Objective To explore the efficacy of vacuum-assisted minimally invasive gyrotomy for benign lesions in the lower quadrant of the breast.Methods From August 2022 to August 2023,90 patients with benign lesions in the lower quadrant of the breast were treated.According to the different surgical methods,they were divided into two groups:the traditional group included 45 cases,which underwent surgery through the trans-areolar incision;the minimally invasive group included 45 cases,which underwent surgery through the trans-mammary fold incision with vacuum-assisted minimally invasive technique.The surgical-related indicators,inflammatory response indicators,patient satisfaction,and safety were compared between the two groups.Results The operation time[(20.45±6.18)min],intraoperative bleeding[(7.78±2.23)ml],hospital stay[(4.37±1.05)d],scar length[(2.32±0.42)cm]and healing time[(3.46±1.08)d]in the minimally invasive group were significantly better than those in the traditional group[(34.52±9.46)min,(23.16±6.44)ml,(8.72±2.73)d,(19.14±4.18)cm and(7.37±2.16)d](P＜0.05).The levels of IL-6[(12.14±2.86)ng/L],IL-10[(14.33±3.74)pg/ml],CRP[(13.85±3.11)mg/L],Cor[(131.27±6.43)nmol/L]and NE[(82.55±8.44)in the minimally invasive group at 3 days after surgery ng/ml were increased and VEGF was decreased[(59.72±7.44)mg/L]than the traditional group[(17.23±3.38)ng/L,(19.62±4.88)pg/ml,(28.36±4.67)mg/L,(196.52±8.84)nmol/L,(117.62±7.14)ng/ml and(88.46±7.89)mg/L](P＜0.05).The satisfaction of patients in minimally invasive group(97.78％,44/45)was significantly higher than that in traditional group(82.22％,37/45)(P＜0.05).The incidence of adverse events in minimally invasive group(4.44％,2/45)was significantly lower than that in traditional group(22.22％,10/45)(P＜0.05).Conclusion Vacuum-assisted minimally invasive rotatory excision can optimize surgical indicators,improve serological indicators,enhance patient satisfaction and treatment safety compared to traditional areola incision surgery.

Background and Aims:Acute pancreatitis(AP)accompanied by intestinal injury and intestinal barrier dysfunction can significantly worsen AP prognosis.Currently,there is no effective clinical treatment for AP-related intestinal dysfunction.Ulinastatin(UTI)is a conventional drug used for AP treatment due to its ability to inhibit trypsin activity and exert anti-inflammatory effects.However,whether UTI directly improves AP-related intestinal injury remains unclear.Therefore,this study was conducted to investigate the therapeutic effects and potential mechanisms of UTI in AP-related intestinal dysfunction.Methods:Thirty rats were equally randomized into three groups and received intraperitoneal injections of PBS(control group),20%L-arginine(AP group),or 20%L-arginine+UTI(UTI group).Tail vein blood samples were collected at 0,24,and 48 h after the initial injection of L-arginine(or PBS),and the rats were euthanized after the final blood collection to obtain pancreatic and terminal ileum tissues.Serum levels of amylase,lipase,intestinal fatty acid-binding protein(I-FABP),and diamine oxidase(DAO)were measured using ELISA.Histopathological examinations of the pancreas and terminal ileum were conducted.Western blot was used to detect the protein expression levels of tumor necrosis factor α(TNF-α),interleukin 6(IL-6),interleukin 1β(IL-1β),and interleukin 10(IL-10)in terminal ileum tissue.Western blot and qRT-PCR were used to assess the protein and mRNA expression levels of Toll-like receptor 4(TLR4)and nuclear factor κB(NF-κB)p-p65 in the terminal ileum.Results:Compared with the control group,both the AP and UTI groups exhibited significant AP changes(elevated serum amylase and lipase levels,pancreatic histopathological damage)and AP-related intestinal injury(decreased I-FABP and DAO levels,ileal histopathological damage).However,these alterations were significantly less severe in the UTI group compared to the AP group(all P<0.01).Compared with the control group,both the AP and UTI groups showed significantly increased protein expression of pro-inflammatory factors(TNF-α,IL-1β,IL-6)and the anti-inflammatory factor IL-10 in the ileal tissue;however,the UTI group exhibited significantly lower levels of pro-inflammatory factors and higher levels of IL-10 compared to the AP group(all P<0.01).Additionally,compared with the control group,both the AP and UTI groups displayed significant upregulation of TLR4 and NF-κB p-p65 protein and mRNA expressions in ileal tissue,but the upregulations were significantly lower in the UTI group compared to the AP group(all P<0.01).Conclusion:UTI can inhibit the activation of the TLR4/NF-κB signaling pathway in the ileal tissue of AP rats,thereby reducing pro-inflammatory cytokine levels and increasing anti-inflammatory cytokine levels.Therefore,in addition to its anti-pancreatitis effects,UTI may have a direct therapeutic effect on AP-related intestinal dysfunction.

In line with the rising global incidence of cancer,tumor metastasis has become the leading cause of mortality among cancer patients.Formation of the pre-metastatic niche(PMN)creates an optimal microenvironment for tumor cell colonization and metastasis,thus facilitating tumor dissemination.In this context,cancer-associated fibroblasts(CAFs)have garnered significant attention as a result of their multifaceted roles in tumor progression.CAFs enhance the formation of the PMN and promote the invasive behavior of tumor cells by remodeling the extracellular matrix,inducing epithelial-mesenchymal transition,stimulating angiogenesis and modulating the tumor immune microenvironment.These processes not only expedite metastasis but also enable tumor immune evasion.This paper reviews the fundamental mechanisms and functions of CAFs in tumor metastasis,examines their potential applications in cancer research and therapy,and offers new perspectives and directions for the development of anti-tumor metastasis strategies.

Background and Aims:Acute pancreatitis(AP)accompanied by intestinal injury and intestinal barrier dysfunction can significantly worsen AP prognosis.Currently,there is no effective clinical treatment for AP-related intestinal dysfunction.Ulinastatin(UTI)is a conventional drug used for AP treatment due to its ability to inhibit trypsin activity and exert anti-inflammatory effects.However,whether UTI directly improves AP-related intestinal injury remains unclear.Therefore,this study was conducted to investigate the therapeutic effects and potential mechanisms of UTI in AP-related intestinal dysfunction.Methods:Thirty rats were equally randomized into three groups and received intraperitoneal injections of PBS(control group),20%L-arginine(AP group),or 20%L-arginine+UTI(UTI group).Tail vein blood samples were collected at 0,24,and 48 h after the initial injection of L-arginine(or PBS),and the rats were euthanized after the final blood collection to obtain pancreatic and terminal ileum tissues.Serum levels of amylase,lipase,intestinal fatty acid-binding protein(I-FABP),and diamine oxidase(DAO)were measured using ELISA.Histopathological examinations of the pancreas and terminal ileum were conducted.Western blot was used to detect the protein expression levels of tumor necrosis factor α(TNF-α),interleukin 6(IL-6),interleukin 1β(IL-1β),and interleukin 10(IL-10)in terminal ileum tissue.Western blot and qRT-PCR were used to assess the protein and mRNA expression levels of Toll-like receptor 4(TLR4)and nuclear factor κB(NF-κB)p-p65 in the terminal ileum.Results:Compared with the control group,both the AP and UTI groups exhibited significant AP changes(elevated serum amylase and lipase levels,pancreatic histopathological damage)and AP-related intestinal injury(decreased I-FABP and DAO levels,ileal histopathological damage).However,these alterations were significantly less severe in the UTI group compared to the AP group(all P<0.01).Compared with the control group,both the AP and UTI groups showed significantly increased protein expression of pro-inflammatory factors(TNF-α,IL-1β,IL-6)and the anti-inflammatory factor IL-10 in the ileal tissue;however,the UTI group exhibited significantly lower levels of pro-inflammatory factors and higher levels of IL-10 compared to the AP group(all P<0.01).Additionally,compared with the control group,both the AP and UTI groups displayed significant upregulation of TLR4 and NF-κB p-p65 protein and mRNA expressions in ileal tissue,but the upregulations were significantly lower in the UTI group compared to the AP group(all P<0.01).Conclusion:UTI can inhibit the activation of the TLR4/NF-κB signaling pathway in the ileal tissue of AP rats,thereby reducing pro-inflammatory cytokine levels and increasing anti-inflammatory cytokine levels.Therefore,in addition to its anti-pancreatitis effects,UTI may have a direct therapeutic effect on AP-related intestinal dysfunction.

Diabetes mellitus type 2(T2DM)is a common chronic metabolic disease,compared to non-diabetics,T2DM patients have a higher risk of heart disease,and their risk of vascular diseases is twice that of non-diabetic individu-als.Multiple clinical trials have confirmed that glucagon-like peptide-1 receptor agonists(GLP-1RA),in addition to their function of lowering blood glucose,can also decrease the risk of cardiovascular events in T2DM patients.This article re-views the mechanisms of GLP-1RA-mediated cardioprotection.It provides a comprehensive review of the recent progress in GLP-1RA-mediated cardiac protective mechanisms,elaborating on the protective effects of GLP-1RA on specific heart cell and further discussing its impact on heart failure(HF),provide assistance for clinical treatment of diabetic cardiomyopathy.

Objective:To explore the feasibility of the new auxiliary analysis software in chromosomal aberration analysis of radiation workers during occupational health examinations.Methods:Health examination data of 2 469 radiation workers in Henan province were collected. Manual analysis of chromosomal aberrations in peripheral blood lymphocytes was conducted using the new auxiliary software and the Ikaros software. Then, the chromosomal aberrations detected using both software tools were compared.Results:The new auxiliary software yielded a lower chromosomal aberration rate among radiation workers compared with the Ikaros software [(0.314 ± 0.014)% vs. (0.391 ± 0.022)%, χ2 = 9.24, P = 0.002]. Notably, the new auxiliary software yielded a significantly lower rate of acentric fragments (ace) [(0.136 ± 0.009)% vs. (0.209 ± 0.020)%, χ2= 17.76, P < 0.001]. However, no statistically significant differences were observed between the result of the two software tools in the rates of dicentrics plus rings (dic + r) and translocations ( P > 0.05). According to the GBZ/T 248-2014 standard, the differences in abnormality rates of chromosomal aberrations between the two groups had no statistically significance ( P > 0.05), with both groups showing an abnormality rate of 0 for ace. Furthermore, the new auxiliary software could double the detection efficiency. Among pre-service radiation workers of various occupations, the differences in the chromosomal aberrations detected using the two software tools exhibited statistical significance ( χ2 = 10.26, P = 0.001). In contrast, the differences in the chromosomal aberrations among in-service and post-service radiation workers had no statistically different significance ( P>0.05). The Poisson regression analysis result demonstrated that the rate of chromosomal aberrations excluding ace was affected by age ( z = 2.73, P = 0.006), while gender, analysis method, service status, and occupation had no impact. Conclusions:The two software tools yielded largely consistent result in detecting chromosomal aberrations induced by exposure to ionizing radiation. Notably, the new auxiliary software can significantly improve detection efficiency, indicating the feasibility of applying it to chromosomal aberration analysis among radiation workers.

The key pathological feature of age-related macular degeneration(AMD)is dysfunction of retinal pigment epithelial cells.Cell adhesion,serving as the biological basis for dynamic interactions between cells and between cells and the extracellular matrix,regulates tissue homeostasis through transmembrane signaling networks mediated by adhesion molecules.Studies have shown that the aberrant expression of E-cadherin,which offers advantages such as dynamic plas-ticity,tissue specificity,and signal transduction capability,is closely associated with the pathological mechanism of AMD.Targeting E-cadherin-related molecules may thus serve as a potential strategy for AMD intervention.This article reviews re-cent advances in the molecular regulatory mechanisms and therapeutic research concerning E-cadherin in AMD,aiming to provide a theoretical basis for its clinical translation.

Objective To investigate the application value of different doses of remifentanil combined with sevoflurane under pain threshold index(PTi)monitoring in ambulatory laparoscopic cholecystectomy.Methods 152 patients undergoing laparoscopic cholecystectomy under general anesthesia were selected from December 2023 to June 2024 at the Second Affiliated Hospital of Kunming Medical University.Patients were randomly divided into R1 group(n=38),R2 group(n=38),R3 group(n=38),and R4 group(n=38)using a random number table.On the basis of sevoflurane at 0.7 minimum alveolar concentration(MAC),patients in R1～R4 groups were combined with 0.1,0.2,0.3,and 0.4 μg/kg·min remifentanil,respectively.The changes in PTi at different time points,pre-and post-operative blood stress indicators[cortisol(Cor),norepinephrine(NE),and blood glucose(Glu)concentrations]were compared,and the incidence of intraoperative hypertension,hypotension,tachycardia,bradycardia,and postoperative nausea and vomiting were recorded.Results Compared with R1 group,PTi in R2,R3,and R4 groups decreased from the start of surgery(T3)to 5 min after extubation(T11)(P<0.05);compared with R2 group,PTi in R3 and R4 groups was lower at T3～T11(P<0.05);no statistically significant difference was found in PTi changes between R3 and R4 groups at different time points(P>0.05).Postoperative Cor,NE,and Glu concentrations showed statistically significant differences among the four groups(P<0.001),but no significant difference was found preoperatively(P>0.05).Compared with preoperative values,Cor,NE,and Glu levels significantly increased in all groups(P<0.001),with R1 group>R2 group>R4 group>R3 group.The incidence of intraoperative hypertension,hypotension,bradycardia,and tachycardia showed statistically significant differences(P<0.001),with R4>R1>R2=R3.The incidence of postoperative nausea and vomiting also showed statistically significant differences(P<0.001),with R1 group>R4 group>R2 group>R3 group.Conclusion Sevoflurane at 0.7 MAC combined with 0.3 μg/kg·min remifentanil provides good analgesic effects for patients undergoing ambulatory laparoscopic cholecystectomy,reduces stress response,and has high safety,making it worthy of clinical promotion.

Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins.Lysosome is an important organelle in eukaryotic cells,containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules.It is closely related to intracellular transport and autophagy,and is important for maintaining cellular homeostasis.This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes.Lysosomal dysfunction can lead to neurodegenerative diseases such as AD.Modulation of lysosomal function is a promising treatment strategy for AD.It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.