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.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.

Objective:To explore the split-face phenomenon in patients with bulbar-involved amyotrophic lateral sclerosis (ALS) through clinical and electrophysiological studies.Methods:A total of 52 clinically definite and clinically probable cases of bulbar-involved ALS, diagnosed according to the World Federation of Neurology El Escorial criteria, were retrospectively collected in the Third Central Hospital of Tianjin from September 2019 to November 2022. And 58 patients with idiopathic facial nerve paralysis with onset time≤7 days who visited the Department of Neurology of the Third Central Hospital of Tianjin during the same period were collected as control group. The firm eye closure (FC) score and cheek bulge (CB) score were used to assess the clinical involvement of facial muscles (dividing into facial muscle involvement group and non-facial muscle involvement group) and the presence of the split-face phenomenon (strong eye closure and weak cheek bulging) in ALS patients. The compound muscle action potential (CMAP) amplitudes of the bilateral orbicularis oculi and orbicularis oris muscles were measured using the Nicolet EDX Viking electromyography/evoked potential system. The CMAP amplitude ratio was calculated. The facial nerve electrophysiological differences were compared between ALS patients with bulbar involvement and patients with idiopathic facial nerve paralysis. The analysis of electrophysiological data across various groups was carried out utilizing the Kruskal-Wallis H test, while pairwise comparisons between groups were executed employing the Bonferroni correction method. Additionally, a stepwise binary Logistic regression analysis was implemented to ascertain the factors associated with facial muscle involvement in patients with bulbar-involved ALS. The receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of facial nerve electrophysiological testing in diagnosing ALS in the presence of symptoms of facial muscle involvement. Results:Among the 52 ALS patients with bulbar involvement, there were 20 cases (38.5%) with facial muscle involvements, all of which were bilateral; 16 patients (30.8%) exhibited weakness solely in the ability to puff their cheeks, 1 patient (1.9%) presented with weakness exclusively in closing the eyes, and 3 patients (5.8%) experienced weakness in both closing the eyes and puffing the cheeks. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score of the facial muscle involvement group was lower compared to the non-facial muscle involvement group (36.90±9.20 vs 40.75±5.21, t=2.419, P=0.019), while the FC score and CB score were higher in the facial muscle involvement group [FC score: 0(0, 1) vs 0(0, 0), U=5.854, P<0.001; CB score: 4(3, 4) vs 0(0, 0), U=9.069, P<0.001], showing statistically significant differences. There was no statistically significant difference in the CMAP amplitude of the orbicularis oculi muscle between the facial muscle involvement group and the healthy side of the idiopathic facial nerve paralysis group, the affected side of the idiopathic facial nerve paralysis group, and the non-facial muscle involvement group (all P>0.05). The CMAP amplitude of the orbicularis oris muscle in the facial muscle involvement group [1 100.00 (775.00, 1 375.00) μV] was lower than that in the healthy side of the idiopathic facial nerve paralysis group [1 800.00 (1 400.00, 2 300.00) μV] and the non-facial muscle involvement group [1 555.00 (1 202.50, 1 980.00) μV], with statistically significant differences ( H=5.884, P<0.001; H=4.114, P<0.001). There was no statistically significant difference in the CMAP amplitude of the orbicularis oris muscle between the facial muscle involvement group and the affected side of the idiopathic facial nerve paralysis group ( P>0.05). The CMAP amplitude ratio of the orbicularis oculi/orbicularis oris muscles in the facial muscle involvement group [0.83(0.51, 1.14)] was higher than that in the healthy side of the idiopathic facial nerve paralysis group [0.55(0.39, 0.73)], the affected side of the idiopathic facial nerve paralysis group [0.57(0.40, 0.73)], and the non-facial muscle involvement group [0.60(0.42, 0.71)], with statistically significant differences ( H=-3.440, P=0.003; H=-3.433, P=0.004; H=-3.225, P=0.008). Logistic regression analysis revealed that the CMAP amplitude of orbicularis oris muscle ( OR=0.998,95% CI 0.997-0.999, P<0.001) and ALSFRS-R score ( OR=0.916,95% CI 0.857-0.979, P=0.010) were factors associated with facial muscle involvement in ALS patients with bulbar involvement. The ROC curve analysis results showed that the area under the curve (AUC) of the orbicularis oculi muscle CMAP was 0.629, the AUC of the orbicularis oris muscle CMAP was 0.838, and the AUC of the CMAP amplitude ratio of the orbicularis oculi/orbicularis oris muscles was 0.690 in the facial muscle involvement group. Conclusions:Patients with bulbar-involved ALS have split-face phenomenon characterized by strong eye closure and weak cheek bulging. When bulbar-involved ALS patients have symptoms of facial muscle involvement, the CMAP amplitude of the orbicularis oris muscle decreases significantly, whereas the CMAP amplitude of the orbicularis oculi muscle remains relatively stable, further illustrating the split phenomenon.

Objective:To analyze the clinical and electrophysiological characteristics of patients with sensory neuronopathies (SNN), and to evaluate the significance of electrophysiological markers in the diagnosis and assessment of disease progression.Methods:A retrospective analysis was performed to evaluate the clinical manifestations, electrophysiological characteristics, and spinal cord magnetic resonance imaging (MRI) features of 8 cases diagnosed with SNN at the Third Central Hospital of Tianjin between 2015 and 2023. The neurophysiological examination mainly included limb nerve conduction study (NCS), same core needle electrode electromyography, somatosensory evoked potential (SEP), skin sympathetic reflex (SSR), and contact heat evoked potential (CHEP).Results:Among the 8 cases with SNN, 7 cases exhibited asymmetrical onset and a non-length-dependent pattern. All the 8 cases presented with severe deep sensory ataxia, accompanied by superficial sensory abnormalities and tendon areflexia. Paraneoplastic SNN were the most prevalent etiological subtype (4 cases), all of whom presented peripheral neuropathy as the initial symptom. Among these 4 cases, malignancies were identified in 3 cases and 3 cases presented with anti-Hu antibodies. Among the remaining 4 patients, 2 cases were autoimmune and the other 2 cases were idiopathic. NCS results of the 8 cases revealed decrease or absence of sensory nerve action potential (SNAP) amplitudes, with normal sensory conduction velocities. Six cases showed abnormal SEP, including 2 cases of central damage and 4 cases of peripheral damage, 5 cases had abnormal SSR, and 2 cases exhibited abnormal CHEP. Motor nerve conduction studies were normal in all 8 cases. Six patients underwent spinal MRI, and 4 exhibited abnormal signals in dorsal columns.Conclusions:The hallmark clinical manifestation of SNN is sensory ataxia, characterized by substantial impairment of superficial sensation, typically manifesting in a non-length-dependent distribution. Beyond the widespread and significant reduction in SNAP amplitudes, SNN may also exhibit additional electrophysiological impairments, such as those observed in SEP, SSR and CHEP.SEP combined with spinal cord MRI can improve the detection rate for damages in the central sensory conduction pathway.

Objective:To analyze the differences in heart size，shape and function between fetuses with tetralogy of Fallot（TOF）and fetuses with malalignment ventricular septal defect（VSD）and pulmonary stenosis（PS）（named as，mild TOF）by fetal heart quantification（fetal HQ）and multi-parameter fetal echocardiography.Methods:From June 2021 to June 2023，50 fetuses with TOF（TOF group）diagnosed by fetal echocardiography at the Department of Diagnostic Ultrasound & Echocardiography Sir Run Run Shaw Hospital，Zhejiang University College of Medicine and 34 fetuses with VSD and PS matched to gestational age（mild TOF group）were retrospectively selected. Cardiovascular parameters were measured by 2D echocardiography，M-mode echocardiography and fetal HQ，including aortic dimension（AO）and its Z-score（AO Z-score），pulmonary artery diameter（PA）and its Z-score（PA Z-score），PA/AO ratio，main pulmonary artery diameter（MPA）and its Z-score（MPA Z-score），left pulmonary artery diameter（LPA）and its Z-score（LPA Z-score），right pulmonary artery diameter（RPA）and its Z-score（RPA Z-score），McGoon index（MGI），tricuspid annular diameter（TV）and its Z-score（TV Z-score），mitral annular diameter（MV）and its Z-score（MV Z-score），and MV/TV ratio. Measurements of global ventricular morphologic parameters included cardiac axis，left and right ventricular transverse diameters（LVW，RVW）and their ratio（LVW/RVW），left and right ventricular long diameters（LVL，RVL）and LVL/RVL ratio，left and right ventricular areas（LVA，RVA）and LVA/RVA ratio，global spherical index（GSI）and its Z-score，four chamber view transverse diameter（4CV-Width-ED），four chamber view end-diastolic longitudinal diameter（4CV-Length-ED），four chamber view end-diastolic area（4CV-Area-ED）. Measurements of left and right global ventricular functional parameters included fractional left ventricular and right ventricular area changes（LVFAC，RVFAC），left ventricular ejection fraction（LVEF），left ventricular and right ventricular global longitudinal strains（LVGLS，RVGLS）；end diastolic width diameter（Width-ED），SI and fractional shortening rate（FS）of 24 segments of left and right ventricles. The differences of the above parameters between the two groups were analyzed and compared，and the relationships between absolute values of GLS in left and right ventricles of TOF fetus and PA Z-score，MPA Z-score and PA/AO were analyzed. Binary Logistic regression model was used to select the best variables，and ROC curve was adopted to analyze the predictive values of ultrasonic parameter variables on TOF.Results:There were statistically significant differences in MV，TV，RVW，RVL，LVL，LVA，RVA，4CV-Length-ED，LVGLS，RVGLS，RVFAC，PA/AO，MPA，RPA，LPA，MGI，PA and PA Z-score between TOF group and mild TOF group（all P<0.05）. The Width-ED values of all segments of left ventricle were statistically different between TOF group and mild TOF group（all P<0.05）. There were statistical differences in SI between LV segments 4~6 and 8~24，and RV segments 1~21（all P<0.05）. The FS values between the 8th and 10th to 18th segments of RV revealed statistical differences（all P<0.05）. There were no statistical differences in the other parameters（all P>0.05）. The absolute value of LVGLS in TOF fetuses was positively correlated with PA Z-score，MPA Z-score and PA/AO（ r = 0.313，0.344，0.304，all P<0.05），and the absolute value of RVGLS was positively correlated with PA Z-score，MPA Z-score，and PA/AO（ r = 0.323，0.334，0.357，all P<0.05）. Binary Logistic regression model analysis confirmed that LVGLS，RVFAC and PA/AO were predictive variables. ROC curve analysis showed that the areas under the curves of LVGLS，RVFAC and PA/AO for predicting TOF were 0.746，0.693 and 0.849 respectively. The combined prediction efficiency was higher，and the area under the curve was 0.906. Conclusions:Fetal HQ combined with multiple fetal echocardiographic quantification indices can evaluate the differences in fetal heart size，shape and function between TOF and mild TOF. It is expected to provide important reference information in prenatal diagnosis and consultation for fetuses with TOF and mild TOF.

Hepatocellular carcinoma (HCC) is one of the fastest growing cancers in the world, ranking fourth among the causes of cancer-induced death in the world. At present, the field of HCC treatment is developing rapidly, and immunotherapy has been recognized as a promising treatment method, in which T cells play a key role in HCC immunotherapy. However, in the case of virus infection or in tumor microenvironment (TME), T cells will be continuously stimulated by antigens and then fall into the state of T cell exhaustion (Tex). This state will not only reduce the immunity of patients but also lead to poor efficacy of immunotherapy. Therefore, to deeply analyze the mechanism of Tex and to explore effective strategies to reverse Tex is the key point in the immunotherapy for HCC. This review aims to summarize the mechanism of Tex in HCC patients, and the current situation and shortcomings of drug research and development to reverse Tex at this stage, in order to provide theoretical basis for the optimization of immunotherapy regimen for HCC patients.
Humans ; Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Immunotherapy/methods* ; T-Lymphocytes/immunology* ; Tumor Microenvironment/immunology* ; Animals ; T-Cell Exhaustion

BACKGROUND: Lung cancer has the highest mortality rate among all malignant tumors, and non-small cell lung cancer (NSCLC) accounts for about 80%-85% of all lung cancers. Lobectomy and lymph node dissection are one of the most important treatment methods, and lymph node dissection, as an important part, has attracted much attention. And its mode and scope of dissection may affect postoperative complications, particularly the occurrence of chronic cough. The aim of this study is to investigate the effect of lymph node dissection on postoperative chronic cough in patients with NSCLC undergoing lobectomy, and to provide clinical evidence for optimizing surgical strategy and reducing postoperative chronic cough. METHODS: A retrospective analysis was conducted on the clinical data of 365 NSCLC patients who underwent lobectomy at the First Affiliated Hospital of University of Science and Technology of China from December 2020 to December 2023. The relationship between clinical characteristics and postoperative chronic cough was analyzed. The Chinese version of the Leicester Cough Questionnaire (LCQ-MC) scores were collected from the patients at 2 time points: 1 day before surgery and 8 weeks after surgery. Patients were divided according to lymph node dissection methods, to explore the relationship between lymph node dissection and chronic cough after lobectomy. Additionally, patients were divided into chronic cough and non-chronic cough groups based on the presence of postoperative chronic cough, to investigate whether perioperative data, lymph node dissection methods, and lymph node dissection regions were influencing factors. RESULTS: Patients undergoing lobectomy were more likely to have chronic cough after surgery in the systematic lymph node dissection group than in the lymph node sampling group (P<0.05). LCQ-MC scale evaluation showed that the psychological, physiological, social and total score of the patients in systematic lymph node dissection group were significantly lower than those in lymph node sampling group (P<0.05). Multivariate analysis showed that anesthesia time, operation site, lymph node dissection method, whether to perform upper mediastinal lymph node dissection, number of upper mediastinal lymph node dissection, whether to perform lower mediastinal lymph node dissection and total number of lymph node dissection were independent risk factors for postoperative chronic cough in NSCLC patients (P<0.05). CONCLUSIONS When NSCLC patients underwent lobectomy, lymph node sampling was associated with a significantly lower risk of chronic cough than systematic lymph node dissection. Dissecting lymph nodes in the upper and lower mediastinal regions and the number of lymph nodes dissected may increase the risk of postoperative cough and reduce the quality of life of patients after surgery.
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Male ; Female ; Lung Neoplasms/surgery* ; Middle Aged ; Cough/etiology* ; Retrospective Studies ; Lymph Node Excision/methods* ; Aged ; Chronic Disease ; Postoperative Complications/etiology* ; Adult ; Lymph Nodes/surgery* ; Pneumonectomy/adverse effects* ; Chronic Cough

Objective To analyze the risk factors for chronic cough following pulmonary surgery in patients with non-small cell lung cancer (NSCLC). Methods A retrospective analysis was conducted on 427 NSCLC patients who underwent pulmonary surgery in the Department of Thoracic Surgery, The First Affiliated Hospital of the University of Science and Technology of China, between January 2021 and June 2023. Patients were categorized into a chronic cough group (103 patients) and a non-chronic cough group (324 patients) based on the presence of cough at 8 weeks post-surgery. A comparative analysis was performed between the two groups, considering gender, age, smoking history, comorbidities, preoperative pulmonary function indicators, pleural adhesion, anesthesia duration, surgical site, operative techniques, lymph node dissection methods, tumor maximum diameter, and postoperative chest tube duration. Factors showing statistical significance in univariate analysis underwent multivariate logistic regression analysis. Results Among the 427 patients undergoing pulmonary surgery, there were 165 males and 262 females, with an average age of (59.93±12.11) years. The incidence of chronic cough was 24.12%. Univariate analysis revealed significant differences in smoking history, preoperative pulmonary function indicators, pleural adhesion, anesthesia duration ≥135.5 minutes, surgical site, operative techniques, lymph node dissection methods, tumor maximum diameter, and postoperative chest tube duration (P<0.05). Multivariate logistic regression analysis indicated that the surgical site (right upper lung), operative techniques (lobectomy), lymph node dissection, and anesthesia time ≥135.5 minutes were independent risk factors for chronic cough following pulmonary surgery. Conclusion Patients undergoing right upper lung surgery, lobectomy, lymph node dissection, and experiencing anesthesia duration ≥135.5 minutes are at a higher risk of developing chronic cough post-pulmonary surgery.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis