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.

ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.

BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.

AIM: To investigate the current status of retinopathy of prematurity(ROP)in premature infants in Xiamen and analyze its influencing factors, aiming to provide a scientific basis for clinical treatment and preventive strategies.METHODS: A retrospective study was conducted on the case data of 363 preterm infants with a gestational age of <32 wk who underwent fundus examination at Xiang'an Hospital of Xiamen University from February 11, 2020 to February 25, 2023. The incidence of ROP was statistically analyzed based on the screening results. All premature infants were divided into ROP group(37 cases, 64 eyes)and non-ROP group(326 cases, 652 eyes). General clinical data and perinatal-related information of the two groups were compared, and multivariate Logistic regression analysis was used to identify factors influencing the occurrence of ROP in premature infants.RESULTS: A total of 363 premature infants were included in this study. The fundus screening results showed that a total of 37 cases(64 eyes)of premature infants were detected with ROP, including 10 cases(10 eyes)monocular and 27 cases(54 eyes)binocular, with an overall incidence of 10.2%(37/363). The severity was determined according to the ROP international classification standard(ROP is divided into 5 stages, with stage I being the least severe and stage V the most severe). Among the 64 eyes, 30 eyes(46.9%)were in stage I, 20 eyes(31.3%)were in stage II, 10 eyes(15.6%)were in stage III, 4 eyes(6.3%)were in stage IV, and there were no cases in stage V. By comparing the clinical data of the two groups, no significant differences were found in gender, mode of delivery, singleton or multiple births, premature rupture of membranes, history of asphyxia, patent ductus arteriosus(PDA), or neonatal respiratory distress syndrome(NRDS)between the two groups(all P>0.05). However, premature infants in the ROP group had significantly younger gestational age and lower birth weight compared to those in the non-ROP group(all P<0.05). Additionally, the ROP group had higher proportions of longer hospital stays, bronchopulmonary dysplasia(BPD), neonatal sepsis, anemia, oxygen therapy for more than 1 wk, oxygen concentration above 40%, and blood transfusion treatment(all P<0.05). Multivariate Logistic regression analysis revealed that combined neonatal sepsis(OR=166.985, 95% CI: 35.239-791.277, P<0.001), anemia(OR=8.111, 95% CI: 2.064-31.871, P=0.003), oxygen use time >1 wk(OR=10.216, 95% CI: 2.543-41.039, P=0.001), oxygen therapy concentration >40%(OR=7.647, 95% CI: 1.913-30.566, P=0.004), and receiving blood transfusion therapy(OR=5.879, 95% CI: 1.412-24.470, P=0.015)were the main risk factors affecting the occurrence of ROP in preterm infants, and the higher birth weight of preterm infants was a protective factor for ROP(OR=0.093, 95% CI: 0.022-0.394, P=0.001).CONCLUSION: The incidence of ROP in premature infants is relatively high, and there are multiple influencing factors. Low birth weight, neonatal sepsis, anemia, oxygen therapy, and blood transfusion treatment are high-risk factors for ROP in premature infants. Clinical attention should be given to such infants, and fundus screening should be conducted in a standardized manner to provide early treatment, thereby further reducing the risk of ROP in premature infants.

Colorectal cancer (CRC), a major global health concern, necessitates innovative treatments. Chimeric antigen receptor (CAR) T cells have shown promises, yet they grapple with challenges. The spotlight pivots to the rising heroes: CAR natural killer (NK) cells, offering advantages such as higher safety profiles, cost-effectiveness, and efficacy against solid tumors. Nevertheless, the specific mechanisms underlying CAR NK cell trafficking and their interplay within the complex tumor microenvironment require further in-depth exploration. Herein, we provide insights into the design and engineering of CAR NK cells, antigen targets in CRC, and success in overcoming resistance mechanisms with an emphasis on the potential for clinical trials.
Colorectal Neoplasms/immunology* ; Humans ; Killer Cells, Natural/metabolism* ; Receptors, Chimeric Antigen/genetics* ; Immunotherapy, Adoptive/methods* ; Tumor Microenvironment/immunology* ; Animals

AIM:To investigate the challenges and needs of individual ophthalmologists participated in the training and their countries in the prevention and treatment of blindness and visual impairment, sum up the training effects, and discuss how to promote the development of eye health in the Belt and Road countries in the future.METHODS:A total of 48 ophthalmologists from 6 countries, including Kenya, Zambia, Nigeria, South Africa, Malawi, Botswana between August 1 and August 30, 2022, were trained and anonymous questionnaire survey was conducted. The questionnaire consists of 15 questions covering three aspects: challenges and strategies related to vision impairment and blindness in the country, training satisfaction, and recommendations for establishing optometric centers in Africa.RESULTS: A total of 48 questionnaires were distributed and 47 valid questionnaires were collected. The ophthalmologists hold the view that the biggest challenge of their countries in prevention and treatment of ocular diseases was high nursing costs, accounting for 36.17%, the biggest challenge faced by ophthalmologists was low wages, accounting for 29.79%. Building more eye specialist hospitals(38.30%)and providing more training opportunities(65.96%)can effectively help the countries and the ophthalmologists. The organizational satisfaction with the training courses reached 98%, the content and the lecturers' satisfaction were 100%.CONCLUSION:There are urgent needs to build more ophthalmic hospitals and provide more professional training opportunities to solve the difficulties in the prevention and treatment of eye diseases of the countries and the ophthalmologists. This training program has high satisfaction and good feedback.

Objective:To understand the current status of anemia, iron deficiency, and iron-deficiency anemia among preschool children in China.Methods:A cross-sectional study was conducted with a multi-stage stratified sampling method to select 150 streets or townships from 10 Chinese provinces, autonomous regions, or municipalities (East: Jiangsu, Zhejiang, Shandong, and Hainan; Central: Henan; West: Chongqing, Shaanxi, Guizhou, and Xinjiang; Northeast: Liaoning). From May 2022 to April 2023, a total of 21 470 children, including community-based children aged 0.5 to<3.0 years receiving child health care and kindergarten-based children aged 3.0 to<7.0 years, were surveyed. They were divided into 3 age groups: infants (0.5 to<1.0 year), toddlers (1.0 to<3.0 years), and preschoolers (3.0 to<7.0 years). Basic information such as sex and date of birth of the children was collected, and peripheral blood samples were obtained for routine blood tests and serum ferritin measurement. The prevalence rates of anemia, iron deficiency, and iron-deficiency anemia were analyzed, and the prevalence rate differences were compared among different ages, sex, urban and rural areas, and regions using the chi-square test.Results:A total of 21 460 valid responses were collected, including 10 780 boys (50.2%). The number of infants, toddlers, and preschoolers were 2 645 (12.3%), 6 244 (29.1%), and 12 571 (58.6%), respectively. The hemoglobin level was (126.7±14.8) g/L, and the serum ferritin level was 32.3 (18.5, 50.1) μg/L. The overall rates of anemia, iron deficiency, and iron-deficiency anemia were 10.4% (2 230/21 460), 28.3% (6 070/21 460), and 3.9% (845/21 460), respectively. The prevalence rate of anemia was higher for boys than for girls (10.9% (1 173/10 780) vs. 9.9% (1 057/10 680), χ2=5.58, P=0.018), with statistically significant differences in the rates for infants, toddlers and preschoolers (18.0% (475/2 645), 10.6% (662/6 244), and 8.7% (1 093/12 571), respectively, χ2=201.81, P<0.01), and the rate was significantly higher for children in rural than that in urban area (11.8% (1 516/12 883) vs. 8.3% (714/8 577), χ2=65.54, P<0.01), with statistically significant differences in the rates by region ( χ2=126.60, P<0.01), with the highest rate of 15.8% (343/2 173) for children in Central region, and the lowest rate of 5.3% (108/2 053) in Northeastern region. The prevalence rates of iron deficiency were 33.8% (895/2 645), 32.2% (2 011/6 244), and 25.2% (3 164/12 571) in infants, toddlers, and preschoolers, respectively, and 30.0% (3 229/10 780) in boys vs. 26.6% (2 841/10 680) in girls, 21.7% (1 913/8 821), 40.0% (870/2 173), 27.1% (2 283/8 413), 48.9% (1 004/2 053) in Eastern, Central, Western, and Northeastern regions, respectively, and each between-group showed a significant statistical difference ( χ2=147.71, 29.73, 773.02, all P<0.01). The prevalence rate of iron-deficiency anemia showed a significant statistical difference between urban and rural areas, 2.9% (251/8 577) vs. 4.6% (594/12 883) ( χ2=38.62, P<0.01), while the difference in iron deficiency prevalence was not significant ( χ2=0.51, P=0.476). Conclusions:There has been a notable improvement in iron deficiency and iron-deficiency anemia among preschool children in China, but the situation remains concerning. Particular attention should be paid to the prevention and control of iron deficiency and iron-deficiency anemia, especially among infants and children in the Central, Western, and Northeastern regions of China.

Objective:To establish a carbohydrate metabolism-related genes(CRGs)prognostic model for clear cell renal cell carcinoma(ccRCC)and investigate its clinical value.Methods:ccRCC mRNA expression data were sourced from The Cancer Genome Atlas(TCGA)data-base.CRGs were retrieved from the MSigDB and KEGG databases.A prognostic model based on CRGs was constructed using the LASSO lin-ear regression model,and the risk score(RS)was calculated.Patients were assigned into high-and low-risk groups according to the median RS.Differences in survival,immune infiltration,mutation,and immune response between the two groups were analyzed using Kaplan-Meier curves and bioinformatics methods.Constructing a nomogram based on the RS and clinical features and validating its accuracy of prognostic predictions.The expression of CRGs in the ccRCC samples was detected using RT-qPCR.Results:A total of eight key genes were utilized to construct a prognostic risk model for ccRCC.Survival analysis revealed that patients in the low-risk group had a better prognosis(P<0.001).Bioinformatics analysis showed that the RS correlated with immune cell infiltration,mutation,and immune responses.The nomogram based on the RS and clinical features demonstrated a strong predictive ability for prognosis.In vitro experiments confirmed notable differences in the expression of the eight CRGs between ccRCC and adjacent non-malignant tissues.Conclusions:A prognostic model based on CRGs can effectively predict the prognosis of patients with ccRCC.

Objective:To investigate the effects of sclerostin (SOST) and WNT/CTNNB1 signaling pathway on the cell cycle, migration and invasion of human uveal melanoma (UM) cells and its related mechanism.Methods:UM tissues from 20 cases of epithelioid UM and 16 cases of spindle cell type UM were collected.The contents of SOST, Wnt-1 and Catenin beta-1 proteins in the collected tissues were detected by immunohistochemical staining.Three human UM tissue derived cell lines OCM-1 (primary spindle cell type), Mum-2B (metastatic epithelioid) and Mum-2C (metastatic spindle cell type) were selected and divided into three groups, blank control group not transfected, empty vector group transfected with SOST negative control vector and SOST siRNA group transfected with SOST siRNA.After 24-hour transfection, the mRNA and protein expression levels of SOST, CTNNB1, WNT protein family 1 (WNT1), CCND1, matrix metalloproteinase (MMP)2 and MMP9 were detected by real-time fluorescence quantitative PCR and Western blot, respectively.The invasion and migration ability of the transfected cells were measured by transwell method, and the cell cycle distribution was detected by flow cytometry.Another 9 female BALB/c nude mice were selected and randomized into OCM-1 group, OCM-1 empty vector group and SOST shRNA group, inoculated with OCM-1 without lentivirus infection, OCM-1 with blank lentivirus infection and OCM-1 with SOST shRNA lentivirus infection, respectively.Six weeks after inoculation, the in situ formation of tumor was observed.The interaction between SOST and low density lipoprotein receptor related protein(LRP)-5/6 in OCM-1 cells was explored by co-immunoprecipitation assay.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (2018KY[L]-20).Results:Immunohistochemical staining results showed that the SOST expression level was higher and the expression levels of Wnt-1 and Catenin beta-1 were lower in spindle cell type UM tissues than in epithelioid UM tissues, and the differences were all statistically significant (all at P<0.01). The real-time fluorescence quantitative PCR results showed that the relative expression of SOST mRNA was significantly lower and the relative expressions of CCND1, WNT1 and MMP9 mRNA were significantly higher in SOST siRNA groups than in corresponding empty vector groups in the three cell lines (all at P<0.05). In OCM-1 and Mum-2C cell lines, the relative expressions of CTNNB1 mRNA were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Western blot results showed that the relative expression of SOST protein was significantly lower and the relative expressions of Wnt-1, Catenin beta-1, cyclin-D1, MMP2 and MMP9 proteins were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Transwell assay showed that the cell invasion and migration ability of SOST siRNA group was significantly higher than that of blank control group and empty vector group in the three cell lines (all at P<0.01). Flow cytometry showed that the proportion of G1-phase cells and the G1/S-phase ratio were significantly lower in SOST siRNA group than in blank control groups and empty vector groups (all at P<0.01). The eyeball volume of OCM-1 group, OCM-1 empty vector group and SOST shRNA group was (42.7±4.6), (49.0±22.9) and (135.2±32.7)mm 3, respectively, showing a significant overall difference ( F=19.963, P<0.01). The eyeball volume of SOST shRNA group was larger than that of OCM-1 group and OCM-1 empty vector group, and the differences were statistically significant (both at P<0.05). Co-immunoprecipitation results showed that SOST could interact with LRP-5 and LRP-6 by binding to them, respectively. Conclusions:Silencing SOST can promote the invasion and migration of UM cells, and increase the proportion of UM cells in the division phase.Silencing SOST can promote tumor growth in eyes of nude mice.SOST may play this function by interacting with the membrane receptor LRP-5/LRP-6 and then regulating the WNT/CTNNB1 signal pathway.

Objective:To establish a risk assessment system focusing on surgical and anesthesian-related indicators for the incidence of complications and mortality of hip fracture surgery in senile patients, and to evaluate its prediction accuracy, sensitivity and specificity.Methods:From January 2020 to February 2021, a total of 1 086 elderly patients (493 males and 593 females) aged 76±5 years (ranging from 60 to 94 years) underwent hip fracture surgery in Tianjin Hospital were collected. A total of 543 patients were randomly selected for the establishment of the hip fracture scoring system in senile patients, including 253 males and 290 females, aged 75±6 years (ranging from 60 to 92 years). With the preoperative physiological factor score and surgical risk factor score as independent variables and the occurrence of complications and death as dependent variables, binary logistic regression analysis was performed to establish a surgical risk scoring system for hip fracture in senile patients. The remaining 543 patients, including 240 males and 303 females, aged 74±7 years (range 60-94 years), their data were used to compare AUC, sensitivity, specificity, and compliance of the physiological and operative severity score for the enumeration of mortality and morbidity (POSSUM), Daping orthopedics operative risk scoring system for senile patient (DORSSSP), and our surgical risk scoring system for hip fracture in senile patients through receiver operating characteristic (ROC) curves, and to compare the predictive value of these systems for complication incidence and mortality.Results:The predictive model equation of the elderly hip fracture scoring system is: ln R1/ (1- R1) =-7.13+0.112× PS+0.148× OS; ln R2/ (1- R2) =-6.14+0.124× PS+0.136× OS; [ R1 is the incidence of complications, R2 is the mortality, PS (physiology score) is the score of preoperative physiological factors, and OS (operation score) is the score of surgical risk factors]. Among the 543 patients whose data were used to compared with the hip fracture scoring system, POSSUM and DORSSSP, 72 actually developed complications and 36 died. The complication rate predicted by surgical risk scoring system for hip fracture in senile patients was 12.05%±6.34% (range 6.18%-61.29%), and 64 cases were predicted to have complications. The predicted mortality was 6.05%±3.26% (range 2.45%-58.36%), and 29 cases were predicted to die. The complication rate predicted by POSSUM was 25.36%±13.95% (range 9.16%-76.34%), and 126 cases were predicted to have complications. The predicted mortality rate was 10.46%±5.31% (range 6.23%-59.34%), and 54 deaths were predicted. The predicted complication rate of DORSSSP was 19.34%±9.67% (range 8.36%-70.85%), and 99 cases were predicted to have complications. The predicted mortality was 10.12%±5.16% (range 7.35%-57.54%), and 52 deaths were predicted. In predicting the incidence of complications, the AUC of surgical risk scoring system for hip fracture in senile patients, POSSUM and DORSSSP were 0.95, 0.82 and 0.75, the sensitivity was 0.89, 0.83 and 0.85, the specificity was 0.80, 0.86 and 0.92, and the compliance rate was 0.94, 0.93 and 0.94, respectively. In the prediction of mortality, the AUC of surgical risk scoring system for hip fracture in senile patients, POSSUM and DORSSSP were 0.87, 0.67 and 0.71, the sensitivity was 0.85, 0.69 and 0.75, the specificity was 0.73, 0.94, 0.95, and the compliance rate was 0.94, 0.93 and 0.94, respectively. Conclusion:Compared with POSSUM and DORSSSP, hip fracture scoring system in elderly patients has improved its ability to predict surgical risk, and can accurately predict the incidence of complications and mortality in elderly patients undergoing hip surgery.