Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Objective To evaluate the feasibility,reliability and validity of the symptom identification scale for kidney yang deficiency syndrome.Methods The symptom identification scale for kidney yang deficiency syndrome developed in previous research was administered to 200 vascular cognitive impairment patients from September 2020 to September 2022 to assess feasibility through recall rate,completion rate,and completion time;reliability was measured using retest reliability,split-half reliability,homogeneity reliability,and inter-rater reliability;and validity was evaluated based on discriminant and structural validity.Results A total of 200 scales were sent out,and all of them cooperated and were completed and retrieved within 20 min.The results of reliability analysis showed that the retest reliability of the scale was 0.828 for the dimension of yang deficiency and 0.718 for the dimension of kidney qi deficiency;the Spearman-Brown coefficient of split-half reliability was 0.784;the Cronbach coefficient of the dimension of yang deficiency was 0.799,and the Cronbach coefficient of the dimension of kidney qi deficiency in the homogeneity reliability was 0.670.The results of the analysis showed that the differences between the kidney yang deficiency syndrome group and the non-kidney yang deficiency syndrome group in the yang deficiency dimension,kidney qi deficiency dimension scores and total scale scores in the discriminant validity were statistically significant(P<0.001);the KMO value in the structural validity was 0.842,and a total of two factors with eigenvalues greater than 1 were extracted,with a cumulative variance contribution rate of 58.227%.Conclusion The symptom identification scale for kidney yang deficiency syndrome demonstrates adequate reliability and validity,potentially enhancing the prediction of kidney yang deficiency in vascular cognitive impairment.However,the validity of the scale is somewhat limited and requires further refinement for clinical application.

Objective:To analyze the factors influencing the poor effect of short-term electrical spinal cord stimulation in the treatment of postherpetic neuralgia (PHN).Methods:The medical records of PHN patients of either sex, aged 40-85 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, who received short-term electrical spinal cord stimulation from July 2017 to July 2022, were retrospectively collected. The therapeutic effect was evaluated using the modified MacNab criteria at 3 months after operation, and the patients were divided into good efficacy group (excellent and good efficacy) and poor efficacy group (fair and poor efficacy). General information, disease course, lesion site, complicated diseases, ossification of the yellow ligament in the diseased spinal segment, severity of pain in the herpetic stage, standard antiviral therapy in the herpetic stage (for more than 7 days) and use of neurotrophic drugs in the herpetic stage (for more than 7 days) were collected. Multivariate logistic regression analysis was used to screen the influencing factors for the poor effect of electrical spinal cord stimulation in the treatment of PHN.Results:A total of 168 patients were eventually enrolled, among which 69 had poor curative effect, and the rate of poor curative effect was 41.1%. The results of multivariate logistic regression analysis showed that the patient′s age ( OR=2.230, P=0.015), course of disease ( OR=2.191, P=0.027), complication with diabetes mellitus( OR=8.859, P=0.010), ossification of ligamentum flavum at the same segment ( OR=6.602, P=0.019), severity of pain in the herpetic stage ( OR=5.788, P=0.038) and non-standard antiviral therapy in the herpetic stage ( OR=6.765, P=0.021) were the influencing factors for the poor effect of electrical spinal cord stimulation in the treatment of PHN. Conclusions:Age, course of disease, complication with diabetes mellitus, ossification of ligamentum flandum at the same segment, severity of pain in the herpetic stage and non-standard antiviral therapy in the herpetic stage are the factors influencing the poor effect of short-term electrical spinal cord stimulation in the treatment of PHN.

Objective:To analyze the influencing factors of clinically relevant postoperative pancreatic fistula (CR-POPF) in children with pancreatic tumors after surgery.Methods:The clinical data of 123 children undergoing surgery for pancreatic tumor in Beijing Children's Hospital, Capital Medical University from January 2007 to March 2020 were retrospectively analyzed, including 39 males and 84 females, with a median age of 9.8 years (6.7 to 11.8). Patients without pancreatic fistula and with biochemical leakage were included in control group ( n=95), while patients with grade B and C pancreatic fistula were divided into CR-POPF group ( n=28). The independent influencing factors of CR-POPF were analyzed by univariate and multivariate logistic regression. Results:Among 123 children, 28 cases (22.8%) developed CR-POPF, including 24 cases (85.7%, 24/28) of grade B pancreatic fistula and 4 cases (14.3%, 4/28) of grade C pancreatic fistula. There were significant differences between CR-POPF and control groups in the age > 8 years and 4 months, tumor location, operation time >390 min and procedures (all P<0.05). Multivariate logistic regression analysis showed an increased risk of CR-POPF in children aged > 8 years and 4 months ( OR=8.226, 95% CI: 1.813-37.333, P=0.006) and undergoing duodenum-preserving pancreatic head resection (DPPHR) ( OR=3.353, 95% CI: 1.282-8.767, P=0.014). Conclusion:Age>8 years and 4 months and DPPHR are independent risk factors for CR-POPF in children with pancreatic tumors after surgery.

The negative effects of low temperature can readily induce a variety of diseases. We sought to understand the reasons why cold stress induces disease by studying the mechanisms of fine-tuning in macrophages following cold exposure. We found that cold stress triggers increased macrophage activation accompanied by metabolic reprogramming of aerobic glycolysis. The discovery, by genome-wide RNA sequencing, of defective mitochondria in mice macrophages following cold exposure indicated that mitochondrial defects may contribute to this process. In addition, changes in metabolism drive the differentiation of macrophages by affecting histone modifications. Finally, we showed that histone acetylation and lactylation are modulators of macrophage differentiation following cold exposure. Collectively, metabolism-related epigenetic modifications are essential for the differentiation of macrophages in cold-stressed mice, and the regulation of metabolism may be crucial for alleviating the harm induced by cold stress.
Acetylation ; Animals ; Cold-Shock Response ; Epigenesis, Genetic ; Macrophages/metabolism* ; Mice ; Mitochondria/metabolism*

Objective To explore the effects of LINC00649/miR-424-5p/IGF1R on ERs-mediated apoptosis of cervical carcinoma (CC) cells. Methods CC-related data was obtained from GEO database, then the differentially-expressed miRNAs were analyzed. The bioinformatics database was used to predict the upstream and downstream targets of miR-424-5p. LINC00649 and IGF1R were included. Dual luciferase reporter assay was adopted to confirm the targeting relationship. qRT-PCR was used to detect the expression levels of LINC00649, miR-424-5p and IGF1R in CC tissue and cells. CCK-8 and flow cytometry were used to evaluate the proliferation and apoptosis of CC cells. Western blot was used to detect the expression of ERs-related proteins GRP78, CHOP and Caspase-12. Results Compared with paracancerous tissue and H8 cells, LINC00649 and IGF1R were up-regulated in CC tissue and cells, while miR-424-5p was down-regulated (both P < 0.05). The abnormally high expression of LINC00649 in CC was related to poor prognosis. The knockdown of LINC00649 inhibited CC cell viability and induced cell apoptosis by promoting ERs (all P < 0.05). LINC00649 upregulated the expression of IGF1R via absorbing miR-424-5p. miR-424-5p inhibitor or IGF1R overexpression partially reversed the effects of LINC00649 knockdown on CC cells (both P < 0.05). Conclusion LINC00649 could reduce cell apoptosis and improve cell viability by inhibiting the ERs process via regulating miR-424-5p/IGF1R axis in CC.

Objective:To summarize the clinical characteristics, treatment response and long-term postoperative complications in children with neuroblastoma (NB) in the pelvic and sacral regions as the primary site.Methods:The clinical characteristics of 16 NB children (8 males and 8 females) with primary pelvic and sacral admitted to the Department of Hematology Oncology Center in Beijing Children′s Hospital, Capital Medical University from March 2007 to June 2019 were analyzed retrospectively with respect to the age at first diagnosis, primary tumor site, tumor size, clinical stage, risk grouping, and other clinical characteristics.The clinical characteristics of the patients who were followed up for regular treatment were analyzed, and the postoperative complications of the patients were summarized, and the Kaplan-Meier method was used for survival analysis.Results:The median age at diagnosis of these 16 children was 23.0 months (5.7-102.0 months), of which 6 cases (37.5%) were younger than 12 months old.All these children received chemotherapy, with a median of 6 (1-8) courses of chemotherapy.Fifteen children received surgical resection of the pelvic tumor, with complete resection in 12 cases (80%). The surgical approach was mainly transabdominal (86.7%, 13/16 cases). The median follow-up time of these children was 33.5 (8-136) months.The patella was absent in 3 patients (18.8%) after the operation, and no permanent neurological damage occurred in all patients.Five-year overall survival (OS) rate was 100%.Conclusions:A single-center summary showed a high survival rate for NB patients in the pelvic and sacral regions.Complete tumor resections combined with chemotherapy could be effective measures and rare cases occurred permanent postoperative neurological complications.