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.

Intrahepatic cholangiocarcinoma is a malignant tumor with an extremely poor prognosis， and its pathogenesis is complex and remains unclear. In recent years， more and more studies have focused on the role of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma. Bile-gut axis refers to the complex interaction between bile and gut microbiota， including bile salt metabolism， dynamic changes of microbiota， inflammatory response， and immune system regulation. This article elaborates on the potential mechanisms of bile-gut axis in intrahepatic cholangiocarcinoma， especially gut microbiota dysbiosis， abnormal bile salt metabolism， chronic inflammatory response， and immune system interaction， this article aims to provide new perspectives and possible therapeutic targets for future research and promote the early diagnosis and effective treatment of intrahepatic cholangiocarcinoma.

ObjectiveTo perform a genome-wide association study of rubella virus vaccine strain BRD-Ⅱ, so as to fully grasp the sequence characteristics of this genome. MethodsSecond-generation sequencing method was used to conduct the whole-genome sequencing on the vaccine strain BRD-Ⅱ, and the affinity tree of this genome with some vaccine strains and wild-type rubella virus strains was analyzed using the maximum likelihood method. The average genetic distance of nucleic acid sequence of each vaccine strain protein was determined. And homology comparison of structural proteins of each rubella vaccine strain, plus the comparison between this genome with the AY258323.1 genome sequence, were conducted to analyze the homology of E1 protein between the wild-type rubella virus reference strain and vaccine strain BRD-Ⅱ. ResultsThe sequencing results showed that the BRD-Ⅱ strain was a single-molecule single-stranded positive-strand ribonucleic acid (RNA), composed of 9 778 nucleotides, with a GC content of 69.35 %. The C protein was composed of 300 amino acids, the E2 glycoprotein was composed of 282 amino acids, and the E1 glycoprotein was composed of 481 amino acids. The results of preliminary analysis showed that the average genetic distances of nucleic acid sequences were 0.066 700 for the P150 protein, 0.061 933 for the P90 protein, 0.057 850 for the C protein, 0.068 167 for the E2 protein, and 0.068 833 for the E1 protein, respectively. The amino acid sequences in the E2 protein and E1 protein regions of the two BRD-Ⅱ strains did not change, confirming the conserved regions of the E1 protein by comparison. ConclusionThe sequence characteristics of the genome are clarified, which have laid a broad foundation for the subsequent detection of the genetic stability of the main antigen genes.

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

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

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

Objective To evaluate the efficacy and further analyze the application prospects of the combined multitarget fecal FIT-DNA assay in the early screening of colorectal cancer.Methods Subjects were selected from a population attending the Inner Mongolia Medical University Hospital.Each subject underwent a combined multi-target fecal FIT-DNA test(experimental group),a serum tumor marker test and enteroscopy(control group).The pathological results were used as the gold standard to evaluate the efficacy of novel fecal molecular testing techniques for colorectal cancer screening with timely intervention given to screen positive individuals.Results The data of 115 individuals were analyzed.Serum tumor markers test had a sensitivity of 63.2%(43/68)and a specificity of 74.5%(35/47).The enteroscopy had a sensitivity of 97.1%(66/68)and a specificity of 80.7%(38/47);the combined multitarget fecal FIT-DNA test had a sensitivity of 89.7%(61/68)and a specificity of 87.2%(41/47).Conclusion The sensitivity and specificity of multitarget fecal FIT-DNA combined detection are better than those of serum tumor marker detection.Although its sensitivity is lower than enteroscopy,its operation is simpler and can be tested at home.

BACKGROUND:Nowadays,there are increasing reports on the digitization and visualization system of acupuncture points for adults in traditional Chinese medicine,and the digitization and visualization system of acupuncture points for children in traditional Chinese medicine and the simulation system of acupuncture manipulation for Mongolian medicine training have been reported.However,there are no reports on relevant systems for children in Mongolian medicine. OBJECTIVE:To develop a simulation system of acupuncture points for children in Mongolian medicine,in the hope that it can be used for clinical teaching,manipulation practice and research on acupuncture safety. METHODS:Based on the tomographic anatomical dataset of preschool boys,a three-dimensional(3D)digital virtual anatomical model of children with multiple internal organs and tissues was constructed by using PhotoShop.2021 and Digihuman Reconstruction System software.The relevant annotation information database of 27 acupoints such as Dinghui acupoint of Mongolian medicine was compiled by the Unity database language.The Mongolian gold needle and silver needle were selected to record the acupuncture point teaching video on the 3D printed head and neck resin model of children.In Unity3D software,children's anatomical model,acupoint annotation information database and acupuncture operation video were integrated and coded,and a 3D digital children's Mongolian acupuncture acupoint visualization system integrating simulation acupuncture training,clinical teaching and acupuncture safety research was successfully created. RESULTS AND CONCLUSION:This study was based on real children's specimens.In order to reduce the error of two-dimensional segmentation,the manual layer-by-layer segmentation section image method was used to ensure the accuracy of the 3D model to the greatest extent.The Digihuman Reconstruction System was used to extract and save the individual segmentation data while maximizing the accuracy of the 3D model.PhotoShop.2021 software was used to complete the 3D reconstruction of the outer skin of the head and neck of children and the internal bony structure,cervical spinal cord,blood vessels and nerves,muscles and ligaments.After 3D reconstruction,the basic morphology of each independent structure and the integrity of the overall contour were verified in MeshLab software and the final fine adjustment and anatomical position confirmation were conducted using 3-matic research 13.0 software.The real anatomical morphology of the head and neck of preschool children was successfully simulated and restored.Unity3D software was used to integrate the 3D model of children,acupuncture operation video and acupoint annotation database,and the 3D digital Mongolian acupuncture acupoint visualization system for children was successfully constructed.Based on the real continuous fault ultra-thin dataset of preschool boys in China,China's first 3D digitization and visualization system of acupuncture points in the head and neck of children in Mongolian medicine was developed.Compared with the previous acupuncture soft works,this system is more suitable for the anatomical morphological development characteristics of Asian children,and has a high value of application in the fields of research on the safety of acupuncture in Mongolian medicine,clinical teaching and acupuncture simulation training.

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.

Objective To explore the clinical effect and safety of remimazolam combined with alfentanil in painless gastroenteroscopy in elderly patients.Methods 188 elderly patients who were scheduled to undergo painless gastroenteroscopy from October 2021 to February 2023 were selected and divided into group A,group B,group C,and group D by random number table method,with 47 cases in each group.The group A,group B and group C were used remimazolam 0.2,0.3 and 0.4 mg/kg,and alfentanil 3 μg/kg respectively,and the remimazolam 2.5 mg/time was added during the operation.The group D was used propofol 1.5 mg/kg and alfentanil 3 μg/kg,and a single dose of propofol 0.5 mg/kg was added during the operation.The hemodynamics at different time points[3 min before anesthesia administration(T0),immediately after endoscopy(T1),3 min after endoscopy(T2),at the end of examination(T3),at the time of awakening(T4)],anesthesia onset time,sedation success rate,gastrointestinal endoscopy time,awakening time,time to leave the observation room and intraoperative/postoperative complications were compared,and the test results of neurobehavioral cognitive state examination(NCSE)were compared at different times.Results The percutaneous arterial oxygen saturation(SpO2)at T1 and T2 time point were higher than group C and group D,and the differences were statistically significant(P<0.05).There was no statistically significant difference in the heart rate(HR)and mean arterial pressure(MAP)among group A,group B,group C and group D at each time point(P>0.05).There was no statistically significant difference in SpO2 between group A and group B at each time point(P>0.05).There was no statistically significant difference in the success rate of sedation,gastrointestinal endoscopy examination time and time of leaving the observation room among the four groups(P>0.05),but the onset time of anesthesia in group A was longer than that in group B,group C and group D,and the awakening time in group A and group B was shorter than that in group C and group D,and the differences were statistically significant(P<0.05).There was no statistically significant difference in awakening time between group A and group B(P>0.05).The incidence rate of bradycardia in group A and group B was lower than in group D,and the incidence rates of hypoxemia,respiratory depression,hypotension,and dizziness in group A were lower than those in group D,and the incidence rate of injection pain in group A,group B and group C was lower than that in group D,and the differences were statistically significant(P<0.05).After 10 minutes of complete wakefulness,there was no statistically significant difference in the passing rates of calculation ability and the memory tests between group A and group B(P>0.05),but the passing rates of calculation ability and memory test in group A were higher than those in group C and group D,and the differences were statistically significant(P<0.05).Conclusion During painless gastroenteroscopy in elderly patients,the sedative effect of using 0.3 mg/kg remimazolam combined with alfentanil is good,and it has stable hemodynamics,and the occurrence rate of complications such as bradycardia and espiratory depression is low,and the early postoperative cognitive function is recovered well.