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.

Liver fibrosis is the common pathological process in the progression of various chronic liver diseases to liver cirrhosis， and it greatly affects the prognosis of patients with chronic liver diseases. As a novel adipokine， Chemerin participates in the metabolism of glucose and lipids and inflammation， and various studies have shown that the expression level of Chemerin is correlated with the degree of liver fibrosis， suggesting that Chemerin may be involved in the process of liver fibrosis by regulating metabolism and inflammation. Chemerin has shown certain potential in the auxiliary diagnosis of liver fibrosis and the intervention against the progression of liver fibrosis. This article reviews the potential role and mechanism of action of Chemerin in the process of liver fibrosis， in order to provide new ideas for the diagnosis and treatment of liver fibrosis.

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 investigate the effects of red laser versus plasma transurethral enucleation of the prostate (TUEP) on urinary and sexual function in patients under 65 years of age with benign prostatic hyperplasia (BPH).Method:This study was a retrospective analysis. Eighty BPH patients under 65 years old, admitted to the Affiliated Hospital of Yan'an University between January 2020 and January 2023 were selected. Among them, 40 patients who underwent 980 nm semiconductor red laser TUERP with pre-resection of the urethral mucosa 1 cm proximal to the verumontanum at the prostatic apex and preservation of bladder neck integrity were assigned to the Red Laser Group. Another 40 patients who underwent conventional TURP with a plasma resectoscope were assigned to the Plasma Group. Clinical data and 6-month postoperative follow-up data were collected. Changes in the International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), International Index of Erectile Function-5 (IIEF-5) score, ejaculatory function score, and ejaculatory discomfort score before and after surgery were compared between the two groups. The incidence rates of decreased semen volume, retrograde ejaculation, and painful ejaculation at 6 months postoperatively were also compared.Results:At 6 months postoperatively, IPSS decreased in both groups compared to preoperative levels and was lower in the Red Laser Group than in the Plasma Group [(4.7±1.3) points vs. (6.3±2.2) points, t=-4.46, P<0.001]. Qmax increased in both groups compared to preoperative levels and was higher in the Red Laser Group than in the Plasma Group [(25.7±1.3) ml/s vs. (22.6±1.2) ml/s, t=10.76, P<0.001]. The ejaculatory function score in the Plasma Group was lower than its own preoperative level [(5.9±0.7) points vs. (11.1±1.6) points, t=5.33, P<0.001] and lower than that in the Red Laser Group [(5.9±0.7) points vs. (11.4±0.9) points, t=7.56, P<0.001]. The ejaculatory discomfort score in the Plasma Group was higher than its own preoperative level [(3.0±1.5) points vs. (0.8±0.6) points, t=4.26, P<0.001] and higher than that in the Red Laser Group [(3.0±1.5) points vs. (0.8±0.6) points, t=5.83, P<0.001]. The incidence rates of decreased semen volume and retrograde ejaculation in the Red Laser Group were lower than those in the Plasma Group [12.5% (5/40) vs. 50.0% (20/40), 10.0% (4/40) vs. 45.0% (18/40), χ2=15.84, 12.65, respectively, both P<0.001]. Conclusions:Using 980 nm semiconductor red laser TUERP with pre-resection of the urethral mucosa 1 cm proximal to the verumontanum and preservation of bladder neck integrity can improve urinary and sexual function in BPH patients under 65 years of age.

AIM:This study aims to investigate the mechanism by which Qingfei-Jiedu-Huatan Formula(QJHF)regulates autophagy in alveolar macrophages through mTOR in the treatment of severe pneumonia(SP)in rats.METHODS:Sixty SPF-grade male rats were randomly assigned to six groups:control,model,QJHF,moxifloxacin(MOX),rapamycin(RAPA),and QJHF+RAPA,with ten rats in each group.An SP rat model was established using Klebsiella pneumoniae.After seven days of treatment,changes in IL-33 and IFN-γ levels in bronchoalveolar lavage fluid(BALF)were measured using ELISA.Histopathological alterations in lung tissue were assessed via HE staining,and the autophagy of alveolar macrophages was detected using immunofluorescence co-localization methods.The expression levels of mTOR,beclin-1,and LC3 mRNA in lung tissue were analyzed using qPCR,while Western blot was employed to assess the protein levels of p-mTOR/mTOR,beclin-1,and LC3-II/LC3-I.RESULTS:Compared to the control group,the model group exhibited a deteriorated condition,characterized by alveolar wall rupture and thickening,significant inflammatory cell infiltration in the alveolar cavity,and extensive lung tissue damage(P<0.01).Elevated levels of IL-33 and IFN-γ in BALF were also observed(P<0.01),along with increased colocalization of CD68 and LC3 in immunofluorescence analy-sis.The mTOR mRNA expression in lung tissue decreased(P<0.01),while LC3 and beclin-1 mRNA expressions in-creased(P<0.01).Additionally,the protein expression ratio of p-mTOR/mTOR decreased(P<0.01),whereas LC3-II/LC3-I and beclin-1 protein levels increased(P<0.01).In comparison to the model group,significant improvements were noted after treatment with QJHF and MOX(P<0.01),while RAPA treatment led to a worsening of these indicators(P<0.05).A slight improvement was observed with the QJHF combined with RAPA intervention,though this was not statisti-cally significant.No significant differences were found between the MOX and QJHF groups.However,the QJHF+RAPA group displayed notable improvements in various indicators compared to the RAPA group(P<0.05).CONCLUSION:The QJHF can mitigate the inflammatory response associated with severe pneumonia,potentially by activating mTOR phos-phorylation activity,which in turn inhibits excessive autophagy in alveolar macrophages.

AIM:This study aims to investigate the mechanism by which Qingfei-Jiedu-Huatan Formula(QJHF)regulates autophagy in alveolar macrophages through mTOR in the treatment of severe pneumonia(SP)in rats.METHODS:Sixty SPF-grade male rats were randomly assigned to six groups:control,model,QJHF,moxifloxacin(MOX),rapamycin(RAPA),and QJHF+RAPA,with ten rats in each group.An SP rat model was established using Klebsiella pneumoniae.After seven days of treatment,changes in IL-33 and IFN-γ levels in bronchoalveolar lavage fluid(BALF)were measured using ELISA.Histopathological alterations in lung tissue were assessed via HE staining,and the autophagy of alveolar macrophages was detected using immunofluorescence co-localization methods.The expression levels of mTOR,beclin-1,and LC3 mRNA in lung tissue were analyzed using qPCR,while Western blot was employed to assess the protein levels of p-mTOR/mTOR,beclin-1,and LC3-II/LC3-I.RESULTS:Compared to the control group,the model group exhibited a deteriorated condition,characterized by alveolar wall rupture and thickening,significant inflammatory cell infiltration in the alveolar cavity,and extensive lung tissue damage(P<0.01).Elevated levels of IL-33 and IFN-γ in BALF were also observed(P<0.01),along with increased colocalization of CD68 and LC3 in immunofluorescence analy-sis.The mTOR mRNA expression in lung tissue decreased(P<0.01),while LC3 and beclin-1 mRNA expressions in-creased(P<0.01).Additionally,the protein expression ratio of p-mTOR/mTOR decreased(P<0.01),whereas LC3-II/LC3-I and beclin-1 protein levels increased(P<0.01).In comparison to the model group,significant improvements were noted after treatment with QJHF and MOX(P<0.01),while RAPA treatment led to a worsening of these indicators(P<0.05).A slight improvement was observed with the QJHF combined with RAPA intervention,though this was not statisti-cally significant.No significant differences were found between the MOX and QJHF groups.However,the QJHF+RAPA group displayed notable improvements in various indicators compared to the RAPA group(P<0.05).CONCLUSION:The QJHF can mitigate the inflammatory response associated with severe pneumonia,potentially by activating mTOR phos-phorylation activity,which in turn inhibits excessive autophagy in alveolar macrophages.

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.

Objective:To investigate the effects of red laser versus plasma transurethral enucleation of the prostate (TUEP) on urinary and sexual function in patients under 65 years of age with benign prostatic hyperplasia (BPH).Method:This study was a retrospective analysis. Eighty BPH patients under 65 years old, admitted to the Affiliated Hospital of Yan'an University between January 2020 and January 2023 were selected. Among them, 40 patients who underwent 980 nm semiconductor red laser TUERP with pre-resection of the urethral mucosa 1 cm proximal to the verumontanum at the prostatic apex and preservation of bladder neck integrity were assigned to the Red Laser Group. Another 40 patients who underwent conventional TURP with a plasma resectoscope were assigned to the Plasma Group. Clinical data and 6-month postoperative follow-up data were collected. Changes in the International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), International Index of Erectile Function-5 (IIEF-5) score, ejaculatory function score, and ejaculatory discomfort score before and after surgery were compared between the two groups. The incidence rates of decreased semen volume, retrograde ejaculation, and painful ejaculation at 6 months postoperatively were also compared.Results:At 6 months postoperatively, IPSS decreased in both groups compared to preoperative levels and was lower in the Red Laser Group than in the Plasma Group [(4.7±1.3) points vs. (6.3±2.2) points, t=-4.46, P<0.001]. Qmax increased in both groups compared to preoperative levels and was higher in the Red Laser Group than in the Plasma Group [(25.7±1.3) ml/s vs. (22.6±1.2) ml/s, t=10.76, P<0.001]. The ejaculatory function score in the Plasma Group was lower than its own preoperative level [(5.9±0.7) points vs. (11.1±1.6) points, t=5.33, P<0.001] and lower than that in the Red Laser Group [(5.9±0.7) points vs. (11.4±0.9) points, t=7.56, P<0.001]. The ejaculatory discomfort score in the Plasma Group was higher than its own preoperative level [(3.0±1.5) points vs. (0.8±0.6) points, t=4.26, P<0.001] and higher than that in the Red Laser Group [(3.0±1.5) points vs. (0.8±0.6) points, t=5.83, P<0.001]. The incidence rates of decreased semen volume and retrograde ejaculation in the Red Laser Group were lower than those in the Plasma Group [12.5% (5/40) vs. 50.0% (20/40), 10.0% (4/40) vs. 45.0% (18/40), χ2=15.84, 12.65, respectively, both P<0.001]. Conclusions:Using 980 nm semiconductor red laser TUERP with pre-resection of the urethral mucosa 1 cm proximal to the verumontanum and preservation of bladder neck integrity can improve urinary and sexual function in BPH patients under 65 years of age.