Most patients with pancreatic cancer are already in the locally advanced or metastatic stage at initial diagnosis. While systemic chemotherapy provides clinical benefits for those with mid-to-late-stage pancreatic cancer, its efficacy is often limited by patient tolerance. In response to the dual clinical demands of robust antitumor activity and high targeting specificity, antibody-drug conjugate (ADC) has emerged as a promising solution. By conjugating highly selective monoclonal antibodies with potent cytotoxic small-molecule drugs, ADC achieves precise tumor-targeting while minimizing damage to healthy tissues, which thereby improves treatment tolerance. However, due to the complex pathological features of pancreatic cancer, no ADC has yet been approved for clinical use for this disease. A comprehensive evaluation of factors including ADC-specific targets, payload selection, antibody-drug linkage strategies, drug delivery mechanisms, tissue distribution variability, and tumor heterogeneity will be crucial to advancing the clinical translation of ADC for pancreatic cancer treatment.

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

This study aimed to elucidate the mechanism of action of metformin (MET) in inhibiting the malignant progression of hepatocellular carcinoma (HCC) by regulating the degradation of aldo-keto reductase family 1 member C3 (AKR1C3). The correlation between the sensitivity of different hepatocellular carcinoma cell lines to MET and their basal expression levels of AKR1C3 was firstly evaluated. MET was found to significantly reduce the level and accelerate the degradation rate of AKR1C3 protein by Western blot. The interaction between MET and AKR1C3 protein was confirmed by cellular thermal shift assay (CETSA). Proteasome inhibitor MG132 and the lysosomal inhibitor chloroquine (CQ) were used to screen the degradation pathway, and confirm, in combination with the HBSS starvation-induced autophagy model, that MET mediated the degradation of AKR1C3 through the autophagy lysosome pathway. Ubiquitylation assay showed that MET specifically enhanced the K63-linked polyubiquitylation modification of AKR1C3. Sequestosome 1 (SQSTM1/p62) knockdown, immunoprecipitation, and immunofluorescence co-localization analyses confirmed that the autophagy receptor p62 plays a key role in mediating MET-induced degradation of AKR1C3. The adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) inhibitor compound C was used to demonstrate that the regulatory effect of MET on AKR1C3 is independent of the classical AMPK signaling pathway. The experimental results showed that metformin promoted the ubiquitination modification of AKR1C3 by targeting AKR1C3, enhanced the binding of AKR1C3 to autophagy receptor p62, then degraded the AKR1C3 protein through selective autophagy-like pathway, and ultimately inhibited the malignant phenotypes of hepatocellular carcinoma cells, which is a regulatory mechanism free of the classical AMPK activation pathway of metformin.

The esophagus is referred to as the conduit for food and drink.It can be categorized into three distinct phases:an era characterized by written descriptions,a phase marked by anatomical illustrations,and a period of integration between Chinese and Western medical practices.In the initial phase of written descriptions,seminal texts such as The Yellow Emperor's Inner Classic and The Classic of Difficult Issues documented aspects regarding both length and function of the esophagus;however,these accounts were relatively succinct.The subsequent phase saw advancements in anatomical illustrations that refined our comprehension of esophageal structure and functionality.During the period of the integration of Chinese and Western medicine,insights from Western anatomy prompted a reevaluation within Chinese medicine concerning both anatomy and physiology related to the esophagus;concurrently,clini-cal cases involving esophageal disorders emerged prominently.Consequently,Chinese medicine's grasp on esophageal physiology,pa-thology,anatomy,and function became increasingly comprehensive over time.Choosing the esophagus as the starting point for observ-ing the theory of viscera in Chinese medicine is intended to illustrate that Chinese medicine's understanding of life,health and disease is based on the observation and continuous improvement of the anatomical functions of the viscera,integrating the physiological func-tions to form a highly integrated system with functional states,so as to facilitate the use of natural medicines for regulation and treatment.This is a distinctive feature different from Western medicine,and it can keep pace with the times and absorb modern re-search results,and continuously improve the theory and treatment system,so as to obtain strong vitality and benefit mankind.

Acute kidney injury （AKI） is a clinical syndrome characterized by a rapid decline in renal function over a short period due to various etiologic factors. If left untreated， AKI can progress to chronic kidney disease （CKD） or even end-stage renal disease （ESRD）. Although continuous renal replacement therapy （CRRT） can manage severe AKI， effective pharmacological treatments for AKI remain largely unavailable. Chinese medicine， with its multi-target and multi-pathway approaches， has accumulated substantial theoretical and practical knowledge in treating AKI and related complications. Rehmanniae Radix is a commonly used Chinese medicinal， known for its functions in clearing heat， cooling blood， nourishing yin， and promoting fluid production. The primary active ingredients of Rehmanniae Radix include catalpol， acteoside， and aucubin. In this study， we summarized recent research on the effect of the active ingredients of Rehmanniae Radix in preventing and treating AKI. We found that the key mechanisms underlying its anti-AKI effects include amelioration of inflammation， alleviation of oxidative stress， and inhibition of apoptosis. Additionally， the antifibrotic properties of the active ingredients of Rehmanniae Radix suggest its potential in slowing CKD progression. We reviewed the mechanisms of Rehmanniae Radix in treating AKI and its antifibrotic effects to provide a scientific basis for developing new AKI drugs， promoting the utilization of Rehmanniae Radix resources， and reducing the transition from AKI to CKD.

Objective To explore the differences in scapular motion and shoulder function between patients suffering from rotator cuff tears(RCT)with and without type Ⅲ scapular dyskinesis(SD).Meth-ods Between September 2021 and March 2023,sixteen patients suffering from rotator cuff tears with SD(SD group)and 17 counterparts without SD(non-SD group)were recruited from the Sports Hospital of the General Administration of Sport of China.Their scapular motion was assessed by measuring three parameters in the X-rays,including scapular spine line(LSS),scapular upward rotation angle(SU-RA),and coracoid upward shift distance(CUSD).Moreover,their shoulder range of motion in flexion,abduction and external rotation were recorded,and further evaluated using the Pain Visual Analog Scale(VAS)and American Shoulder and Elbow Surgeons Score(ASES).Results No significant differenc-es were found between the two groups in the average score of SURA,CUSD and LSS at 0°～30° shoul-der abduction,or in that of CUSD and LSS at 60°～90°shoulder abduction.However,the average SU-RA score of the SD group at 60°～90°shoulder abduction was significantly greater than the other group(P<0.05).The shoulder ranges of motion during active flexion,abduction and external rotation were significantly smaller in the SD group than in the non-SD group(P<0.05).Moreover,the average VAS score in the SD group was significantly higher than the non-SD group(P<0.05),while the average ASES score was significantly lower than the latter group(P<0.05).Conclusions RCT patients type III SD exhibits greater scapular upward rotation during shoulder abduction compared to those without SD.Moreover,the former patients suffer from more severe pain and have worse shoulder range of motion and functional performance than the latter.

Objective To explore the application value of 1 024×1 024 reconstruction matrix combined with iterative reconstruc-tion algorithm(Karl)in deep inferior epigastric artery(DIEA)computed tomography angiography(CTA).Methods A total of 40 patients who underwent DIEA CTA were prospectively selected and the original data were reconstructed by grouping.Group A was reconstructed using a conventional 512×512 matrix combined with Karl 5 grade.Group B was reconstructed using 1 024×1 024 recon-struction matrix combined with Karl 5,7,and 9 grades,respectively,and 3 subgroups B1-B3 were obtained.The CT and standard devia-tion(SD)values of the external iliac artery and psoas major muscle were measured on axial images,and signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were calculated.A 3-point scale was used to evaluate the perforating vessels from the DIEA,intramuscular course,point of emergence,superficial inferior epigastric artery(SIEA)and superficial inferior epigastric vein(SIEV)on volume ren-dering(VR)and maximum intensity projection(MIP)images by two observers,and a 5-point scale was used to evaluate the overall image quality on axial images.Results With the increase of Karl grade in groups B1 to B3,the SD value of the external iliac artery decreased gradually(P＜0.05),while SNR and CNR increased gradually(P＜0.05).The SD values of the external iliac artery in group B2 and group B3 were lower than those in group A(P＜0.05),and SNR and CNR were higher than those in group A(P＜0.05).There was a good consistency in the subjective evaluation between the two observers(Kappa values=0.773-0.872,P＜0.05).The perforating vessels from the DIEA,intramuscular course,point of emergence,SIEA and SIEV display and overall image quality subjective scores of group B2 and group B3 were better than those of group A(P＜0.05),and the scores of group B2 showed the greatest improvement.Conclusion The 1 024 × 1 024 reconstruction matrix combined with the Karl 7 reconstruction algorithm can optimize the image quality and improve the display of the DIEA and perforator microvessels.

2 patients with lateral orbital malignant tumors were treated by tumor resection and autologous pedicled coronoid-temporalis muscle flap repair of the orbital wall defect.The flaps survived well without obvious facial collapse deformity and with good orbital wall func-tion and aesthetic effect,the mouth open pattern,the intra-oral occlusion and the masticatory function were satisfactory.

Embryo implantation involves a complex interaction between the embryo and the endometrium of the mother, the study of which faces a variety of problems. The modeling of endometrial epithelial organoids and endometrial assembloids provides a new way to study the process of embryo implantation in vitro. This paper summarized the latest research progress in embryo implantation, the regulation mechanism of endometrial receptivity by estrogen- progesterone coordination and embryo-derived signals, the establishment of endometrial organoids, and the development and application of endometrial assembloids in the research on mother-embryo interaction, providing new strategies for studying the communication between embryo and maternal uterus during implantation.
Endometrium/physiology* ; Organoids/cytology* ; Embryo Implantation/physiology* ; Female ; Animals ; Progesterone/pharmacology* ; Pregnancy ; Estrogens/metabolism* ; Humans

Ferroptosis is a novel form of cell death with iron dependence,which has been confirmed to play an important role in the pathophysiology of various diseases.This review summarizes the main metabolic pathways of ferroptosis,including iron metabolic pathways,lipid metabolic pathways and the classic GSH/GPX4 metabolic pathways.At the same time,this review discusses the regulatory effect and mechanism of ferroptosis metabolism on ulcerative colitis,aiming to provide new ideas and research directions for the treatment of ulcerative colitis.