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 surgical outcomes of congenital cervicothoracic scoliosis (CTS) patients with Klippel-Feil syndrome (KFS) and prognostic characteristics across different subtypes.Methods:A retrospective case series study is conducted. Clinical and radiographic data of 41 CTS patients with KFS who underwent hemivertebra resection with instrumentation at Department of Orthopedic Surgery, Nanjing Drum Tower Hospital from March 2012 to September 2022, with a minimum follow-up of two years, were analyzed. The cohort included 16 males and 25 females, aged (8.6±3.7) years (range: 3 to 15 years). Preoperative, immediate postoperative, and final follow-up cervicothoracic deformity parameters were compared. Patients were classified into three subtypes based on preoperative coronal alignment: shoulder-neck type (type A, 16 cases), trunk-tilt type (type B, 16 cases), and thoracic compensatory curve type (type C, 9 cases). The severity of KFS and the incidence of distal curve progression among subtypes were analyzed. Repeated measurement data were compared by repeated measurement ANOVA, pairwise comparison within groups was performed by Bonferroni method, and categorical variables were compared by Chi-square test or Fisher exact probability method.Results:All patients underwent successful surgery. Twenty-one patients (53.7%) had cervical fusion of ≥3 segments, and 63.1% (82/130) of fused cervical segments were located proximally to the instrumentation. Postoperative cervicothoracic Cobb angle, head tilt, head shift, neck tilt, and clavicle angle significantly improved (all P<0.05). The proportion of patients with cervical fusion of ≥3 segments was higher in types B and C (17/25) than that in type A (5/16) ( χ2=5.299, P=0.021). Four type B (4/16) and 5 type C (5/9) patients underwent long-segment fixation, with stable coronal alignment postoperatively. The remaining patients received short-segment fixation. In the short-segment group, the incidence of distal curve progression was significantly higher in types B and C (8/16) than that in type A (1/16) ( P=0.015). Ultimately, 3 type B patients underwent revision surgery, and 1 type C patient met the criteria for revision (distal compensatory thoracic or lumbar curve>40°). Conclusions:CTS patients with KFS are predisposed to develop significant coronal malalignment involving trunk tilt (type B) or thoracic compensatory curve (type C) before surgery. Following hemivertebra resection with short-segment fixation, such patients have a high risk of distal curve progression and potential need for revision surgery.

Objective:To investigate the surgical outcomes of congenital cervicothoracic scoliosis (CTS) patients with Klippel-Feil syndrome (KFS) and prognostic characteristics across different subtypes.Methods:A retrospective case series study is conducted. Clinical and radiographic data of 41 CTS patients with KFS who underwent hemivertebra resection with instrumentation at Department of Orthopedic Surgery, Nanjing Drum Tower Hospital from March 2012 to September 2022, with a minimum follow-up of two years, were analyzed. The cohort included 16 males and 25 females, aged (8.6±3.7) years (range: 3 to 15 years). Preoperative, immediate postoperative, and final follow-up cervicothoracic deformity parameters were compared. Patients were classified into three subtypes based on preoperative coronal alignment: shoulder-neck type (type A, 16 cases), trunk-tilt type (type B, 16 cases), and thoracic compensatory curve type (type C, 9 cases). The severity of KFS and the incidence of distal curve progression among subtypes were analyzed. Repeated measurement data were compared by repeated measurement ANOVA, pairwise comparison within groups was performed by Bonferroni method, and categorical variables were compared by Chi-square test or Fisher exact probability method.Results:All patients underwent successful surgery. Twenty-one patients (53.7%) had cervical fusion of ≥3 segments, and 63.1% (82/130) of fused cervical segments were located proximally to the instrumentation. Postoperative cervicothoracic Cobb angle, head tilt, head shift, neck tilt, and clavicle angle significantly improved (all P<0.05). The proportion of patients with cervical fusion of ≥3 segments was higher in types B and C (17/25) than that in type A (5/16) ( χ2=5.299, P=0.021). Four type B (4/16) and 5 type C (5/9) patients underwent long-segment fixation, with stable coronal alignment postoperatively. The remaining patients received short-segment fixation. In the short-segment group, the incidence of distal curve progression was significantly higher in types B and C (8/16) than that in type A (1/16) ( P=0.015). Ultimately, 3 type B patients underwent revision surgery, and 1 type C patient met the criteria for revision (distal compensatory thoracic or lumbar curve>40°). Conclusions:CTS patients with KFS are predisposed to develop significant coronal malalignment involving trunk tilt (type B) or thoracic compensatory curve (type C) before surgery. Following hemivertebra resection with short-segment fixation, such patients have a high risk of distal curve progression and potential need for revision surgery.

Recent developments indicated that Bowman capsule rupture (BCR) is observed in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN). We aimed to explore the relationship between BCR and clinical manifestations, pathological changes, and prognosis in children with myeloperoxidase (MPO)-AAGN. Methods: A total of 56 children with MPO-AAGN were divided into BCR (+) and BCR (–) groups according to the status of Bowman’s capsule. Results: After retrospective analysis of the data, 24 children (42.9%) were found to have BCR. The results showed that BCR positively correlated with intrarenal immune cell infiltrates, obsolescence and crescents in glomeruli, tubulointerstitial inflammation, tubulitis, and tubular atrophy negatively correlated with normal glomeruli and immunoglobulin G deposition in the kidney. The clinical features and kidney pathological changes were more severe in the BCR (+) group than BCR (–) group, and the renal survival rate was significantly poorer in the BCR (+) group than BCR (–) group (χ2 = 5.45, p = 0.02). Moreover, estimated glomerular filtration rate (≤15 mL/ min/1.73 m2), BCR and ANCA renal risk score (ARRS) were independent risk factors for the development of end-stage kidney disease (ESKD) in children with MPO-AAGN. After combining BCR with the Berden classification and ARRS, our data suggested that the Berden classification + BCR and ARRS + BCR showed better predictive values for ESKD than those of the Berden classification and ARRS, respectively. Conclusion: BCR is an important pathological lesion that correlates with severe clinical manifestations, pathological changes, and poor prognosis in children with MPO-AAGN.

Objective:To investigate the prognostic value of peripheral blood absolute monocyte count(AMC)in non-severe aplastic anaemia(NSAA)patients.Methods:178 patients with NSAA who attended the Affiliated Hospital of Xuzhou Medical University from April 2008 to September 2020 were retrospectively analyzed,and the optimal cut-off value of peripheral blood AMC was determined by the receiver operating characteristic curve of the subjects,and they were divided into low AMC group(48 patients)and normal AMC group(130 patients),and the differences in clinical characteristics between the two groups were compared.Overall survival(OS)and progression-free survival(PFS)were analyzed by Kaplan-Meier.Univariate and multivariate Cox regression analysis were used to determine the independent prognostic value of AMC.Results:Among 178 NSAA patients,105(59.0％)were male and 73(41.0％)were female,with a median age of 31(18-87)years old,a median follow-up time of 58 months(range:6 months-175 months),and a median AMC of 0.15 × 109/L[range:(0.01-0.59)× 109/L)].The proportion of granulocytes(27.5％vs 36.0％,P＜0.05),and the proportion of mature monocytes(1％vs 2％,P＜0.05)in the low AMC group were lower than that in the normal AMC group;the proportion of mature lymphocytes in the low AMC group was higher than that in the normal AMC group(54％vs 50％,P＜0.05).However,there was no significantly different in the proportion of erythropoietic cells and stages of the erythropoietic cells between the two groups(P＞0.05).CR(27.7％vs 10.4％)and ORR(75.4％vs 56.3％)in the normal AMC group were higher than that in the low AMC group.Compared with patients in the low AMC group,AA patients in the normal AMC had better 5-year OS(98.5％vs 86.9％,P＜0.01),and the 5-year PFS(86.0％vs 58.9％,P＜0.01).Also,the 10-year survival rate of patients in the normal AMC group was higher than that in the low AMC group(98.5％vs 60.5％,P＜0.01).Univariate analysis showed that age,reticulocyte count,AMC＜0.1 × 109/L and the proportion of bone marrow mature monocytes were related with patients survival.Multivariate Cox regression analysis showed that monocyte count reduction was not an independent poor prognostic factor in NSAA patients(HR=4.474,95％CI:0.508-44.390;P=0.172).Conclusion:Low AMC level at initial diagnosis is not an independent prognostic factor for NSAA patients,but still suggest potential prognostic value of AMC.

Objective:To investigate the risk factors for severe distal curve progression after posterior hemivertebra (HV) resection and short-segment fixation in patients with congenital cervicothoracic scoliosis (CTS), and to analyze the surgical revision strategy.Methods:Imaging and clinical data of patients who underwent posterior HV resection and short-segment fixation for CTS between August 2012 and August 2021 at Nanjing Drum Tower Hospital were retrospectively analyzed. A total of 55 patients were recruited, including 27 females and 28 males with an average age of 8.5±3.6 years (range 3-15 years) at surgery and an average Risser grade of 0.7±1.4 (range 0-4). The number of fused segments averaged 6.9±1.6 (range 4-10), and the mean follow-up was 38.7±18.9 months (range 9-94 months). According to the severity of distal curve progression, the recruited patients were divided into three groups: non-progression group (NPG), mild progression group (MPG), and severe progression group (SPG). The latter two groups were collectively called the progression group (PG). The cervicothoracic Cobb angle, T1 tilt angle, coronal balance distance (CBD), neck tilt angle, clavicular angle, head tilt angle, head shift, and upper (UIV) and lower instrument vertebra (LIV) tilt angle on the standing whole spine X-ray were measured before and after surgery and at the last follow-up. The correction rate of the Cobb angle in the osteotomy area was measured and calculated on CT three-dimensional reconstruction, and the proportion of patients with Klippel-Feil syndrome (KFS) was recorded. Statistical analysis was conducted on the various parameters between the two groups. For factors with statistical significance in the single-factor analysis, binary logistic regression analysis was performed to identify the high-risk factors for distal curve progression.Results:There were 38 cases in the NPG, 11 in the MPG, and 6 in the SPG. Compared to the NPG, the PG showed more severe coronal imbalance preoperatively, with CBD of 35.6±22.3 mm and 11.6±7.1 mm respectively; more severe neck tilt and head shift, with neck tilt angle of 17.4°±8.3° and 12.4°±6.9° respectively, and head shift of 22.8±17.7 mm and 13.9±9.8 mm respectively; and a higher proportion of KFS, 65% (11/17) and 34% (13/38) respectively, all with statistical significance ( P<0.05). Postoperatively, the PG showed more severe coronal imbalance compared with the NPG, with 17.3±12.7 mm and 9.6±8.1 mm respectively; more evident residual deformity, with cervical tilt angles of 9.4°±4.6° and 6.4°±5.3° respectively, and head shift of 14.7±7.4 mm and 9.1±5.9 mm respectively; lower correction of Cobb angle in the apical osteotomy region, with rates of 40.1%±15.2% and 50.3%±19.9% respectively; more significant UIV and LIV tilt, with UIV tilt angles of 14.3°±7.4° and 9.8°±5.3° respectively, and LIV tilt angles of 8.1°±5.5° and 4.5°±3.6° respectively, all with statistical significance ( P<0.05). SPG showed only more severe coronal imbalance preoperatively compared with the MPG, with 50.7±31.3 mm and 27.3±9.6 mm respectively; and head shift, with 33.5±25.0 mm and 16.9±11.0 mm respectively, all with statistical significance ( P<0.05). Logistic regression analysis demonstrated a significant correlation between significant preoperative coronal imbalance and postoperative distal scoliosis progression [ OR=1.299, 95% CI (1.101, 1.531), P=0.002]. Five cases (83.3%) in SPG underwent revision surgery with an average follow-up of 25 months, and selecting the LIV down to the stable region was the major revision strategy. Conclusion:Combined KFS, residual cervicothoracic deformities, and tilting of UIV and LIV are key causes, whereas significant preoperative coronal imbalance is an independent risk factor predisposing to the distal curve progression.

To understand the distribution of ticks in the Wuwei Region,enrich tick species data,and provide a basis for the prevention of tick-borne diseases,tick were collected using flagging and tick-picking methods during the highest activity period from April to September in 2021 and 2022 in the mountainous areas of Wuwei City.The ticks were identified based on morpho-logical and molecular biological characteristics,and characteristic sequences were obtained.A systematic evolutionary tree was constructed using the neighbor-joining method in MEGA 11.0 software.In total,7 342 ticks collected in Wuwei,which be-longed to 5 species from 4 genera with in the Ixodidae family,which included Dermacentor nuttalli,Hyalomma asiaticum,Ixodes canisuga,Haemaphysalis longicornis and Haema-physalis danieli.Ticks of the same species clustered together into the same branch of an evolutionary tree.In the Wuwei Re-gion,five common tick species are found across various habi-tats,with each habitat featuring different distributions of tick species and populations.The Dermacentor nuttalli is the dom-inant tick species in this area.

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.
Humans ; Antigens, CD19 ; B-Cell Maturation Antigen/therapeutic use* ; Bilirubin ; Immunotherapy, Adoptive ; Liver ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; T-Lymphocytes