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 explore the characteristics and survival of connective tissue disease (CTD) patients with both of pulmonary arterial hypertension (PAH) arnd interstitial lung disease (ILD),and to compare with CTD patients with isolated PAH.Methods All adult CTD patients who visited one of the three referral centers in China with a diagnosis of PAH confirmed by right heart catheterization from July 2006 to May 2011 were enrolled.They were then divided into two groups (ILD with and without-ILD group) based on chest CT and then the comparison of baseline characteristics and survival at the endpoint of follow up were made between the two groups.T test,Mann-Whitney U test,x2 test,Kaplan-Meier survival analysis and Cox regression analysis were used for statistical analyses.Results One hundred and twenty-six patients were recruited into the study.Patients with ILD (n=27) were older than those without ILD (n=99).Lung function results including FVC [(75±18)％ vs (83±13)％,t=2.212,P=0.037] and DLCO [(54±22)％ vs (68±20)％,t=2.392,P=0.019] in ILD group were significantly wose than those without-ILD group.Although some important hemodynamic parameters such as mean pulmonary arterial pressure and pulmonary vascular resistance were better in the ILD group than the without-ILD group,Kaplan-Meier analysis showed that the short term survival of ILD group was significantly worse than that of the without-ILD group (72.7％ versus 94.7％ at 1 year and 63.6％ versus 81.1％ at 3 year,P=0.047).In ILD group,Cox regression analysis showed that SvO2 was the only independent factor for the short term survival [HR=0.19,95％CI (0.04,0.83),P=0.027],and Kaplan-Meier analysis showed patients with SvO2＜60％ had significantly lower short term survival than patients with SvO2 ≥60％ (1 and 2 year survival were 60.0％ and 40.0％ versus 92.9％ and 77.4％ respectively,P=0.002).Conclusion Patients with both PAH and ILD is a special subtype in CTD.Although with the superiority of hemodynamics,these patients have significantly worse survival than CTD patients with isolated PAH.Low SvO2 is the independent risk factor for the short term mortality in patients of CTD complicated by both PAH and ILD.More attention should be paid to these patients and the management strategy should be investigated further.

Objective: To summarize the peri-operative management experience of pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: A total of 56 CTEPH patients received PEA in our hospital from 2015-01 to 2016-11 were retrospectively analyzed. Our study was focused on the medication in respiratory and circulatory system during ICU stay, peri-operative application of vasoactive drug and target drug to pulmonary hypertension (HP), usage of ventilators, mechanical assisted devices and other management experiences. Results: No peri-operative death occurred. There were 2/56 (3.6%) patients with lung reperfusion, 2 (3.6%) with PH crisis. Compared with pre-operation, the post-operative pulmonary artery hemodynamics parameters were improved as right heart catheter measured pulmonary artery systolic pressure (PASP) decreased from (85.05±22.40) mmHg to (36.83 ±17.21) mmHg and pulmonary vascular resistance decreased from (773.84±342.95) dyn·s·cm-5 to (293.59±214.95) dyn·s·cm-5. Post-operative oxygen saturation was maintained at (95-100) % in all patients. Echocardiography found that PASP from pre-operation (85.03±25.78) mmHg decreased to (39.44±19.24) mmHg at follow-up period, P<0.01.Conclusion: A comprehensive peri-operative management of PEA was helpful to improve pulmonary hemodynamics in CTEPH patients; meanwhile, effective prevention and treatment of severe complication could obviously reduce peri-operative mortality.