Antibody-drug conjugates （ADCs） are a novel class of anti-tumor agents composed of a targeted monoclonal antibody， a cytotoxic drug， and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer （TNBC） is characterized by high aggressiveness， elevated risks of recurrence and metastasis， and poor prognosis， largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 （such as trastuzumab deruxtecan）， trophoblast cell surface antigen 2 （such as sacituzumab govitecan and datopotamab deruxtecan）， zinc transporter LIV-1 （such as ladiratuzumab vedotin）， HER-3 （such as patritumab deruxtecan）， epidermal growth factor receptor （such as AVID100）， and glycoprotein non-metastatic melanoma protein B （such as glembatumumab vedotin） have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities， ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.

OBJECTIVE: To investigate the diagnostic efficacy of ^99mTc-MDP three-phase bone scintigraphy (TPBS) combined with C-reactive protein (CRP) for periprosthetic joint infection (PJI). METHODS: The clinical data of 198 patients who underwent revision surgery of artificial joint between January 2017 and January 2024 and received TPBS examination before surgery were retrospectively analyzed. There were 77 males and 121 females with an average age of 63.74 years ranging from 24 to 92 years. There were 90 cases of hip arthroplasty and 108 cases of knee arthroplasty. PJI was diagnosed according to the 2013 American Musculoskeletal Infection Society (MSIS) standard diagnostic criteria. The sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predict value (PPV) were calculated. The receiver operating characteristic (ROC) curve was used to compare the diagnostic performance of the three methods, and the area under curve (AUC) was used to evaluate the diagnostic performance. RESULTS: According to the 2013 MSIS criteria, 116 cases were diagnosed as PJI, and the remaining 82 cases were aseptic loosening. The cases of PJI diagnosed by TPBS, CRP, and TPBS-CRP were 125, 109, and 137 respectively, and the cases of aseptic loosening were 73, 89, and 61 respectively. The sensitivity, accuracy, NPV, and PPV of TPBS-CRP combination in the diagnosis of PJI were higher than those of TPBS and CRP, but the specificity was lower than that of TPBS and CRP. ROC curve analysis further showed that the AUC value of TPBS-CRP combination was better than that of TPBS and CRP. The severity of bone defect and the duration of symptoms in patients with false positive TPBS diagnosis were worse than those in patients with true negative TPBS diagnosis (P<0.05), but there was no significant difference in the survival time of prosthesis between the two groups (P>0.05). Among the patients diagnosed with PJI by TPBS, CRP, and TPBS-CRP, 49, 35, and 54 patients had received antibiotic treatment 2 weeks before diagnosis, respectively. There was no significant difference in the diagnostic accuracy of TPBS and TPBS-CRP before diagnosis between patients treated with and without antibiotics and those not treated (P>0.05). The diagnostic accuracy of antibiotic therapy before CRP diagnosis was significantly lower than that of untreated patients (P<0.05). CONCLUSION TPBS and CRP have limited specificity in differentiating PJI from aseptic loosening. The TPBS-CRP combination diagnostic method can synergize the local bone metabolic characteristics and systemic inflammatory response to achieve higher diagnostic accuracy, but caution should be exercised in patients with severe bone defects and longer symptom duration.
Humans ; Prosthesis-Related Infections/blood* ; Middle Aged ; Male ; Female ; Aged ; C-Reactive Protein/metabolism* ; Retrospective Studies ; Adult ; Radionuclide Imaging/methods* ; Arthroplasty, Replacement, Knee/adverse effects* ; Aged, 80 and over ; Technetium Tc 99m Medronate ; Arthroplasty, Replacement, Hip/adverse effects* ; Sensitivity and Specificity ; Knee Prosthesis/adverse effects* ; ROC Curve ; Reoperation ; Radiopharmaceuticals ; Young Adult

[This corrects the article DOI: 10.1016/j.apsb.2024.09.010.].

ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill （SQTLP） on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus （T2DM） mice based on nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） pathway. MethodA total of 60 7-week-old male db/db mice ［specific pathogen-free （SPF） grade］ were selected and fed for one week for adaption. They were divided into the model control group， SQTLP low-， medium- and high-dose （19， 38， and 76 g·kg^-1） groups and metformin group （0.26 g·kg^-1） by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose （FBG） was detected. Fasting serum insulin （FINS） levels were detected by enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment-insulin resistance （HOMA-IR） index and the homeostasis model assessment-insulin sensitivity index （HOMA-ISI） were calculated. Oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were conducted. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） and the contents of malondialdehyde （MDA） and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species （ROS） and 4-hydroxynonenal （4-HNE） in skeletal muscle tissue were detected by immunofluorescence （IF）. The expression levels of Nrf2， HO-1， NQO1 and glutamate-cysteine ligase catalytic subunit （GCLC） proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group， FBG， FINS and HOMA-IR in the model group were significantly increased （P<0.05）， while HOMA-ISI was decreased （P<0.05）. The results of OGTT and ITT showed that blood glucose was significantly increased at all time points （P<0.05）， and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased （P<0.05）， and MDA and NADPH contents were significantly increased （P<0.05）. In skeletal muscle tissues， the arrangement of muscle fibers was loose， the nucleus was disordered， and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly decreased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the metformin group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points （P<0.05）. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly increased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased （P<0.05）， and the NADPH content was decreased （P<0.05）. The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05）. Compared with those in the SQTLP low-dose group， FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05） in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice， and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway， promoting the expression of antioxidant enzymes， and thus improving the oxidative stress injury in the skeletal muscle.

ObjectiveTo explore the effect of Qingre Huayu Jianpi prescription （QHJ） on colitis-associated colorectal cancer （CAC） in mice， and its related mechanism. MethodC57BL/6 mice were randomly divided into four groups including the normal， model， QHJ low-dose （QHJ-L， 10 g·kg^-1）， and QHJ high-dose （QHJ-H， 40 g·kg^-1） groups. Azoxymethane （AOM） and dextran sodium sulfate （DSS） were combined to chemically build a CAC mouse model for 14 weeks. Each drug group was given intragastrically from the 5^th week to the 14^th week， once per day. An equal volume of water was fed to the normal and model groups. The mouse survival rate， colon length， weight， and pathological alterations were assessed. The protein expressions of Wnt-3a protein signaling （Wnt3a）， β-catenin， Non-phosphor-β-catenin （Non-p-β-catenin）， and cholesterol-binding glycoproteins 133 （CD133） were detected by Western blot. The localization and expression of the cluster of differentiation （CD） 80 and CD11 antigen-like family member B （CD11b） were detected by immunohistochemistry （IHC）. The colon organoids derived from CAC mice were isolated and cultured to detect the expression of Wnt signaling pathway-related proteins. ResultThe survival rate of the CAC mice was improved by QHJ treatment and the number of colon tumors was inhibited significantly. Compared with those in the normal group， the expression levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in colon tissues in the model group were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， the levels of Wnt3a and β-catenin in the QHJ-L group were significantly decreased （P<0.01）， and the protein levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in the QHJ-H group were significantly decreased （P<0.05， P<0.01）. Meanwhile， the expression level of CD11b in the model group was significantly increased compared with that in the normal group while the CD80 level was significantly decreased （P<0.05， P<0.01）. Compared with those in the model group， CD11b in QHJ-L and QHJ-H groups was significantly decreased， and CD80 was significantly increased（P<0.05， P<0.01）. The expressions of Non-p-β-catenin and CD133 in colonic organoids of CAC model mice were significantly increased， while QHJ treatment could inhibit the expressions of Non-p-β-catenin and CD133 in colonic organoids （P<0.01）. ConclusionQHJ could inhibit the inflammation-cancer development in CAC mice， the mechanism of which might be related to regulating the microenvironment and inhibiting the over-activation of Wnt signaling.

Objective To predict the target and molecular mechanism of Huayu Xiaopi decoction in the intervention of Precancerous lesions of gastric cancer(PLGC)based on network pharmacology and molecular docking technology,and to conduct experimental verification.Methods A total of 60 SPF SD male rats were randomly selected as blank control,and the other rats were replicated in PLGC model.After successful modeling,the rats were randomly divided into model group,folic acid group(2 mg·kg-1·d-1),Huayu Xiaopi decoction high,medium and low dose groups(24.8,12.4,6.2 g·kg-1·d-1),which were continuously administered for 90 days.The body mass and food intake of rats at 3 h were recorded,and the gastric histopathology was observed by HE staining.Network pharmacology and molecular docking techniques were used to predict the potential targets of Huayu Xiaopi decoction in PLGC intervention,and the core targets were verified by Western blot technique.Results Compared with the blank group,the body mass and 3 h food intake of rats in the model group were significantly decreased(P<0.05),the gastric mucosa of rats was significantly thinner,the glands were significantly reduced and disordered,and the intestinal metaplasia goblet cells and a large number of inflammatory cells were visible in some areas.Compared with the model group,the body mass and 3 h food intake of rats in each administration group were improved to varying degrees.Huayu Xiaopi Decoction improved significantly in medium and high doses(P<0.05),the gastric mucosa was repaired in different degrees,the glandular arrangement tended to be orderly,and the inflammatory cells in the interstitial were gradually reduced.The results of network pharmacology and molecular docking showed that TP53,JUN and MAPK3/1(ERK1/2)were the core targets of Huayu Xiaopi decoction in the intervention of PLGC.Molecular biological detection results showed that compared with blank group,the protein phosphorylation levels of TP53,c-Jun and ERK1/2 in gastric tissue of model group were significantly increased(P<0.05).Compared with model group,the protein phosphorylation levels of TP53,c-Jun and ERK1/2 in gastric tissue of rats in all administration groups were decreased to different degrees,and significantly decreased in Huayu Xiaopi decoction high-dose and medium-dose groups(P<0.05).Conclusion Huayu Xiaopi Decoction can significantly improve the survival condition of PLGC rats and promote gastric mucosal repair,the specific mechanism of which may be related to the decrease of ERK1/2,c-Jun and TP53 protein phosphorylation levels in gastric tissue of PLGC rats,and then regulate the downstream signaling molecular response.

Objective To observe the value of artificial intelligence(AI)knowledge graph and image classification for quality control(QC)of chest posterior-anterior position X-ray radiograph(abbreviated as chest film).Methods Totally 9 236 chest films from 595 medical institutions in Anhui province imaging cloud platform were retrospectively enrolled.QC knowledge graph containing 21 classification labels were constructed.Firstly,QC of chest films based on the above knowledge graph were performed by 10 technicians for 2 rounds of single person and 1 round of multi person,and the results were recorded as A,B and C,respectively.Then AI algorithms were used to classify and evaluate based on knowledge graph,and the result was recorded as D.Finally,a QC expert reviewed results C and D to determine the final QC results and taken those as references to analyze the efficiency of the above 4 QC.Results The area under the curve(AUC)of AI algorithm for QC of chest films were all ≥0.780,with an average value of 0.939.The average precision of QC for chest films of A,B,C and D was 81.15％,85.47％,91.65％and 92.21％,respectively.Conclusion AI knowledge graph and image classification technology could be effectively used for QC of chest posterior-anterior position X-ray radiograph.

Purpose Develop deep learning models to assess the clarity of chest X-ray images and validate the model's effectiveness by comparing it with the subjective evaluations of radiologists.Materials and Methods A retrospective collection of 9 135 chest X-ray images from 590 hospitals in Anhui Province,spanning from June 2015 to August 2022,was organized involving multiple radiologists who repeatedly evaluated the clarity of the images using a five-level scoring system.Individual assessments were designated as A and B,whereas the collective result of multiple assessments was designated as C.By constructing a deep learning model based on ResNet-50,image clarity evaluations of chest X-ray images were performed,we used the result C as the training and testing data for the model.The model's evaluation results were denoted as D.A radiology quality control expert conducted an audit assessment of the model's evaluation results and the multi-person assessments of physicians,serving as the reference standard for image clarity.Their assessment results were labeled as E.Statistical analysis,including Spearman's rank correlation coefficient,root mean square error(RMSE)and accuracy was employed to evaluate the effectiveness of the model.Results Compared with the reference standard E,D achieved an average accuracy of 0.85,exceeding the accuracy of C,which stood at 0.84.The ρ values for A,B,C,D and E were 0.58(0.54,0.62),0.59(0.55,0.63),0.74(0.71,0.77)and 0.80(0.78,0.82),respectively.The model exhibited the highest correlation with E.The ρ between A and B was 0.45(0.41,0.49),indicating a lower correlation between two individual subjective assessments of image clarity.The RMSE values for A,B,C,D and E were 0.99,0.94,0.72,and 0.71,respectively.The model's RMSE was lower than that of manual assessments.Conclusion This research model is capable of accurately assessing the clarity of chest X-ray images,and reducing the subjective interference of manual evaluation through deep learning methods,thereby providing an effective and objective evaluation tool for the assessment of clarity in clinical radiographic images.

Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20～29 to 70～79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.

Objective To investigate the intervention mechanism of Shenqi Yiliu Prescription in a rat model of precancerous lesions of gastric carcinoma(PLGC)based on transcriptomics.Methods A PLGC rat model was constructed using composite factor modeling method.Rats were randomly divided into blank group,model group,folic acid group(0.002 g/kg),and Shenqi Yiliu Prescription high-,medium-and low-dosage groups(39.6,19.8 and 9.9 g/kg),with 10 rats in each group.They were given corresponding solutions for gavage for 90 consecutive days.The general condition of rats was observed,HE staining was used to observe the morphology gastric mucosa,immunofluorescence staining was used to detect the expression of PCNA protein in gastric tissue,transcriptomics obtains differentially expressed mRNA in gastric tissue and enriches differentially expressed pathways,ELISA was used to detect the contents of Bcl-xL,C-myc and Cyclin D1 in gastric tissue,RT-qPCR was used to detect the expression of Bcl-xL,C-myc and Cyclin D1 mRNA in gastric tissue,Western blot was used to detect the expressions of IL-6,JAK2,STAT3,p-JAK2 and p-STAT3 protein in gastric tissue.Results Compared with the blank group,rats in the model group showed decreased body mass(P<0.05),with structural disorders of the gastric mucosa,the expression of PCNA protein in gastric tissue increased(P<0.05),the contents and mRNA expression Bcl-xL,C-myc and Cyclin D1 in gastric tissue significantly increased(P<0.05),the expression of IL-6,JAK2,STAT3,p-JAK2,p-STAT3 protein significantly increased(P<0.05).Compared with the model group,the body mass of rats in Shenqi Yiliu Prescription high-and medium-dosage groups increased to varying degrees(P<0.05),the abnormal morphology of the gastric mucosa were improved to different degrees,and the expression of PCNA protein in Shenqi Yiliu Prescription high-,medium-and low-dosage groups significantly decreased(P<0.05).The results of transcriptomics experiments confirmed that the JAK-STAT signalling pathway showed significant differences between the blank group and model group,as well as the model group and Shenqi Yiliu Prescription high-dosage group.The content and mRNA expression of Bcl-xL,C-myc and Cyclin D1 in gastric tissue of Shenqi Yiliu Prescription high-and medium-dosage groups significantly decreased(P<0.05),and the protein expression of IL-6,JAK2,STAT3,p-JAK2 and p-STAT3 significantly decreased(P<0.05).Conclusion Shenqi Yiliu Prescription can improve the abnormal morphology of gastric mucosa in PLGC model rats,and its mechanism is related to regulating the IL-6/JAK2/STAT3 signaling pathway,thereby inhibiting cell proliferation.