BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.
Cholangiocarcinoma/drug therapy* ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Bile Duct Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Animals ; Signal Transduction/drug effects*

Antibody-drug conjugates (ADCs) represent a promising class of targeted cancer therapeutics that combine the specificity of monoclonal antibodies with the potency of cytotoxic payloads. Despite their therapeutic potential, the use of ADCs faces significant challenges, including off/on-target toxicity and resistance development. This review examines the current landscape of ADC development, focusing on the critical aspects of target selection and antibody engineering. We discuss strategies to increase ADC efficacy and safety, including multitarget approaches, pH-dependent antibodies, and masked peptide technologies. The importance of comprehensive antigen expression profiling in both tumor and normal tissues is emphasized, highlighting the role of advanced technologies, such as single-cell sequencing and artificial intelligence, in optimizing target selection. Furthermore, we explore combination therapies and innovations in linker‒payload chemistry, which may provide approaches for expanding the therapeutic window of ADCs. These advances pave the way for the development of more precise and effective cancer treatments, potentially extending ADC applications beyond oncology.
Humans ; Immunoconjugates/adverse effects* ; Neoplasms/immunology* ; Animals ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents/therapeutic use*

OBJECTIVE: Angiogenesis is a critical target for hepatocellular carcinoma (HCC) treatment. The previous studies indicated that Jiedu Fang (JDF) could inhibit hypoxia-induced angiogenesis through interleukin-8 (IL-8). Therefore, the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis. METHODS: Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo. A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform. Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels, respectively. The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells. The orthotopic tumor xenograft model was established, and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression, while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels. RESULTS: In vitro and in vivo assays showed that IL-8 promoted angiogenesis, and JDF could antagonize this effect. Bioinformatics analysis indicated that aurora kinase A (Aurora A) was an important candidate, which can promote IL-8 expression through activation of signal transducer and activator of transcription 3 (STAT3). The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration, invasion, and angiogenesis, which was partly inhibited by JDF. Such effects were validated by in vivo assays. Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A. CONCLUSION JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway. Therefore, JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis. Please cite this article as: Zhong MF, Luo YJ, Guo YY, Xiang S, Lin WF. Jiedu Fang inhibits hypoxia-induced angiogenesis in hepatocellular carcinoma by targeting Aurora A/STAT3/IL-8 signaling pathway. J Integr Med. 2025; 23(6):683-693.
Carcinoma, Hepatocellular/blood supply* ; Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-8/metabolism* ; Liver Neoplasms/blood supply* ; Aurora Kinase A/metabolism* ; Neovascularization, Pathologic/drug therapy* ; Animals ; Signal Transduction/drug effects* ; Mice ; Drugs, Chinese Herbal/therapeutic use* ; Cell Line, Tumor ; Mice, Inbred BALB C ; Mice, Nude ; Angiogenesis

Objective:To analyze the levels of antibody to measles virus in cord blood of newborns in Ankang city, and provide reference for the development of measles prevention and control measures and strategies.Methods:From January to December, 2023, 1 058 pregnant women from 10 county-level general hospitals in Ankang city were recruited in this study. Neonatal umbilical cord blood samples were collected for detecting IgG antibody against measles with ELISA. SPSS 21.0 software was used to analyze the positive rate of antibody to measles virus and the influencing factors.Results:The overall positive rate of IgG antibody to measles virus was 89.22% (944/1 058), and the geometric mean concentration (GMC) was 570.26 mlU/ml. The positive rates of IgG antibody against measles virus in umbilical cord blood of neonates born to women aged ≤20, 21-25, 26-30, 31-35, and ≥36 years old were 91.07% (51/56), 90.27% (232/257), 89.54% (351/392), 88.12% (230/261), and 86.96% (80/92), respectively (χ 2=1.355, P=0.852). Multivariate logistic regression analysis showed that the positive rate of IgG antibody against measles virus in umbilical cord blood samples was higher in neonates with gestational age ≥37 weeks than in those with gestational age <37 weeks [OR (95%CI): 0.403 (0.262-0.622)]. Besides, the positive rate was also higher in newborns with a birth weight of 3.0-3.5 kg than in those with birth weight <3 kg or ≥3.5 kg [OR (95%CI): 0.868 (0.462-1.629), 1.765(1.087-2.865)]. Conclusions:The positive rate and the GMC of IgG antibody to measles virus in neonatal umbilical cord blood decrease with maternal age. It is recommended that women of childbearing age should receive supplementary immunization with measles-containing vaccine before pregnancy.

AIM To investigate the effects of Zuogui Jiangtang Tongmai Recipe on necroptosis pathway in a rat model of type 2 diabetes mellitus(T2DM)complicated with cerebral infarction(CI).METHODS The SD rats were randomly divided into the sham operation group,the model group,the metformin group(0.045 g/kg),and the low,medium and high dose Zuogui Jiangtang Tongmai Recipe groups(6.5,13,26 g/kg),with 9 rats in each group.In contrast to rats of the sham operation group,rats of the other groups were given 4 weeks feeding of high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish a T2DM rat model with one week stable blood glucose,followed by gavage of corresponding drugs 3 days before the establishment of the middle cerebral artery occlusion(MCAO)model.After 7 days of administration,the rats had their CI injury assessed by mNSS method and TTC staining;their level of blood glucose detected by blood glucose meter;their levels of glycated serum protein,serum TNF-α and IL-1β detected by ELISA;their cerebral mRNA expressions of FADD,RIPK1,RIPK3 and MLKL detected by RT-qPCR;and their cerebral protein expressions of FADD,p-RIPK1,p-RIPK3 and p-MLKL detected by Western blot.RESULTS Compared with the sham operation group,the model group displayed increased levels of blood glucose value,glycosylated serum protein,neurological function score,cerebral infarction volume,cerebral FADD,RIPK1,RIPK3 and MLKL mRNA expressions,cerebral FADD,p-RIPK1,p-RIPK3 and p-MLKL protein expressions,serum TNF-α and IL-1β levels(P＜0.01);and more disordered and morphologically diverse neurons with smaller nucleus.Compared with the model group,the groups intervened with medium or high dose Zuogui Jiangtang Tongmai Recipe,or metformin shared improvement in terms of the aforementioned indices(P＜0.05,P＜0.01);and more neurons with regular morphology neat arrangement,and reduced cell gap.CONCLUSION Zuogui Jiangtang Tongmai Recipe can improve the neurological dysfunction of the rat model of T2DM complicated with CI,which may associate with the inhibited activation of necroptosis signaling pathway.

Objective:To investigate the clinicopathological, molecular pathological features, and family genetic pedigree of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT).Methods:A total of 16 cases of SCCOHT diagnosed in Obstetrics and Gynecology Hospital of Fudan University from January 2013 to January 2023 were collected. The clinicopathologic features, SMARCA4/2/B1 protein expression, outcomes and SMARCA4 gene detection were reported. A follow-up study was also carried out.Results:The average age at diagnosis was 28.7 years (range 17-38 years). The preoperative calcium level was evaluated in 3 of 6 patients. The tumor was unilateral in all 16 cases, ranged from 8 to 26 cm (average 15.8 cm) in the greatest dimension. Extraovarian spread was present in 7 cases. In 10 cases, the tumors were initially misinterpreted as other ovarian neoplasms. BRG1 and BRM expression by immunohistochemistry were all lost in detected cases, while INI1 exhibited retained nuclear expression. All BRM-negative SCCOHTs also lacked BRG1 protein,but retained INI1 expression. SCCOHTs were only focally positive for EMA, CKpan, Calretinin, SALL4, and diffusely positive for WT1. Two of nine cases exhibited mutation-type p53 immunoreactivity. Ki-67 index was 58% on an average. ER, PR, FOXL2, α-inhibin, chromogranin A and LCA were negative in all the cases. SMARCA4 sequencing was available in 8 cases of SCCOHT, which revealed a germline SMARCA4 mutation in one patient, and others carried somatic mutation. Furthermore, two daughters, mother and an aunt of a patient with germline mutation were reported to be SMARCA4 mutation carriers. Follow-up was available for 15 patients, and the 6-month, 1-year and 2-year survival rate was 65.8%, 45.1%, and 22.6%, respectively. For patients in FIGO stages Ⅱ+Ⅲ, 6-month, 1-year survival rate was 53.6% and 35.7% respectively, compared to 80% (6-month) and 60% (1-year) in patients of staged I ( P=0.358). Conclusions:With dismal prognosis of SCCOHT, accurate diagnosis is necessary. The typical age distribution, a panel of various staining results, especially concomitant loss of BRG1 and BRM may be of diagnostic aid and can be used to distinguish SCCOHT from its histological mimics. After the diagnosis of SCCOHT, genetic testing and genetic counseling are recommended.

Objective:To investigate the correlation between bone marrow microvascular density,angiogenesis factors and bortezomib resistance in multiple myeloma(MM).Methods:The data of 200 patients with MM treated in our hospital from January 2020 to August 2023 were retrospectively analyzed,and the patients with MM were divided into drug-resistant group(n=68)and non-drug-resistant group(n=132)according to their drug resistance during bortezomib treatment.The univariate and multivariate logistic analysis were used to screen the independent influencing factors of bortezomib resistance in MM patients during treatment.The receiver operating characteristic(ROC)curve and clinical decision curve(DCA)were used to evaluate the predictive performance and clinical application value of the risk prediction model,the consistency between the actual incidence rate and the predicted incidence rate was judged by validating the calibration chart,and the goodness-of-fit of the model was judged by H-L test.Results:68 of the 200 MM patients developed resistance and poor clinical efficacy during bortezomib treatment,and the clinical resistance rate of bortezomib was 34.0％.The results of multivariate analysis showed that high bone marrow microvessel density(MVD)and high bone marrow supernatant VEGF,HGF,and bFGF expression levels were independent risk factors for bortezomib resistance in MM patients(P＜0.05).The area under the ROC curve(AUC)of the model jointly constructed by bone marrow MVD,serum VEGF,HGF,bFGF and TNF-α levels was 0.924,and its sensitivity and specificity were 92.6％and 78.8％,which were higher than those of the bone marrow MVD model(AUC=0.743)and the vasogenesis factor model(AUC=0.878).The calibration curve of the joint prediction model was close to the standard curve,indicating that the model is more consistent.The results of H-L goodness-of-fit test showed x2=14.748,P=0.164,the joint prediction model had a good fit.The DCA curve showed that the clinical net benefit of intervention in the range of 0.0～1.0 was greater than that of full intervention and no intervention.Conclusion:The prediction model based on bone marrow MVD and vasogenesis factors(VEGF,HGF,bFGF)in MM patients has higher clinical evaluation performance and predictive value.

OBJECTIVE To investigate the effect and mechanism of action of KRT8 small interfering RNA(si-KRT8)in exosomes derived from patient serum with hypopharyngeal carcinoma on chemosensitivity to 5-fluorouracil(5-FU)in human pharyngeal squamous cell carcinoma FaDu cell line.METHODS The cancerous tissues of hypopharyngeal cancer patients and The serum,cancerous tissues and paracancerous tissues of drug-resistant patients after treatment were collected.A 5-FU-resistant cell line of FaDu(FaDu/R)was constructed for subsequent experiments.Exosomes were isolated from patient serum by ultrafast gradient centrifugation,identified using transmission electron microscopy and Western blot(WB)techniques.si-KRT8 was encapsulated into exosomes(Exosome@si-KRT8)using electroporation technology and subsequently used to treat cells.Real-time fluorescence quantitative PCR(RT-qPCR)and WB were used to detect the expression levels of KRT8 in different tissues,exosomes after electroporation of si-KRT8,and FaDu cells,respectively.Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,migration invasion technique and WB were used to detect the effects of Exosome@si-KRT8 on viability,apoptosis,and epithelial-mesenchymal transition of FaDu/R cells.RESULTS The expression level of KRT8 in drug-resistant tissues of hypopharyngeal carcinoma and FaDu/R cells was elevated compared with that in paraneoplastic tissues,cancer tissues and normal FaDu cells(t=15.79,P＜0.01).Isolated patient serum exosomes showed a double membrane structure and expressed both CD63 and TSG101 proteins,and KRT8 expression in exosomes was decreased after electro-transfection with si-KRT8(t=6.70,P＜0.01).Exosome@si-KRT8 inhibited KRT8 protein expression levels in FaDu/R cells(t=123.50,P＜0.01).Compared with the 5-FU group and the 5-FU+Exosome group,Exosome@si-KRT8 was able to inhibit the viability of FaDu/R cells(t=17.07,P＜0.01),promote the level of apoptosis in FaDu/R cells,and inhibit the expression of drug-resistance-associated proteins in FaDu/R cells(P-gp:t=103.20,MDR1:t=238.60,P＜0.01),and Exosome@si-KRT8 was able to suppress the expression of metastasis of FaDu/R cells(t=42.30,t=122.00,P＜0.01)and promoted the expression of E-cadherin while inhibiting the expression level of N-cadherin(t=130.80,t=83.90,P＜0.01).CONCLUSION Serum-derived exosome encapsulation of si-KRT8 enhances chemosensitivity of hypopharyngeal carcinoma cells and its mechanism of action may be related to inhibition of epithelial-mesenchymal transition.