Targeting drug delivery systems mediated by nanoparticles has shown great potential in the diagnosis and treatment of cancer. However, influences of different tumor progressions on the accumulation of nanoparticles, especially the ligand-modified active targeting nanoparticles are seldom exploited. In this work, the accumulation and penetration of RGD-modified gold nanoparticles (active AuNPs) with different sizes were investigated in orthotopic breast cancer with different tumor progressions. The results showed that the smallest active AuNPs had better accumulation and permeation effects in early tumor tissues with the relatively looser extracellular matrix, larger gaps, lower interstitial fluid pressure, and less receptor expression, which was due to size effects. However, the larger active AuNPs had better accumulation and penetration effects in late tumor tissues with highly expressed target receptors integrin α _v β ₃ because of the multivalent interactions between larger active nanoparticles and integrin α _v β ₃. In the midterm, tumor accumulation of active AuNPs was equally influenced by size effects and multivalent interactions. Therefore, RGD-modified nanoparticles with sizes of 7 and 90 nm accumulated more in tumors. This study will guide a rational design of active targeting nanoparticles for enhancing the diagnosis and treatment of tumors based on their progressions.

Objective To compare the clinical efficacy of intraoperative intravenous tirofiban versus preoperative loading dose dual antiplatelet therapy in the acute phase LVIS stent-assisted coil embolization treatment for ruptured wide-necked intracranial aneurysms.Methods Patients with acutely ruptured,wide-neck intracranial aneurysms underwent LVIS stent-assisted coil embolization in the Department of Neurosurgery at Heze Municipal Hospital were retrospectively and consecutively enrolled from January 2017 to June 2023.According to the Chinese expert consensus on antiplatelet therapy for intracranial aneurysms,patients were divided into two groups based on the types of antiplatelet therapy they received:the loading-dose dual antiplatelet therapy(DAPT)group and the tirofiban group.Baseline and clinical data were collected and compared between the two groups,including age,sex,hypertension,diabetes mellitus,coronary artery disease,history of cerebral hemorrhage,preoperative Hunt-Hess grade,maximum aneurysm diameter,aneurysm neck width,and aneurysm location.Perioperative ischemic and hemorrhagic complications were collected and compared between the two groups.Perioperative ischemic complications included:intraoperative stent thrombosis(defined as filling defects in the parent artery,and,occlusion of the parent artery or stented branch during the procedure),and symptomatic ischemic infarction within 24 h postoperatively(confirmed by imaging with corresponding neurological deficits).Perioperative hemorrhagic complications included:intraoperative rupture of the target aneurysm(contrast extravasation or acute hemorrhage during embolization)and intracranial hemorrhage within 24 h postoperatively(new or worsened subarachnoid hemorrhage or intraparenchymal hemorrhage on CT).Clinical outcomes at 90 days were collected via telephone or outpatient follow-up,and evaluated using favorable prognosis defined as modified Rankin scale(mRS).A mRS score of 0-2 were defined as favorable prognosis and 3-6 as poor prognosis.Six-month postoperative imaging follow-up were collected,angiographic outcomes were categorized into four groups based on comparison with immediate post-embolization results:complete occlusion,total absence of contrast filling in the aneurysm sac;improved,reduced contrast filling;stable,unchanged contrast filling;and,recurrence,increased contrast filling.Results Totals of 108 patients with intracranial aneurysms treated by LVIS stent-assisted coiling were enrolled,with 30 males and 78females,aged32-75years(median age63[50,66]years).Among the108cases,55cases were assigned into the DAPT group,and 53 cases were included in the tirofiban group.(1)No statistically significant differences were observed between the tirofiban group and the DAPT group in baseline and clinical characteristics(all P＞0.05).(2)All patients underwent successful LVIS stent-assisted coiling,with a technical success rate of 100%.The total perioperative ischemic complications were 12.0%(13/108),including 4.6%(5/108)intraoperative stent thrombosis and 7.4%(8/108)symptomatic ischemic infarction within 24h after surgery.The total perioperative hemorrhagic complications rate was 1.9%(2/108),including 1 case of intraoperative aneurysm rupture and 1 case of postoperative intracranial hemorrhage within24h.92.6%(100/108)of the patients exhibited favorable prognosis and 7.4%(8/108)showed poor prognosis at the 90-day follow-ups.78.7%(85/108)of the patients accomplished at 6-month imaging follow-ups,the complete occlusion ratio was 94.1%(80/85)and the recurrence ratio was 2.4%(2/85).(3)The overall perioperative ischemic complication rates were 13.2%(7/53)in the tirofiban group and 10.9%(6/55)in the DAPT group,with no statistically significant difference(P=0.720).Intraoperative stent thrombosis occurred more frequently in the DAPT group(9.1%[5/55]vs.0,P=0.025),while symptomatic ischemic infarction within 24 h post-procedure was lower in the DAPT group(1.8%[1/55]vs.13.2%[7/53],P=0.028).The hemorrhagic complications occurred only in the DAPT group,with a rate of 3.6%(2/55),while no events observed in the tirofiban group.At the 90-day follow-up,the proportion of patients with favorable outcomes was 94.3%(50/53)in the tirofiban group and 90.9%(50/55)in the DAPT group,with no statistically significant difference between the groups(P=0.754).Conclusions Both intraoperative intravenous tirofiban and preoperative loading-dose DAPT demonstrated comparable safety profile and favorable clinical efficacy in the acute-phase treatment of ruptured wide-necked intracranial aneurysms with LVIS stent-assisted coil embolization.The results require further validation through large-scale prospective studies.

Objective To analyze the current status of outcome measures in randomized controlled trials(RCTs)of acupuncture treatment for vascular dementia(VD)and promote the development of a standardized set of outcome measures.Methods Chinese and English literature databases were searched,including the Chinese Medical Periodical Full-Text Database,the Chinese Biology Medicine disc,China National Knowledge Infrastructure,Wanfang Data,VIP Database,PubMed,Embase,the Cochrane Library,MEDLINE,Web of Science,Chinese Clinical Trials Registry,and the International Traditional Medicine Clinical Trial Registry.Two researchers independently screened RCT literature on acupuncture treatment for VD between January 1,2015 and January 1,2025,risk of bias was assessed using the Cochrane Risk of Bias 2 tool.Extract basic study information,intervention measures,diagnostic criteria for both Chinese and Western medicine,TCM syndromes,and outcome measures.Summarize the indicator domains of RCT studies on acupuncture treatment for VD,and analyze the basic information and outcome measures of the included studies.Results A preliminary search identified 2,898 articles,of which 93 RCTs were ultimately included.These studies involved 84 outcome measures,covering six indicator domains:symptoms/signs(23.81%),traditional Chinese medicine(TCM)syndromes(3.57%),medical checkups(60.71%),quality of life(5.95%),safety assessment(4.76%),and prognosis follow-up(1.19%).A total of 91(97.85%)RCTs reported treatment duration,ranging from 2 to 24 weeks;72(77.42%)RCTs used clinical efficacy as the outcome indicator;11 studies(11.83%)reported safety assessments and adverse events.Conclusion Currently,the RCT study design for acupuncture treatment of VD lacks unified standards and has numerous methodological issues.These include insufficient description of sample size estimation processes,strong reliance on subjective rating scales,ambiguous definitions of primary and secondary outcome measures,incomplete integration of Chinese and Western medical indicators,and insufficient reflection of individualized syndrome differentiation and treatment characteristics.In addition,safety assessments and follow-up mechanisms remain relatively weak.Future research should focus on the essential nature of VD,establish a core set of indicators aligned with the clinical characteristics of traditional Chinese medicine,promote the scientific and standardized development of acupuncture research for VD,and provide more compelling evidence-based support for clinical practice.

Objective To analyze the current status of outcome measures in randomized controlled trials(RCTs)of acupuncture treatment for vascular dementia(VD)and promote the development of a standardized set of outcome measures.Methods Chinese and English literature databases were searched,including the Chinese Medical Periodical Full-Text Database,the Chinese Biology Medicine disc,China National Knowledge Infrastructure,Wanfang Data,VIP Database,PubMed,Embase,the Cochrane Library,MEDLINE,Web of Science,Chinese Clinical Trials Registry,and the International Traditional Medicine Clinical Trial Registry.Two researchers independently screened RCT literature on acupuncture treatment for VD between January 1,2015 and January 1,2025,risk of bias was assessed using the Cochrane Risk of Bias 2 tool.Extract basic study information,intervention measures,diagnostic criteria for both Chinese and Western medicine,TCM syndromes,and outcome measures.Summarize the indicator domains of RCT studies on acupuncture treatment for VD,and analyze the basic information and outcome measures of the included studies.Results A preliminary search identified 2,898 articles,of which 93 RCTs were ultimately included.These studies involved 84 outcome measures,covering six indicator domains:symptoms/signs(23.81%),traditional Chinese medicine(TCM)syndromes(3.57%),medical checkups(60.71%),quality of life(5.95%),safety assessment(4.76%),and prognosis follow-up(1.19%).A total of 91(97.85%)RCTs reported treatment duration,ranging from 2 to 24 weeks;72(77.42%)RCTs used clinical efficacy as the outcome indicator;11 studies(11.83%)reported safety assessments and adverse events.Conclusion Currently,the RCT study design for acupuncture treatment of VD lacks unified standards and has numerous methodological issues.These include insufficient description of sample size estimation processes,strong reliance on subjective rating scales,ambiguous definitions of primary and secondary outcome measures,incomplete integration of Chinese and Western medical indicators,and insufficient reflection of individualized syndrome differentiation and treatment characteristics.In addition,safety assessments and follow-up mechanisms remain relatively weak.Future research should focus on the essential nature of VD,establish a core set of indicators aligned with the clinical characteristics of traditional Chinese medicine,promote the scientific and standardized development of acupuncture research for VD,and provide more compelling evidence-based support for clinical practice.

Objective To compare the clinical efficacy of intraoperative intravenous tirofiban versus preoperative loading dose dual antiplatelet therapy in the acute phase LVIS stent-assisted coil embolization treatment for ruptured wide-necked intracranial aneurysms.Methods Patients with acutely ruptured,wide-neck intracranial aneurysms underwent LVIS stent-assisted coil embolization in the Department of Neurosurgery at Heze Municipal Hospital were retrospectively and consecutively enrolled from January 2017 to June 2023.According to the Chinese expert consensus on antiplatelet therapy for intracranial aneurysms,patients were divided into two groups based on the types of antiplatelet therapy they received:the loading-dose dual antiplatelet therapy(DAPT)group and the tirofiban group.Baseline and clinical data were collected and compared between the two groups,including age,sex,hypertension,diabetes mellitus,coronary artery disease,history of cerebral hemorrhage,preoperative Hunt-Hess grade,maximum aneurysm diameter,aneurysm neck width,and aneurysm location.Perioperative ischemic and hemorrhagic complications were collected and compared between the two groups.Perioperative ischemic complications included:intraoperative stent thrombosis(defined as filling defects in the parent artery,and,occlusion of the parent artery or stented branch during the procedure),and symptomatic ischemic infarction within 24 h postoperatively(confirmed by imaging with corresponding neurological deficits).Perioperative hemorrhagic complications included:intraoperative rupture of the target aneurysm(contrast extravasation or acute hemorrhage during embolization)and intracranial hemorrhage within 24 h postoperatively(new or worsened subarachnoid hemorrhage or intraparenchymal hemorrhage on CT).Clinical outcomes at 90 days were collected via telephone or outpatient follow-up,and evaluated using favorable prognosis defined as modified Rankin scale(mRS).A mRS score of 0-2 were defined as favorable prognosis and 3-6 as poor prognosis.Six-month postoperative imaging follow-up were collected,angiographic outcomes were categorized into four groups based on comparison with immediate post-embolization results:complete occlusion,total absence of contrast filling in the aneurysm sac;improved,reduced contrast filling;stable,unchanged contrast filling;and,recurrence,increased contrast filling.Results Totals of 108 patients with intracranial aneurysms treated by LVIS stent-assisted coiling were enrolled,with 30 males and 78females,aged32-75years(median age63[50,66]years).Among the108cases,55cases were assigned into the DAPT group,and 53 cases were included in the tirofiban group.(1)No statistically significant differences were observed between the tirofiban group and the DAPT group in baseline and clinical characteristics(all P＞0.05).(2)All patients underwent successful LVIS stent-assisted coiling,with a technical success rate of 100%.The total perioperative ischemic complications were 12.0%(13/108),including 4.6%(5/108)intraoperative stent thrombosis and 7.4%(8/108)symptomatic ischemic infarction within 24h after surgery.The total perioperative hemorrhagic complications rate was 1.9%(2/108),including 1 case of intraoperative aneurysm rupture and 1 case of postoperative intracranial hemorrhage within24h.92.6%(100/108)of the patients exhibited favorable prognosis and 7.4%(8/108)showed poor prognosis at the 90-day follow-ups.78.7%(85/108)of the patients accomplished at 6-month imaging follow-ups,the complete occlusion ratio was 94.1%(80/85)and the recurrence ratio was 2.4%(2/85).(3)The overall perioperative ischemic complication rates were 13.2%(7/53)in the tirofiban group and 10.9%(6/55)in the DAPT group,with no statistically significant difference(P=0.720).Intraoperative stent thrombosis occurred more frequently in the DAPT group(9.1%[5/55]vs.0,P=0.025),while symptomatic ischemic infarction within 24 h post-procedure was lower in the DAPT group(1.8%[1/55]vs.13.2%[7/53],P=0.028).The hemorrhagic complications occurred only in the DAPT group,with a rate of 3.6%(2/55),while no events observed in the tirofiban group.At the 90-day follow-up,the proportion of patients with favorable outcomes was 94.3%(50/53)in the tirofiban group and 90.9%(50/55)in the DAPT group,with no statistically significant difference between the groups(P=0.754).Conclusions Both intraoperative intravenous tirofiban and preoperative loading-dose DAPT demonstrated comparable safety profile and favorable clinical efficacy in the acute-phase treatment of ruptured wide-necked intracranial aneurysms with LVIS stent-assisted coil embolization.The results require further validation through large-scale prospective studies.

ObjectiveTo analyse the clinical characteristics of different traditional Chinese medicine （TCM） syndromes in patients with heart failure based on information from electronic medical record. MethodsA cross-sectional study was conducted to collect clinical data of all inpatients with heart failure in the Department of Cardiology， Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 1， 2019 to December 31， 2020. A database of clinical TCM data was established to explore the characteristics of clinical data of basic information， syndromes and syndrome element types， and biochemical indexes. The distribution of TCM syndromes and syndrome elements in heart failure patients were also analysed， and the basic information and biochemical indexes of the patients with top 7 different TCM syndrome types were compared. ResultsA total of 1676 inpatients with heart fai-lure were included. The top 7 TCM syndromes of heart failure were syndrome of phlegm turbidity and blood stasis （477 cases， 28.46%）， syndrome of qi deficiency and blood stasis （439 cases， 26.19%）， syndrome of qi deficiency and blood stasis with water retention （274 cases， 16.35%）， syndrome of yang deficiency with water retention （145 cases， 8.65%）， syndrome of qi and yin deficiency （104 cases， 6.21%）， syndrome of qi and yin deficiency with blood stasis （80 cases， 4.77%）， syndrome of heart yang deficiency （59 cases， 3.52%）. Among the 1676 patients， 6 syndrome elements accounted for more than 5%. Blood stasis accounted for the highest proportion of TCM syndrome element type （1292 cases， 77.09%）， followed by qi deficiency （919 cases， 54.83%）， phlegm （498 cases， 29.71%）， water retention （434 cases， 25.89%）， yang deficiency （215 cases， 12.82%） and yin deficiency （191 cases， 11.40%）. Among the 1676 patients， 1308 cases of acute heart failure mainly showed syndrome of phlegm turbidity and blood stasis （386 cases， 29.51%）， and 368 of chronic heart fai-lure mainly showed syndrome of qi deficiency and blood stasis （118 cases， 32.07%）. Patients with syndrome of phlegm turbidity and blood stasis had the shortest disease duration of 0.3 months， while those with syndrome of heart yang deficiency had the longest disease duration of 15 months. The proportion of syndrome of phlegm turbidity and blood stasis was the highest in patients with heart failure combined with coronary artery disease， the proportion of syndrome of qi deficiency and blood stasis with water retention was the highest in patients with heart failure combined with atrial fibrillation， and the proportion of patients with syndrome of qi deficiency and blood stasis with water retention and syndrome of yang deficiency with water retention in those applying diuretics during the hospital stay was the highest with more than 86%. The different 7 TCM syndromes showed statistically difference in patients with complications including coronary artery disease， old myocardial infarction， atrial fibrillation， pre and post-admission medication usage including intravenous vasodilators， cardiac stimulants， diuretics， and level of blood chloride， blood urea， blood creatinine， blood bicarbonate， blood albumin， and blood total bilirubin （P＜0.05）. ConclusionThe most common TCM syndromes in patients with heart failure are syndrome of phlegm turbidity and blood stasis and syndrome of qi deficiency and blood stasis. Different TCM syndromes have different characteristics in gender， disease complications， medication before and after admission， and blood indexes.

Objective:To compare the short-term and long-term efficacies and safety of short-term spinal cord stimulation (st-SCS) and pulsed radiofrequency (PRF) in treating zoster-associated pain (ZAP).Methods:A total of 208 ZAP patients who received treatment in Department of Pain Management, Provincial Hospital Affiliated to Shandong University from January 2019 to September 2021 were selected. They were divided into st-SCS group ( n=107) and PRF group ( n=101) according to different treatments. After differences of baseline data being balanced by 1∶1 propensity score matching between the two groups, scores of numerical rating scale (NRS), NRS remission rate, drug dosage, Pittsburgh Sleep Quality Index (PSQI) and complications of 86 patients from each 2 groups were compared and analyzed before surgery, 3 and 7 d after surgery, at discharge, and 1, 3, 6, 12 and 24 months after surgery. Results:NRS scores in st-SCS group and PRF group 3 and 7 d after surgery, at discharge, and 1, 3, 6, 12 and 24 months after surgery were significantly lower than those before surgery ( P<0.05). NRS scores in st-SCS group were significantly lower than those in PRF group at discharge and 1, 3, 6 and 12 months after surgery ( P<0.05). NRS remission rate in st-SCS group was significantly higher than that in PRF group at discharge and 1, 3, 6, 12 and 24 months after surgery, and total effective rate in st-SCS group was significantly higher than that in PRF group 1, 3, 6, and 12 months after surgery ( P<0.05). The pregabalin and gabapentin dosages in st-SCS group and PRF group 1, 3, 6, 12, and 24 months after surgery were significantly lower than those before surgery, and the gabapentin dosage in st-SCS group was significantly lower than that in PRF group 3 months after surgery ( P<0.05). PSQI in st-SCS group and PRF group at discharge and 6, 12 and 24 months after surgery was significantly decreased compared with that before surgery, and PSQI in st-SCS group at discharge and 6, 12 and 24 months after surgery was significantly decreased compared with that in PRF group ( P<0.05). No serious complications as spinal epidural hematoma or spinal nerve root and spinal cord injuries occurred in st-SCS group and PRF group. Conclusion:Both st-SCS and PRF can treat ZAP safely and effectively, but st-SCS has more advantages than PRF.

Objective:To establish a sequencing method for the genome of severe fever with thrombocytopenia syndrome virus (SFTSV) based on next-generation sequencing (NGS).Methods:SFTSV RNA was extracted from serum samples of patients with severe fever with thrombocytopenia syndrome. SFTSV-specific primers were designed using Primer 5.0 software. A multiplex PCR method was constructed and used to amplify the nucleotide sequence of SFTSV. Whole-genome sequencing was performed on the NGS platform.Results:The whole genes of SFTSV isolates in 28 serum samples were amplified by the multiplex PCR with a coverage over 94%. Sequencing and phylogenetic analysis of those strains revealed that the predominant strains ( n=20) belonged to genotype A, followed by genotypes B ( n=4) and E ( n=3). Conclusions:A high-throughput sequencing method for SFTSV based on multiplex PCR was established in this study. This method was characterized by high specificity and good quality and could improve the sequencing efficiency.

Objective To explore the values of apparent diffusion coefficients (ADC) in staging the lesions of multiple sclerosis (MS) through analysing the differences of ADC in different types of lesions.Methods 137 lesions identified in 29 patients with MS,were characterized by their enhancement pattern on contrast-enhanced T1-weighted MR images and whether they were changing in appearance, size or signal.The lesions were classified into four groups:homogeneously enhancing lesions (HELs), ring-enhancing lesions (RELs), active nonenhancing lesions (ANELs), and inactive nonenhancing lesions (INELs).The mean ADC values for each type of lesions were calculated and compared.Results The ADC values for HELs, RELs, ANELs and INELs were (91.09±13.63)× 10 5 · m2 · s-1, (105.66±9.92) × 10-5 · m2 · s-1, (136.80±20.31) × 10-5 · m2 · s-1 and (127.46±13.65) ×10-5 · m2 · s-1.There were significant differences between the ADC values of any two groups in the four groups except the ADC values between ANELs and INELs.Conclusion ADC values are useful to differentiate each type of lesion,which can help stage the lesions of MS.