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.

Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes. However, therapeutic decision-making is relatively complex for epilepsies associated with channelopathy. Therefore, in the present study, we used a patient-derived organoid model with a novel SCN2A mutation (p.E512K) to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds. The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation. Immunofluorescence staining of patient-derived cortical organoids (COs) displayed normal neurodevelopment. Multielectrode array (MEA) recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts. Moreover, the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine. Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
Organoids/physiology* ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Humans ; Anticonvulsants/pharmacology* ; Epilepsy/drug therapy* ; Mutation ; Cerebral Cortex/drug effects* ; Action Potentials/drug effects* ; Carbamazepine/pharmacology*

Objective:To investigate the clinical efficacy of neuroendoscopic hematoma removal versus soft channel drainage in the treatment of chronic subdural hematoma (CSDH) and their effects on neurological function and quality of life. Methods:The clinical data of 97 patients with CSDH who received treatment between February 2018 and December 2019 were retrospectively analyzed. These patients were divided into group A ( n = 48, soft channel drainage) and group B ( n = 49, neuroendoscopic hematoma removal) according to different surgical methods. Clinical indicators, neurological function, quality of life, and incidence of complications were compared between groups A and B. Results:Operative time, length of hospital stay, and latency to hematoma disappearance in group B were (31.3 ± 2.18) minutes, (8.16 ± 1.32) days, (7.45 ± 1.49) days, which were significantly shorter than those in group A [(35.15 ± 4.32) minutes, (13.18 ± 1.56) days, (11.32 ± 1.88) days, t = 5.53, 17.12, 11.25, all P < 0.001]. At 3 months after surgery, the score of each dimension of SF-36 in each group was increased. The scores of physiological functioning, bodily pain, mental health, general health perceptions, social role functioning, vitality, role limitations due to emotional health, role limitations due to physical health in group B were (84.94 ± 7.25) points, (84.02 ± 6.29) points, (82.85 ± 8.16) points, (84.36 ± 9.15) points, (83.51 ± 10.39) points, (82.68 ± 8.36) points, (84.93 ± 10.15) points, (86.12 ± 9.13) points, which were significantly higher than those in group A [(62.68 ± 5.47) points, (71.39 ± 7.42) points, (69.51 ± 6.39) points, (72.68 ± 7.36) points, (72.81 ± 8.15) points, (73.12 ± 10.13) points, (77.91 ± 9.52) points, (75.32 ± 7.51) points, t = 19.82, 18.34, 19.75, 16.71, 17.94, 20.57, 18.22, 16.44, all P < 0.001]. At 7 days after surgery, neurotrophic factor, neuron specific enolase, hydrogen sulfide and S100B protein levels in group B were (42.53 ± 6.09) μg/L, (6.52 ± 2.79) μg/L, (203.17 ± 15.03) μmol/L, (0.25 ± 0.05) μg/L, respectively, which were significantly lower than those in group A [(67.38 ± 7.42) μg/L, (9.18 ± 2.27) μg/L, (242.79 ± 14.08) μmol/L, (0.36 ± 0.07) μg/L, t = 17.94, 5.12, 13.33, 8.86, all P < 0.001]. There was no significant difference in the incidence of complications between group B and group A [8.16% (4/49) vs. 18.75% (9/48), χ2 = 2.22, P = 0.136]. Conclusion:Compared with soft channel drainage, neuroendoscopic hematoma removal can better improve clinical indicators, neurological function, and quality of life in patients with CSDH, and is highly safe Neuroendoscopic hematoma removal is of certain clinical application value and innovation.

Objective: To investigate the relationship between childhood abuse and recent negative life events with suicidal ideation and attempt, and to provide reference for prevention and control of suicidal behaviors in middle school students. Methods: Stratified cluster sampling method was used to select 7 986 middle school students from Shenzhen, Nanchang and Shenyang as participants. Questionnaire survey was conducted to collect information on demographic indicators, childhood abuse, negative life events, suicidal ideation and suicide attempt, etc. Logistic regression was used to analyze the relationship between childhood abuse experience and negative life events with suicidal ideation and suicide attempt. Results: The prevalence of suicidal ideation and suicide attempt was 22.9% and 4.7%. After adjusted for confounding variables, with the increase of childhood abuse and negative life events, suicidal ideation and attempt in middle school students showed an increasing trend(P<0.05). Compared those with low level of childhood abuse and negative life events, students with high childhood abuse and high negative life events had a higher suicidal ideation and suicide attempt risk, the multiple adjusted odds ratio was 10.43 and 19.75(P<0.05). Conclusion Childhood abuse and negative life events are important risk factors affecting suicidal ideation and attempt in middle school students. Strategies to reduce childhood abuse and negative life events should be an integral component of targeted mental health interventions.

Objective    To describe the effect of sequential pulmonary balloon angioplasty for patients with chronic thromboembolic pulmonary hypertension, who was accompanied with progressed pulmonary hypertension after pulmonary endarterectomy surgeries. Methods    From 2014 to December 2017, 7 patients were treated with a combination therapy of pulmonary endarterectomy and sequential pulmonary balloon angioplasty. There were 1 male and 6 females at age of 58 (43–59) years. A follow-up period of more than 1 year was accomplished. The result of right sided heart catheterization and ultrasonic cardiogram between and after the pulmonary endarterectomy or balloon angioplasty was collected. Results    Seven patients were treated with a combination of pulmonary endarterectomy and sequential pulmonary balloon angioplasty, which included 1 patient of single pulmonary balloon angioplasty and 6 patients of multiple pulmonary balloon angioplasties. The balloon dilation times was 2 (2–6), and the number of segments during each single balloon dilatation was 3–5, compared with the first clinical results before  the first balloon dilation, systolic pulmonary artery pressure [53 (47–75) mm Hg vs. 45 (40–54) mm Hg, P=0.042), mean pulmonaryartery pressure [38 (29–47) mm Hg vs. 29 (25–39) mm Hg, P=0.043], N terminal-B type natriuretic peptide [1 872 (1 598–2 898) pg/ml vs. 164 (72–334) pg/ml, P=0.018] improved significantly after the last balloon angioplasty. Heart function classification (NYHA) of all the 7 patients were recovered to Ⅰ-Ⅱclasses (P<0.05). Conclusion    Sequential pulmonary balloon angioplasty after pulmonary endarterectomy can further reduce the patient's right heart after load, improve the heart function for patients with progressed pulmonary hypertension after pulmonary endarterectomy surgeries.

Objective:This study was performed using preclinical transplanted animal experiments to analyce the effects and mechanisms of third-generation EGFR-TKIs combined with anti-angiogenic therapy, thereby providing theoretical basis for further clinical trials. Methods:Researchers constructed the transplant BALB/C nude mice models with H1975 lung adenocarcinoma cell line (EGFR T790M) and divided the mice into four groups and treated them with osimertinib (2.5 or 5 mg/kg/day, gavage) alone or plus bevacizumab (5 mg/kg/twice weekly, i.p.) when the tumors reached approximately 0.4-0.6 cm3 in volume. The tumor growth curve of tumor volume was drawn according to the time in every group. After 2 weeks of treatment, the mice were killed and the tumors were processed for immunohistochemical staining and Western blot analysis. Immunostaining was performed to detect:HIF-1α, VEGF, and microvessel density (MVD) by using SP method on paraffin sections. Western blot analysis was used to analyze the protein expression levels of EGFR, AKT, and ERK signal transduction pathways. Results:After 2 weeks of treatment in high-and low-dose osimertinib alone, tumor volume in the high-dose group was significantly less than in low-dose osimertinib-alone group (P<0.05). VEGF, HIF-1αexpression, and MVD were significantly low in the high-dose osimertinib-alone group (P<0.05). Increasing doses of osimertinib induced dose-dependent weakening of the p-EGFR, p-AKT, and p-ERK expression levels (P<0.05). In the low-dose osimertinib-plus-bevacizumab group and low-dose osimertinib-alone group, no significant difference in tumor volume and the above factors was observed. In the low-dose osimertinib-plus-bevacizumab group and high-dose osimertinib-alone group, tumor volumes did not exhibit significant difference (P=0.178). Moreover, VEGF, HIF-1αexpression, and MVD exhibited no significant difference. No significant difference in the p-EGFR, p-AKT, and p-ERK expression levels was found between high-dose osimertinib-alone group and low-dose osimertinib-plus-bevacizumab group (P>0.05). In the high-dose osimertinib-plus-bevacizumab group, tumor growth was not significantly greater than that in the high-dose osimertinib-alone group (P=0.642). No significant difference was observed in the above factors.In the high-and low-dose osimertinib-plus-bevacizumab groups, tumor volume and the above factors did not exhibit significant differences (P>0.05). Conclusion:Osimertinib has obvious antitumor effects in EGFR-mutant lung adenocarcinoma with T790M mutation cell xenografts. Bevacizumab has a synergetic inhibitory effect with osimertinib against EGFR-mutant lung adenocarcinoma with T790M mutation cell xenografts. Bevacizumab enhanced the antitumor effects of osimertinib by reducing VEGF expression and the microvascular density of the tumor, thereby improving the tumor microenvironment. Bevacizumab can enhance the effect of osimertinib by suppressing EGFR, ERK, and AKT phosphorylation, thereby synergistically inhibiting EGFR activation and downstream signaling.

Objective To investigate the combined effects of invasive intracranial pressure and transcranial Doppler (TCD) monitoring in the treatment for posttraumatic acute diffuse brain swelling (PADBS).Methods The clinical data of 120 patients with PADBS admitted from January 2014 to January 2016 were retrospectively analyzed by case-control study.There were 88 males and 32 females,aged 19-70 years (mean,43.6 years).Patients were divided into three groups based on whether they had accepted invasive intracranial pressure and TCD:Group A (37 cases) with neither invasive intracranial pressure nor TCD,Group B (40 cases) with invasive intracranial pressure only,and Group C (43 cases) with both intracranial pressure and TCD.The hospitalization time in ICU,better prognosis [Glasgow outcome scale (GOS) scored 4-5] at 12 months after injury,Barthel index (BI),and mini-mental status examination (MMSE),mydriasis rate,and decreased values of Glasgow coma scale (GCS) were compared among three groups.Results (1) The ICU length of stay in the Groups of A,B and C was respective (9.6 ± 6.8) days,(9.2 ± 5.4) days and (8.9 ± 5.7) days (P ＞ 0.05).The ratio of better prognosis in the Groups of A,B and C was respective 46％ (17/37),65％ (26/40) and 72％ (31/43),showing a better result in Groups B and C than Group A (P ＜ 0.05).However,there was no significant difference in ratio of better prognosis between Groups B and C (P ＞ 0.05).The BI in the Groups of A,B and C was respective (51.0 ± 36.7) points,(58.0 ± 35.7) points and (70.2 ± 34.6) points,while the MMSE was respective (17.3 ± 12.5) points,(18.8 ± 12.0) points and (21.2 ± 11.4) points.Both BI and MMSE in Groups B and C were higher than those in Group A (P ＜ 0.05),moreover,those in Group B were also statistically lower than those in Group C (P ＜ 0.05).(2) The ratio of mydriasis from admission to initiation of operation in Groups A,B and C was respective 33％ (9/27),13％ (4/30) and 7％ (2/28),showing a higher ratio in Group A than Groups B and C (P ＜ 0.05).But there were no statistical difference in the ratio of mydriasis between Groups B and C (P ＞ 0.05).The decreased value of GCS from admission to initiation of operation in Groups A,B and C was (1.4 ± 1.3) points,(0.7 ± 0.5) points and (0.6 ± 0.4) points respectively,showing a larger decrease in Group A than Groups B and C (P ＜ 0.05).But there was no statistical difference in the decreased value of GCS between Groups B and C (P ＞ 0.05).Conclusion Application of invasive intracranial pressure and TCD monitoring can present a timely and precise condition changes,improve the better prognosis rate,daily activity abilities and cognitive function,indicating that it has protective effects on the brain function.

Objective To investigate the related factors of intracranial infection and intracranial hemorrhage from invasive intracranial pressure monitoring so as to provide a reference for reducing the incidence rate of complications from invasive intracranial pressure monitoring.Methods The clinical data of 349 patients dealt with invasive intracranial pressure monitoring and admitted from October 2009 to June 2016 were retrospectively analyzed by case series study.The possible factors leading to intracranial infection included gender,age,disease classification,type of intracranial pressure probe,implantation method of the intracranial pressure probe,intracranial pressure probe retention time,implementation of craniotomy or not,surgery time,and combination with skull base fracture or not.The possible factors related to complicated intracranial hemorrhage included gender,age,hypertension,international standardized ratio (INR) before intracranial pressure probe implantation,platelet count,serum fibrinogen level,type of intracranial pressure probe,implantation method of the intracranial pressure probe,and the combination with brain contusion or bleeding around intracranial pressure probe implantation site or not.The related factors and independent risk factors of intracranial infection and intracranial hemorrhage were evaluated by univariate analysis and multivariate Logistic regression analysis.Results The univariate analysis showed disease classification (ruptured intracranial aneurysms vs other diseases (P ＜ 0.05),intracranial pressure probe implantation method (P ＜ 0.05),retention time of intracranial pressure probe (P ＜ 0.05),and combination of basal skull fracture (P ＜ 0.05) were the related factors of intracranial infection.Multivariate Logistic regression analysis showed that the disease classification (P ＜ 0.05) and implantation method of intracranial pressure probe (P ＜ 0.05) were independent risk factors for intracranial infection.In addition,probe type (P ＜ 0.05) and implantation method of intracranial pressure probe P ＜0.05) were independent risk factors for intracranial hemorrhage.Conclusions Ruptured intracranial aneurysms and implantation method for intracranial pressure probe (craniotomy or skull drilling) are independent risk factors for intracranial infection from invasive intracranial pressure monitoring.Type of probe (ventricular intracranial pressure probe) and implantation method for intracranial pressure probe (skull cone) are independent risk factors for intracranial hemorrhage from invasive intracranial pressure monitoring.In clinical practice,the indications of invasive intracranial pressure monitoring should be strictly supervised and the relevant risk factors should be prevented to reduce the complications of invasive intracranial pressure monitoring.