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 treatment of bi （痹） disease in The Inner Canon of Yellow Emperor （《黄帝内经》） is mainly based on acupuncture therapy. There are differences in needling depth， angle， needling techniques， number of needles and the selection of needle instruments. By reviewing literature， it is found that in The Inner Canon of Yellow Emperor， five body constituents （skin， vessel， flesh， sinew， bone） disease location differentiation is taken as the principle for the diagnosis and treatment of bi disease， guiding the needle to the lesion level where the disease is located， and according to the severity of the disease， the characteristics of pathological qi and other factors， the choice of specific acupuncture method and needles are made. This paper summarized and grouped the 17 kinds of acupuncture methods for the treatment of bi disease according to the different five body consitutuents disease location. For needle instruments， filiform needles which can softly unblock and regulate qi are often used in the treatment of bi disease. Lance needles are good at treating vessel bi with the function of clearing blood and moving qi. Round-sharp needles and fire needles are applicable for sinew bi， among which fire needles are especially good at that induced by cold. Long needles have advantages for deep-seated bi disease due to their long needle body. The puncturing method should be in accordance with the needle instruments. The five body instituents disease location differentiation and treatment is a unique system of acupuncture in the treatment of bi disease， which is worthy of more inheritance and application.

Interactions between gut microbiome and host immune system are fundamental to maintaining the intestinal mucosal barrier and homeostasis. At the host-gut microbiome interface, cell wall-derived molecules from gut commensal bacteria have been reported to play a pivotal role in training and remodeling host immune responses. In this article, we review gut bacterial cell wall-derived molecules with characterized chemical structures, including peptidoglycan and lipid-related molecules that impact host health and disease processes via regulating innate and adaptive immunity. Also, we aim to discuss the structures, immune responses, and underlying mechanisms of these immunogenic molecules. Based on current advances, we propose cell wall-derived components as important sources of medicinal agents for the treatment of infection and immune diseases.
Gastrointestinal Microbiome ; Intestinal Mucosa ; Bacteria ; Immune System ; Symbiosis ; Immunity, Mucosal ; Immunity, Innate

Objective:To explore the mediating role of self-hating in the influence of adverse childhood experiences on adolescents' negative emotions.Methods:A questionnaire method was used to collect demographic variables, and 7 012 valid questionnaires were obtained from adolescents by applying the revised adverse childhood experiences questionnaire, patient health questionnaire-4, and self-hate scale from May 1 to May 30, 2022, in five high schools(90 classes) and five junior high schools(60 classes) in Rizhao city, Shandong province, China. Data entry and analysis were performed by SPSS 22.0 software.Mann-Whitney U test was used for the comparison between demographic variables and other variables, and the correlations between variables were expressed by Spearman correlation coefficient. AMOS 23.0 software was applied for testing the mediating and moderating effects of variables. Results:(1)There were significant positive correlations between adverse childhood experiences(0(2)) and negative emotion(3(10))( r=0.459, P<0.01), self-hating(2(4))( r=0.427, P<0.01). There were significant positive correlations between self-hating and negative emotion( r=0.566, P<0.01). (2) Self-hating played a mediating role between adverse childhood experience and adolescent negative emotion, and the mediating effect was 0.299, accounted for 61.27% of the total effect.(3) The mediating pathway of self-hated was moderated by gender, with girls' adverse childhood experiences( Bsimple=2.428, t=39.585, P<0.05) predicting self-hating more than boys( Bsimple=1.641, t=25.355, P<0.05). Conclusion:Adverse childhood experiences can predict adolescents' negative emotions, and self-disgusting can also affect adolescents' negative emotions.Gender plays a moderating role in the mediating pathway.

Objective: To establish a quantitative assay of serum Golgi protein 73 (GP73) using xMAP technology and evaluate its performance. Methods: Monoclonal antibodies against GP73 were prepared and purified, and antibody pair screening was performed by double-antibody sandwich enzyme-linked immunosorbent assay. The screened antibodies were used to construct a Luminex liquid chip detection system, and the analysis performance of the detection system was evaluated. The serum levels of GP73 were detected in 90 clinical samples from healthy controls and patients with chronic hepatitis B infection (CHB) and hepatocellular carcinoma (HCC). Results: Five anti-GP73 monoclonal antibodies were prepared and purified, and 5 antibody pairs were successfully screened. The Luminex liquid chip detection system of GP73 was successfully constructed using 8F10D1 and 10B9F11 antibody pairs. The analytical performance evaluation showed that the sensitivity of this system was 0.25 ng/ml and the dynamic range was 0.25-100 ng/ml. No cross reactivity was observed. The intra- and inter-assay variation for GP73 was <8% and <11%, respectively. The recovery was 83%-92%. The linear regression equation was y=1.141x+ 6.436 (r²=0.998 4, P<0.001). The GP73 concentrations in the serum samples of healthy control, CHB group, and HCC group were 42.8 (38.68, 55.90) ng/ml, 61.49 (43.59, 81) ng/ml, and 122.78 (49.36 liter, 264.55) ng/ml, respectively. The levels of GP73 in HCC group were significantly higher than those in CHB group and healthy controls (P<0.05). Moreover, the levels of GP73 in CHB group were significantly higher than those in healthy controls (P<0.05). Conclusions A liquid chip detection system of GP73 was successfully constructed. It provides a powerful tool for the clinical application of GP73 in the future.

Objective To establish a quantitative assay of serum Golgi protein 73 ( GP73) using xMAP technology and evaluate its performance. Methods Monoclonal antibodies against GP73 were prepared and purified, and antibody pair screening was performed by double?antibody sandwich enzyme?linked immunosorbent assay. The screened antibodies were used to construct a Luminex liquid chip detection system, and the analysis performance of the detection system was evaluated. The serum levels of GP73 were detected in 90 clinical samples from healthy controls and patients with chronic hepatitis B infection ( CHB) and hepatocellular carcinoma ( HCC). Results Five anti?GP73 monoclonal antibodies were prepared and purified, and 5 antibody pairs were successfully screened.The Luminex liquid chip detection system of GP73 was successfully constructed using 8F10D1 and 10B9F11 antibody pairs. The analytical performance evaluation showed that the sensitivity of this system was 0.25 ng／ml and the dynamic range was 0.25?100 ng／ml. No cross reactivity was observed. The intra? and inter?assay variation for GP73 was ＜8% and ＜11%, respectively. The recovery was 83%?92%. The linear regression equation was y＝1.141x+6.436 ( r2 ＝0.998 4, P＜0.001). The GP73 concentrations in the serum samples of healthy control, CHB group, and HCC group were 42.8 (38.68, 55.90) ng／ml, 61.49 (43.59, 81) ng／ml, and 122.78 (49.36 liter, 264.55) ng／ml, respectively.The levels of GP73 in HCC group were significantly higher than those in CHB group and healthy controls (P＜0.05). Moreover, the levels of GP73 in CHB group were significantly higher than those in healthy controls ( P＜0.05). Conclusions A liquid chip detection system of GP73 was successfully constructed. It provides a powerful tool for the clinical application of GP73 in the future.

Objective To establish a quantitative assay of serum Golgi protein 73 ( GP73) using xMAP technology and evaluate its performance. Methods Monoclonal antibodies against GP73 were prepared and purified, and antibody pair screening was performed by double?antibody sandwich enzyme?linked immunosorbent assay. The screened antibodies were used to construct a Luminex liquid chip detection system, and the analysis performance of the detection system was evaluated. The serum levels of GP73 were detected in 90 clinical samples from healthy controls and patients with chronic hepatitis B infection ( CHB) and hepatocellular carcinoma ( HCC). Results Five anti?GP73 monoclonal antibodies were prepared and purified, and 5 antibody pairs were successfully screened.The Luminex liquid chip detection system of GP73 was successfully constructed using 8F10D1 and 10B9F11 antibody pairs. The analytical performance evaluation showed that the sensitivity of this system was 0.25 ng／ml and the dynamic range was 0.25?100 ng／ml. No cross reactivity was observed. The intra? and inter?assay variation for GP73 was ＜8% and ＜11%, respectively. The recovery was 83%?92%. The linear regression equation was y＝1.141x+6.436 ( r2 ＝0.998 4, P＜0.001). The GP73 concentrations in the serum samples of healthy control, CHB group, and HCC group were 42.8 (38.68, 55.90) ng／ml, 61.49 (43.59, 81) ng／ml, and 122.78 (49.36 liter, 264.55) ng／ml, respectively.The levels of GP73 in HCC group were significantly higher than those in CHB group and healthy controls (P＜0.05). Moreover, the levels of GP73 in CHB group were significantly higher than those in healthy controls ( P＜0.05). Conclusions A liquid chip detection system of GP73 was successfully constructed. It provides a powerful tool for the clinical application of GP73 in the future.

Objective To evaluate retrograde transpopliteal access for femoral-popliteal artery total occlusion with blind puncture.Methods Clinical data of 22 cases admitted from Sep 2014 to June 2016 undergoing endovascular treatment of the femoral-politeal artery occlusion with transpopliteal artery retrograde access by blind puncture were analyzed.Results A total of 22 patients underwent retrograde popliteal access with blind puncture after antegrade attempts failed.Puncture above the knee was performed in 18 cases and below the knee in 4 cases.The average increase of ABI was 0.57.Hematoma of puncture site was observed in 2 patients,other complications included pneumonia in 1 case and renal insufficiency in 2 cases.The mean follow-up time was (13 ± 5)months.Restenosis occurred in 8 patiens(36.4％)during the follow-up time.The primary patency was (86.4 ± 0.07) ％ at 6 months and (70.7-± 0.12) ％ at 12 months.There was no major amputation rate and mortality during the follow-up.Conclusions Retrograde transpopliteal access for femoral-popliteal artery occlusion with blind puncture is safe and effective.