Objective:To explore the effects of magnolol on autophagy in intestinal Cajal cells and intestinal motility in rats with acute necrotizing pancreatitis (ANP).Methods:Forty-five Wistar rats were randomly divided into three groups by a random number table: control group, ANP group and magnolol intervention group, with 15 rats in each group. The ANP model was established by intraperitoneal injection of cerulein. The magnolol intervention group received a tail vein injection of 20 μg/kg magnolol ethanol solution 30 minutes after modeling. After 12 hours, ileal tissues were collected for pathological examination and scoring. Intestinal transit rate was measured using the carbon powder propulsion method, and isolated intestinal muscle strips were prepared to assess amplitude and frequency of spontaneous contraction. Oxidative stress markers in intestinal tissues, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels, were measured using xanthine oxidase, thiobarbituric acid, and enzymatic reduction assay kits, respectively. Cajal cells were isolated from intestinal smooth muscle tissues, and the expression of autophagy-related proteins (Beclin1, LC3Ⅱ, LC3Ⅰ, p62) and p-Kit was detected by Western blot. Double immunofluorescence staining was used to trace autophagy in Cajal cells.Results:The pathological scores of ileal tissues in the control, ANP, and magnolol intervention groups were (0.33±0.52), (4.83±0.41), and (3.50±0.55), respectively. The score in ANP group was significantly higher than that in the control group, while the score in the magnolol intervention group was lower than that in the ANP group, with statistically significant differences (all P value <0.05). Intestinal transit rate, amplitude and frequency of spontaneous contraction in the ANP group were significantly slower than those in the control group, while these parameters in the magnolol intervention group were significantly improved compared to the ANP group, with statistically significant differences (all P value <0.05). SOD activity in the control, ANP, and magnolol intervention groups were (73.8±8.1), (42.8±7.2), and (71.2±10.4) N/mg prot, respectively; NO levels were (1.72±0.26), (3.19±0.43), and (1.94±0.23) μmol/g prot; and MDA levels were (1.15±0.38), (3.84±0.30), and (1.68±0.33) nmol/mg prot. SOD activity in the ANP group was significantly lower than that in the control group, while NO and MDA contents were significantly higher. In the magnolol intervention group, SOD activity was significantly higher, and NO and MDA contents were significantly lower than those in the ANP group, with statistically significant differences (all P value <0.01). The levels of Beclin1, LC3Ⅱ/Ⅰ ratio, and p-Kit in the intestinal Cajal cells of ANP group were significantly higher than those in the intestinal Cajal cells of control group, while the p62 level was significantly lower. In the intestinal Cajal cells of magnolol intervention group, the levels of Beclin1, LC3Ⅱ/Ⅰ ratio, and p-Kit were significantly lower while the p62 level was significantly higher than those in the intestinal Cajal cells of ANP group, with statistically significant differences (all P value <0.01). The numbers of c-Kit/GFP-LC3 double-positive Cajal cells in the control group, ANP group, and magnolol intervention group were (9.59±5.06), (11.27±8.30), and (10.27±6.30), respectively. The ANP group had significantly more double-positive cells than the control group, while the magnolol intervention group had significantly less double-positive cells than the ANP group, with statistically significant differences (all P value <0.05). Conclusions:Excessive oxidative stress and autophagy in Cajal cells are important mechanisms underlying ANP-induced intestinal motility dysfunction. Magnolol can improve intestinal motility in ANP by antagonizing oxidative stress and reducing autophagy in Cajal cells. p-Kit may play a regulatory role in this process.

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: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

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.

Objective:To explore the effects of magnolol on autophagy in intestinal Cajal cells and intestinal motility in rats with acute necrotizing pancreatitis (ANP).Methods:Forty-five Wistar rats were randomly divided into three groups by a random number table: control group, ANP group and magnolol intervention group, with 15 rats in each group. The ANP model was established by intraperitoneal injection of cerulein. The magnolol intervention group received a tail vein injection of 20 μg/kg magnolol ethanol solution 30 minutes after modeling. After 12 hours, ileal tissues were collected for pathological examination and scoring. Intestinal transit rate was measured using the carbon powder propulsion method, and isolated intestinal muscle strips were prepared to assess amplitude and frequency of spontaneous contraction. Oxidative stress markers in intestinal tissues, including superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels, were measured using xanthine oxidase, thiobarbituric acid, and enzymatic reduction assay kits, respectively. Cajal cells were isolated from intestinal smooth muscle tissues, and the expression of autophagy-related proteins (Beclin1, LC3Ⅱ, LC3Ⅰ, p62) and p-Kit was detected by Western blot. Double immunofluorescence staining was used to trace autophagy in Cajal cells.Results:The pathological scores of ileal tissues in the control, ANP, and magnolol intervention groups were (0.33±0.52), (4.83±0.41), and (3.50±0.55), respectively. The score in ANP group was significantly higher than that in the control group, while the score in the magnolol intervention group was lower than that in the ANP group, with statistically significant differences (all P value <0.05). Intestinal transit rate, amplitude and frequency of spontaneous contraction in the ANP group were significantly slower than those in the control group, while these parameters in the magnolol intervention group were significantly improved compared to the ANP group, with statistically significant differences (all P value <0.05). SOD activity in the control, ANP, and magnolol intervention groups were (73.8±8.1), (42.8±7.2), and (71.2±10.4) N/mg prot, respectively; NO levels were (1.72±0.26), (3.19±0.43), and (1.94±0.23) μmol/g prot; and MDA levels were (1.15±0.38), (3.84±0.30), and (1.68±0.33) nmol/mg prot. SOD activity in the ANP group was significantly lower than that in the control group, while NO and MDA contents were significantly higher. In the magnolol intervention group, SOD activity was significantly higher, and NO and MDA contents were significantly lower than those in the ANP group, with statistically significant differences (all P value <0.01). The levels of Beclin1, LC3Ⅱ/Ⅰ ratio, and p-Kit in the intestinal Cajal cells of ANP group were significantly higher than those in the intestinal Cajal cells of control group, while the p62 level was significantly lower. In the intestinal Cajal cells of magnolol intervention group, the levels of Beclin1, LC3Ⅱ/Ⅰ ratio, and p-Kit were significantly lower while the p62 level was significantly higher than those in the intestinal Cajal cells of ANP group, with statistically significant differences (all P value <0.01). The numbers of c-Kit/GFP-LC3 double-positive Cajal cells in the control group, ANP group, and magnolol intervention group were (9.59±5.06), (11.27±8.30), and (10.27±6.30), respectively. The ANP group had significantly more double-positive cells than the control group, while the magnolol intervention group had significantly less double-positive cells than the ANP group, with statistically significant differences (all P value <0.05). Conclusions:Excessive oxidative stress and autophagy in Cajal cells are important mechanisms underlying ANP-induced intestinal motility dysfunction. Magnolol can improve intestinal motility in ANP by antagonizing oxidative stress and reducing autophagy in Cajal cells. p-Kit may play a regulatory role in this process.

In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the Expert Consensus on Standard Terminology for Hair Transplantation based on the collation of relevant literature and monographs. By combining Delphi methodology and consensus meetings, the expert group conducted several rounds of consultations on issues such as follicular unit anatomy, harvesting, dissection, and implantation, ultimately presenting 54 terminologies. This consensus considers the original Chinese and English meanings as well as the professional characteristics of terms used in hair transplantation, highlights the unique features and advantages of hair transplantation, and preserves its essence while promoting innovation, with the hope of providing valuable reference for clinical researchers engaged in hair transplantation both domestically and internationally, and better facilitating the standardization and advancement of the field.

In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the Expert Consensus on Standard Terminology for Hair Transplantation based on the collation of relevant literature and monographs. By combining Delphi methodology and consensus meetings, the expert group conducted several rounds of consultations on issues such as follicular unit anatomy, harvesting, dissection, and implantation, ultimately presenting 54 terminologies. This consensus considers the original Chinese and English meanings as well as the professional characteristics of terms used in hair transplantation, highlights the unique features and advantages of hair transplantation, and preserves its essence while promoting innovation, with the hope of providing valuable reference for clinical researchers engaged in hair transplantation both domestically and internationally, and better facilitating the standardization and advancement of the field.

Objective To explore the clinical characteristics and prognostic significance of adrenocorticotropic hormone(ACTH)level in patients with acute myeloid leukemia(AML).Methods A total of 235 AML patients were enrolled from January 2015 to October 2021.The survival curves between ACTH groups were drawn by Kaplan-Meier.The risk factors of overall survival(OS)were analyzed by COX regression analysis.The prognostic model was constructed by R software and verified by calibration curve.Results Among 235 AML patients,the ACTH level of 40 patients were lower than 7.2pg/ml.Kaplan-Meier survival curve analysis indicated that the survival time of patients with low ACTH was significantly shortened.Univariate analysis showed that age,prognosis classification of European Leu-kemia Net(ELN),Eastern Cooperative Oncology Group(ECOG)score,and ACTH were correlated with poor survival in AML patients(P＜0.05).Multivariate COX regression analysis showed that age,prognosis classification of ELN,ECOG score,and ACTH level were the independent factors for patient survival(P＜0.05).A nomogram and calibration curves for predicting overall survival were construc-ted using these factors,which showed that the calibration curve of the model was close to the standard curve,showing a good linear rela-tionship.Conclusion Low ACTH level is an independent prognostic factor for survival in AML patients,and a model of nomogram con-structed based on age,prognostic classification of ELN,ECOG score and ACTH level has a good predictive value.

Single cell RNA sequencing technique provides a strong technical support for the analysis of cell heterogeneity in biological tissues, and has been widely used in biomedical research. In recent years, considerable scRNA-seq data have been accumulated in the research of ocular fundus diseases. The ocular fundus is abundant for the network of vessel and neuron, which leads to the complicated pathogenesis of fundus diseases. Through single cell RNA sequencing technique, the expression of thousands of genes of certain cell types or even subtypes can be obtained in the disease environment. Single cell RNA sequencing technique accurately reveals the pathogenic cell types and pathogenic mechanisms of ocular fundus diseases such as neovascular retinopathy, which provides a theoretical basis for the birth of new diagnosis and treatment targets. The construction of multi-omics single-cell database of ocular fundus diseases will enable high-quality data to be further explored and provide an analysis platform for ophthalmic researchers.