Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective:To investigate the clinical characteristics and prognosis of T-lymphoblastic lymphoma (T-LBL).Methods:A retrospective case series study was conducted. Clinical data of patients diagnosed with T-LBL at the Affiliated Hospital of Jining Medical University from January 2013 to March 2023 were retrospectively analyzed, and their clinical characteristics and prognosis were statistically analyzed.Results:A total of 22 T-LBL patients were included. Among them, there were 19 males (86.4%) and 3 females (13.6%), and the median age at onset was 19.5 (15, 28) years old. Based on Ann Arbor staging, 3 cases (13.6%) were classified as stage Ⅰ-Ⅱ, while 19 cases (86.4%) were stage Ⅲ-Ⅳ; 10 cases (45.5%) presented with B symptoms, 12 cases (54.5%) without B symptoms; 16 cases (72.7%) showed elevated lactic dehydrogenase (LDH) level. At onset, 7 patients (31.8%) had mediastinal masses, 3 patients (13.6%) had central nervous system involvement, and 17 patients (77.3%) had bone marrow involvement. The overall response rate (ORR) and complete remission rate among the 22 patients were 81.82% (18/22) and 31.82% (7/22), respectively. The ORR was 84.21% (16/19) in 19 patients treated with ALL-like regimens. Among 3 patients treated with NHL-like regimens, 1 case achieved complete remission and 1 case achieved partial remission. Seven patients received allogeneic hematopoietic stem cell transplantation, with a median overall survival (OS) time of 22 months; the median OS time of patients without allogeneic hematopoietic stem cell transplantation was 14 months. The 3-year OS rates in the allogeneic hematopoietic stem cell transplantation group and group without allogeneic hematopoietic stem cell transplantation were 64.30% and 16.00%, and the difference in OS between the two groups was statistically significant ( P = 0.043). Two patients with disease progression prior to transplantation died of multidrug-resistant bacterial infections after transplantation. Conclusions:T-LBL is rare, and it is a highly aggressive tumor that predominantly occurs in adolescent males. Allogeneic hematopoietic stem cell transplantation can prolong OS, reduce relapse and improve the prognosis of patients.

Objective To explore the risk factors for postoperative secondary hydrocephalus in patients with severe craniocerebral injury and construct a nomogram prediction model.Methods A total of 360 patients with severe craniocerebral injury were selected as the study subjects,and divided into hydrocephalus group(n=34)and non-hydrocephalus group(n=326)based on the occurrence of postoperative secondary hydrocephalus.Logistic regression analysis was used to screen for risk fac-tors of postoperative secondary hydrocephalus.A nomogram model for predicting postoperative second-ary hydrocephalus in patients with severe craniocerebral injury was constructed based on the identified risk factors,and its predictive performance was validated.Results Among the 360 patients,34 de-veloped secondary hydrocephalus after surgery,with an incidence rate of 9.44％(34/360).Logistic regression analysis revealed that intracranial infection,ventricular hemorrhage,midline shift ≥12 mm,preoperative Glasgow Coma Scale(GCS)score of 3 to 5,decompressive craniectomy and dura mater o-pening were independent risk factors for postoperative secondary hydrocephalus in patients with severe traumatic brain injury(P＜0.05).The concordance index of the nomogram model constructed based on these risk factors was 0.874,and the area under the curve was 0.831.Conclusion The nomogram model constructed in this study based on factors such as intracranial infection,ventricular hemorrhage,midline shift,preoperative GCS score,decompressive craniectomy and dura mater opening,effectively predicts risk of postoperative secondary hydrocephalus in patients with severe traumatic brain injury.This model has clinical significance for early prevention and treatment.

Objective To compare the efficacy and safety of computed tomography (CT)-guided percutaneous versus electromagnetic navigation bronchoscopy (ENB)-guided microwave ablation (MWA) for the treatment of pulmonary nodules. Methods A retrospective analysis was conducted on the data of high-risk pulmonary nodule patients who underwent MWA at the Nanjing Drum Tower Hospital between 2022 and 2023. The pathological diagnosis rate, complications, and progression-free survival (PFS) rate were compared between the CT group and the ENB group. Results There were 61 patients in the CT group, including 30 males and 31 females, with an average age of (67.22±9.13) years. There were 53 patients in the ENB group, including 29 males and 24 females, with an average age of (65.29±13.76) years. The pathological diagnosis rate in the CT group was slightly higher than that in the ENB group (88.52% vs. 71.69%, P=0.03). However, the ENB group exhibited a lower incidence of perioperative complications, including pneumothorax (16.39% vs. 3.77%, P=0.03), hemoptysis (19.67% vs. 5.66%, P=0.05), and pain (22.95% vs. 7.55%, P=0.03). There was no statistically significant difference in PFS rate between the two groups [HR=1.17, 95%CI (0.23, 5.81), P=0.85]. Conclusion Both CT-guided and ENB-guided MWA are effective treatment modalities for high-risk pulmonary nodules.

BackgroundSuicide ideation in adolescent inpatients with depression is a multi-factorial problem， and perceived stress is considered to be closely related to suicide ideation， while its mediating role in suicide ideation among adolescent inpatients with depression remains unclear. ObjectiveTo explore the mediating effect of psychological capital on the relationship between perceived stress and suicide ideation among adolescent inpatients with depression， so as to provide references for preventing the onset of suicide ideation in adolescent inpatients with depression. MethodsA sample of 585 adolescent patients who were hospitalized in Beijing Huilongguan Hospital from June 2021 to March 2023 and fulfilling the International Classification of Diseases， 10th edition （ICD-10） diagnostic criteria for depression were enrolled. All patients were evaluated using self-designed questionnaire， Chinese Perceived Stress Scale （CPSS）， Positive Psychological Capital Questionnaire （PPQ） and Beck Scale for Suicide Ideation-Chinese Version （BSI-CV）. Pearson correlation was used to assess the correlation among the scores of the above scales. Bootstrap method was employed to verify the mediating effect of psychological capital on the relationship between perceived stress and suicide ideation. ResultsCPSS score in adolescent inpatients with depression was positively correlated with BSI-CV score （r=0.375， P<0.01）， and CPSS score and BSI-CV score were negatively correlated with PPQ score （r=-0.481， -0.436， P<0.01）. Psychological capital played a significant yet a partial role in mediating the link between perceived stress and suicide ideation， with an indirect mediating effect value of 0.160 （95% CI： 0.178~0.373）， accounting for 30.42% of the total effect. ConclusionThe perceived stress of adolescent inpatients with depression can affect the onset of suicide ideation both directly and indirectly through psychological capital.

Objective:To investigate the predictive value of controlling nutritional status (CONUT) score in the prognosis of patients with advanced diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 654 patients newly diagnosed with advanced DLBCL diagnosed in 7 medical centers in Huaihai Lymphoma Working Group from October 2009 to January 2022 were retrospectively collected. All the patients received rituximab-based immune chemotherapy regimens. The patients were randomly assigned to the training set (458 cases) and the validation set (196 cases) in a 7:3 ratio. The clinicopathological data of patients were collected, and the CONUT score was calculated based on albumin, lymphocyte count, and total cholesterol. The optimal critical value of CONUT scote was determined by using MaxStat method. Kaplan-Meier method was used to draw survival curves; Cox proportional hazards model was used to make univariate analysis and multivariate analysis on the factors influencing overall survival (OS). The efficacy of CONUT score in combination with the International prognostic index (IPI) and an enhanced IPI (NCCN-IPI) in predicting OS was evaluated by using receiver operating characteristic (ROC) curves.Results:The median follow-up time of 654 patients was 38.1 months (95% CI: 35.3 months- 40.9 months), and the 5-year OS rate was 49.2%. According to the MaxStat method, the optimal critical value for CONUT score was determined to be 6 points. All the patients were classified into the normal nutritional status group (CONUT score ≤ 6 points, 489 cases) and the poor nutritional status group (CONUT score > 6 points, 165 cases). The results of the multivariate analysis showed that CONUT score > 6 points, male, lactate dehydrogenase >240 U/L, high white blood cell count, low hemoglobin level and age > 60 years were independent risk factors for OS of patients with advanced DLBCL (all P < 0.05). Patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group in the overall cohort of advanced DLBCL. Subgroup analysis revealed that among patients with Eastern Cooperative Oncology Group-performance status (ECOG PS) score < 2 points, IPI low-intermediate risk, IPI intermediate-high risk, NCCN-IPI low-intermediate risk, and NCCN-IPI intermediate-high risk, the patients in the poor nutritional status group (CONUT score > 6 points) had worse OS compared with that in the normal nutritional status group (CONUT score ≤ 6 points) (all P < 0.05). Conclusions:CONUT score has a certain value in the assessment of the prognosis of patients with advanced DLBCL, and its predictive efficacy is further improved when combined with IPI and NCCN-IPI.

Objective To investigate the impacts of phillyrin on exudates and lung injury in rats with acute pleurisy by regulating the NLRP3 inflammatory pathway.Methods Ninety rats were randomly divided into the control group,the model group,the low-dose phillyrin(PH-L,5 mg/kg)group,the medium-dose phillyrin(PH-M,10 mg/kg)group,the high-dose phillyrin(PH-H,20 mg/kg)group and the NLRP3 pathway inhibitor(PJ34,10 mg/kg)group.FVC,FEV 0.1 and FEV 0.3 were detected by lung function analyzer.Electronic balance was used to weigh the mass of chest exudate.The number of white blood cells in exudate was detected by Wright staining.Contents of prostaglandin E2(PGE2),monocyte chemoattractant protein-1(MCP-1),interleukin(IL)-6 and tumor necrosis factor-α(TNF-α)in exudate were detected by ELISA.Automatic blood gas analyzer was used to detect p(CO2)and p(O2)of rats.HE staining was used to observe pathological changes of lung tissue.The expression levels of NLRP3 and Caspase-1 protein were detected by immunohistochemistry.Western blot assay was used to detect the expression of NLRP3 pathway protein.Results Compared with the control group,the quality of pleural exudate and the number of white blood cells,the contents of PGE2,MCP-1,IL-6,TNF-α,the expression of p(CO2)and NLRP3 pathway proteins in exudate of the model group increased obviously,FVC,FEV 0.1,FEV 0.3 and p(O2)decreased obviously,and the lung tissue showed obvious pathological damage(P＜0.05).Compared with the model group,the quality of pleural exudate and the number of white blood cells,the contents of PGE2,MCP-1,IL-6,TNF-α,the expression of p(CO2),NLRP3 pathway proteins in the exudate of rats decreased obviously in the PH group and the PJ34 group,FVC,FEV 0.1,FEV 0.3 and p(O2)increased obviously,the pathological injury of lung tissue was obviously improved(P＜0.05).Compared with the PH-H group,there were no significant differences in the above indexes in the PJ34 group(P＞0.05).Conclusion PH can improve lung injury induced by acute pleurisy in rats by inhibiting the activation of NLRP3 pathway and inhibiting inflammatory reaction.

BACKGROUND:High ankle sprain is easily missed and leads to ankle dysfunction.Arthroscopy can detect hidden high ankle sprain.Suture-button elastic fixation can restore the biomechanical stability of the distal tibiofibular syndesmosis. OBJECTIVE:To explore the clinical efficacy of Suture-button elastic fixation for high ankle sprain under ankle arthroscopy. METHODS:A retrospective analysis was performed on 40 cases of high ankle sprain patients treated with Suture-button elastic fixation under ankle arthroscopy from August 2019 to August 2021 in the Department of Foot and Ankle Surgery,Wuhan Fourth Hospital.All patients underwent Suture-button elastic fixation.The American Orthopedic Foot and Ankle Society function score,Visual Analog Scale pain score,ankle range of motion,preoperative imaging data,and arthroscopic tibiofibular syndesmosis separation degree were recorded.Meislin criteria were used to evaluate the curative effect and postoperative complications were recorded. RESULTS AND CONCLUSION:(1)40 patients were followed up for 16-48 months after operation.(2)At the last follow-up,American Orthopedic Foot and Ankle Society score was(88.95±6.64 points).Visual Analog Scale score was(1.78±1.23 points).Ankle dorsiflexion range of motion was(33.50±5.79 degrees).Ankle plantarflexion range of motion was(34.50±5.97 degrees).There were statistically significant differences before and after surgery(P<0.05).(3)There was a low positive correlation between the radiographic separation index and the degree of arthroscopic separation(r=0.612,P<0.01).(4)The curative effect was evaluated by Meislin standard,with an excellent and good rate of 95%(38/40).Postoperative ankle joint pain was relieved,and ankle joint activities were significantly improved.(5)During the follow-up period,all patients had no nerve injury or incision infection.In 1 patient,the internal fixation was removed due to skin irritation and squatting sensation after operation.(6)It is concluded that Suture-button elastic fixation for high ankle sprain is effective under ankle arthroscopy in restoring ankle function and maintaining joint stability without the need for secondary removal,and it is worth clinical application.

Objective:To investigate the clinical phenotype and genotype characteristics of lipoyltransferase 1 deficiency (LIPT1D).Methods:A retrospective analysis of the clinical data was conducted for one case of LIPT1D, admitted to the Department of Neonatology at Shanghai Children's Hospital on May 7, 2023. Key terms "lipoyltransferase 1 deficiency", " LIPT1", and "lipoic acid" were used to search national databases including CNKI, Wanfang Data, VIP, and Yiigle; and international databases PubMed, Embase, and Web of Science until September 15, 2023, to summarize the clinical presentations, biochemical phenotypes, and genotypic characteristics of LIPT1D. Descriptive statistical analysis was employed. Results:(1) The case concerned: At 1.5 h after birth, the infant exhibited cyanosis and poor responsiveness, presenting with uncorrectable metabolic acidosis (blood pH value 6.9, base excess -27 mmol/L, bicarbonate 5.7 mmol/L), and hyperlactatemia (the highest was 24 mmol/L). The condition progressed rapidly, and the infant died 9 h after birth. Whole exome sequencing performed 6 h postnatally identified compound heterozygous variants in the LIPT1 gene (NM_001204830.1) in the infant. Variants c.986C>A (p.Ser329*) from the mother and c.405_406del (p.Arg135Serfs*18) from the father were detected, both suspected to be pathogenic. (2) Literature review: A review of the literature identified seven cases of LIPT1D caused by LIPT1 gene mutations, totaling eight cases including the current one. The main presentations of LIPT1D in these infants were hyperlactatemia, metabolic acidosis, neurodevelopmental delay, and epilepsy, with four cases presenting in the neonatal period and resulting in death. Conclusions:The primary clinical manifestations of LIPT1D are severe hyperlactatemia, metabolic acidosis, and neurological involvement, potentially leading to early neonatal death. Whole-exome sequencing is instrumental in diagnosing this condition.