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 explore the characteristics and correlation between perivascular spaces (PVS) and diffusion tensor image analysis along perivascular spaces (DTI-ALPS) index in patients with amnestic mild cognitive impairment (aMCI). Methods A retrospective study was conducted on a total of 118 participants, including cognitive normal (CN) healthy controls and aMCI patients, recruited from the Department of Neurology, Zhongshan Hospital, Fudan University from September 2020 to September 2022. All participants underwent structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). An automatic segmentation algorithm was used to quantify PVS metrics in the brain, and DTI-ALPS index was calculated based on DTI. Differences in DTI-ALPS index and PVS metrics between the CN and aMCI groups were compared. Multivariate logistic regression was used to identify independent factors influencing aMCI. Correlation analysis was performed to assess relationships among DTI-ALPS index, PVS metrics, and cognitive scores. Results A total of 80 CN healthy controls and 38 aMCI patients were included. The DTI-ALPS index was significantly lower in the aMCI group compared with the CN group (1.28±0.18 vs 1.37±0.21, P＝0.018), while differences in PVS metrics between groups were not statistically significant. Multivariate logistic regression analysis indicated that DTI-ALPS index was an independent factor affecting aMCI (OR＝0.097, 95%CI 0.011–0.833, P＝0.033). Correlation analysis revealed a positive relationship between DTI-ALPS index and MMSE score (r＝0.210, P＝0.023) as well as PVS length in the centrum semiovale (r＝0.216, P＝0.019). Conclusions The DTI-ALPS index may serve as an imaging biomarker for identifying early cognitive impairment, and patients with aMCI exhibit abnormal DTI-ALPS indices, suggesting that brain glymphatic system dysfunction may occur prior to morphological changes.

The HDAs (a subfamily of histone deacetylases), a class of Zn²⁺-dependent histone deacetylases, are highly homologous to the reduced potassium dependency 3 (RPD3) in yeast. HDAs extensively regulate chromosome stability, gene transcription, and protein activity by catalyzing the removal of acetyl group from histone and non-histone lysine residues. HDA-mediated deacetylation is essential for plant growth, development, and responses to abiotic stress. We review the research progress in HDAs regarding the discovery, structures, classification, deacetylation process, and roles in regulating plant responses to abiotic stress. Furthermore, this paper prospects the future research on HDAs, aiming to provide theoretical support for the research on epigenetic regulation mediated by HDAs.
Histone Deacetylases/classification* ; Zinc/metabolism* ; Stress, Physiological/physiology* ; Plants/genetics*

BACKGROUND:Our previous studies have found that poly(vinylidene fluoride)bionic periosteum prepared by electrospinning has good cytocompatibility,but its biocompatibility is unknown. OBJECTIVE:To evaluate the biocompatibility of poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+. METHODS:Poly(vinylidene fluoride),poly(vinylidene fluoride)bionic periosteum doped with 1％Zn2+,doped with 1％Mg2+,and doped with 1％(Zn2++Mg2+)were prepared by electrospinning to make bionic periosteum extract.SD rats were selected as the experimental subjects for hemolysis test,short-term systemic toxicity test,and heat source test.Guinea pigs were selected as the experimental subjects for skin sensitization test.The biocompatibility of bionic periosteum of four groups was tested. RESULTS AND CONCLUSION:(1)The hemolysis test results showed that the hemolysis rates of 1％Zn2+poly(vinylidene fluoride),1％Mg2+poly(vinylidene fluoride),1％Zn2++1％Mg2+poly(vinylidene fluoride)bionic periosteum and poly(vinylidene fluoride)extract were(0.130±0.013)％,(0.149±0.020)％,(0.466±0.018)％,and(0.037±0.018)％,respectively,which met the hemocompatibility standard of biomaterials.(2)The results of short-term systemic toxicity test showed that the four groups of bionic periosteal extract had no toxic signs such as body mass reduction,food intake changes,and dyspnea in SD rats,and had no toxic effects on major organs of rats.(3)Heat source test results showed that after intervention with poly(vinylidene fluoride)bionic periosteum doped with 1％Zn2+,doped with 1％Mg2+,and doped with 1％(Zn2++Mg2+),and poly(vinylidene fluoride)bionic periosteum extract,the elevated body temperature values of SD rats were(0.133±0.058),(0.100±0.010),(0.300±0.010),and(0.300±0.017)℃respectively.All were less than 0.6 ℃and the total temperature increase was less than 1.4 ℃.(4)The results of skin sensitization test showed that no erythema or edema was observed under the skin of guinea pigs after the intervention of bionic periosteum extract of four groups.(5)The results showed that poly(vinylidene fluoride)and poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+had good biocompatibility.

Objective:To investigate the application value of cervical vascular ultrasound(CVUS)combined with transcranial Doppler ultrasound(TCD)in the diagnosis of carotid artery stenosis and collateral circulation in patients with ischemic cerebrovascular disease(ICVD).Methods:In this study,86 patients with ICVD admitted to the Cardio-Cerebrovascular Disease Specialist Hospital of Qinghai Province from January 2021 to January 2023 were selected.All patients underwent CVUS,TCD and digital subtraction cranial angiography(DSA)examination,and the diagnosis results of DSA were taken as the gold standard.To observe and compare the diagnostic efficacy of CVUS and TCD alone and combined CVUS and TCD for carotid artery stenosis and collateral circulation in ICVD patients.Results:Among the 86 patients with ICVD,a total of 597 vascular stenoses were detected by DSA examination,424 vascular stenoses were detected by CVUS,388 vascular stenoses were detected by TCD,and 586 vascular stenoses were detected by CVUS combined with TCD.The diagnostic coincidence rates of CVUS and TCD alone detection were 71.02%(424/597)and 64.99%(388/597),respectively,and the diagnostic coincidence rate of the combined detection of the two methods was 98.16%(586/597).The comparison showed that there was no statistically significant difference in the diagnostic coincidence rate of the degree of vascular stenosis between CVUS combined with TCD detection and DSA(P>0.05).Among the 86 patients with ICVD,collateral circulation formation was detected in 69 cases by DSA,in 55 cases by CVUS,in 51 cases by TCD,and in a total of 67 cases by CVUS combined with TCD.There was no significant difference in the detection rate between the combined detection of CVUS and TCD and that of DSA(P>0.05).Through analysis,it was concluded that the diagnostic sensitivity and accuracy of CVUS combined with TCD detection were both higher than those of CVUS and TCD single detection,and the difference was statistically significant(x2=10.180 and 12.204,P<0.05)14.969 and 18.124,P<0.05).The accuracy rate of the combined detection of CVUS and TCD was 96.51%,the sensitivity was 97.10%,and the specificity was 94.12%,which was highly consistent compared with DSA(Kappa value=0.896).Conclusion:CVUS combined with TCD detection has high clinical application value in the diagnosis of carotid artery stenosis and collateral circulation in ICVD patients.The combined detection of the two methods can further improve the diagnostic sensitivity,and the diagnostic accuracy is close to the gold standard,which can provide a reliable reference for clinical rational treatment and improvement of prognosis.

Objective:To explore the potential of the novel fibroblast activation protein (FAP)-targeted theranostic agent 68Ga/ 177Lu-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-2P (FAP inhibitor (FAPI)) 2 in microsatellite stable (MSS) colorectal cancer, and to evaluate the efficacy and underlying mechanism of 177Lu-DOTA-2P(FAPI) 2 in combination with immune checkpoint inhibitors (ICIs). Methods:This study was a randomized, parallel-group design. DOTA-2P(FAPI) 2 was labeled with 68Ga or 177Lu respectively. The binding performance of DOTA-2P(FAPI) 2 to FAP was validated through in vitro cell experiments. FAP-positive CT26-FAP tumor-bearing mouse model was constructed, and microPET imaging and biodistribution were performed. The in vivo antitumor efficacy was assessed for the 177Lu-DOTA-2P(FAPI) 2 monotherapy, α programmed death-ligand 1 (PD-L1) monotherapy, and the combination of 177Lu-DOTA-2P(FAPI) 2 with αPD-L1 therapy groups. Changes in the tumor microenvironment were analyzed using single-cell RNA sequencing to elucidate the mechanism of the combined treatment. Independent-sample t test was used to analyze data. Survival analysis was performed using the log-rank test. Results:The labeling yields of 68Ga/ 177Lu-DOTA-2P(FAPI) 2 were both >90%, with the radiochemical purities both >95%. In vitro cellular uptake and blocking assays showed that FAPI-46 significantly inhibited the binding of 68Ga-DOTA-2P(FAPI) 2 to FAP in CT26-FAP cells, with the cellular uptake values at 60min of (51.5±0.8)% and (1.0±0.3)%, respectively ( t=102.40, P<0.001). MicroPET imaging showed that the tumor uptake of 68Ga-DOTA-2P(FAPI) 2 remained stable even at 4 h post-injection, with a significantly higher uptake value compared to 68Ga-FAPI-46 ((7.3±1.6) vs (3.7±0.2) percentage activity of injection dose per gram of tissue (%ID/g); t=3.87, P=0.018). The biodistribution results indicated significant tumor uptake of 177Lu-DOTA-2P(FAPI) 2 even at 24 h post-injection ((4.30±0.52)%ID/g). The combination of 177Lu-DOTA-2P(FAPI) 2 and αPD-L1 achieved the 30-day survival rate of 100%, which was significantly superior to that of the control group (saline injection; χ2=9.53, P=0.002). Further mechanistic studies revealed that the combination therapy reprogramed the tumor microenvironment, enhanced anti-tumor intercellular communication, and activated signaling pathways such as Fas-FasL between T cells/natural killer (NK) cells and tumor cells, thereby synergistically inhibiting tumor progression. Conclusions:68Ga/ 177Lu-DOTA-2P(FAPI) 2 exhibits theranostic potential for MSS colorectal cancer. The combination of 177Lu-DOTA-2P(FAPI) 2 with ICIs may significantly prolong survival, demonstrating significant potential for clinical translation.

Objective To observe the value of 68Ga-DOTA-NOC PET/CT for diagnosing pheochromocytoma(PCC)and paraganglioma(PGL).Methods Thirty-eight patients with suspected or confirmed PCC/PGL who underwent 68 Ga-DOTA-NOC PET/CT were retrospectively enrolled,among them 20 cases underwent 131I-metaiodobenzylguanidine(MIBG)SPECT/CT during the same period.The value of 68Ga-DOTA-NOC PET/CT for diagnosing PCC/PGL at individual and lesion levels were analyzed and compared to the results of 131I-MIBG SPECT/CT.Results Among 38 cases,there were 20 cases of PCC,14 cases of PGL,1 case of adrenocortical carcinoma and 3 cases of benign adrenal hyperplasia.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy of 68 Ga-DOTA-NOC PET/CT for diagnosing PCC/PGL in all 38 cases was 87.88％(29/33),60.00％(3/5),93.55％(29/31),42.86％(3/7)and 84.21％(32/38),respectively.Totally 188 lesions were detected in 34 cases,with detection rate of 89.95％(188/209).For 20 patients who underwent both 2 kinds examinations,the detection rate of bone,lymph node,liver,lung metastases and the overall lesions of 68Ga-DOTA-NOC PET/CT were all higher than those of 131I-MIBG SPECT/CT(all P＜0.05).No significant difference of diagnostic accuracy of PCC/PGL was found between 68 Ga-DOTA-NOC PET/CT and 131I-MIBG SPECT/CT(P＞0.05).Conclusion The value of 68 Ga-DOTA-NOC PET/CT for diagnosing PCC/PGL was comparable to that of 131I-MIBG SPECT/CT,but the former showed higher detection rate of metastases,hence being helpful to staging and risk stratification of PCC/PGL.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To investigate the clinical efficacy of internal decompression based on white matter tract preservation in the treatment of malignant middle cerebral artery infarction(MMCAI).Methods A retrospective analysis was conducted on 54 patients with MMCAI.Patients were divided into a study group(n=26)and a control group(n=28)according to the surgical approach.Patients in the study group underwent preoperative fusion of CT,CTP,DWI,and DTI imaging data within a neuronavigation system.This fusion visualized the spatial relationships between the infarct core(IC),ischemic penumbra,and the corticospinal tract(CST).Subsequently,IC resection combined with decompressive craniectomy(DC)was performed while protecting the CST.Patients in the control group underwent DC alone.Key outcome measures included:changes in fractional anisotropy(FA)within the affected CST projection area at 1 month postoperatively;and 6-month postoperative mRS score,mortality,and surgical complications at 6 months postoperatively.Results At 1 month postoperatively,FA in the affected CST projection area were significantly higher in the study group than in the control group(0.092±0.013 vs.0.082±0.008,P<0.05).At the 6-month follow-up,the postoperative mRS score in the study group was significantly lower than that in the control group[2.3(1.3,4.5)vs.3.9(2.4,5.5),P<0.05]and a lower mortality rate(11.5%vs.39.3%,P<0.05)compared to the control group.However,there were no statistically significant differences between the two groups in the incidence of postoperative intracranial hemorrhage,intracranial infection,or epilepsy(P>0.05).Conclusion Internal decompression based on white matter tract protection combined with DC can reduce mortality and contribute to improving function outcomes in patients with MMCAI.

Objective To investigate the clinical efficacy of internal decompression based on white matter tract preservation in the treatment of malignant middle cerebral artery infarction(MMCAI).Methods A retrospective analysis was conducted on 54 patients with MMCAI.Patients were divided into a study group(n=26)and a control group(n=28)according to the surgical approach.Patients in the study group underwent preoperative fusion of CT,CTP,DWI,and DTI imaging data within a neuronavigation system.This fusion visualized the spatial relationships between the infarct core(IC),ischemic penumbra,and the corticospinal tract(CST).Subsequently,IC resection combined with decompressive craniectomy(DC)was performed while protecting the CST.Patients in the control group underwent DC alone.Key outcome measures included:changes in fractional anisotropy(FA)within the affected CST projection area at 1 month postoperatively;and 6-month postoperative mRS score,mortality,and surgical complications at 6 months postoperatively.Results At 1 month postoperatively,FA in the affected CST projection area were significantly higher in the study group than in the control group(0.092±0.013 vs.0.082±0.008,P<0.05).At the 6-month follow-up,the postoperative mRS score in the study group was significantly lower than that in the control group[2.3(1.3,4.5)vs.3.9(2.4,5.5),P<0.05]and a lower mortality rate(11.5%vs.39.3%,P<0.05)compared to the control group.However,there were no statistically significant differences between the two groups in the incidence of postoperative intracranial hemorrhage,intracranial infection,or epilepsy(P>0.05).Conclusion Internal decompression based on white matter tract protection combined with DC can reduce mortality and contribute to improving function outcomes in patients with MMCAI.