OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

ObjectiveTo establish a regional risk assessment system for hospital-acquired infections in neurosurgery department of general hospital, and to evaluate its prevention and control effectiveness. MethodsFailure mode and effect analysis (FMEA) was used to identify the core risk factors for infections in neurosurgery department. The risk priority number (RPN) of each risk factor was calculated to determine the priority intervention targets. Targeted interventions were developed and continuously refined through the plan-do-check-act (PDCA) cycles. Data from January to June 2023 (control group) and July to December 2023 (intervention group) were collected to compare the differences in environmental hygiene monitoring qualification rate, incidence rate of hospital-acquired infections among inpatients, and detection rate of bacterial antimicrobial resistance. ResultsHigh-risk factors for hospital-acquired infections in neurosurgery department included patient-related risk factors, inadequate implementation of isolation measures for special infections, and poor compliance with surgical site infection (SSI) prevention protocols. After intervention, the environmental hygiene qualification rate significantly increased from 81.55% to 100.00% (χ²=120.49, P<0.001). The overall hospital-acquired infection rate among inpatients decreased from 2.62% to 2.45%, the infection rate of per case declined from 3.12% to 2.84%, and the detection rate of multidrug-resistant organism infections reduced from 43.72% to 36.79%. Additionally, antimicrobial utilization rate decreased from 48.75% to 42.53% (χ²=34.09, P<0.001). ConclusionThe FMEA-based risk assessment system can effectively identify critical infection risks in neurosurgery department, and targeted interventions can significantly improve infection prevention and control performance.

Objective To analyze the postoperative complications and survival outcomes of elderly patients with renal cell carcinoma undergoing laparoscopic surgery, and to identify the influencing factors, so as to provide reference for improving the safety of laparoscopic surgery in such patients. Methods A retrospective analysis was conducted on the clinical, surgical, and pathological data of 153 patients aged ≥75 years who underwent laparoscopic nephrectomy for renal cell carcinoma at our hospital during 2012 and 2025.Logistic regression analyses were performed to identify factors influencing postoperative complications, and a nomogram was constructed and validated to predict the complications.Kaplan-Meier method was used to draw the survival curve, and the effects of different surgical approaches on the prognosis and the survival difference in the age subgroups (75-＜80 years, ≥80 years) were analyzed.Cox regression analyses were conducted to determine factors affecting survival outcomes. Results Among the 153 patients, 15 developed postoperative complications, including 5 severe cases. Multivariate logistic regression identified Charlson Comorbidity Index (CCI) ≥3 and prolonged operation time as independent risk factors for postoperative complications (P＜0.05).The C-index of the logistic regression model constructed based on these factors (age, CCI≥3 and operation time) was 0.77 (95%CI:0.64-0.90), with an average absolute error of 1.6%.Subgroup analysis revealed superior overall survival in patients aged 75-＜80 years undergoing partial nephrectomy compared to radical nephrectomy (P=0.005 6).No statistically significant difference in overall survival was observed among patients ≥80 years who received different surgical approaches (P=0.062).Multivariate Cox regression analysis identified preoperative low albumin levels, preoperative renal insufficiency, tumor diameter＞4 cm, and pathological stage as independent risk factors for overall survival (P＜0.05). Conclusion Laparoscopic surgery is safe and effective for elderly patients with renal cell carcinoma, with survival outcomes correlated to nutritional status, renal function, tumor size and pathological staging.Patients aged ≥80 years still derive surgical benefit, and no survival differences exist between different surgical approaches in this age group.

OBJECTIVE To investigate the role of clinical pharmacists in the individualized treatment of a rare case of diffuse pulmonary microabscesses caused by Streptococcus constellatus complicated with organizing pneumonia （OP） in a non-immunocompromised patient. METHODS For a middle-aged， non-immunocompromised patient with a one-year disease course， whose imaging findings showed the coexistence of diffuse microabscesses and OP caused by S. constellatus pulmonary abscess， the clinical pharmacist， based on pharmacokinetics/pharmacodynamics characteristics， assisted the physician in optimizing the previously ineffective anti-infective regimen to Ceftriaxone sodium for injection combined with Metronidazole and sodium chloride injection， so as to enhance coverage of mixed anaerobes and lesion penetration. After the patient’s hemoptysis ceased， the clinical pharmacist recommended timely initiation of low-dose Methylprednisolone sodium succinate for injection to manage OP. Upon discharge， sequential oral therapy with Linezolid tablets， Metronidazole tablets， Methylprednisolone tablets and Omeprazole enteric-coated tablets was prescribed. RESULTS After implementation of the individualized treatment regimen， the patient’s hemoptysis resolved， pulmonary lesions significantly regressed， and the patient was discharged in a stable condition. At the three-month follow-up， the patient remained stable. CONCLUSIONS For chronic persistent pulmonary infection complicated with OP in a non-immunocompromised host， clinical pharmacists assist clinicians in optimizing anti-infective regimens and recommend the timely initiation of anti-inflammatory therapy after infection control， thereby contributing to favorable clinical outcomes. Individualized treatment of such complex cases requires comprehensive consideration of pathogen coverage， pathological barriers， and the timing of anti-inflammatory intervention.

Tumor angiogenesis is a core pathological driver of malignant growth, invasion, and metastasis, and represents a major obstacle to effective anticancer therapy. Conventional antiangiogenic agents, including neutralizing monoclonal antibodies and small-molecule tyrosine kinase inhibitors, are constrained by drug resistance, on-target toxicity, and the compensatory activation of alternative pro-angiogenic pathways. Targeted protein degradation (TPD) has emerged as a promising strategy that may overcome these limitations. Unlike traditional inhibitors that operate through an occupancy-driven mechanism, degraders function through an event-driven catalytic mechanism in which a single degrader molecule can catalytically promote the ubiquitination and subsequent proteasomal or lysosomal degradation of multiple molecules of the same target protein, thereby eliminating the target protein together with all of its functions rather than merely blocking a single active site. This review systematically delineates the pathophysiological basis of tumor angiogenesis, encompassing the angiogenic switch driven by hypoxia-inducible factor-1α (HIF-1α), the aberrant structural and functional features of the tumor vasculature, and the self-reinforcing vicious cycles that sustain malignant progression. We then categorize the principal TPD modalities, with particular emphasis on proteolysis-targeting chimeras (PROTACs) and lysosome-targeting chimeras (LYTACs), and describe their design principles and mechanisms of action. PROTACs recruit E3 ubiquitin ligases to direct intracellular targets to the ubiquitin-proteasome system for degradation, whereas LYTACs engage lysosome-targeting receptors to route extracellular and membrane proteins to the lysosome, thereby expanding the degradable target space beyond the intracellular proteome. We further summarize recent advances in the application of TPD to antiangiogenic intervention at four distinct levels. First, at the signaling initiation level, degradation of vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2) by aptamer-engineered PROTACs, antibody-based LYTACs, and small-molecule VEGFR2 degraders blocks the upstream trigger of the angiogenic cascade. Second, at the signal transduction level, degradation of focal adhesion kinase (FAK), B-Raf proto-oncogene serine/threonine kinase (BRAF), phosphodiesterase 4 (PDE4), and bromodomain-containing protein 4 (BRD4) interrupts intracellular signaling cascades and transcriptional responses. Third, at the microenvironment level, degradation of proviral integration site for Moloney murine leukemia virus (PIM) kinases curtails the pro-angiogenic signals secreted by tumor-associated macrophages. Fourth, multi-target synergistic strategies, exemplified by bispecific degraders that simultaneously target human epidermal growth factor receptor 2 (HER2) and VEGF-A, represent a preliminary exploration of cooperative intervention. Representative degraders reviewed herein elicit diverse antiangiogenic phenotypes, ranging from the direct inhibition of endothelial cell proliferation, migration, and tube formation to reductions in microvessel density and the suppression of vasculogenic mimicry. Finally, we discuss the major challenges that remain, including the precise matching of degradation kinetics with the vascular normalization window, target selectivity and tissue specificity, and the activation of compensatory networks and the emergence of resistance. Since the application of TPD in this setting remains at an early stage, the clinical translation of these approaches will require careful optimization of degradation efficiency, spatiotemporal control, and delivery strategies. We also envision future directions toward immunotherapy-based combination regimens and precision-degradation approaches guided by single-cell and spatial transcriptomics. In our view, TPD should not be regarded merely as a substitute for conventional antiangiogenic drugs, but rather as a molecular tool capable of systematically remodeling the tumor vascular microenvironment. When precise control of degradation efficiency and spatiotemporal regulation are integrated with a thorough understanding of the heterogeneity and compensatory capacity of tumor vessels, the full clinical potential of this strategy can be realized.

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.

[Objective] To explore the diagnosis and treatment experience of tension hydrocele. [Methods] The clinical data of 2 patients with tension hydrocele treated in our hospital were retrospectively analyzed.Relevant literature was retrieved to analyze the clinical characteristics of this disease. [Results] Case 1 was diagnosed due to swelling and pain of the left scrotum after trauma for more than one month, which worsened for one day.Physical examination showed high tension in the left scrotum and positive light transmission test.Ultrasound examination revealed that the blood flow signal in the left testis disappeared.Emergency left scrotal exploration and hydrocelectomy were performed.There was no sign of testis torsion during the operation.Case 2 was diagnosed mainly due to hydrocele of the right testis for 1 year, which worsened for 1 week and complicated with testis distension and pain.Physical examination showed high tension in the right scrotum and positive light transmission test.Ultrasound examination revealed that the blood flow signal in the right testis decreased.After 40ml of fluid was extracted under ultrasound monitoring, the blood flow signal in the right testis recovered.Hydrocelectomy was performed the next day.During the follow-up of 8 months, there was no recurrence of hydrocele.A search of domestic and foreign literature showed that there were no reports in domestic literature, while a total of 11 cases were reported in foreign literature. [Conclusion] Tension hydrocele of the testis is a rare emergency of the scrotum.Surgery or decompression should be performed as soon as possible to restore testicular blood supply, and hydrocelectomy should be performed simultaneously or in stages to prevent recurrence.

BACKGROUND:Individuals with chronic ankle instability are prone to inversion ankle sprains during landing.Moderately increasing the foot toe-out angle during landing may reduce the occurrence of inversion ankle sprains,but no studies have directly demonstrated this effect. OBJECTIVE:To explore the effect of increased toe-out angle during landing on the peak inversion angle,peak angular velocity,and the time to peak inversion among individuals with and without chronic ankle instability. METHODS:A total of 60 participants were recruited for this study,including 30 individuals with chronic ankle instability and 30 without chronic ankle instability.The study utilized a simulated sprain apparatus for drop-landing tests,featuring a platform that could tilt forward by 24° and inward by 15°,thus simulating the foot position during an ankle inversion sprain.Participants were required to perform drop-landing tests under two landing conditions:natural landing and toe-out landing,with the latter involving a greater foot toe-out angle,over 150%more than the former.Kinematic data of participants were recorded using a 12-camera three-dimensional motion capture system.Data analysis was conducted using two-way repeated measures analysis of variance and Spearman correlation analysis. RESULTS AND CONCLUSION:(1)Significant main effects of condition were found for peak inversion angle during drop-landing(P<0.001,η2 p=0.270),peak inversion velocity(P=0.015,η2 p=0.098),and peak inversion time(P<0.001,η2 p=0.260);a significant main effect of group was found for peak inversion velocity(P=0.029,η2 p=0.080).(2)There were significant negative correlations between the foot toe-out angle at landing and the peak ankle inversion angle(P=0.021,r=-0.310;P=0.042,r=-0.278)as well as the peak inversion time(P=0.018,r=-0.312;P=0.021,r=-0.309)in both chronic ankle instability and non-chronic ankle instability groups.Moreover,a significant negative correlation was also found between the foot toe-out angle and peak inversion velocity in the chronic ankle instability group(P=0.021,r=-0.312).(3)It is indicated that increasing the foot toe-out angle at landing can reduce the peak inversion angle,peak inversion velocity,and the peak inversion time during landing in patients with chronic ankle instability and non-chronic ankle instability,thereby decreasing the risk of ankle inversion sprains.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Objective:This study evaluated the accuracy of internal mammary sentinel lymph node biopsy(IM-SLNB)in patients with early-st-age breast cancer after receiving neoadjuvant therapy(NAT).It explored the benefits of IM-SLNB in guiding cancer staging,evaluating progn-osis,and optimizing adjuvant treatment strategies.Methods:A retrospective study was conducted to collect clinical data of patients who re-ceived IM-SLNB following NAT in Shandong Cancer Hospital and Institute from October 2013 to November 2023.We analyzed the influence of clinicopathological characteristics on internal mammary lymph node(IMLN)metastasis and assessed the prognostic significance of IMLN me-tastasis following NAT.Results:The study included 132 breast cancer patients who underwent IM-SLNB following NAT.The metastasis rates of axillary lymph nodes(ALN)and internal mammary lymph nodes(IMLN)were 90.9%(120/132)and 9.1%(12/132),respectively.The perce-ntages of patients in the following groups were as follows:ALN-positive/IMLN-positive(8.3%,11/132),ALN-positive/IMLN-negative(43.1%,57/132),ALN-negative/IMLN-positive(0.7%,1/132),and ALN-negative/IMLN-negative(47.7%,63/132).The detection rate of internal mam-mary sentinel lymph nodes(IM-SLN)after NAT was 98.5%(132/134);two patients could not undergo IM-SLNB owing to surgical difficulties.Among the 12 cases of IMLN metastasis,6 patients experienced a change in postoperative pathological staging:2 shifted from stage ⅢA toⅢC,2 from stage ⅡB to ⅢC,1 from stage ⅡA to ⅢA,and 1 from stage ⅡA to ⅢC.IMLN metastasis was determined to be an independ-ent risk factor for disease-free survival(DFS)and overall survival(OS)(P<0.05).Patients with IMLN metastasis demonstrated significantly lower DFS and OS than those without IMLN metastasis(P<0.05).Conclusions:The pathological status of both ALN and IMLN should be con-sidered in the axillary pathological response after NAT.Patients with detectable IMLN during surgery after NAT should undergo IM-SLNB to ensure comprehensive lymph node staging.The status of IMLN metastasis following NAT serves as an independent prognostic factor.