OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

Elderly patients with lung cancer have a significantly increased risk of perioperative cardiopulmonary complications due to physiological decline, high incidence of complications and reduced surgical tolerance, which directly affects postoperative recovery and long-term survival. Although the concepts of minimally invasive surgery and enhanced recovery after surgery have improved clinical outcomes, early recognition and intervention of postoperative complications in elderly patients remains a significant challenge in the field of thoracic surgery. By integrating recent literature and clinical practice, this paper systematically analyzes the pathophysiological mechanism and risk factors of perioperative cardiopulmonary complications in elderly patients with lung cancer, and discusses individualized intervention strategies based on risk stratification and multidisciplinary team, in order to provide theoretical basis and practical guidance for optimizing perioperative management and improving postoperative prognosis in elderly patients.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

Objective:To evaluate the toxicity of foscarnet sodium injection into the anterior chamber and intravitreal cavity on the cornea and retina.Methods:Thirty-six adult New Zealand White rabbits were randomly divided into control group, intravitreal injection group, and intracameral injection group, with 12 rabbits in each group.In the control group, 0.1 ml of balanced salt solution (BSS) was injected into the vitreous cavity of one eye, and an equal volume of BSS was injected into the anterior chamber of the other eye.In the intracameral injection group and intravitreal injection group, 0.1 ml of sodium foscarnet 1.2 mg was injected into the anterior chamber and vitreous cavity of one eye, respectively.Slit-lamp microscopy, ophthalmoscope, optical coherence tomography (OCT), and in vivo confocal laser scanning microscopy were performed on 3 experimental rabbits from each group on days 1, 7, 14, and 28 after injection.After sacrifice, both eyeballs were removed, and the corneas and retinas were examined using optical microscopy, scanning electron microscopy and transmission electron microscopy to evaluate the toxicity to the cornea and retina comprehensively.The use and care of the animals complied with the ARVO Statement.The study protocol was approved by an Ethics Committee of Peking University Third Hospital (No.IRB00006761-2015197). Results:Slit-lamp microscopy and OCT showed no corneal edema, intraocular inflammation, or other abnormalities in the intravitreal injection and control groups.Mild corneal edema was observed in intracameral injection group 1 day after injection, which resolved 7 days after injection. In vivo confocal laser scanning microscopy revealed normal hexagonal corneal endothelial cell morphology in the intravitreal injection and control groups.There was no significant difference in endothelial cell density at baseline and 1, 7, and 14 days after injection among the three groups ( Fgroup=1.21, P=0.32; Ftime=1.21, P=0.32).Light microscopy revealed no obvious corneal abnormalities.On days 1 and 7 after injection, retinal nerve fiber layer vacuolization and inflammatory cell infiltration were observed in the intravitreal injection and control groups.In the intravitreal injection of BSS group, inflammatory cell infiltration occurred in the retina without vacuolization 1 day after injection.There were no structural changes in the photoreceptor layer, and the nuclear layer was well-organized.Scanning electron microscopy showed no significant abnormalities in the corneal endothelium in the intravitreal injection group 1 day after injection.In the intracameral injection group, a large number of inflammatory cells were deposited and adhered to the corneal endothelium 1 day after injection and disappeared 7 days after injection.Transmission electron microscopy revealed that in the intravitreal injection group, 1 day after injection swelling of corneal endothelial cells, dilatation of the endoplasmic reticulum, and partial mitochondrial swelling were observed, which normalized 14 days after injection and vacuolization was present in the retina and interstitial fluid accumulation persisted until the 28 days after injection.In the intracameral injection group, swollen mitochondrial and endoplasmic reticulum of corneal endothelial cells was observed and resolved by 14 days after injection.However, structural abnormalities in the membranous discs of the photoreceptor outer segments and interstitial fluid accumulation in the optic nerve fiber layer persisted 1 day after injection and did not fully recover 28 days after injection. Conclusions:Intracameral intravitreal and injection of foscarnet sodium have transient toxic effects on the retina, which gradually weaken over time.Intracameral injection of foscarnet sodium was more toxic to corneal endothelial cells than intravitreal injection.

Objective To design a pairs of detection gloves for orthopedic manipulation to solve the problems of orthopedic manipulation in accurate,visual and quantitative description and reproduction in teaching.Methods The orthopedic manipulation detection gloves were mainly composed of a detection body worn on the hands,a main control module and a data visualization system.The detection body was made of multi-layer flexible materials such as rubber,cotton and non-woven fabrics,which integrated inertial sensors,pressure sensors and a data acquisition device;the main control module consisted of a filter circuit,an A/D converter(MCP3008)and a main controller(ARM-STM32 microcontroller);the data visualization system was designed based on the Unity 3D platform.Results The orthopedic manipulation detection gloves effectively detected the rotation angle of the knuckle during the orthopedic process with a high accuracy rate.Conclusion The orthopedic manipulation detection gloves can quantitatively display the abstract orthopedic manipulation,and can provide support for intelligent orthopedic teaching and orthopedic manipulation optimization.[Chinese Medical Equipment Journal,2025,46(7):27-33]

Objective:To implement evidence-based practice for eye management in ICU patients undergoing prone position ventilation and evaluate the effectiveness of applying the best evidence for eye management in this setting.Methods:Through literature retrieval, screening, and evaluation, the best evidence for eye management in ICU patients undergoing prone position ventilation was summarized and compiled into evidence review indicators. From March to June 2024, convenience sampling was used to select 29 ICU prone position ventilation patients and 30 ICU nurses at Shanghai Changzheng Hospital for baseline review to identify obstacles in clinical practice of evidence and develop action strategies based on these obstacles. From July to October 2024, 29 ICU prone position ventilation patients and 29 ICU nurses were selected for evidence-based practice to compare the implementation rates of review indicators before and after evidence-based practice, ICU nurses' knowledge, attitude and practice regarding eye management for prone position ventilation patients, as well as the intraocular pressure during prone position ventilation and the incidence of eye complications within the first week of ICU admission.Results:After evidence-based practice, the implementation rates of all 16 review indicators by ICU nurses were higher than those before evidence-based practice, and the differences were statistically significant ( P<0.05). The total score, knowledge dimension score, and practice dimension score on the Knowledge, Attitude and Practice Questionnaire on Eye Management during Prone Position Ventilation for ICU nurses were higher than those before evidence-based practice, with statistically significant differences ( P<0.05). After evidence-based practice, the intraocular pressure of ICU patients in prone position ventilation for 8 hours and at the end improved, and the differences were statistically significant ( P<0.05). The overall incidence of eye complications within one week of ICU admission decreased from 27.6% to 6.9%, with a statistically significant difference ( P<0.05) . Conclusions:Implementing evidence-based practices for eye management in ICU patients undergoing prone position ventilation can effectively increase nurses' implementation rates of review indicators, enhance their knowledge, attitude, and practice regarding eye management, and reduce the incidence of eye complications in patients.

Objective To explore the functional connectivity(FC)changes of hippocampus and amygdala in type 2 diabetes mellitus(T2DM)patients with erectile dysfunction(DMED),and the central pathological neural mechanisms underlying DMED.Methods 61 T2DM patients who visited Department of Endocrinology,Nanjing First Hospital,Nanjing Medical University from January 2020 to December 2021 were selected and divided into a simple T2DM group(n=30)and a combined DMED group(n=31).Another 47 healthy individuals were selected as control group(NC).The international erectile function scale(IIEF-5)was used to evaluate the erectile function.Resting-state functional magnetic resonance imaging(rs-fMRI)data were acquired from all participants.MRI data were preprocessed by the DPABI software package.Bilateral hippocampus and amygdala were selected as regions of interest(ROI)and the whole brain FC values were calculated.The FC values of brain regions between groups were tested by two-sample t-test with REST software package.Results Left hippocampus as ROI:compared with the NC group,FC values of the left superior temporal gyrus increased in the T2DM group,FC values of the left superior frontal gyrus,left inferior temporal gyrus,left posterior central gyrus and rectus gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left inferior parietal gyrus,left supramarginal gyrus,left middle occipital gyrus and right posterior central gyrus decreased in the DMED group.Right hippocampus as ROI:compared with the NC group,FC values of the right middle temporal gyrus and right rolandic operculum increased while FC values of the right calcarine fissure decreased in the T2DM group;FC values of bilateral anterior cingulate gyrus,right middle temporal gyrus and left rectus gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left middle frontal gyrus,left inferior parietal gyrus and right inferior temporal gyrus decreased in the DMED group.Left amygdala as ROI:compared with the NC group,FC values in the left parahippocampal gyrus,left fusiform gyrus and right insula increased in the T2DM group;FC value of the left middle temporal gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left middle frontal gyrus and left supramarginal gyrus decreased in the DMED group.Right amygdala as ROI:compared with the NC group,FC values of the left insula,right parahippocampal gyrus,right superior temporal gyrus and right supramarginal gyrus increased while FC values in the right caudate decreased in the T2DM group;FC values of the right middle frontal gyrus,left rectus gyrus and left middle occipital gyrus decreased in the DMED group.Compared with the T2DM group,FC values of the left middle frontal gyrus and left inferior parietal gyrus decreased in the DMED group.Conclusions DMED patients have abnormalities in the hippocampus,amygdala and other brain regions,especially the frontal lobe functional cortex,which may be related to changes in their brain function.

OBJECTIVE To explore the mechanism of action of Qihuang Zhuyu formula(QHZYF)in improving depression after myocardial infarction(MI),with a focus on revealing its regulatory effect on the inflammatory response of the heart and brain.METH-ODS The active ingredients of QHZYF and the action targets for intervening in depression after MI were analyzed by using ultra-per-formance liquid chromatography-high-resolution mass spectrometry(UPLC-Q-TOF/MS)combined with network pharmacology and molecular docking.A rat model of depression after MI was established by ligation of the left anterior descending coronary artery com-bined with chronic restraint stress.Echocardiography was used to evaluate cardiac function,hematoxylin-eosin(HE)and Masson stai-ning were used to evaluate myocardial injury,behavioral tests were used to detect melancholic behaviors,Nissl staining was used to e-valuate hippocampal neuron injury.Western blot detection of tumor necrosis factor receptor 2(TNFR2),phosphatidylinositol-3-kinase(PI3K),phosphorylated seronine protein kinase(p-AKT),seronine protein kinase(AKT),tumor necrosis factor receptor 1(TNFR1),phosphorylated nuclear factor κB(p-NF-κB),and nuclear factor κB(NF-κB)in cardiac and hippocampal tissues was conducted.The levels of serum IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay(ELISA),and the expression of TNFR1 and TNFR2 was detected by immunohistochemical technique(IHC).In vitro experiments,co-culture of rat cardiomyocyte line H9C2 cells and rat adrenal pheochromocytoma cell line with high differentiation PC12 cells was conducted,TNFR1 inhibitor(H398)and TNFR2 agonist(C-6His)were administered for intervention,and the expression of TNFR2,PI3K,p-AKT,AKT,TN-FR1,NF-κB,p-NF-κB was detected by Western blot.Observe the apoptosis of cells by TUNEL staining,ELISA was used to detect the levels of IL-6 and IL-10 in the cell supernatant.RESULTS Network pharmacological analysis indicates that the TNF signaling pathway was a key target for the treatment of depression after MI with the QHZYF.In vivo experiments have confirmed that the interven-tion of QHZYF could significantly improve the cardiac function,myocardial tissue and hippocampal neuron structure damage of de-pressed rats after MI,and improve their depression-like behaviors.At the molecular level,the high-dose group of QHZYF significant-ly upregulated TNFR2,p-AKT/AKT,and IL-10 in cardiac and hippocampal tissues(P＜0.01),and downregulated TNFR1,p-NF-κB/NF-κB and IL-6(P＜0.01).In vitro experiments showed that the drug-containing serum of QHZYF significantly upregulated the expression of TNFR2,p-AKT/AKT and IL-10 in H9C2 and PC12 cells(P＜0.01),downregulated the expression of TNFR1,p-NF-κB/NF-κB and IL-6(P＜0.01),and significantly inhibited cell apoptosis(P＜0.01).Furthermore,experiments on the combined ap-plication of H398 or C-6His further confirmed that its protective and anti-inflammatory effects were mediated by regulating the TN-FR2/PI3K/AKT and TNFR1/NF-κB pathways.CONCLUSION QHZYF improves the homeostasis of heart and brain inflammation by regulating the TNF pathway,and ameliorates myocardial injury and depressive state in depressed rats after MI.