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 establish a mouse model of spinal cord injury(SCI),and to investigate the effect of electroacupuncture(EA)intervention on cell apoptosis after acute SCI and its mechanism.Methods:Female C57BL/6 mice were used to establish a model of SCI,and after successful modeling,the mice were randomly divided into SCI group,EA group,and Rosiglitazone group(R group);a sham-operation group(Sham group)was also established.After successful modeling,the mice in the EA group were given EA at bilat-eral Jiaji points and Zusanli once a day for 14 days,those in the R ture,and the number of surviving cells.The EA group and the R group had a significant reduction in the expression of caspase-3 and significant increases in the expression of PPARγ and CD36,and the EA group had significant reductions in the expression of Hba-a1 and Hbb-bt.In addition,RNA-Seq and TMT/iTRAQ techniques,significant analysis,Venn analysis,and dual-omics analysis identi-fied Hba-a1 and Hbb-bt as the target genes of EA.The KEGG pathway enrichment analysis showed that EA had a significant effect on the PPAR signaling pathway.Conclusion:By regulating the PPARγ-CD36 signaling pathway,EA can promote the clearance of Hba-a1 and Hbb-bt after SCI,reduce the expression level of caspase-3,alleviate cell apoptosis,and facilitate the recovery of spinal cord nerve function.

Objective To compare the effect of palliative mitral valve surgeries and medication therapies for secondary non-ischemic mitral regurgitation. Methods The clinical data of patients with non-ischemic functional mitral regurgitation treated in our hospital between 2009 and 2019 were retrospectively analyzed. Patients with a left ventricular ejection fraction (LVEF)＜40% underwent a dobutamine stress test, and a positive result was determined when the LVEF improved by more than 15% compared to the baseline value. Positive patients were divided into a surgery group and a medication group. The surgery group underwent surgical mitral valve repair or replacement, while the medication group received simple medication treatment. Follow-up on survival and cardiac function status through outpatient or telephone visits every six months after surgery, and patients underwent cardiac ultrasound examination one year after surgery. The main research endpoint was a composite endpoint of all-cause death, heart failure readmission, and heart transplantation, and the differences in cardiac function and cardiac ultrasound parameters between the two groups were compared. Results Ultimately 41 patients were collected, including 28 males and 13 females with an average age of 55.5±11.1 years. Twenty-five patients were in the surgery group and sixteen patients in the medication group. The median follow-up time was 16 months, ranging 1-96 months. The occurrence of all-cause death in the surgery group was lower than that in the medication group (HR=0.124, 95%CI 0.024-0.641, P=0.034). The difference between the two groups was not statistically significant in the composite endpoint (HR=0.499, 95%CI 0.523-1.631, P=0.229). The New York Heart Association (NYHA) grade of the surgery group was better (NYHA Ⅰ-Ⅱ accounted for 68.0% in the surgury group and 18.8% in the medication group, P<0.01) as well as the grade of mitral valve regurgitation (87.5% of the patients in the medication group had moderate or above regurgitation at follow-up, while all the patients in the surgery group had moderate below regurgitation, P<0.01). There was no statistical difference in preoperative and follow-up changes in echocardiograph parameters between the two groups (P＞0.05). Conclusion For non-ischemic functional mitral regurgitation, if the cardiac systolic function is well reserved, mitral valve surgery can improve survival and quality of life compare to simple medication therapy.

Objective:To explore the genetic etiology of a fetus with Coffin-Siris syndrome2 (CSS2).Methods:A fetus with abnormal ultrasound findings detected at Luoyang Maternal and Child Health Care Hospital in July 2023 was selected as the study subject. Clinical data were analyzed retrospectively. Whole exome sequencing was carried out on fetal tissue and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and pathogenicity analysis. This study was approved by Medical Ethics Committee of the Luoyang Maternal and Child Health Hospital (Ethics No. LYFY-YCCZ-2023011).Results:Color Doppler ultrasound at 16 + gestational weeks revealed bilateral ventriculomegaly and cerebellar hypoplasia in the fetus. Trio-WES found that the fetus has harbored a heterozygous c. 553C>T (p.Gln185Ter) variant of the ARID1A gene, which was verified by Sanger sequencing to have a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 553C>T (p.Gln185Ter) variant of the ARID1A gene was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:The fetus was diagnosed with CSS type 2, and the heterozygous c. 553C>T (p.Gln185Ter) variant of the ARID1A gene probably underlay its brain malformations.

Objective:To explore the safety and early prognosis of robot assisted living donor kidney transplantation(KT)and plot the learning curve of mastering the operation.Methods:From July 2020 to March 2021, 30 cases of living robot assisted KT were completed.The follow-up period was 3 months.Cumulative sum analysis was performed for plotting the learning curve.According to the learning curve, they were divided into two groups of practice period(the first 17 cases)and proficiency period(the last 13 cases). Time of each operative stage and early prognosis were compared.Kidney function and perioperative complications of two groups were compared for evaluating the safety and effectiveness of robot assisted KT.Results:The average operative duration was (221.4±36.1)min.No intestinal obstruction, delayed graft function, urinary leakage and incision infection occurred during perioperative period.The average anal exhaust time was(1.9±0.2)days.During follow-ups, both pulmonary infection(2 cases)and acute rejection(1 case)improved after treatment.According to the learning curve, venous anastomosis(10 cases), arterial anastomosis(12 cases), warm ischemic time(12 cases)and ureteral anastomosis(17 cases)should be performed for reaching a proficiency level.An average of 15 operations was required for achieving proficiency throughout operations.Significant inter-group differences existed in operative duration [(235.5±31.6)vs(203.0±34.3)min, P=0.012] and warm ischemic time [(63.7±24.9)vs(47.0±11.3)min, P=0.033]. At some postoperative timepoints, creatinine of proficiency group was lower than that of practice group, such as Day 7 post-operation [(192.7±135.2)vs(107.8±27.9)μmol/L, P=0.022] and Day 30 post-operation [(147.8±46.3)vs(112.3±28.0)μmol/L, P=0.021]. However, no significant difference existed in estimated glomerular filtration rate at Day 7 post-operation [(56.1±34.1)ml/(min·1.73m 2)vs(72.0±18.5)ml/(min·1.73m 2), P=0.14] and Day 30 post-operation [(56.2±18.9)ml/(min·1.73m 2)vs(68.7±15.3)ml/(min·1.73m 2), P=0.14]. Conclusions:Robot assisted KT is both safe and feasible.And the learning curve requires 17 cases for reaching a proficiency level.

Objective:To retrospectively analyze the urodynamics quality in Southwest China, and find out the main issues of urodynamics quality in Southwest China and try to find out the improvement ways.Methods:In this study, a two-stage sampling method was used.In the first stage, 10 medical institutions in Southwest China were selected by cluster sampling from March to June, 2020.In the second stage, according to the development of UDS in Southwest China, the sample size estimation formula was adopted, and the loss of follow-up rate in reports extraction was considered, the initial sample size was 350. As the workload of UDS in the 10 medical institutions involved in the study was equivalent, 35 urodynamics traces from each medical institution were selected. The initial samples should also meet the inclusion criteria: ①patients with clear medical history and complete clinical data; ②UDS traces were clear; ③UDS system was water filled system; ④age>18, and 150 urodynamic traces were included in the final study. We evaluated the quality of enrolled urodynamics traces, and the quality evaluation standard according to the guidelines established by the International Continence Society (ICS). The evaluation conducted by two independent urologist with more than 10 years working experience. Artifacts were divided into non-technical artifacts: abnormal abdominal pressure changes, urine volume <150 ml when did the uroflow test, and technical artifacts: non-standard zero setting, fail to record all urodynamics parameters, baseline drift, catheter displacement, misjudgment of detrusor physiological contraction and detrusor overactive in voiding phase, misjudgment between detrusor overactive and bladder low compliance in filling phase.Results:non-technical artifacts: 32 cases were found abnormal abdominal pressure changes (21.3%), 21 cases (14.0%) were found when did the uroflow test the urine volume <150 ml, and technical artifacts: Non-standard zero setting in 28 cases (18.7%), fail to record all urodynamics parameters in 8 cases, baseline drift in 16 cases, catheter displacement in 9 cases and misjudgment of detrusor physiological contraction and detrusor overactive in voiding phase in 12 cases, misjudgment between detrusor overactive and bladder low compliance in filling phase in 24 cases (16.0%).Conclusions:At present, the urodynamics quality in Southwest China need to be improved. The main issues were that the operator didn’t obey the basic operation and quality control process, and the operator did not have enough basic knowledge of urodynamics. It can be improved by strictly carry out the operation standard of UDS, identifying and correcting artifacts in time, and promoting the standardized urodynamic training courses.

OBJECTIVE: To investigate the role of IL-17A in promoting the activation of lung fibroblasts and the secretion of chemokine CXCL12, and to explore the possible mechanism. METHODS: Lung tissues of BALB/c mice were collected after intraperitoneal injection of recombinant mouse IL-17A (rmIL-17A). Real-time RT-PCR and Western blotting were used to detect the expression levels of α-smooth muscle actin (α-SMA) and collagen I in lung tissues, and immunohistochemical staining and real-time RT-PCR were used to determine the expression of CXCL12. Normal mouse primary lung fibroblasts were isolated and cultured, and identified by immunofluorescence staining with optical microscopy. Cells and supernatant of culture medium were collected after stimulation with rmIL-17A at different concentrations. mRNA levels of α-SMA, collagen I, and CXCL12 in the cells were determined by real-time RT-PCR, and the levels of collagen I and CXCL12 in the supernatant of culture medium were determined by ELISA. RESULTS: The mRNA and protein levels of α-SMA and collagen I in the lung tissue of mice injected with rmIL-17A were significantly increased compared with the control group (all CONCLUSIONS s: IL-17A can promote the activation of lung fibroblasts and translation into myofibroblast. The secretion of collagen is increased, which promote the deposition of extracullular matrix, and leads to the occurrence and development of lung fibrosis. CXCL12, a chemokine secreted by activated fibroblasts, may be involved in this process.
Actins/genetics* ; Animals ; Cells, Cultured ; Chemokine CXCL12/metabolism* ; Fibroblasts/metabolism* ; Interleukin-17/pharmacology* ; Lung/metabolism* ; Mice ; Mice, Inbred BALB C

Objective: : This study aimed to investigate the changes and significance of microRNA155 levels in serum of patients with cerebral small vessel disease (CSVD). Methods: : Thirty patients with CSVD who met the inclusion criteria were selected and divided into eight patients with lacunar infarction (LI) group and 22 patients with multiple lacunar infarction (MLI) combined with white matter lesions (WML) group according to the results of head magnetic resonance imaging (MRI). Thirty samples from healthy volunteers without abnormalities after head MRI examination were selected as the control group. The levels of serum microRNA155 in each group were determined by real-time polymerase chain reaction, and the correlation between microRNA155 in the serum of patients with CSVD and the increase of imaging lesions was analyzed by Spearman correlation analysis. Results: : Compared with the control group, the serum microRNA155 level in the LI group, MLI combined with WML group increased, the difference was statistically significant (p<0.05); serum microRNA155 level was positively correlated with the increase of imaging lesions (p<0.05). Conclusion : The change of serum microRNA155 level in patients with CSVD may be one of its self-protection mechanisms, and the intensity of this self-protection mechanism is positively correlated with the number of CSVD lesions.

Mitochondrial dysfunctions play major roles in ageing. How mitochondrial stresses invoke downstream responses and how specificity of the signaling is achieved, however, remains unclear. We have previously discovered that the RNA component of Telomerase TERC is imported into mitochondria, processed to a shorter form TERC-53, and then exported back to the cytosol. Cytosolic TERC-53 levels respond to mitochondrial functions, but have no direct effect on these functions, suggesting that cytosolic TERC-53 functions downstream of mitochondria as a signal of mitochondrial functions. Here, we show that cytosolic TERC-53 plays a regulatory role on cellular senescence and is involved in cognition decline in 10 months old mice, independent of its telomerase function. Manipulation of cytosolic TERC-53 levels affects cellular senescence and cognition decline in 10 months old mouse hippocampi without affecting telomerase activity, and most importantly, affects cellular senescence in terc cells. These findings uncover a senescence-related regulatory pathway with a non-coding RNA as the signal in mammals.

Animals ; Brain ; physiology ; Consciousness ; physiology ; Humans ; Mice ; Neurotransmitter Agents ; physiology ; Optics and Photonics ; Synaptic Transmission ; physiology