Objective To evaluate the therapeutic effects of different intracranial pressure lower-ing regimens in patients with acute large-area cerebral infarction based on electrical impedance tomo-graphy(EIT)technology.Methods A total of 75 patients with acute large-area cerebral infarction were selected as the study subjects and randomly divided into study group(n=40,using mannitol combined with albumin to decrease intracranial pressure)and control group(n=35,using mannitol alone to decrease intracranial pressure).EIT technology was used to continuously monitor the changes in intracranial pressure within 48 hours in the patients.Clinical data of the two groups were collected,and the 24-hour intracranial pressure change rate,48-hour intracranial pressure change rate,ICU stay duration,hospitalization duration,antibiotic use duration,and National Institutes of Health Stroke Scale(NIHSS)score at discharge were observed and compared between the two groups.A 90-day sur-vival follow-up was also conducted.Results There was no statistically significant difference in the 24-hour intracranial pressure change rate between the two groups(P＞0.05).The 48-hour intracrani-al pressure change rate in the study group was higher than that in the control group,and the difference was statistically significant(P＜0.05).The ICU stay duration,hospitalization duration,and antibiotic use duration in the study group were all shorter than those in the control group,and the NIHSS score at discharge in the study group was lower than that in the control group,with statistically significant differences(P＜0.05).The follow-up results showed that the survival duration in the study group was longer than that in the control group,and the 90-day cumulative survival rate in the study group was higher than that in the control group,but the differences were not statistically significant(P＞0.05).The modified Rankin Scale score in the study group was lower than that in the control group,and the difference was statistically significant(P＜0.05).Conclusion Compared with the use of mannitol alone,early use of mannitol combined with albumin can effectively decrease the in-tracranial pressure within 48 hours,shorten the hospitalization duration,and improve neurological function in patients with acute large-area cerebral infarction.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Premature ejaculation (PE), a common ejaculatory dysfunction in men with high prevalence, is a frequent cause of low sexual satisfaction for both patients and their partners.The etiology of PE is complex, including psychological, anatomical, neurobiological, and behavioral medicine factors, making it difficult to cure.Currently, treatments of PE include psychological interventions, local anesthetics, medications such as dapoxetine, and surgical treatments.Hyaluronic acid (HA) gel injection is an alternative treatment method.By subcutaneously injecting HA gel into the glans penis, the sensory input from nerve endings can be blocked, thereby reducing glans sensitivity.This approach can significantly extend the intravaginal ejaculatory latency time (IELT) and improve patient satisfaction.Moreover, it has advantages such as safety and high tolerability, making it a promising treatment option.In this paper, the technique, efficacy and safety of HA injection therapy for PE are introduced in detail on the basis of exploring other therapies for PE.

Purpose To investigate the expression of C1GALT1 in gastric cancer and its effect on the biological be-havior of BGC-823 in gastric cancer cells.Methods The ex-pression of C1GALT1 mRNA and protein in gastric cancer tis-sues and normal gastric mucosa,gastric cancer cells and normal gastric mucosal cells was analyzed by bioinformatics,qRT-PCR and Western blot;the transient transfection of siRNA into BGC-823 cells was designed with C1GALT1 cDNA sequence as the target.Transwell assay was used to detect the effect of C1GALT1-siRNA on the migration and invasion ability of BGC-823 cells in gastric cancer.Western blot method detected the expression of epithelial-mesenchymal transition(EMT)-related proteins in BGC-823 after transfection of C1GALT1-siRNA.Re-sults C1GALT1 was highly expressed in gastric cancer tissues and cell lines BGC-823,SGC-7901 and MGC-803,and the ex-pression levels were positively correlated with gastric cancer pathological stages Ⅰ and Ⅱ(P＜0.05).After interfering with C1GALT1 in BGC-823 cells,the ability of migration and inva-sion decreased(P＜0.05),epithelial cell markers E-cadherin and Claudin-1 protein expression increased,while mesenchymal cell markers vimentin and Slug protein expression decreased(P＜0.05).Conclusion C1GALT1 is highly expressed in gastric cancer tissues and cells,silencing of C1GALT1 can inhibit mi-gration and invasion ability of gastric cancer,the mechanism may be related to EMT.

AIM:To investigate the effect of ankyrin repeat domain 49(ANKRD49)on epithelial-mesenchy-mal transition(EMT)in NCI-H1299 cells,and to explore its mechanism.METHODS:The ANKRD49 was over-ex-pressed in NCI-H1299 cells.The morphological changes of ANKRD49-overpressing NCI-H1299 cells were observed under microscope.The mRNA and protein expression levels of EMT-related markers[E-cadherin,transforming growth factor-β1(TGF-β1),vimentin and α-smooth muscle actin(α-SMA)]and EMT-related transcription factors(Snail1,Slug,Twist and ZEB1)were detected by RT-qPCR Western blot.Immunofluorescence staining was performed to observe the localiza-tion and expression of E-cadherin and vimentin in ANKRD49-overexpressing cells or control cells.Immunohistochemical method was performed to examine the levels of E-cadherin,α-SMA,Snail,Slug and ZEB1 in lung tissues of nude mice in-oculated with ANKRD49-overexpressing H1299 cells or control cells.RESULTS:Compared with the control group,the ANKRD49 overexpressing cells showed mesenchymal cell morphology(fusiform and less tight connections).RT-qPCR and Western blot results showed that the mRNA and protein levels of mesenchymal markers vimentin and α-SMA in ANKRD49 overexpressing cells were significantly higher than those in cells of control group,while the mRNA and protein levels of epithelial marker E-cadherin were lower than those in cells of control group.Compared with control group,the im-munofluorescence intensity of E-cadherin of H1299 cells decreased in after ANKRD49 overexpression,while that of vimen-tin increased significantly.Snail,Slug and ZEB1 expression were significantly elevated in ANKRD49 overexpressing cells compared with control group.The levels of E-cadherin in lung tissues of nude mice inoculated with ANKRD49-overexpressing H1299 cells declined,while the levels of α-SMA,Snail,Slug and ZEB1 increased compared with those in control mice.CONCLUSION:ANKRD49 promoted EMT of NCI-H1299 cells by increasing the expression of Snail1,Slug and ZEB1 and consequent downreguation of E-cadherin and upregulation of vimentin and α-SMA.

Objective:To explore the efficacy of adjuvant chemotherapy and adjuvant immunotherapy combined chemotherapy after radical cystectomy for muscle-invasive bladder cancer (MIBC) with high recurrence risk (pT 2 with positive lymph nodes, and pT 3-4a with or without positive lymph nodes). Methods:A retrospective analysis was conducted on clinical data of 217 patients with bladder cancer admitted to Tianjin Medical University Second Hospital from August 2016 to January 2022. Among them, 183 were male (84.3%) and 34 were female (15.7%), with an average age of (67.3±8.6) years old. All 217 patients underwent radical cystectomy with pelvic lymph node dissection. Based on postoperative adjuvant treatment, the patients were divided into an observation group (147 cases, 67.7%) and a treatment group (70 cases, 32.3%). The observation group and treatment group had similar demographic and pathological characteristics. The age of the observation group and treatment group was (67.4±9.0) years and (66.3±7.6) years, respectively ( P=0.14). The postoperative pathological stages T 2 with lymph node positivity were observed in 8 cases (5.4%) in the observation group and 6 cases (8.6%) in the treatment group. For stages T 3-4awith lymph node positivity, there were 34 cases (23.1%) in the observation group and 18 cases (25.7%) in the treatment group. And there were 105 cases (71.5%) in the observation group and 46 cases (65.7%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Tumor diameter ≥3 cm was found in 118 cases (80.3%) in the observation group and 54 cases (77.1%) in the treatment group ( P>0.05), while tumor diameter <3 cm was observed in 29 cases (19.7%) in the observation group and 16 cases (22.9%) in the treatment group ( P>0.05).In the treatment group, 36 patients (16.6%) received postoperative chemotherapy with gemcitabine (1 000 mg/m 2, days 1 and 8) and cisplatin (75 mg/m 2, days 2 to 4) (chemotherapy group), while 34 patients (15.7%) received postoperative immunotherapy with checkpoint inhibitors (intravenous infusion of sintilimab 200 mg, terlizumab 200 mg, or toripalimab 240 mg on day 1) in combination with albumin-bound paclitaxel (200 mg on day 2)(immunotherapy combined chemotherapy group). The age of the chemotherapy group and immunotherapy combined chemotherapy group was (66.8±8.4) years and (65.8±6.8) years, respectively ( P>0.05). Postoperative pathological stages T 2 with lymph node positivity were observed in 3 cases (8.3%) in the chemotherapy group and 3 cases (8.8%) in the immunotherapy combined chemotherapy group ( P>0.05). For stages T 3-4awith lymph node positivity, there were 6 cases (16.7%) in the chemotherapy group and 12 cases (35.3%) in the immunotherapy combined chemotherapy group. And there were 27 cases (75.0%) in the observation group and 19 cases (55.9%) in the treatment group of stages T 3-4a without lymph node positivity, respectively( P>0.05). Lymph node involvement was seen in 9 cases (25.0%) in the chemotherapy group and 15 cases (44.1%) in the immunotherapy combined chemotherapy group ( P>0.05). Tumor diameter ≥3 cm was found in 30 cases (83.3%) in the chemotherapy group and 10 cases (29.4%) in the immunotherapy combined chemotherapy group ( P>0.05), while tumor diameter <3 cm was observed in 6 cases (16.7%) in the chemotherapy group and 24 cases (70.6%) in the immunotherapy combined chemotherapy group ( P>0.05). Kaplan-Meier method and multivariate Cox regression test were used to analyze the overall survival (OS) at 1 and 3 years in the observation group and treatment group, as well as the disease-free survival (DFS) at 1 and 3 years in the chemotherapy group and immunotherapy combined chemotherapy group. Additionally, common adverse events were evaluated and compared between the chemotherapy group and immunotherapy combined chemotherapy group based on the criteria published by the U. S. Department of Health and Human Services. Results:The median follow-up time in this study was 18.4 (8.2, 34.7) months. The median follow-up time in the observation group and treatment group was 19.0 (8.3, 35.2) months and 17.5 (7.9, 33.2) months, respectively. The 1-year survival rate was significantly higher in the treatment group compared to the observation group (90.0% vs. 76.2%, χ2=6.92, P=0.009). Similarly, the 3-year survival rate was significantly higher in the treatment group compared to the observation group (82.9% vs. 57.8%, χ2=13.22, P<0.01). The median OS was 35.9 months in the observation group and was not reached in the treatment group, with a statistically significant difference ( HR=2.51, 95% CI 1.36-4.65, P=0.003).In the chemotherapy group and immunotherapy combined chemotherapy group, the median follow-up time was 10.7 (7.4, 22.1) months and 14.4 (6.3, 40.7) months, respectively. The 1-year disease-free survival rate was significantly higher in the immunotherapy combined chemotherapy group compared to the chemotherapy group (91.2% vs. 67.6%, χ2=4.60, P=0.032). The 3-year disease-free survival rate was significantly higher in the chemotherapy group compared to the immunotherapy combined chemotherapy group (88.2% vs. 55.6%, χ2=8.37, P=0.004). The median DFS was 27.7 months in the chemotherapy group and was not reached in the immunotherapy combined chemotherapy group, with a statistically significant difference ( HR=3.39, 95% CI 1.46-7.89, P=0.016).The treatment group had complications classified as follows: 140 cases of grade 1, 39 cases of grade 2, 8 cases of grade 3, 2 cases of grade 4, and 0 case of grade 5 adverse reactions. In the chemotherapy group and the immunotherapy combined chemotherapy group, there were both 5 cases with adverse reactions of grade 3 or higher. Specifically, in the chemotherapy group, there were 2 cases of anemia, 2 cases of decreased platelet count, and 1 case of decreased neutrophil count. In the immunotherapy combined chemotherapy group, there was 1 case of anemia, 1 case of decreased platelet count, and 2 cases of decreased neutrophil count. Additionally, there was 1 case with elevated gamma-glutamyltransferase (γ-GT) in the immunotherapy combined chemotherapy group. The incidence of adverse events of grade 3 or higher in the chemotherapy group and immunotherapy combined chemotherapy group was 13.9% and 14.7%, respectively, with no statistically significant difference( χ2=0.01, P=0.922). Conclusions:Adjuvant therapy significantly prolongs the overall survival in high risk of recurrence for MIBC patients after radical cystectomy. For patients intolerant to platinum-based chemotherapy or refusing platinum-based adjuvant chemotherapy, immunotherapy with checkpoint inhibitors combined with albumin-bound paclitaxel can be considered as an effective and well-tolerated adjuvant treatment after radical cystectomy.

Objective To investigate the clinicopathological characteristics and the factors affecting the prognosis of patients with resectable sarcomatoid carcinoma of the bladder(SCB).Methods A retrospective analysis was conducted with the clinical data of patients with resectable SCB treated at the Second Hospital of Tianjin Medical University between September 2008 and December 2023.The patients were divided into two groups,a bladder-preserving surgery(BPS)group and a radical cystectomy(RC)group,according to the specific surgical approach used for each patient.Kaplan-Meier survival curves were used to evaluate overall survival(OS)in both groups,and Cox regression models were employed to identify risk factors affecting survival.Results A total of 77 patients with resectable SCB were included.Among them,35 patients(45.5％)underwent BPS,while 42 patients(54.5％)underwent RC.Ki-67 expression≥30％was observed in 91.7％of the patients.A total of 92.2％of the patients was tested positive for cytokeratin(CK)and 98.1％for vimentin.In addition,62.5％and 37.5％of patients had the human epidermal growth factor receptor 2(Her-2)scores of 0 and 1+,respectively.The median follow-up time was 23.2 months(ranging from 0.4 to 164.7 months).The 1-year,3-year,and 5-year survival rates for the BPS group and the RC group were as follows,76.2％vs.84.9％,46.7％vs.61.1％,and 35.6％vs.43.2％,respectively.Multivariate Cox regression analysis revealed that in the RC group,age ≥ 75 years old(hazard ratio[HR]=3.836,95％confidence interval[CI]:1.168-12.595,P=0.027),tumor multiplicity(HR=3.439,95％CI:1.235-9.574,P=0.018),and lack of adjuvant therapy(HR=3.164,95％CI:1.015-9.862,P=0.047)were independent risk factors affecting survival.In the BPS group,female sex was identified as an independent risk factor for survival(HR=3.601,95％CI:1.200-10.804,P=0.022).Conclusion Ki-67,CK,and vimentin are significantly overexpressed in SCB patients,while Her-2 is either unexpressed or expressed at low levels.In the RC group,tumor multiplicity,age ≥75 years,and lack of postoperative adjuvant therapy are independent risk factors for overall survival.Female sex is an independent risk factor affecting prognosis in the BPS group.

Objective: To evaluate the effectiveness of craniocervical flexion training using pressure biofeedback combined with cervical traction among patients with cervical spondylotic radiculopathy (CSR). Methods: Sixty patients with CSR receiving treatment in Center of Rehabilitation, Zhejiang Hospital from January 2020 to December 2021 were enrolled and randomly assigned into the control and treatment groups, of 30 patients in each group. All patients were given cervical traction, and patients in the treatment group were given additional craniocervical flexion training using pressure biofeedback for successive four weeks. The effectiveness of craniocervical flexion training combined with cervical traction was evaluated using Visual Analogue Scale (VAS), Neck Disability Index (NDI) and the active range of motion (AROM) of cervical flexion, and the neck pain and cervical functions were compared between the two groups before and after treatments using repeated-measures analysis of variance. Results: Fifteen men were included in the treatment group, with a mean age of (49.47±5.33) years, mean disease course of (5.53±2.89) months, and mean VAS score of (4.73±1.39) points, and there were no significant differences between the control and treatment groups in terms of gender, age, course of disease or VAS score (P>0.05). The VAS score and NDI were lower 4 weeks post-treatment than pretreatment in both the treatment [VAS score: (2.13±1.01) vs. (4.73±1.39); NDI: (12.17±2.12) vs. (20.20±3.78)] and control groups [VAS score: (2.93±1.11) vs. (4.90±1.21); NDI: (15.23±2.39) vs. (19.60±3.30)], and the AROM of cervical flexion was significantly higher 4 weeks post-treatment than pretreatment in both the treatment [(42.87°±2.99°) vs. (37.50°±2.80°)] and control groups [(41.80°±3.61°) vs. (38.07°±2.99°)]; there was an interaction between time and group, and a higher improvement for cervical functions was seen in the treatment group than in the control group (FVAS =5.119, P=0.027; FNDI=15.473, P<0.001; FAROM=11.443, P<0.001). Conclusion Craniocervical flexion training using pressure biofeedback combined with cervical traction may effectively alleviate the neck pain and increase the AROM among patients with CRS, which is more effective to improve patients' cervical functions than cervical traction alone.