OBJECTIVE To prepare Arg-Gly-Asp（RGD）-modified doxorubicin （DOX）-loaded “core-shell” nanoparticles （RGD@DOX-LPNs）， characterize the nanoparticles， and investigate their antitumor effects. METHODS RGD@DOX-LPNs were prepared using the nanoprecipitation method. Their morphology was examined by visual inspection and electron microscopy. Particle size， polydispersity index （PDI）， and Zeta potential were determined， and differential scanning calorimetry （DSC） and X-ray diffraction （XRD） were employed. Encapsulation efficiency （EE）， drug loading （DL）， and stability were evaluated. The in vitro release kinetics， mucus diffusion， and tumor cell uptake [tracked using coumarin 6 （COU）] were investigated. The in vivo tissue distribution and gastrointestinal retention [labeled with 11-chloro-1， 1′-dipropyl-3， 3， 3′， 3′-tetramethyl-10， 12- trimethyleneindotricarbocyanine iodide （IR780）] were investigated. Using 4T1 tumor-bearing mice as the experimental subjects， the effects of the prepared formulation on tumor volume， tumor weight， and cell apoptosis rate were evaluated. RESULTS RGD@DOX-LPNs presented as orange transparent liquid with uniform and near-spherical particles. The particle size was （159.67± 8.02） nm， PDI was 0.15±0.06， and Zeta potential was （－19.70±0.79） mV. After modification with RGD， the thermal absorption peak and crystalline diffraction peak of DOX disappeared. EE and DL of RGD@DOX-LPNs were （72.65±4.37）% and （4.62± 0.38）% ， respectively. No obvious changes in appearance， particle size， or EE were observed after storage at 4 ℃ and 25 ℃ for 7 days. The cumulative drug release at 4 h was approximately 73%， which was lower than that of free DOX（almost completely released within 1 h）. The amount of COU in the first segmental mucus layer of COU-LPNs was significantly lower than that in the corresponding segment of RGD@COU- LPNs， whereas it was significantly higher in the 2nd to 5th segmental mucus layers compared to RGD@COU-LPNs （P＜0.01）. Cellular uptake of RGD@COU-LPNs was significantly higher than that of COU-LPNs（P＜0.05）. The isolated tissue fluorescence intensity of RGD@IR780-LPNs was stronger than that of IR780-LPNs， indicating better small intestinal retention. Compared with free DOX and unmodified nanoparticles （DOX-LPNs）， RGD@DOX-LPNs exhibited a higher tumor inhibition rate of 65.74%， significantly reduced tumor volume and weight， and increased apoptosis rate（P＜0.01）. CONCLUSIONS RGD@DOX-LPNs are successfully prepared with sustained release properties， which can improve gastrointestinal mucus retention， enhance cellular uptake of DOX， and have potent antitumor activity against breast cancer.

Objective To discuss the clinical efficacy of catheter-directed thrombolysis(CDT)in treating acute pulmonary embolism(APE).Methods A total of 215 patients with APE,who were admitted to the Second Affiliated Hospital of Shandong First Medical University of China,were enrolled in this study.Pulmonary angiography was performed in all the patients.After the location of the thrombus was identified,the pigtail catheter was rotated so as to break the thrombus into small pieces,which was followed by local infusion of thrombolytic agent urokinase to make recanalization of the occluded pulmonary artery.The postoperative clinical symptoms,blood oxygen saturation,mean pulmonary artery pressure,BNP,D-dimer,RV/LV diameter ratio were compared with their preoperative values.PESI scoring was used to evaluate the severity of the pulmonary embolism.Patients with PESI grade-Ⅲ and PESI grade-Ⅳ were classified into medium-risk group,and patients with PESI grade-V were classified into higher-risk group.Results Symptom relief immediately after surgery was observed in 210 patients,complete recanalization of pulmonary artery was achieved in 200 patients,and partial recanalization of pulmonary artery was seen in 15 patients.The preoperative mean pulmonary artery pressure,blood oxygen saturation,BNP,D-dimer,RV/LV diameter ratio were(46.24±5.32)mmHg,(90.36±3.23)％,(8 000.12±750.56)pg/mL,(7.5±2.3)mg/L and(1.63±0.22)respectively;at one week after surgery the above indicators were(26.12±3.36)mmHg,(98.74±2.12)％,(240.35±33.52)pg/mL,(1.75±0.36)mg/L and(1.11±0.13)respectively;the differences were statistically significant(all P＜0.05).In the patients who had symptoms of hemoptysis,shock and syncope before surgery,all these symptoms were completely disappeared in one week after CDT,and the symptoms of dyspnea,chest pain,and palpitations were significantly relieved after CDT,the differences were statistically significant(all P＜0.05).The difference in survival time between different PESI grade groups was statistically significant(P＜0.05).No serious postoperative complications such as severe arrhythmia,cerebral hemorrhage,or gastrointestinal bleeding occurred.Postoperative 3-month CT pulmonary angiography(CTPA)showed that the main pulmonary artery was well visualized and no thrombus-produced filling defect shadow was detected.Conclusion For the treatment of APE,CDT can promptly and rapidly open the obstructed pulmonary artery lumen,restore pulmonary artery hemodynamics,and correct hypoxemia.Therefore,CDT is a safe,effective and quick treatment for APE.

Objective:To investigate the efficacy of preserving the urethral ridge during Holmium laser enucleation of the prostate（HoLEP）in preventing postoperative retrograde ejaculation and to evaluate its impact on sexual function.Methods:This prospective cohort study enrolled patients with benign prostatic hyperplasia（BPH）who underwent HoLEP at Xiamen Haicang Hospital（Haicang Hospital Affiliated to Xiamen Medical College）from November 2022 to June 2024. Inclusion criteria were as follows：diagnosis of BPH confirmed by color Doppler ultrasound；International Prostate Symptom Score（IPSS）> 7；maximum urinary flow rate（Q max）< 15 ml/s；prostate-specific antigen（PSA）< 4 ng/ml；and an active sexual life with intact antegrade ejaculation. Exclusion criteria included neurogenic bladder，active urinary tract infection（UTI），and other relevant conditions. Patients were grouped based on the operating surgeon's comprehensive judgment during surgery，considering the degree of prostatic median lobe hyperplasia（preserved if hyperplasia was mild，not preserved if severe）. The EP-HoLEP group underwent “tunnel technique” enucleation of the middle lobe hyperplasia with preservation of the urethral ridge，while the HoLEP group underwent conventional prostate enucleation. Primary outcomes included postoperative retrograde ejaculation rate，International Index of Erectile Function（IIEF），Ejaculation Projection Score（EPS），IPSS，Quality of Life Score（QOL），Q max，post-void residual urine volume（PVR），operative time，and postoperative complications. Univariate analysis was used to screen potential influencing factors，followed by multivariate logistic regression to identify independent predictors. Results:Seventy patients with BPH were enrolled，with 35 in each group. Baseline characteristics，including age［（69.97 ± 5.14）years vs.（72.34 ± 5.08）years］，body mass index（BMI）［（22.99 ± 1.41）kg/m2 vs.（23.16 ± 1.38）kg/m2］，prostate volume［47.4（31.9，59.4）ml vs. 44.2（34.9，61.7）ml］，PSA［4.0（1.9，8.2）ng/ml vs. 3.1（2.6，5.0）ng/ml］，hemoglobin［（130.09 ± 12.92）g/L vs.（125.69 ± 17.26）g/L］，IPSS［17（10，22）vs. 17（10，27）］，QOL［5（4，5）vs. 4（4，5）］，Q max［7.5（6.3，9.1）ml/s vs. 7.0（5.9，8.9）ml/s］and PVR［65（22，167）ml vs. 60（16，150）ml］showed no statistically significant differences between the two groups（ P > 0.05）. Operative time［65（55，76）min vs. 63（55，73）min］，postoperative 2-hour hemoglobin［（124.17 ± 14.89）g/L vs.（120.11 ± 15.44）g/L］，and postoperative hospital stay［（3.94 ± 1.89）days vs.（3.66 ± 1.53）days］were also comparable between the two groups（ P > 0.05）. No significant difference was observed in the decrease in IIEF score［1（0，2）vs. 2（0，6）， P = 0.203］. EPS at 3 months［2（1，3）vs. 1（0，2）， P < 0.001］and at 6 months［2（1，2）vs. 1（0，2）， P < 0.001］postoperatively were significantly higher in the EP-HoLEP group. The incidence of postoperative UTI did not differ significantly［5.7%（2/35）vs. 2.9%（1/35）， P = 1.00］. Two cases of urinary retention occurred after catheter removal in the EP-HoLEP group，while none occurred in the HoLEP group. No blood transfusions or urethral strictures were reported in either group. The incidence of retrograde ejaculation was significantly lower in the EP-HoLEP group［28.6%（10/35）vs. 68.6%（24/35）， P <0.001］. Multivariable logistic regression analysis showed that urethral ridge preservation was an independent protective factor for retrograde ejaculation after HoLEP（ OR = 0.159，95% CI 0.053 ? 0.476， P = 0.001）. Conclusions:Urethral ridge preservation during HoLEP is safe and feasible，significantly reduces retrograde ejaculation，and preserves ejaculatory function，though it offers limited erectile function preservation. This approach is suitable for middle-aged，young，or younger elderly patients who prioritize ejaculatory quality，and provides clinical evidence for surgical optimization.

Sigmoid sinus thrombophlebitis(SST) as a severe complication of otogenic infections in children, its early diagnosis and treatment are crucial for improving prognosis. This study reports three cases (aged 2 years, 9 months to 4 years) of otogenic SST in children diagnosed by imaging, all secondary to acute otitis media. The clinical features mainly included recurrent high fever, ear pain, and postauricular swelling, with one case complicated by abducens nerve palsy and otorrhea. Imaging characteristics revealed: HRCT of the temporal bone showed destruction of the anterior wall of the sigmoid sinus; characteristic MRI findings of the ear included high T2WI signal in the sigmoid sinus area, ring enhancement post-contrast, and restricted diffusion on DWI; MRV of the ear clearly displayed the extent of venous sinus thrombosis. Treatment involved a comprehensive approach of surgical drainage combined with sensitive antibiotics and anticoagulant therapy, and all children achieved clinical cure. Through literature review, it was found that SST in children has an insidious onset, and high vigilance is required when otogenic infection patients present with the "otitis media triad" (fever, ear pain, headache) accompanied by neurological symptoms. Imaging examination is crucial for early diagnosis, and standardized treatment (clearance of infection foci and adequate course of anti-infection and anticoagulation) can significantly improve prognosis, providing a reference for the clinical management of SST in children.

Objective:To explore the alterations in gray matter morphology and contributing factors in patients with post-infectious olfactory dysfunction (PIOD) using voxel-based morphometry (VBM) and surface-based morphometry (SBM), thereby providing scientific insights into the neuropathological mechanisms underlying PIOD.Methods:A total of 46 PIOD patients (PIOD group) and 46 normosmic volunteers (control group) were recruited from the Smell and Taste Disorders Clinic of Beijing Anzhen Hospital, Capital Medical University, between January 2020 and December 2024. All participants underwent olfactory psychophysical tests (Sniffin′ Sticks) and olfactory event-related potential (oERP) examination. High-resolution T1-weighted 3D MRI structural images were obtained for both groups. VBM was employed to analyze inter-group differences in gray matter volume, while SBM was used to assess cortical thickness and folding index. Correlations between gray matter volume in significant difference brain regions and disease duration, Sniffin′ Sticks scores, oERP parameters were analyzed. A two-tailed P<0.05 was considered statistically significant. Results:No significant differences were observed in age, sex, education level, or Mini-Mental State Examination (MMSE) scores ( t=1.80, χ2=0.41, t=0.17, t=1.77, all P>0.05). Compared with controls, the PIOD group showed significantly lower Sniffin′ Sticks scores ( t=28.70, P<0.001), prolonged oERP latencies and reduced amplitudes (all P<0.001). VBM revealed significantly reduced gray matter volume in the right orbitofrontal cortex (OFC) in the PIOD group ( t=5.38, P<0.001). SBM demonstrated decreased cortical thickness in the right OFC ( t=5.27, P<0.001), with no significant differences in folding index. The gray matter volume in the right OFC was negatively correlated with disease duration ( r=-0.61, P<0.001), but no significant correlations were found with Sniffin′ Sticks scores or oERP parameters. Conclusion:Patients with PIOD show atrophy in the right OFC, which correlates with disease duration, suggesting that persistent olfactory dysfunction may be associated with neurodegenerative changes.

Sigmoid sinus thrombophlebitis(SST) as a severe complication of otogenic infections in children, its early diagnosis and treatment are crucial for improving prognosis. This study reports three cases (aged 2 years, 9 months to 4 years) of otogenic SST in children diagnosed by imaging, all secondary to acute otitis media. The clinical features mainly included recurrent high fever, ear pain, and postauricular swelling, with one case complicated by abducens nerve palsy and otorrhea. Imaging characteristics revealed: HRCT of the temporal bone showed destruction of the anterior wall of the sigmoid sinus; characteristic MRI findings of the ear included high T2WI signal in the sigmoid sinus area, ring enhancement post-contrast, and restricted diffusion on DWI; MRV of the ear clearly displayed the extent of venous sinus thrombosis. Treatment involved a comprehensive approach of surgical drainage combined with sensitive antibiotics and anticoagulant therapy, and all children achieved clinical cure. Through literature review, it was found that SST in children has an insidious onset, and high vigilance is required when otogenic infection patients present with the "otitis media triad" (fever, ear pain, headache) accompanied by neurological symptoms. Imaging examination is crucial for early diagnosis, and standardized treatment (clearance of infection foci and adequate course of anti-infection and anticoagulation) can significantly improve prognosis, providing a reference for the clinical management of SST in children.

Objective:To explore the alterations in gray matter morphology and contributing factors in patients with post-infectious olfactory dysfunction (PIOD) using voxel-based morphometry (VBM) and surface-based morphometry (SBM), thereby providing scientific insights into the neuropathological mechanisms underlying PIOD.Methods:A total of 46 PIOD patients (PIOD group) and 46 normosmic volunteers (control group) were recruited from the Smell and Taste Disorders Clinic of Beijing Anzhen Hospital, Capital Medical University, between January 2020 and December 2024. All participants underwent olfactory psychophysical tests (Sniffin′ Sticks) and olfactory event-related potential (oERP) examination. High-resolution T1-weighted 3D MRI structural images were obtained for both groups. VBM was employed to analyze inter-group differences in gray matter volume, while SBM was used to assess cortical thickness and folding index. Correlations between gray matter volume in significant difference brain regions and disease duration, Sniffin′ Sticks scores, oERP parameters were analyzed. A two-tailed P<0.05 was considered statistically significant. Results:No significant differences were observed in age, sex, education level, or Mini-Mental State Examination (MMSE) scores ( t=1.80, χ2=0.41, t=0.17, t=1.77, all P>0.05). Compared with controls, the PIOD group showed significantly lower Sniffin′ Sticks scores ( t=28.70, P<0.001), prolonged oERP latencies and reduced amplitudes (all P<0.001). VBM revealed significantly reduced gray matter volume in the right orbitofrontal cortex (OFC) in the PIOD group ( t=5.38, P<0.001). SBM demonstrated decreased cortical thickness in the right OFC ( t=5.27, P<0.001), with no significant differences in folding index. The gray matter volume in the right OFC was negatively correlated with disease duration ( r=-0.61, P<0.001), but no significant correlations were found with Sniffin′ Sticks scores or oERP parameters. Conclusion:Patients with PIOD show atrophy in the right OFC, which correlates with disease duration, suggesting that persistent olfactory dysfunction may be associated with neurodegenerative changes.

Objective:To investigate the efficacy of preserving the urethral ridge during Holmium laser enucleation of the prostate（HoLEP）in preventing postoperative retrograde ejaculation and to evaluate its impact on sexual function.Methods:This prospective cohort study enrolled patients with benign prostatic hyperplasia（BPH）who underwent HoLEP at Xiamen Haicang Hospital（Haicang Hospital Affiliated to Xiamen Medical College）from November 2022 to June 2024. Inclusion criteria were as follows：diagnosis of BPH confirmed by color Doppler ultrasound；International Prostate Symptom Score（IPSS）> 7；maximum urinary flow rate（Q max）< 15 ml/s；prostate-specific antigen（PSA）< 4 ng/ml；and an active sexual life with intact antegrade ejaculation. Exclusion criteria included neurogenic bladder，active urinary tract infection（UTI），and other relevant conditions. Patients were grouped based on the operating surgeon's comprehensive judgment during surgery，considering the degree of prostatic median lobe hyperplasia（preserved if hyperplasia was mild，not preserved if severe）. The EP-HoLEP group underwent “tunnel technique” enucleation of the middle lobe hyperplasia with preservation of the urethral ridge，while the HoLEP group underwent conventional prostate enucleation. Primary outcomes included postoperative retrograde ejaculation rate，International Index of Erectile Function（IIEF），Ejaculation Projection Score（EPS），IPSS，Quality of Life Score（QOL），Q max，post-void residual urine volume（PVR），operative time，and postoperative complications. Univariate analysis was used to screen potential influencing factors，followed by multivariate logistic regression to identify independent predictors. Results:Seventy patients with BPH were enrolled，with 35 in each group. Baseline characteristics，including age［（69.97 ± 5.14）years vs.（72.34 ± 5.08）years］，body mass index（BMI）［（22.99 ± 1.41）kg/m2 vs.（23.16 ± 1.38）kg/m2］，prostate volume［47.4（31.9，59.4）ml vs. 44.2（34.9，61.7）ml］，PSA［4.0（1.9，8.2）ng/ml vs. 3.1（2.6，5.0）ng/ml］，hemoglobin［（130.09 ± 12.92）g/L vs.（125.69 ± 17.26）g/L］，IPSS［17（10，22）vs. 17（10，27）］，QOL［5（4，5）vs. 4（4，5）］，Q max［7.5（6.3，9.1）ml/s vs. 7.0（5.9，8.9）ml/s］and PVR［65（22，167）ml vs. 60（16，150）ml］showed no statistically significant differences between the two groups（ P > 0.05）. Operative time［65（55，76）min vs. 63（55，73）min］，postoperative 2-hour hemoglobin［（124.17 ± 14.89）g/L vs.（120.11 ± 15.44）g/L］，and postoperative hospital stay［（3.94 ± 1.89）days vs.（3.66 ± 1.53）days］were also comparable between the two groups（ P > 0.05）. No significant difference was observed in the decrease in IIEF score［1（0，2）vs. 2（0，6）， P = 0.203］. EPS at 3 months［2（1，3）vs. 1（0，2）， P < 0.001］and at 6 months［2（1，2）vs. 1（0，2）， P < 0.001］postoperatively were significantly higher in the EP-HoLEP group. The incidence of postoperative UTI did not differ significantly［5.7%（2/35）vs. 2.9%（1/35）， P = 1.00］. Two cases of urinary retention occurred after catheter removal in the EP-HoLEP group，while none occurred in the HoLEP group. No blood transfusions or urethral strictures were reported in either group. The incidence of retrograde ejaculation was significantly lower in the EP-HoLEP group［28.6%（10/35）vs. 68.6%（24/35）， P <0.001］. Multivariable logistic regression analysis showed that urethral ridge preservation was an independent protective factor for retrograde ejaculation after HoLEP（ OR = 0.159，95% CI 0.053 ? 0.476， P = 0.001）. Conclusions:Urethral ridge preservation during HoLEP is safe and feasible，significantly reduces retrograde ejaculation，and preserves ejaculatory function，though it offers limited erectile function preservation. This approach is suitable for middle-aged，young，or younger elderly patients who prioritize ejaculatory quality，and provides clinical evidence for surgical optimization.

Objective To discuss the clinical application of intravoxel incoherent motion-diffusion weighted imaging(IVIM-DWI)in evaluating the efficacy and prognosis of transcatheter arterial chemoembolization(TACE)using different embolization materials for the treatment of hepatocellular carcinoma(HCC).Methods The clinical data of a total of 84 patients with inoperable HCC,who received TACE treatment at the Second Affiliated Hospital of Shandong First Medical University of China and the First Affiliated Hospital of Xinjiang Medical University of China between June 30,2019 and December 30,2022,were collected.According to the patient's condition,different embolization materials were used during TACE.IVIM-DWI check-up was performed before treatment as well as at one,6,12 months after treatment.Based on the fixed b-value set by IVIM-DWI sequence,the ADC value of the order index model for different embolization materials and the pure diffusion coefficient of double exponential model(D value),the pseudo-diffusion coefficient(D*value)and perfusion fraction(f value)were analyzed.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST)and the embolization material used,the patients were divided into the stable group and progression group,and the changes in the ADC value,D value,D*value and f value were compared between the two groups.Multivariate Cox regression analysis was used to analyze the four clinical parameters(including age,Child-Pugh grade,AFP level and tumor size)and the eight functional quantitative indexes(including preoperative and postoperative ADC value,D value,D* value and f value)so as to determine the IVIM parameters with prognostic predictive value.Receiver operating characteristic(ROC)was adopted to analyze the diagnostic value and cut-off value of IVIM parameters with predictive value.Results After treatment,the ADC value of drug-loaded microspheres group(n=36)was significantly higher than that of iodized oil group(n=27),the D*value of drug-loaded microspheres group and iodized oil group was remarkably lower than that of PVA particle group(n=21),and the f value of drug-loaded microspheres group was strikingly lower than that of iodized oil group,the differences were statistically significant(all P＜0.01).In the stable group,the efficacy of drug loaded microspheres group was obviously better than that of the iodized oil group and the PVA particle group.In the progression group,the iodized oil group was more likely to develop disease progression than the drug-loaded microspheres group and the PVA particle group.The preoperative f value in the stable group was prominently higher than that in the progression group(P=0.005),and the postoperative ADC value in the stable group was obviously higher than that in the progression group(P=0.029).ROC analysis showed that the median follow-up time in the drug-loaded microspheres group,iodized oil group,and PVA particle group was 30,19,and 26 months respectively,the overall average survival time was 25 months,and the difference was statistically significant(P＜0.01).Multivariate Cox regression analysis showed that the preoperative D value(AUC=0.878),D*value(AUC=0.554)and postoperative D value(AUC=0.791),D*value(AUC=0.552),f value(AUC=0.467)were the independent factors affecting the short-term efficacy of TACE(all P＜0.05).The preoperative and postoperative D value had higher diagnostic efficacy,while a preoperative D value of＜0.505×10-3 mm2/s and a postoperative D value of＜0.785×10-3 mm2/s predicted a poor prognosis.Conclusion The preoperative and postoperative D value is the optimal parameter for predicting the curative efficacy of TACE using different embolization materials for the treatment of HCC.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).