Early identification of adolescent depression requires objective biomarkers. This study investigated the functional near-infrared spectroscopy (fNIRS) activation patterns and mismatch negativity (MMN) characteristics in adolescents with first-episode mild-to-moderate depression. We enrolled 33 patients and 33 matched healthy controls, measuring oxyhemoglobin (Oxy-Hb) concentration in the frontal cortex during verbal fluency tasks via fNIRS, and recording MMN latency/amplitude at Fz/Cz electrodes using event-related potentials (ERP). Compared with healthy controls, the depression group showed significantly prolonged MMN latency [Fz: (227.88 ± 31.08) ms vs. (208.70 ± 25.35) ms, P < 0.01; Cz: (223.73 ± 29.03) ms vs. (204.18 ± 22.43) ms, P < 0.01], and obviously reduced Fz amplitude [(2.42 ± 2.18) μV vs. (5.65 ± 5.59) μV, P = 0.03]. A significant positive correlation was observed between MMN latencies at Fz and Cz electrodes ( P < 0.01). Oxy-Hb in left frontopolar prefrontal channels (CH15/17) was significantly decreased in patient group ( P < 0.05). Our findings suggest that adolescents with depression exhibit hypofunction in the left prefrontal cortex and impaired automatic sensory processing. The combined application of fNIRS and ERP techniques may provide an objective basis for early clinical identification.
Humans ; Spectroscopy, Near-Infrared/methods* ; Adolescent ; Prefrontal Cortex/physiopathology* ; Evoked Potentials/physiology* ; Depression/physiopathology* ; Female ; Male ; Oxyhemoglobins ; Electroencephalography

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.

Objective To conduct basic research on the structure and function of the heart in cynomolgus monkeys older than 10 years to provide data for animal selection in elderly disease research.Methods A total of 144 cynomolgus monkeys＞10 years old were selected as research subjects,including 37 females and 66 males in the 10～15 years group,and 21 females and 20 males in the 16～20 years group.Basic data on cardiac structure and function in middle-aged and elderly cynomolgus monkeys were obtained through comparative analysis of general indicators(body mass index,blood pressure,and heart rate),blood biochemical indicators(blood glucose,blood lipids,and ion indicators),and cardiac structure and function indicators.Results General indicators for the 10～15 years and 16～20 years groups were compared.As age increased,the blood pressure and heart rate of female and male monkeys increased,and there was a significant difference in blood pressure changes between male monkeys.A comparison of two sets of blood biochemical indicators showed that,as age increased,blood glucose,triglycerides,total cholesterol,low-density lipoprotein cholesterol,blood calcium,blood sodium,and blood potassium increased,while lactate dehydrogenase decreased,in female and male monkeys.Among these,blood glucose,triglycerides(males),total cholesterol,high-density lipoprotein cholesterol(males),low-density lipoprotein cholesterol(males),blood calcium,blood sodium,blood potassium,and lactate dehydrogenase showed significant changes.A comparison of cardiac contractile function between the two groups showed that,as age increased,the anterior and posterior diameters of the left atrium significantly decreased in both female and male monkeys.Female monkeys showed a significant decrease in the interventricular septal end systolic diameter,left ventricular end diastole and systolic diameters,left ventricular end diastolic and systolic volumes,and left ventricular mass index,while no significant changes were seen in male monkeys.A comparison of diastolic function between the two groups showed that,as age increased,the late diastolic velocity of the mitral valve decreased significantly in male monkeys,while the early diastolic velocity of the left ventricular sidewall increased significantly in female monkeys.Correlation analysis was conducted between the metabolic indicators and the cardiac structure and function indicators of female and male monkeys.The correlations between metabolic indicators and cardiac structure and function indicators were weak in female monkeys,for which the maximum absolute Γ value did not exceed 0.39.However,the correlations between metabolic indicators and cardiac structure and function indicators were relatively strong in male monkeys,for which the maximum absolute Γ value reached 0.66.Conclusions Based on ultrasound analysis combined with metabolic indicators,the heart function of cynomolgus monkeys was studied,and basic data related to the structure and function of the heart in middle-aged and elderly cynomolgus monkeys were obtained.As age increased,blood glucose and lipid indicators increased in cynomolgus monkeys,while cardiac systolic and diastolic functions show a downward trend,similar to changes in middle-aged and older adult human populations.These data provide support for animal selection in research on age-related diseases related to heart function.

Objective:To explore the genetic background and clinical features of patients with long QT syndrome type 3 (LQT3).Methods:This retrospective cohort included patients diagnosed with LQT3 at the Department of Cardiology, Renmin Hospital of Wuhan University from January 1998 to December 2022. Patients were categorized into compound type group and single type group based on the presence of a single SCN5A mutation. The two groups were followed up and the differences in baseline characteristics, electrocardiograms, and clinical events between the two groups and probands were compared. Kaplan-Meier curves were used for survival analysis, and the log-rank test was employed to compare the event-free survival rates of first cardiac events between the groups and probands.Results:A total of 97 LQT3 patients were enrolled, including 59 probands. The age at diagnosis was (23.45±19.86) years, with 46 patients (47.4%) being male. Among them, 89 patients were classified as single type group, while 8 patients were classified as compound type group. Genetic testing identified 49 SCN5A mutations, with missense mutations being the majority (91.8%), primarily located in transmembrane regions (40.8%, n=20), interdomain linker regions (28.6%, n=14), and C-terminus (22.4%, n=11). The first cardiac event occurred in 44 patients (45.4%), with an onset age of (13.82±12.50) years. The main trigger was identified as rest or sleep (54.5%, n=24). Compared with patients in single type group, patients in compound type group were younger at diagnosis ((10.35±10.28) years vs. (24.63±20.13) years, P=0.040), had a significantly higher proportion of syncope (87.5% (7/8) vs. 33.7% (30/89), P=0.009), aborted cardiac arrest (62.5% (5/8) vs. 11.2% (10/89), P=0.001), and a lower incidence of event-free survival rates of first cardiac events (12.5% (1/8) vs.58.4% (52/89), log-rank P=0.001). The probands in compound type group had a significantly higher proportion of aborted cardiac arrest comparing to probands in single type group (62.5% (5/8) vs. 17.6% (9/51), P=0.020), while the difference in the incidence rate of event-free survival rates of first cardiac events between the probands in two groups was not statistically significant (12.5% (1/8) vs. 39.2% (20/51), log-rank P=0.08). Conclusion:Compound type LQT3 patients are not uncommon. Such patients are diagnosed at a younger age and exhibit more severe phenotypes, requiring close follow-up and proactive intervention strategies.

In various types of inspections and self-inspections, it was found that compliance and rationalization in diagnosis and charging were the more common problems in hospital, leading to refusal of medical insurance payment. In 2022, the failure mode and effect analysis was conducted in a Grade-A tertiary hospital in Jinhua to identify the high-risk points in the process of diagnosis and treatment and charging, and building six major information technology transformation scenarios and formulating specific transformation measures, to avoid or reduce the refusal of medical insurance payment in advance. Through the digital transformation of medical insurance supervision system, a whole process intelligent supervision has been implemented, including pre event review, mid event reminder and intelligent correction, and post event big data precise analysis. It promoted compliant diagnosis and treatment of medical personnel and accurate charging, which could provide reference for other medical institutions to use medical insurance funds reasonably.

Objective To investigate the correlation between muscle mass and gait parameters in patients with cerebral small vessel disease(CSVD),as well as the impact of reduced muscle mass on the occurrence of falls in CSVD patients.Methods This study was employed a cross-sectional design.Ninety-five inpatients with CSVD confirmed by the Department of Neurology of the Seventh Medical Center of Chinese People's Liberation Army General Hospital from January 1,2022 to June 1,2023 were included consecutively.The 95 patients with CSVD were divided into two groups,namely the reduced muscle mass group and the normal muscle mass group,based on the criteria of appendicular skeletal muscle mass(ASM)≤7.0 kg/m2 for males and ASM ≤5.7 kg/m2 for females as reduced muscle mass.Baseline data(sex,age,years of schooling,number of accompanying diseases[hypertension,hyperlipidemia,diabetes,angina pectoris,myocardial infarction,and migraines]),cognitive function assessment results(mini-mental status examination[MMSE],verbal fluency test[VFT],clock drawing test[CDT],and trail-making test part-B[TMT-B]),gait characteristics(basic gait parameters[gait speed,stride time,stride length,stride frequency]and reanalysis gait parameters[variation coefficient of gait speed,stride time,stride length,stride frequency,and time-phase coordination index,gait asymmetry index]),CSVD imaging findings(cerebral microbleeds,lacunar infarcts,and white matter hyperintensities),and history of falls.The differences in baseline data,cognitive function assessment results,and gait characteristics between the reduced muscle mass group and the normal muscle mass group were compared and analyzed.Linear regression was used to analyze the correlation between muscle mass and gait parameters.The 95 CSVD patients were divided into fall group and non-fall group,and the differences in baseline data,cognitive function assessment results,gait characteristics,CSVD imaging findings,and muscle mass between the two groups were compared.Binary Logistic regression analysis was used to evaluate the impact of reduced muscle mass on falls.Results(1)The majority of patients in the reduced muscle mass group were females(67.7％[21/31]).There was a statistically significant difference in the sex distribution between the reduced muscle mass group and the normal muscle mass group(x2=6.143,P=0.013).There were no statistically significant differences in the other baseline characteristics and cognitive function between the two groups(all P＞0.05).(2)Compared to the normal muscle mass group,patients in the reduced muscle mass group had slower gait speed([0.72±0.16]m/s vs.[0.94±0.15]m/s),longer stride time([1.22±0.12]s vs.[1.08±0.08]s),shorter stride length([0.84±0.19]m vs.[1.00±0.14]m),and lower step frequency([100±9]steps/min vs.[112±8]steps/min).The coefficients of variation for gait speed(11.579[8.163,15.870]％vs.7.304[5.873,9.959]％),stride time(3.876[2.778,5.769]％vs.2.480[1.874,3.001]％),stride length(7.800[5.400,10.700]％vs.5.600[4.100,7.950]％),step frequency(5.313[3.568,7.272]％vs.3.674[3.099,5.082]％),and time-phase coordination index(5.894[4.392,9.080]％vs.3.828[3.031,5.972]％)were all increased,and the differences were statistically significant(all P＜0.05).There was no statistically significant difference in gait asymmetry index between the two groups(P＞0.05).Further analysis with sex and lacunar infarction as potential confounding factors showed that there were statistically significant differences in baseline gait parameters between the normal muscle mass group and the reduced muscle mass group(all P＜0.01).In the reanalysis of gait parameters,only the differences in the coefficients of variation for gait speed and stride time were statistically significant(both P＜0.05).(3)When analyzing ASM as a continuous variable,age and CDT as potential confounders,and stratifying by sex,the results showed that in male patients,baseline gait parameters(gait speed,stride time,stride length,and step frequency with 95％CI ranging from 0.057 to 0.152,-0.105 to-0.023,0.013 to 0.097,and 1.686 to 8.854,respectively),as well as coefficients of variation for stride time(95％CI-0.016 to-0.003)and stride length(95％CI-0.026 to-0.006),were correlated with muscle mass reduction(all P＜0.05).In female patients,gait speed(95％CI0.034 to 0.166)and coefficient of variation for gait speed(95％CI-0.059 to-0.010),stride time(95％CI-0.110 to-0.011),coefficient of variation for stride time(95％CI-0.025 to-0.001),and stride length(95％CI 0.018 to 0.163)were correlated with muscle mass reduction(all P＜0.05).(4)Muscle mass reduction was an independent risk factor for falls(OR,5.044,95％CI 1.840 to 13.827,P=0.002).Conclusions The preliminary analysis of this study suggests that there is a certain correlation between muscle mass and gait parameters in patients with CSVD.Additionally,the study indicates that a decrease in muscle mass among CSVD patients may increase the risk of falls.Therefore,it is important to prioritize the management of muscle mass in CSVD patients.

Objective:To evaluate the treatment of infected nonunion after internal fixation of subtrochanteric fracture with a reconstruction stent of external fixation.Methods:A retrospective study was conducted to analyze the data of 5 male patients with infected nonunion after internal fixation of subtrochanteric fracture who had been treated and completely followed up at The Great Wall Orthopaedics and Hand Surgery Hospital from January 2017 to October 2022. The patients were (30.0±13.5) years old. Seinsheimer fracture types: ⅢA (1 case), ⅢB (1 case), Ⅳ (2 cases), and Ⅴ (1 case); original internal fixation: intramedullary system (4 cases) and plate fixation (1 case); the Cierny-Mader anatomical classification: type Ⅳ (diffuse type) for all. After complete debridement at stage one, 2 or 3 hydroxyapatite (HA) coated screws were placed at both fracture ends from the lateral side of the femur for unilateral reconstruction external fixation. Next, a hybrid external fixation scaffold was added with a 1/3 ring at the sagittal position and 1 or 2 HA screws in 4 cases while unilateral reconstruction external fixation was constructed at both sides by inserting 2 HA screws into both fracture ends from the anterior femur at the sagittal position in 1 case. Antibiotic bone cement was used to fill bone defects of (3.8±1.8) cm. At 6 to 8 weeks after debridement when infection did not recur, antibiotic bone cement was removed before autogenous iliac bone grafting was performed in 3 patients and osteotomy bone transport in 2 patients. Infection control, bone union time, time for removal of external fixation stent, complications, Sanders hip function score and Paley bone outcome score were recorded.Results:The 5 patients were followed up for (23.4±8.1) months after surgery. Infection at the fracture ends was controlled after 1 time of debridement in 3 patients and after 2 times of debridement in 2 patients. The loosening HA screws were replaced twice due to infection at the proximal nail tract, and autologous bone grafting was performed at the opposite fracture ends in 1 case; no complications occurred in the other 4 cases. Bony union was achieved at the extended segment and fracture ends in all patients. The time for imaging union after bone reconstruction was (10.2±3.4) months. The time for wearing a stent of external fixation was (18.0±4.5) months. There was no recurrent infection or lingering infection. According to the Sanders hip function score at the last follow-up, 4 cases were excellent and 1 case was good; according to the Paley bone outcome score, the curative effect was excellent in all.Conclusion:Application of a reconstruction stent of external fixation combined with antibiotic bone cement can control infection at the first stage and conduct bone reconstruction at the second stage to successfully treat the infected nonunion and preserve the hip function after internal fixation of subtrochanteric fracture.

Objective:To compare the gait characteristics of cognitive and motor dual task walking (DTW) in patients with cerebral small vessel disease (CSVD), and determine the best gait parameters to diagnose CSVD and judge the severity of the disease.Methods:A total of 106 patients with CSVD and 21 healthy individuals were included from September 1, 2020 to July 1, 2021 in the Seventh Medical Center of Chinese People′s Liberation Army General Hospital. According to the Fazekas scores, the subjects were divided into mild ( n=34, 1 point), moderate ( n=34, 2 points), severe ( n=38,3 points) groups and control group ( n=21). Participants were recorded parameters under single task walking (STW) and DTW conditions, and calculated dual task effect (DTC) through the difference between single task and dual task. The differences in gait variances and their DTC were shown by generalized estimation equations when performed in STW and DTW and 4 groups of the severity of disease. Post-hoc comparisons were corrected using Bonferroni′s method. Spearman analyses were applied to explore the correlations between gait parameters and their DTC during STW or DTW and severity of disease. Based on the Logistic model, combining predictors or probabilities were gained and applied to establish receiver operating characteristic curve in order to calculate sensitivity, specificity, and the area under the curve. Results:In the control group, there was no statistically significant difference in gait parameters between STW and DTW. In the CSVD group, the gait parameters of STW were significantly better than cognitive or motor DTW (all P<0.05). In the control group, there was no statistically significant difference in basic gait parameters under different tasks (all P>0.05). In cognitive DTW, temporal gait parameters (stride frequency and stride time) deteriorated significantly only in moderate and severe groups [stride frequency:moderate group 100.220±1.795/min,severe group 94.525±2.139/min;stride time:moderate group (1.227±0.024) s, severe group (1.299±0.031) s], but spatial parameters [stride length: control group (1.050±0.021) m, mild group (0.974±0.022) m, moderate group (0.903±0.025) m, severe group (0.793±0.026) m; stride speed: control group (0.944±0.028) m/s, mild group (0.866±0.030) m/s, moderate group (0.751±0.027) m/s, severe group (0.606±0.022) m/s] were significantly different among all groups (except the control group and mild group;all P<0.05). The DTC of all gait parameters during cognitive DTW was higher than that during motor DTW (all P<0.05) for CSVD patients. While no any difference was found between cognitive DTW and motor DTW in the control group (all P>0.05). Similarly, the temporal parameters′ DTC of cognitive DTW was abnormal only in the late stage of disease, while the spatial parameters′ DTC showed statistically significant difference among all the groups (including the control group and the mild group;all P<0.05). Correlation coefficients of the spatial parameters and their DTC in condition of cognitive DTW were significantly higher than temporal parameters and their DTC (0.50< r<0.64 vs 0.15< r<0.39). The area under curve of the combined predictor was significantly higher than that of any single index. Conclusions:Cognitive DTW can better reflect the abnormal gait of CSVD patients. The spatial parameters and DTC of cognitive DTW could effectively diagnose CSVD and distinguish the disease of severity. And DTC might be better indicators. For diagnosis of CSVD, there was no significant discrepancy between the spatial parameters and DTC, but the combined predictor could significantly improve the sensitivity and reduce the false negative rate.

Objective:To investigate the surgical method and clinical effects of the modified proper digital artery island flap in repairing complex fingertip defects.Methods:A retrospective observational study was conducted. From January 2017 to December 2021, 15 patients (15 fingers) with complex fingertip defects, involving the pulp, nail bed, and lateral wall of the nail, who met the inclusion criteria were admitted into General Hospital of Northern Theater Command, including 11 males and 4 females, aged from 18 to 55 years. The area of the post debridement wound was from 2.5 cm×2.0 cm to 3.5 cm×3.5 cm, and all the wounds were repaired by using modified proper digital artery island flap (including 3 parts: main flap, tongue-shaped flap, and triangular flap), of which the main flap was used to cover the finger pulp defect, the tongue-shaped flap was used to cover the nail bed and the nail lateral wall defect, and the triangular flap was inserted into the edge of the finger pulp wound to cover the vessel pedicle. The range of the flap ranged from 3.0 cm×2.0 cm to 4.5 cm×3.0 cm. The wound at the donor site was repaired with full-thickness skin graft of the groin, and the donor site of the skin graft was sutured directly. After operation, the survival of the flap and skin graft as well as and the appearance of the affected finger were observed. During the follow-up, the fingertip morphology of the affected finger was observed, two-point discrimination distance of the affected finger pulp was measured, and the patients' satisfaction with the efficacy (including very satisfied, satisfied, and dissatisfied) was asked, and the affected finger function was evaluated by the total active movement (TAM) system evaluation standard recommended by American Academy for Surgery of Hand.Results:After operation, the main flaps and skin grafts in 15 patients all survived; but the incision at the edge of tongue-shaped flap in one patient healed poorly, and one patient developed venous stasis at the distal end of the tongue-shaped flap; the triangular flap at the pedicle was slightly bloated in the early postoperative period and became smooth after 2 to 3 months. Overall, two patients developed subcutaneous hematoma in their flaps. All the complications were healed by appropriate dressing change, suture removal, or compression bandaging. After operation, the appearance of the flap was full and formed a prominent fingertip shape. During the follow-up of 6 months to 5 years, the fingertips of the affected fingers were prominent and full; the two-point discrimination distance of the affected finger pulp was (8.6±1.4) mm; 8 patients were very satisfied with the efficacy, 6 patients were satisfied, and one patient was dissatisfied; the functional assessment of the affected fingers were all excellent.Conclusions:The modified proper digital artery island flap can repair complex fingertip defects involving the pulp, nail bed, and lateral wall of the nail. The operation is simple, and the shape and function of the fingertip are good after surgery.