Objective:To develop an artificial intelligence (AI)-based automatic scoring model for magnetic resonance imaging-detected extramural vascular invasion (AI-mrEMVI) and evaluate its performance and prognostic value in patients with rectal cancer.Methods:In this multicenter retrospective cohort study, a total of 2 501 rectal cancer patients from seven centers between November 2012 and December 2020 were included and divided into completely independent training ( n=1 830) and validation ( n=671) cohorts. A nnUNet-based AI-mrEMVI scoring model was constructed. Manual mrEMVI scores assigned by two radiologists served as the reference standard for accessing the accuracy of the AI-mrEMVI scoring. Kaplan-Meier survival analysis and Cox regression were used to evaluate the prognostic stratification ability of the AI-mrEMVI scores. The concordance index (C-index) was calculated to evaluate prognostic performance. Results:In the validation cohort, the manual mrEMVI scores were 0-2 in 425 patients (63.3%), 3 in 89 (13.4%), and 4 in 157 (23.4%). The AI-mrEMVI model identified 0-2 in 375 patients (55.9%), 3 in 95 (14.2%), and 4 in 201 (30.0%), with an overall accuracy of 81.1% (544/671, 95% CI 77.9%-84.0%). The 3-year disease-free survival (DFS) rates for patients with AI-mrEMVI scores of 0-2, 3, and 4 were 85.2%, 70.0%, and 58.2%, respectively, and the 5-year overall survival (OS) rates were 87.2%, 81.6%, and 62.6%, respectively (DFS: χ2=48.74, P<0.001; OS: χ2=30.04, P<0.001). Multivariable Cox regression showed that for DFS, AI-mrEMVI scores of 3 and 4 were associated with hazard ratios ( HR) of 1.75 (95% CI 1.11-2.77, P=0.016) and 2.65 (95% CI 1.86-3.78, P<0.001), respectively. For OS, an AI-mrEMVI score of 4 was associated with an HR of 2.56 (95% CI 1.62-4.03, P<0.001). The C-index values of the AI-mrEMVI scoring model for predicting DFS and OS were 0.647 (95% CI 0.608-0.686) and 0.650 (95% CI 0.598-0.702), respectively. Conclusion:The proposed AI-mrEMVI automatic scoring model demonstrated high diagnostic accuracy and performed favorably in predicting DFS and OS prognostic risk in patients with rectal cancer.

Objective:To develop an artificial intelligence (AI)-based automatic scoring model for magnetic resonance imaging-detected extramural vascular invasion (AI-mrEMVI) and evaluate its performance and prognostic value in patients with rectal cancer.Methods:In this multicenter retrospective cohort study, a total of 2 501 rectal cancer patients from seven centers between November 2012 and December 2020 were included and divided into completely independent training ( n=1 830) and validation ( n=671) cohorts. A nnUNet-based AI-mrEMVI scoring model was constructed. Manual mrEMVI scores assigned by two radiologists served as the reference standard for accessing the accuracy of the AI-mrEMVI scoring. Kaplan-Meier survival analysis and Cox regression were used to evaluate the prognostic stratification ability of the AI-mrEMVI scores. The concordance index (C-index) was calculated to evaluate prognostic performance. Results:In the validation cohort, the manual mrEMVI scores were 0-2 in 425 patients (63.3%), 3 in 89 (13.4%), and 4 in 157 (23.4%). The AI-mrEMVI model identified 0-2 in 375 patients (55.9%), 3 in 95 (14.2%), and 4 in 201 (30.0%), with an overall accuracy of 81.1% (544/671, 95% CI 77.9%-84.0%). The 3-year disease-free survival (DFS) rates for patients with AI-mrEMVI scores of 0-2, 3, and 4 were 85.2%, 70.0%, and 58.2%, respectively, and the 5-year overall survival (OS) rates were 87.2%, 81.6%, and 62.6%, respectively (DFS: χ2=48.74, P<0.001; OS: χ2=30.04, P<0.001). Multivariable Cox regression showed that for DFS, AI-mrEMVI scores of 3 and 4 were associated with hazard ratios ( HR) of 1.75 (95% CI 1.11-2.77, P=0.016) and 2.65 (95% CI 1.86-3.78, P<0.001), respectively. For OS, an AI-mrEMVI score of 4 was associated with an HR of 2.56 (95% CI 1.62-4.03, P<0.001). The C-index values of the AI-mrEMVI scoring model for predicting DFS and OS were 0.647 (95% CI 0.608-0.686) and 0.650 (95% CI 0.598-0.702), respectively. Conclusion:The proposed AI-mrEMVI automatic scoring model demonstrated high diagnostic accuracy and performed favorably in predicting DFS and OS prognostic risk in patients with rectal cancer.

The aim of this study is to identify the linear Fc-binding epitope for IgG1 on bovine IgG Fc receptor Ⅱ(boFcγRⅡ)to understand the molecular basis of IgG-Fcγ interaction.The boFcγRⅡ molecules were expressed on cell surface of the boFcγR Ⅱ-transfected COS-7 cells.The extracel-lular domain of boFcγRⅡ was expressed in NS0 cells,and the boFcγRⅡ recombinant protein was purified from ascites by Ni-chelation chromatography.Peptides derived from the membrane-distal extracellular domain(EC2)of boFcγR Ⅱ were synthesized and conjugated to a carrier protein of IgG-free bovine serum albumin(BSA).Binding of bovine IgG1 to the different peptides was tested by dot-blot assay,and the IgG-binding peptide was further modified by truncation and mutation to identify the Fc-binding epitope as well as its key amino acids for Fc-binding.The inhibition effect of the Fc-binding peptide was determined by competitive ELISA and Fc-rosetting inhibition assay,re-spectively.The results showed that boFcγR Ⅱ molecules were stably expressed on surface of the transfected COS-7 cells,which showed about 90％rosetting with IgG1-RBCs.The soluble boFcγRⅡ recombinant protein specifically bound to bovine IgG1.The minimal effective peptide of 122FYQDRKSKIF131 of boFcγRⅡ was able to bind bovine IgG1 specifically,suggesting it repre-sents a linear Fc-binding epitope located in the putative C-C'loop of the EC2 domain on the recep-tor.The Ala-substitution of Phe122,Tyr123,Arg126,Lys127,Ser128,Lys129 or Phe131 within the linear epitope led to a complete loss of its IgG1-binding capability,indicating those residues are critical for IgG1-binding on boFcγRⅡ.The Fc-binding peptide inhibited bovine IgG1 binding to the soluble recombinant protein of boFcγRⅡ with IC50 of 20.05 μmol/L,and inhibited the rosette formation of bovine IgG1-sensitized RBCs on the boFcγRⅡ transfected cells with IC50 of 80.15 μmol/L.The re-sults indicate that boFcγRⅡ possesses the linear epitope for Fc-binding,and the Fc-binding pep-tide showed well capability of regulating boFcγR Ⅱ-IgG1 interaction on cell surface,thereby provi-ding a research foundation for understanding the IgG-Fcγ interaction.

The aim of this study is to identify the linear Fc-binding epitope for IgG1 on bovine IgG Fc receptor Ⅱ(boFcγRⅡ)to understand the molecular basis of IgG-Fcγ interaction.The boFcγRⅡ molecules were expressed on cell surface of the boFcγR Ⅱ-transfected COS-7 cells.The extracel-lular domain of boFcγRⅡ was expressed in NS0 cells,and the boFcγRⅡ recombinant protein was purified from ascites by Ni-chelation chromatography.Peptides derived from the membrane-distal extracellular domain(EC2)of boFcγR Ⅱ were synthesized and conjugated to a carrier protein of IgG-free bovine serum albumin(BSA).Binding of bovine IgG1 to the different peptides was tested by dot-blot assay,and the IgG-binding peptide was further modified by truncation and mutation to identify the Fc-binding epitope as well as its key amino acids for Fc-binding.The inhibition effect of the Fc-binding peptide was determined by competitive ELISA and Fc-rosetting inhibition assay,re-spectively.The results showed that boFcγR Ⅱ molecules were stably expressed on surface of the transfected COS-7 cells,which showed about 90％rosetting with IgG1-RBCs.The soluble boFcγRⅡ recombinant protein specifically bound to bovine IgG1.The minimal effective peptide of 122FYQDRKSKIF131 of boFcγRⅡ was able to bind bovine IgG1 specifically,suggesting it repre-sents a linear Fc-binding epitope located in the putative C-C'loop of the EC2 domain on the recep-tor.The Ala-substitution of Phe122,Tyr123,Arg126,Lys127,Ser128,Lys129 or Phe131 within the linear epitope led to a complete loss of its IgG1-binding capability,indicating those residues are critical for IgG1-binding on boFcγRⅡ.The Fc-binding peptide inhibited bovine IgG1 binding to the soluble recombinant protein of boFcγRⅡ with IC50 of 20.05 μmol/L,and inhibited the rosette formation of bovine IgG1-sensitized RBCs on the boFcγRⅡ transfected cells with IC50 of 80.15 μmol/L.The re-sults indicate that boFcγRⅡ possesses the linear epitope for Fc-binding,and the Fc-binding pep-tide showed well capability of regulating boFcγR Ⅱ-IgG1 interaction on cell surface,thereby provi-ding a research foundation for understanding the IgG-Fcγ interaction.

Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Fibrosis ; Liver Diseases/drug therapy* ; Treatment Outcome ; Liver Cirrhosis/drug therapy*

Objective:To explore the knowledge-attitude-practice (KAP) level in patients with diabetic retinopathy (DR) and analyze the correlation between these factors and KAP.Methods:Totally 318 DR patients were selected using cluster sampling and investigated for their demographic information and KAP from March 2018 to March 2019. Spearman correlation analysis was used to analyze the factors related to KAP.Results:The total KAP score of the 315 DR patients was (19.26±5.77) , and their score of DR prevention and control knowledge was (9.37±4.08) , with an accuracy rate of 43.81%. The most common way for DR patients to obtain knowledge is was "mobile phone / WeChat / other online channels", followed by "communication with patients"; the most desired way for DR patients to obtain knowledge was "health lectures by doctors / nurses", and the DR-related service that they wanted the most was "free blood sugar and fundus examination". The DR attitude score was (4.61±1.33) . The positive response rate for "glycemic monitoring and control is very important for DR, and all patients must control blood glucose within the normal range" was 86.03%, ranking the highest, while the positive response rate for "willing to receive psychological guidance" was 19.68%, ranking the lowest. The DR behavior score was (5.28±1.96) . The positive response rate for "ask family, friends, or medical professionals for help with vision problems" was 89.52%, ranking the highest, while the positive rate for "able to abide by the principles of diabetes diet on holidays, birthdays, or outing" was 34.29%, ranking the lowest. Spearman correlation analysis revealed that there were positive correlations between the course of disease and the total score of KAP ( r=0.510, P=0.032) , education levels ( r=0.171, P=0.011) and DR prevention knowledge, the average monthly family income ( r=0.922, P=0.021) , with or without complications ( r=0.671, P=0.027) and DR attitude, and living style ( r=0.381, P=0.013) , average monthly household income ( r=0.884, P=0.024) and DR behavior. Conclusions:The overall level of KAP in DR patients is low, and health education for medical staff needs to be strengthened. KAP is closely related to factors such as age, education, complications, average family income, and living style. KAP in DR patients should be improved through many ways in clinical practice.

Objective To investigate the distribution and constituent of drug‐resistant bacteria of lower respiratory tract in‐fection among different regions (outpatient department ,wards ,RICU) to provide the basis for the clinical reasonable application of antimicrobial agents .Methods The K‐B disc diffusion method and the instrument method (VITEK‐TWO) were adopted and the detection results were interpreted according to the standards of CLSI 2010 .The detection data of 480 drug‐resistant strains isolated from the sputum ,branchoalveolar lavage fluid samples submitted in 3 regions of respiratory outpatients department by bacterial cul‐ture identification and drug susceptibility test were analyzed by using the WHONET5 .6 statistical software .Results The distribu‐tion and constituent of drug‐resistant bacteria of lower respiratory tract infection had obvious difference among 3 different regions . The top 4 of drug resistant bacteria were dominated by Gram‐negative bacteria .The drug resistance rate of Klebsiella pneumoniae in RICU was higher than that in the respiratory outpatients department and wards(P<0 .05) ,the resistance rate in the respiratory outpatients department ,wards and RICU to commonly used antibacterial drugs was similar;the multiple drug resistance of ESBLs‐producing strains was obviously higher than that of non‐ESBLs‐producing strains (P<0 .05) .Pseudomonas aeruginosa maintained the higher antibacterial activity to quinolone ,aminoglucosides ,cefepime ,imipenem ,cefoperazone/sulbactam ,and piperacillin/tazobactam ,but the resistance rate in RICU was significantly higher that in the respiratory outpatient department and wards (P<0 .05);the drug resistance of Acinetobacter baumanii in the respiratory wards and RICU was higher than that in the respiratory out‐patient department ,the resistances to imipenem were 64 .6% and 70 .4% respectively .The resistance of MRSA to rifampin in RICU was higher than that in the respiratory outpatient department and wards(P<0 .05) .Conclusion The distribution constituent and drug‐resistance rates have obvious differences among the respiratory outpatient department ,wards and RICU .Except being familiar with the drug resitant bacterial distribution and drug resistance rate monitoring situation ,clinical doctors should grasp the drug re‐sistance situation of drug resistant bacteria among different areas in various departments of own unit in order to rationally and effec‐tively use antibacterial drugs .

OBJECTIVETo study long-term effect on renal function exposed to environmental cadmium.

METHODSStratified random sampling and cluster sampling method of epidemiological investigations were carried out in northern Guangdong province between April, 2011 and August, 2012. A total of 167 residents who lived in high cadmium exposure area for more than 15 years, aged above 40 were selected in exposed group. Moreover, A total of 145 residents who had similar living and economic conditions and lived in local for more than 15 years, aged above 40 were selected in control group. We used health questionnaires and medical examinations in order to acquire their health status. Home-harvested rice and vegetables were collected using quartering method for detection of cadmium level. Urine specimens of residents were collected for detection of cadmium level and creatinine as well as renal dysfunction biomarkers, namely, N-acetyl-beta-D-glucosamidase (NAG), β2-microglobulin (β2-MG), and retinol binding protein(RBP), respectively. The analysis of spearman rank correlation and multiple regression were used to investigate the relationships between age, urinary cadmium levels and renal injury biomarkers.

RESULTSThe cadmium levels in rice and vegetables of exposed group were 0.75 and 0.10 mg/kg, both were significantly higher than 0.07 and 0.01 mg/kg in the control group (Z values were -6.32 and -7.84, all P values < 0.001). The urinary cadmium level of exposed group was 8.29 µg/g · cr, which was higher than that of the control group 2.03 µg/g · cr with significant difference (Z value was -11.39, P < 0.001). After stratified the total population by age, the urinary cadmium level in 40-49 years, 50-59 years and ≥ 60 years subgroups were 7.22, 8.71, and 13.10 µg/g · cr, which both were significantly higher than 1.80, 2.04, and 2.05 µg/g · cr in the control group (Z values were -5.22, -7.41, and -7.14, all P values < 0.001). After stratified the total population by gender, the urinary cadmium level of male and female were 5.12 and 12.36 µg/g · cr, which both were significantly higher than 1.79 and 2.16 µg/g · cr in the control group (Z values were -7.68 and -9.03, all P values < 0.001). Comparing the differences of renal dysfunction biomarkers (NAG, β2-MG, RBP) between two groups. The level of urinary β2-MG and RBP of exposed group were 0.21 and 0.04 µg/g · cr, which were higher than 0.05 and 0.00 µg/g · cr of the control group with significant difference (Z value was -7.08 and -9.65, all P values < 0.001). Pearson correlation analysis showed that NAG, β2-MG and RBP were positively correlated with urinary cadmium and age, the correlation coefficients were 0.57, 0.49, 0.21 and 0.22, 0.26, 0.23 respectively (all P values < 0.001). After adjusting the effect of age, it was appeared that urinary cadmium levels contributed most to the alteration of NAG, β2-MG and RBP, the standardized regression coefficients were 0.57, 0.49 and 0.20 (all P values < 0.001), and suggested that the cadmium body burden was one of the most important factors for renal dysfunction.

CONCLUSIONResidents, who had cadmium contaminated rice and vegetables for a long time, would take the risk of increasing body burden of cadmium and urinary early biomarkers of renal tubular injury that referred to occurrence of renal dysfunction.

Adult ; Aged ; Cadmium ; Creatinine ; Environmental Exposure ; Epidemiologic Studies ; Female ; Food Contamination ; Humans ; Kidney Diseases ; Male ; Middle Aged ; Multivariate Analysis ; Oryza ; Risk ; Time ; Vegetables

Objective To study long-term effect on renal function exposed to environmental cadmium. Methods Stratified random sampling and cluster sampling method of epidemiological investigations were carried out in northern Guangdong province between April, 2011 and August, 2012 . A total of 167 residents who lived in high cadmium exposure area for more than 15 years, aged above 40 were selected in exposed group. Moreover, A total of 145 residents who had similar living and economic conditions and lived in local for more than 15 years, aged above 40 were selected in control group. We used health questionnaires and medical examinations in order to acquire their health status. Home-harvested rice and vegetables were collected using quartering method for detection of cadmium level . Urine specimens of residents were collected for detection of cadmium level and creatinine as well as renal dysfunction biomarkers, namely, N-acetyl-beta-D-glucosamidase(NAG), β2-microglobulin(β2-MG), and retinol binding protein(RBP), respectively. The analysis of spearman rank correlation and multiple regression were used to investigate the relationships between age, urinary cadmium levels and renal injury biomarkers. Results The cadmium levels in rice and vegetables of exposed group were 0.75 and 0.10 mg/kg, both were significantly higher than 0.07 and 0.01 mg/kg in the control group (Z values were-6.32 and-7.84, all P values<0.001). The urinary cadmium level of exposed group was 8.29μg/g·cr, which was higher than that of the control group 2.03μg/g·cr with significant difference(Z value was-11.39, P<0.001). After stratified the total population by age, the urinary cadmium level in 40-49 years, 50-59 years and≥60 years subgroups were 7.22, 8.71, and 13.10μg/g·cr, which both were significantly higher than 1.80, 2.04, and 2.05μg/g·cr in the control group (Z values were-5.22,-7.41, and-7.14, all P values<0.001). After stratified the total population by gender , the urinary cadmium level of male and female were 5.12 and 12.36μg/g · cr, which both were significantly higher than 1.79 and 2.16 μg/g · cr in the control group (Z values were-7.68 and-9.03, all P values<0.001). Comparing the differences of renal dysfunction biomarkers (NAG, β2-MG, RBP) between two groups. The level of urinaryβ2-MG and RBP of exposed group were 0.21 and 0.04μg/g · cr, which were higher than 0.05 and 0.00 μg/g · cr of the control group with significant difference(Z value was-7.08 and-9.65, all P values<0.001). Pearson correlation analysis showed that NAG,β2-MG and RBP were positively correlated with urinary cadmium and age, the correlation coefficients were 0.57,0.49,0.21and 0.22, 0.26, 0.23 respectively (all P values<0.001). After adjusting the effect of age, it was appeared that urinary cadmium levels contributed most to the alteration of NAG, β2-MG and RBP, the standardized regression coefficients were 0.57, 0.49 and 0.20 (all P values<0.001), and suggested that the cadmium body burden was one of the most important factors for renal dysfunction. Conclusion Residents, who had cadmium contaminated rice and vegetables for a long time, would take the risk of increasing body burden of cadmium and urinary early biomarkers of renal tubular injury that referred to occurrence of renal dysfunction.

Objective To study long-term effect on renal function exposed to environmental cadmium. Methods Stratified random sampling and cluster sampling method of epidemiological investigations were carried out in northern Guangdong province between April, 2011 and August, 2012 . A total of 167 residents who lived in high cadmium exposure area for more than 15 years, aged above 40 were selected in exposed group. Moreover, A total of 145 residents who had similar living and economic conditions and lived in local for more than 15 years, aged above 40 were selected in control group. We used health questionnaires and medical examinations in order to acquire their health status. Home-harvested rice and vegetables were collected using quartering method for detection of cadmium level . Urine specimens of residents were collected for detection of cadmium level and creatinine as well as renal dysfunction biomarkers, namely, N-acetyl-beta-D-glucosamidase(NAG), β2-microglobulin(β2-MG), and retinol binding protein(RBP), respectively. The analysis of spearman rank correlation and multiple regression were used to investigate the relationships between age, urinary cadmium levels and renal injury biomarkers. Results The cadmium levels in rice and vegetables of exposed group were 0.75 and 0.10 mg/kg, both were significantly higher than 0.07 and 0.01 mg/kg in the control group (Z values were-6.32 and-7.84, all P values<0.001). The urinary cadmium level of exposed group was 8.29μg/g·cr, which was higher than that of the control group 2.03μg/g·cr with significant difference(Z value was-11.39, P<0.001). After stratified the total population by age, the urinary cadmium level in 40-49 years, 50-59 years and≥60 years subgroups were 7.22, 8.71, and 13.10μg/g·cr, which both were significantly higher than 1.80, 2.04, and 2.05μg/g·cr in the control group (Z values were-5.22,-7.41, and-7.14, all P values<0.001). After stratified the total population by gender , the urinary cadmium level of male and female were 5.12 and 12.36μg/g · cr, which both were significantly higher than 1.79 and 2.16 μg/g · cr in the control group (Z values were-7.68 and-9.03, all P values<0.001). Comparing the differences of renal dysfunction biomarkers (NAG, β2-MG, RBP) between two groups. The level of urinaryβ2-MG and RBP of exposed group were 0.21 and 0.04μg/g · cr, which were higher than 0.05 and 0.00 μg/g · cr of the control group with significant difference(Z value was-7.08 and-9.65, all P values<0.001). Pearson correlation analysis showed that NAG,β2-MG and RBP were positively correlated with urinary cadmium and age, the correlation coefficients were 0.57,0.49,0.21and 0.22, 0.26, 0.23 respectively (all P values<0.001). After adjusting the effect of age, it was appeared that urinary cadmium levels contributed most to the alteration of NAG, β2-MG and RBP, the standardized regression coefficients were 0.57, 0.49 and 0.20 (all P values<0.001), and suggested that the cadmium body burden was one of the most important factors for renal dysfunction. Conclusion Residents, who had cadmium contaminated rice and vegetables for a long time, would take the risk of increasing body burden of cadmium and urinary early biomarkers of renal tubular injury that referred to occurrence of renal dysfunction.