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.].

Background and purpose:Modified radical mastectomy is an important approach for treating breast cancer,but the risk of postoperative incision infection rate is relatively high,which can seriously affect the treatment outcome and prognosis of these patients.This study aimed to investigate the etiological characteristics,related risk factors and changes of serum inflammatory factors such as procalcitonin(PCT),C reactive protein(CRP),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in patients undergoing modified radical mastectomy.Methods:The clinical data of breast cancer patients admitted to the Third People's Hospital of Zhengzhou from February 2019 to February 2022 were analyzed retrospectively.The pathogenic bacteria distribution and related risk factors of postoperative incision infection and the changes of serum inflammatory factors such as PCT,CRP,TNF-α and IL-6 were explored.This study has been approved by the Medical Ethics Committee of the Third People's Hospital of Zhengzhou(No.:2025-04-014-K01)and acquired the informed consent.The Strengthening the Reporting of Observational Studies in Epidemiology(STROBE)checklist was followed for this case control study.Results:A total of 128 patients were enrolled in this study.All patients underwent modified radical mastectomy were divided into infected group(n=22)and non-infected group(n=106)according to whether incision infection occurred after surgery.The incision infection rate after modified radical mastectomy was 17.19%(22/128).Twenty-six strains of pathogenic bacteria were isolated and cultured from 22 patients with postoperative incision infection.Among these,16 strains were Gram-positive,accounting for 61.54%(16/26),mainly staphylococcus aureus and enterococcus faecalis.There were 10 Gram-negative strains,accounting for 38.46%(10/26),mainly escherichia coli and pseudomonas aeruginosa.The influencing factors of incision infection after modified radical mastectomy included preoperative neoadjuvant chemotherapy,intraoperative blood loss≥300 mL,postoperative drainage volume≥800 mL,drainage time≥7 d,albumin＜35 g/L,and white blood cell count＜4×109/L(P＜0.05).Multivariate logistic regression analysis showed that preoperative neoadjuvant chemotherapy,blood loss≥300 mL,postoperative drainage volume≥800 mL,duration of drainage time≥7 d,albumin＜35 g/L and white blood cell count＜4×109/L were the independent influencing factors of incision infection after modified radical mastectomy(P＜0.05).The peripheral blood levels of PCT,CRP,TNF-α and IL-6 in both groups increased compared with those before surgery,and those in the infected group were higher than those in the non-infected group(P＜0.05).Conclusion:staphylococcus aureus and escherichia coli were the main pathogens after modified radical breast mastectomy.Preoperative neoadjuvant chemotherapy,blood loss≥300 mL,postoperative drainage volume≥800 mL,drainage time≥7 d,albumin＜35 g/L and white blood cell count＜4×109/L were the independent influencing factors.The levels of serum PCT,CRP,TNF-α and IL-6 could be used as effective indicators to predict postoperative incision infection.

Objective:To investigate the neuroprotective effects of ginsenoside Rb1 in neonatal mice with Hypoxic Ischemia(HI)and analyze its potential molecular mechanisms.Methods:Seven-day-old C57BL/6 neonatal mice were randomly assigned to three groups:Sham group,hypoxic-ischemic(HI)model group,and HI model+ginsenoside Rb1 intervention group(HI+Rb1),with 10 mice per group.The modified Rice-Vannucci method was used to establish the HI model,and ginsenoside Rb1(20 mg/kg)was administered via intraperitoneal injection for 7 consecutive days post-surgery(once per day).Brain damage was assessed on days 7 and 14 post-surgery by evaluating cortical neurons and glial cell numbers,as well as the activation status of the ERK signaling pathway.Additionally,in utero electroporation(IUE)was used to overexpress the ERK signaling pathway in the cortical neurons,and the impact of ERK activation on glial cell development was observed.Further,IUE was used to overexpress ERK in the cortex of P0 neonatal mice,fol-lowed by the HI model on day 7 to analyze the effects of enhanced ERK signaling on oligodendrocyte development and myelin regeneration.Results:Compared to the HI group,the HI+Rb1 intervention group showed significant improve-ment in motor ability,reduction in brain injury area,less mature neuron loss,and increased newborn neurons.Addi-tionally,the number of oligodendrocytes in the cortex was increased,and the activation of the ERK signaling pathway was enhanced.In mice with overexpression of the ERK signaling pathway in the cortex,there was a significant increase in oligodendrocytes.In the HI model with ERK overexpression,an increased number of oligodendrocyte precursor cells were found around the brain injury area,consistent with the results of ginsenoside Rb1 intervention.Conclusion:Gin-senoside Rb1 exerts neuroprotective effects in neonatal mice with hypoxic-ischemic brain injury,potentially through the enhancement of ERK signaling,promoting oligodendrocyte proliferation and myelin regeneration.

Objective:To explore the feasibility of applying deep learning image reconstruction (DLIR) in low-radiation dose liver dual-energy CT to further improve image quality, diagnostic confidence of lesion, and accuracy of iodine concentration (IC) measurement.Methods:This prospective cohort study enrolled 60 patients scheduled for enhanced liver CT at the First Affiliated Hospital of Anhui Medical University from June 2023 to January 2024. The participants were randomly assigned into the standard dose group and low radiation dose group with 30 cases in each using randomized block method. The standard radiation dose group underwent standard-radiation dose 120 kVp scans during the venous phase, while the low radiation dose group underwent low radiation dose scans with a rapid kVp-switching spectral scanning mode at 80 kVp and 140 kVp. The effective radiation dose (ED) was calculated for both groups. The standard radiation dose group was reconstructed using adaptive statistical iterative reconstruction-V (ASIR-V) algorithm 40% (AR40 120 kVp). The low radiation dose group using high-intensity DLIR (DLIR-H) to reconstructed 40 keV and 50 keV virtual monoenergetic images (VMI) (DH-VMI 40 keV, DH-VMI 50 keV). The image quality of the above three groups was objectively evaluated through the measurement of image noise and calculation of contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) for the liver and portal vein; and the image quality was subjectively scored for image noise, contrast, lesion conspicuity, and diagnostic confidence. In the low radiation dose group, DLIR-H and ASIR-V40% reconstructed iodine maps were used to measure the liver and portal vein of IC values, standard deviations (SD), and coefficients of variation (CV). One-way analysis of variance or Kruskal-Wallis H test was used to compare the differences of subjective and objective image quality among the three groups, and paired t-test was used to compare the differences in measurement indexes between DLIR-H and ASIR-V40% reconstructed iodine maps. Results:The ED in the low radiation dose group [(2.2±0.5) mSv] was reduced by 56.8% compared to the conventional radiation dose group [(5.4±1.4) mSv]. Objective evaluations demonstrated that DH-VMI 40 keV had higher image noise, CNR, and SNR for liver and portal veins compared to AR40 120 kVp ( P<0.001). DH-VMI 50 keV had lower image noise ( P=0.200), with higher CNR and SNR for the liver and portal vein compared to AR40 120 kVp( P<0.001). In subjective evaluation, there was no statistically significant difference in image noise scores between DH-VMI 40 keV and AR40 120 kVp ( P>0.05), while the image noise score for DH-VMI 50 keV was lower than that of AR40 120 kVp ( P<0.05). Both DH-VMI 40 keV and DH-VMI 50 keV had higher scores for contrast, lesion conspicuity, and diagnostic confidence compared to those of AR40 120 kVp ( P<0.05). In the low radiation dose group, there was no statistically significant difference in IC values for the liver and portal vein between the ASIR-V40% and DLIR-H algorithm reconstructed iodine maps ( P>0.05). The SD and CV of liver and portal vein in the DLIR-H reconstructed iodine maps were lower than those in the ASIR-V40% reconstructed iodine maps ( P<0.001). Conclusions:DLIR can effectively reduce the image noise of low-energy (40, 50 keV) VMI, enhance lesion conspicuity and diagnostic confidence, and improve measurement accuracy without affecting IC values.

Objective To explore the predictive value of radiomics nomogram based on multiparameter MRI for the status of human epidermal growth factor receptor 2(HER-2)in endometrial cancer(EC).Methods A total of 154 patients with pathologically proved EC were retrospectively selected and randomly divided into training set(108 cases)and validation set(46 cases)according to the ratio of 7∶3.Radiomics features were extracted from the preoperative multiparameter MRI images of the patients.The predictive performance of different machine learning algorithms was evaluated by receiver operating characteristic(ROC)curves,and the nomogram was constructed in combination with clinical risk factors.Results The degree of differentiation and depth of myometrial invasion were clinical risk factors for predicting HER-2 positivity in EC patients.The support vector machine(SVM)was selected as the best radiomics model.The nomogram showed the highest predictive performance in the training and validation sets,with area under the curve(AUC)of 0.926 and 0.897,respectively.Conclusion The radiomics nomogram based on multiparameter MRI can accurately predict the HER-2 status of EC patients before surgery and can be used to guide clinical treatment decisions.

Objective:To investigate the clinical manifestations and genetic characteristics of a Chinese Han family with Axenfeld-Rieger syndrome (ARS).Methods:A pedigree study was conducted.Three people from a Chinese Han family with ARS who visited Henan Eye Hospital in January 2024 were included, including 1 patient.Clinical data of the proband and her parents were collected.Comprehensive ophthalmic examination and general physical examination were performed on the proband and her parents.Peripheral blood samples were obtained from family members for DNA extraction.Whole exome sequencing was performed on the proband, and the copy number of the ZBED1P1, ENPEP, PITX2, and FAM241A genes in family members were validated using the real-time fluorescent quantitative PCR.Axenfeld-Rieger syndrome, Axenfeld-Rieger Syndrome, and PITX2 were used as keywords to search across databases such as OMIM, ClinVar, PubMed, CNKI, Wanfang, VIP, DECIPHER, and Google Scholar.The clinical manifestations and microdeletion types of different patients in ARS literature related to PITX2 microdeletions in China population were summarized, and the relationship between genotype and clinical phenotype was analyzed.The study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEEC-2024[34]).All subjects understood the purpose of the study and voluntarily signed the informed consent form. Results:The proband was a 25-year-old female, exhibiting diminutive cornea in both eyes, polycoria, deformation and displacement of pupils, a flat mid-face, maxillary dysplasia, tooth loss, and a protruding umbilicus, among other symptoms.Parents of the proband were phenotypically normal.DNA sequencing identified a 1.06 MB microdeletion on chromosome 4q25 in the proband.Real-time quantitative PCR confirmed that this microdeletion encompassed the PITX2 and ENPEP genes, and it was absent in the proband's parents.The ClinGen CNV pathogenicity scoring indicated that the deletion involving the PITX2 gene represented a novel pathogenic copy number variation (CNV).Five studies related to 4q25 microdeletion in Chinese families with Axenfeld-Rieger syndrome was screened, including 13 patients.Clinical manefestations of the 13 patients included corneal disorders (accounting for 100%), umbilical hernia and dental anomalies (accounting for 92%), irregular intraocular pressure (accounting for 62%), iris atrophy (accounting for 46%), and posterior corneal embryotoxon (accounting for 31%). Conclusions:For this Chinese family diagnosed with ARS, a novel pathogenic 4q25 microdeletion variant encompassing the PITX2 gene was found in the proband, which is associated with characteristic phenotypes including microcornea, congenital iris dysplasia, polycoria, tooth loss, and a protruding umbilicus.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Objective:To investigate the effects of arthroscopic meniscus suturing on pain indicators and knee joint function in patients with meniscus injury.Methods:A retrospective analysis was conducted on the clinical data of 132 patients with meniscus injury admitted to the Linhai Second People's Hospital from January 2021 to June 2024. Based on different surgical methods, the patients were divided into two groups: the resection group ( n = 66) undergoing arthroscopic meniscectomy and the suture group ( n = 66) undergoing arthroscopic meniscus suturing. The Visual Analogue Scale scores of both groups were compared at 1, 3, and 5 days after surgery. Postoperative complications were also compared between the two groups. The levels of inflammatory factors, including interleukin-1β, interleukin-6, and tumor necrosis factor-α, were compared between the two groups before surgery and 1 week after surgery. Additionally, the knee joint range of motion and the Lysholm knee score were compared between the two groups before surgery and 3 months after surgery. Results:At 1, 3, and 5 days after surgery, the Visual Analogue Scale scores for patients in the suture group were (3.85 ± 0.43), (1.85 ± 0.29), and (0.85 ± 0.10), respectively, all of which were significantly lower than those in the resection group [(4.23 ± 0.23), (2.12 ± 0.34), (1.15 ± 0.25), t = 6.33, 4.91, 9.05, all P < 0.001]. There was no significant difference in the incidence of postoperative complications between the suture and resection groups [3.03% (2/66) vs. 1.52% (1/66), χ2 = 0.0, P = 1.000]. At 1 week after surgery, the levels of interleukin-1 β, interleukin-6, and tumor necrosis factor-α in the suture group were (0.15 ± 0.01) ng/L, (5.15 ± 0.38) ng/L, and (5.72 ± 0.59) ng/L, respectively. The values were significantly lower than those in the resection group [(0.17 ± 0.0) ng/L, (5.55 ± 0.56) ng/L, (6.10 ± 0.66) ng/L, t = 7.27, 4.80, 3.49, all P < 0.001]. At 3 months after surgery, the Lysholm knee scores and knee joint range of motion for patients in the suture group were (86.73 ± 2.85) and (126.52 ± 4.29)°, respectively. These values were significantly higher than those in the resection group [(84.15 ± 3.92), (120.65 ± 4.52)°, t = 4.33, 7.65, both P < 0.001]. Conclusions:Arthroscopic meniscus suturing causes less damage compared with arthroscopic meniscectomy. Patients undergoing meniscus suturing experience less postoperative pain, a milder inflammatory response, faster recovery, better restoration of knee joint function, and fewer complications, making the procedure safer and more reliable.