to epidemic foci of dengue fever was evaluated through standard space index (SSI), the interval from disease onset to case reporting and the percentage of isolation in hospital. Results A total of 3 656 dengue fever cases were reported in Guangzhou City in 2024, including 3 102 local cases and 554 imported cases. Of all cases, 67.86% (2 481 cases) occurred at ages of 20 to 59 years, and the three most common occupations included housework/unemployment (793 cases, 21.69%), business servants (744 cases, 20.35%) and retirees (669 cases, 18.30%). The peak of dengue fever epidemics was concentrated during the period from the 39th to the 45th weeks in 2024, when a total of 2 317 local cases were reported, accounting for 74.69% of all local cases in 2024. Dengue fever cases were reported across all 11 districts in Guangzhou City in 2024, with local cases concentrated in Baiyun District (754 cases, 24.31%), Liwan District (398 cases, 12.83%), Panyu District (365 cases, 11.77%), Haizhu District (332 cases, 10.70%) and Tianhe District (328 cases, 10.57%). Imported dengue fever cases were predominantly domestically imported (492 cases, 88.81%), with the majority imported from Foshan City (377 cases), and overseas imported cases were predominantly imported from southeastern Asian countries. The mean proportion of case isolation in hospital was 9.16% (284/3 102), and the mean interval from disease onset to case reporting was (3.99 ± 2.70) days, while the percentages of mosquito density meeting the required standard were 61.68% (462/ 749) and 66.32% (126/190) on the 4th and 7th day of emergency responses to epidemic foci, respectively. Conclusions The prevention and control cycle of dengue fever in Guangzhou in 2024 took longer than in previous years, with a larger scale of the epidemic. Although some progress has been made in epidemic management, there are still problems such as unsustainable mosquito vector control and low hospitalization isolation rates for cases. Further optimization of control measures in mosquito vector control, case monitoring and management is required to improve the effectiveness of dengue fever control measures.

OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment of "biaoben acupoint combination" on cardiomyocyte mitochondrial fission in the rats with myocardial ischemia-reperfusion injury (MIRI) and explore its mechanism. METHODS: Fifty male SD rats were randomly divided into a sham-operation group, a model group, an EA pretreatment group, an EA pretreatment + Compound C group and an EA pretreatment+ML385 group, 10 rats in each group. In the EA pretreatment, the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, EA was delivered at bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, with continuous wave and 2 Hz of frequency, 1 mA of current, once daily for consecutive 7 days. On day 8, in the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, 30 min before model preparation, the intraperitoneal injection with Compound C (0.3 mg/kg) and ML385 (30 mg/kg) was administered respectively. Except in the sham-operation group, the ligation of the left anterior descending coronary artery was performed to prepare MIRI rat model in the rest groups. In the sham-operation group, the thread was not ligated. After modeling, the content of reactive oxygen species (ROS) in the ischemic area was measured by flow cytometry, superoxide dismutase (SOD) was detected using xanthine oxidase method, and malondialdelyde (MDA) was detected using thiobarbituric acid (TBA) chromatometry. The morphology of myocardial tissue in the ischemic area was observed with HE staining, and the mitochondria ultrastructure of cardiomyocytes observed under transmission electron microscopy. Using immunofluorescence analysis, the positive expression of mitochondrial fission factor (MFF), mitochondrial fission 1 protein antibody (Fis1) and dynamin-related protein 1 (Drp1) was detected; and with immunohistochemical method used, the protein expression of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor E2-associated factor2 (Nrf2) and Drp1 in the ischemic area was detected. RESULTS: Compared with the sham-operation group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 increased in the model group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 decreased (P<0.01), and the protein expression of Drp1 elevated (P<0.01). Compared with the model group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01), and the protein expression of Drp1 declined (P<0.01); and in the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the positive expression of MFF, Fis1 and Drp1, and the protein expression of Drp1 were all reduced (P<0.01). When compared with the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01, P<0.05), and the protein expression of Drp1 decreased (P<0.05). In comparison with the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the cardiac muscle fiber rupture, cell swelling and mitochondrial disorders were obviously alleviated in the EA pretreatment group. The morphological changes were similar among the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group. CONCLUSION Electroacupuncture pretreatment of "biaoben acupoint combination" attenuates myocardial injury in MIRI rats, probably through promoting the phosphorylation of AMPK and Nrf2, inhibiting the excessive mitochondrial fission induced by Drp1, and reducing mitochondrial dysfunction caused by mitochondrial fragmentation and vacuolation.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Myocardial Reperfusion Injury/physiopathology* ; Myocytes, Cardiac/cytology* ; Rats ; Acupuncture Points ; Mitochondrial Dynamics ; Humans ; Reactive Oxygen Species/metabolism* ; NF-E2-Related Factor 2/genetics* ; Superoxide Dismutase/metabolism*

Objective To explore the factors for chemotherapy-induced nausea and vomiting(CINV)in patients with advanced colorectal cancer receiving moderately emetic chemotherapy regimens.Methods 296 patients with colorectal cancer treated with oxaliplatin/irinotecan combination therapy and standard antiemetic prophylaxis regimen at the First Hospital of Jiaxing from July 1,2022 to June 30,2024 were selected,including 164 patients in oxaliplatin combination therapy group and 132 patients in irinotecan combination therapy group.Evaluated the nausea and vomiting status of patients within 5 days after the start of chemotherapy.Analyzed demographic data,medical history data,follow-up data.Results The incidence of CINV in oxaliplatin combination therapy group was 61.59％,and that in irinotecan combination therapy group was 53.79％.The incidence of delayed CINV and severe acute CINV in oxaliplatin combination therapy group were significantly higher than those in irinotecan combination therapy group(P＜0.05).Multivariate analysis showed that the risk factors for acute CINV in the oxaliplatin-based combination regimen were smoking history and CINV history.The risk factors for delayed CINV were age,no history of drinking,history of pregnancy-induced vomiting,motion sickness history,CINV history,and first use of the regimen.For the irinotecan-based combination regimen,the risk factors for acute CINV were motion sickness history and CINV history.The risk factors for delayed CINV were CINV history and anxious emotions.Conclusion When useing standard anti-emetic prophylaxis that still have a high incidence of CINV by moderate emetic chemotherapy drugs in advanced colorectal cancer patients.Patients with high risk factors should actively take preventive measures to control CINV.

Objective:To compare the efficacy of laminoplasty via the intermuscular approach or posterior midline approach for treating spinal cord injury without radiographic abnormality (SCIWORA).Methods:A multi-center retrospective cohort study was conducted to analyze the clinical data of 135 patients with SCIWORA admitted to Honghui Hospital Affiliated to Xi'an Jiaotong University School of Medicine, Xi'an No.5 Hospital, Henan Provincial People's Hospital, Zhengzhou Orthopedic Hospital, Xuanwu Hospital of Capital Medical University from February 2021 to June 2023, including 75 males and 60 females, aged 35-78 years [(55.3±8.1)years]. The injury segments involved C 3-C 6. All the patients underwent posterior cervical open-door laminoplasty, among whom 70 patients were treated via the intermuscular approach (intermuscular group) and 65 via the posterior midline approach (posterior midline group). The operation duration, intraoperative blood loss, postoperative drainage volume, and length of hospital stay were recorded. The visual analogue scale (VAS) score, Japanese Orthopedic Association (JOA) score, neck disability index (NDI), Barthel index, cervical Cobb angle, and cervical range of motion (ROM) were measured preoperatively, at 3, 6, 12 months postoperatively and at the final follow-up. The American Spinal Injury Association (ASIA) scale was evaluated preoperatively, at 3, 12 months postoperatively and at the final follow-up. The postoperative complication rate was recorded as well. Results:All the patients were followed up for 15-19 months [(16.3±1.6)months]. The operation duration, intraoperative blood loss, postoperative drainage and length of hospital stay were (125.0±23.0)minutes, (210.4±34.8)ml, and (165.3±23.7)ml, and (5.3±0.1)days in the intermuscular group, which were significantly shorter or less than (168.0±27.6)minutes, (260.2±45.3)ml, (196.4±31.6)ml, and (6.4±0.2)days in the posterior midline group ( P<0.01). The preoperative VAS score, JOA score, NDI and Barthel index showed no significant differences between the two groups ( P>0.05). The VAS score and JOA score also showed no significant differences between the two groups at 3, 6, 12 months postoperatively or at the final follow-up ( P>0.05). The NDI and Barthel index also showed no significant differences between the two groups at 3 months postoperatively ( P>0.05). At 6, 12 months postoperatively and at the final follow-up, the NDI were (15.4±2.5)points, (11.8±2.1)points and (8.6±1.5)points in the intermuscular group, significantly lower than (19.1±3.4)points, (14.3±2.4)points and (11.9±1.4)points in the posterior midline group ( P<0.01). At 6, 12 months postoperatively and at the final follow-up, the Barthel index were (71.4±6.2)points, (83.4±5.8)points and (89.2±7.1)points in the intermuscular group, significantly higher than (59.6±4.7)points, (74.2±3.9)points and (78.8±6.2)points in the posterior midline group ( P<0.01). Both groups showed significant improvements in VAS score, JOA score, NDI and Barthel index at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05). Among them, the VAS score, NDI and Barthel index were further improved over time ( P<0.05). Simultaneously, the JOA score was significantly improved at 6, 12 months postoperatively and at the last follow-up when compared to that at 3 months postoperatively ( P<0.05), with no significant difference at later time points between the two groups ( P>0.05). The preoperative cervical Cobb angle and ROM showed no significant differences between the two groups ( P>0.05). There was no significant difference in the Cobb angle between the two groups at 3, 6 or 12 months postoperatively ( P>0.05), while it was (13.6±2.4)° in the intermuscular group at the final follow-up, significantly larger than (10.4±2.8)° in the posterior midline group ( P<0.01). At 3, 6, 12 months postoperatively and at the final follow-up, the cervical ROM were (34.1±6.4)°, (32.6±7.3)°, (31.8±9.1)° and (29.6±8.7)° in the intermuscular group, significantly larger than (23.7±8.3)°, (22.3±7.8)°, (22.5±8.1)° and (20.6±9.3)° in the posterior midline group ( P<0.01). In the intermuscular group, the cervical Cobb angle showed no significant changes at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P>0.05). In the posterior midline group, the Cobb angles were significantly reduced at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05), showing significant decrease at 12 months postoperatively and at the final follow-up from those at 3, 6 months postoperatively ( P<0.05), no significant difference at 6 months postoperatively from that at 3 months postoperatively ( P>0.05), and significant decrease at the final follow-up from that at 12 months postoperatively ( P>0.05). In the intermuscular group, the cervical ROM were significantly improved at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively and showed further improvement over time ( P<0.05). In the posterior midline group, the cervical ROM were significantly improved at 3, 6, 12 months postoperatively and at the final follow-up when compared to those preoperatively ( P<0.05), showing significant decreases at 6, 12 months postoperatively and at the final follow-up from that at 3 months postoperatively ( P<0.05), significant decreases at the final follow-up from those at 6, 12 months postoperatively ( P<0.05), and no significant difference at 12 months postoperatively from that at 6 months postoperatively ( P>0.05). The ASIA grades showed no significant difference between the two groups preoperatively, at 3, 12 months postoperatively and at the final follow-up ( P>0.05) , but were gradually improved over time in both groups ( P<0.05). The postoperative complication rate was 9%(6/70) in the intermuscular group, significantly lower than 48%(31/65) in the posterior midline group ( P<0.01). Conclusion:Compared to the posterior midline approach, the intermuscular approach for laminoplasty in patients with SCIWORA possesses advantages, including shorter operative time and length of hospital stay, reduced intraoperative blood loss and postoperative drainage, less postoperative neck disability, higher daily life quality, better long-term preservation of cervical lordosis and motion, and a lower complication rate.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.