BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

[摘 要] 目的：探讨程序性死亡蛋白1（PD-1）抑制剂与恶性黑色素瘤患者癌性疲劳（CRF）之间的关系及其影响因素。方法：选取2019年4月至2024年4月期间在济南市人民医院接受治疗的100例恶性黑色素瘤患者作为研究对象，使用中文版Piper疲劳量表评估这些患者在接受首次PD-1抑制剂治疗前后3个月内的疲劳状况。结果：使用PD-1抑制剂前后的患者疲劳评分存在显著差异（P < 0.001）。单变量分析发现，性别、吸烟史、肿瘤位置以及使用的PD-1抑制剂类型对于疲劳程度没有明显影响（均P > 0.05），而与年龄、疾病分期、贫血状态、白细胞减少症、继发性甲状腺机能减退（甲减）、继发性肾上腺皮质醇功能减退（AI）、继发性促肾上腺皮质激素降低（P < 0.05或P < 0.01或P < 0.001）相关联。进一步的多变量回归分析揭示，继发性甲减、继发性AI、贫血、白细胞减低是导致此类患者出现严重CRF的关键独立风险因素（均P < 0.05）。结论: PD-1抑制剂的不良反应继发性甲减、继发性AI、贫血、白细胞减低是恶性黑色素瘤患者CRF的独立风险因素。

BACKGROUND: There is little literature describing the artificial intelligence (AI)-aided diagnosis of severe pneumonia (SP) subphenotypes and the association of the subphenotypes with the ventilatory treatment efficacy. The aim of our study is to illustrate whether clinical and biological heterogeneity, such as ventilation and gas-exchange, exists among patients with SP using chest computed tomography (CT)-based AI-aided latent class analysis (LCA). METHODS: This retrospective study included 413 patients hospitalized at Xinhua Hospital diagnosed with SP from June 1, 2015 to May 30, 2020. AI quantification results of chest CT and their combination with additional clinical variables were used to develop LCA models in an SP population. The optimal subphenotypes were determined though evaluating statistical indicators of all the LCA models, and clinical implications of them such as guiding ventilation strategies were further explored by statistical methods. RESULTS: The two-class LCA model based on AI quantification results of chest CT can describe the biological characteristics of the SP population well and hence yielded the two clinical subphenotypes. Patients with subphenotype-1 had milder infections ( P <0.001) than patients with subphenotype-2 and had lower 30-day ( P <0.001) and 90-day ( P <0.001) mortality, and lower in-hospital ( P = 0.001) and 2-year ( P <0.001) mortality. Patients with subphenotype-1 showed a better match between the percentage of non-infected lung volume (used to quantify ventilation) and oxygen saturation (used to reflect gas exchange), compared with patients with subphenotype-2. There were significant differences in the matching degree of lung ventilation and gas exchange between the two subphenotypes ( P <0.001). Compared with patients with subphenotype-2, those with subphenotype-1 showed a relatively better match between CT-based AI metrics of the non-infected region and oxygenation, and their clinical outcomes were effectively improved after receiving invasive ventilation treatment. CONCLUSIONS A two-class LCA model based on AI quantification results of chest CT in the SP population particularly revealed clinical heterogeneity of lung function. Identifying the degree of match between ventilation and gas-exchange may help guide decisions about assisted ventilation.
Humans ; Tomography, X-Ray Computed/methods* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Artificial Intelligence ; Aged ; Pneumonia/diagnosis* ; Latent Class Analysis ; Adult

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

Objective:To investigate the surgical method of preoperative computed tomography angiography(CTA) combined with color Doppler ultrasonography(CDU) vascular localization assisted by downstream vascularized medial femoral condylar bone flap and its clinical effect in the treatment of refractory scaphoid fracture nonunion.Methods:Retrospective analysis of case data from January 2018 to June 2022 in the Department of Orthopedics at Xingtai General Hospital of North China Medical and Health Group, using a free medial femoral condylar bone flap with descending knee artery as the blood supply to repair old fractures of the scaphoid bone with bone damage. Prior to surgery, CTA combined with CDU technology was used to locate the descending knee artery, and the medial femoral condylar bone flap was designed based on the localization result and bone defects. Follow-up was conducted using outpatient and telephone method. The degree of wrist pain was evaluated using the visual analogue scale (VAS), wrist function was evaluated using the improved Mayo scoring method, the degree of scaphoid arch back deformity was evaluated based on the angle of the scaphoid bone, and stability between the carpal bones was evaluated based on the angle of the scaphoid moon. The normal distribution metric data was represented as Mean±SD, and paired sample t-tests were used to compare the preoperative CDU measurement and the actual intraoperative measurement of the vessel diameter at the origin of the descending knee artery, as well as the distance to the inferior edge of the medial femoral condyle. The VAS score for pain before and after surgery, the Mayo score for wrist function, wrist grip strength, range of motion, scaphoid angle, and scaphoid angle are also compared. Results:A total of 12 patients were enrolled, including 9 males and 3 females; age ranged from 23 to 56 years old, with an average of 36 years old. There were 7 cases of right side fractures, 5 cases of left side fractures, 8 cases of scaphoid waist fractures, and 4 cases of proximal pole fractures. There was no difference between the preoperative CDU location and the actual vessel diameter at the origin of the descending geniculate artery [(1.7±0.5) mm vs. (1.8±0.7) mm] and the distance to the inferior border of the medial femoral condyle [(11.9±2.1) cm vs. (12.1±1.9) cm]( P>0.05). All patients were followed up after the operation, the specific time ranged from 6 months to 2 years, with an average of 13 months. The X-ray films showed that the scaphoid bone healed in all patients after operation, and the average healing time was 15 weeks. After 6 months of follow-up, the VAS scores (3.7±0.9 vs. 0.5±0.1), Mayo scores (46.1±3.8 vs. 86.2±6.1), scapholunar angle [(65.3±4.1)° vs. (47.9±3.5)°], scaphoid angle [(37.1±3.9)° vs. (22.8±2.3)°], wrist flexion and extension range of motion [(79.0±11.7)° vs. (118.5±15.8)°], grip strength [(6.7±4.6) kg vs. (26.1±5.3) kg]were compared before and after surgery, the differences were statistically significant (all P<0.05). Conclusion:The free medial femoral condyle bone flap with a vascular pedicle is one of the ideal method to repair the old navicular fracture with osteonecrosis. The preoperative vascular positioning technique effectively guides the design and cutting of the bone flap and ensures fast and accurate operation during the operation.

Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(＜65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P＞0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein＞400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P＞0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged＜65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.

Objective:To investigate the surgical method of preoperative computed tomography angiography(CTA) combined with color Doppler ultrasonography(CDU) vascular localization assisted by downstream vascularized medial femoral condylar bone flap and its clinical effect in the treatment of refractory scaphoid fracture nonunion.Methods:Retrospective analysis of case data from January 2018 to June 2022 in the Department of Orthopedics at Xingtai General Hospital of North China Medical and Health Group, using a free medial femoral condylar bone flap with descending knee artery as the blood supply to repair old fractures of the scaphoid bone with bone damage. Prior to surgery, CTA combined with CDU technology was used to locate the descending knee artery, and the medial femoral condylar bone flap was designed based on the localization result and bone defects. Follow-up was conducted using outpatient and telephone method. The degree of wrist pain was evaluated using the visual analogue scale (VAS), wrist function was evaluated using the improved Mayo scoring method, the degree of scaphoid arch back deformity was evaluated based on the angle of the scaphoid bone, and stability between the carpal bones was evaluated based on the angle of the scaphoid moon. The normal distribution metric data was represented as Mean±SD, and paired sample t-tests were used to compare the preoperative CDU measurement and the actual intraoperative measurement of the vessel diameter at the origin of the descending knee artery, as well as the distance to the inferior edge of the medial femoral condyle. The VAS score for pain before and after surgery, the Mayo score for wrist function, wrist grip strength, range of motion, scaphoid angle, and scaphoid angle are also compared. Results:A total of 12 patients were enrolled, including 9 males and 3 females; age ranged from 23 to 56 years old, with an average of 36 years old. There were 7 cases of right side fractures, 5 cases of left side fractures, 8 cases of scaphoid waist fractures, and 4 cases of proximal pole fractures. There was no difference between the preoperative CDU location and the actual vessel diameter at the origin of the descending geniculate artery [(1.7±0.5) mm vs. (1.8±0.7) mm] and the distance to the inferior border of the medial femoral condyle [(11.9±2.1) cm vs. (12.1±1.9) cm]( P>0.05). All patients were followed up after the operation, the specific time ranged from 6 months to 2 years, with an average of 13 months. The X-ray films showed that the scaphoid bone healed in all patients after operation, and the average healing time was 15 weeks. After 6 months of follow-up, the VAS scores (3.7±0.9 vs. 0.5±0.1), Mayo scores (46.1±3.8 vs. 86.2±6.1), scapholunar angle [(65.3±4.1)° vs. (47.9±3.5)°], scaphoid angle [(37.1±3.9)° vs. (22.8±2.3)°], wrist flexion and extension range of motion [(79.0±11.7)° vs. (118.5±15.8)°], grip strength [(6.7±4.6) kg vs. (26.1±5.3) kg]were compared before and after surgery, the differences were statistically significant (all P<0.05). Conclusion:The free medial femoral condyle bone flap with a vascular pedicle is one of the ideal method to repair the old navicular fracture with osteonecrosis. The preoperative vascular positioning technique effectively guides the design and cutting of the bone flap and ensures fast and accurate operation during the operation.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Objective:To design an improved lamina hook system and compare its biomechanical properties with traditional lamina hook system in fixation of lumbar spondylolysis.Methods:The thin layer CT data of the lumbosacral vertebrae of 20 healthy young male servicemen who underwent physical examination in the outpatient department of the 940th Hospital of Joint Logistics Support Force of PLA from January 2021 to August 2022 were collected. The age of the subjects was 20-30 years [(25.0±3.0)years]. A 3-dimensional model of the L 5 vertebral body was constructed using the 3-dimensional modeling software. The new improved lamina hook was designed according to the measurements including the thickness of the middle area, the longest longitudinal diameter, the curvature radius of the lower edge, the angle between the upper and lower tail ends, the thickness of the lower edge, and the longest diameter of the lower edge of the bilateral L 5 vertebral plates. One serviceman was selected from the aforementioned group to construct a linear finite element model of segments L 4-S using the 3-dimensional virtual software (normal model, model A), based on which, the L 5 bilateral spondylolysis model (model B), improved lamina hook model (model C) and traditional lamina hook models (model D) were designed. By constraining both sides of the sacrum and applying a longitudinal load of 400 N on the L 4 vertebral body, the upper 1/3 gravity of the body was simulated, and with a bending moment of 10 N·m along the X, Y, and Z directions, motions of forward flexion, backward extension, lateral bending, rotation, etc were simulated. The range of motion of segment L 4/5 and L 5/S 1 of model A was evaluated and compared with the findings of the previous researches to verify its effectiveness. The overall range of motion of models A, B, C, and D, the range of motion of segment L 4/5 and L 5/S 1, the maximum overall displacement, the maximum displacement and stress of the isthmus, the stress distribution and maximum stress of internal fixation of models C and D, and the stress distribution and maximum stress of the vertebral body of models C and D were compared. Results:(1) During forward flexion, backward extension, lateral bending and rotation, the range of motion of model A was 5.01°, 4.03°, 3.91° and 1.42° in segment L 4/5, and was 4.62°, 2.51°, 2.40° and 1.23° in segment L 5/S 1. (2) The overall range of motion, range of motion of segment L 4/5 and L 5/S 1 and maximum overall displacement of models A, C, and D were similar in axial compression, forward flexion, backward extension, left bending, and left rotation, while those of model B were significantly increased. (3) There was no significant difference in the maximum displacement of the isthmus of models A, C, and D under different motion modes, while the maximum displacement of model B in the isthmus was significantly larger than that of models A, C, and D, especially during rotation, increased by 295%, 277%, and 276% respectively. The maximum stress of the isthmus of model C was 0.938 MPa, 1.698 MPa, 0.410 MPa, 2.775 MPa, and 1.554 MPa respectively. The maximum stress in the isthmus of model D was 0.590 MPa, 1.297 MPa, 0.520 MPa, 3.088 MPa, and 2.072 MPa respectively. The maximum stress of the isthmus of models C and D was similar during axial compression and forward flexion, while the stress of the isthmus of model C was smaller than that of model D during backward extension, lateral bending, and rotation, decreased by 21.1%, 10.2%, and 25.0% respectively compared with model D. (4) The maximum stress of internal fixation in models C and D during forward flexion, backward extension, left bending, and left rotation was 135.220 MPa, 130.180 MPa, 200.940 MPa and 306.340 MPa respectively, and was 131.840 MPa, 112.280 MPa, 349.980 MPa and 370.140 MPa respectively. The maximum stress of internal fixation in the two models of internal fixation during forward flexion and backward extension was similar, while it was decreased by 42.6% and 17.2% in model C during left bending and left rotation, compared with model D. (5) The maximum stress of the vertebral body during forward flexion, backward extension, left bending, and left rotation was 79.787 MPa, 36.857 MPa, 37.943 MPa and 96.965 MPa respectively in model C, but was 80.104 MPa, 64.236 MPa, 196.010 MPa and 193.020 MPa respectively in model D. The maximum stress of models C and D was all distributed in the contact area with the internal fixation, and especially during backward extension, left bending, and left rotation, when it was reduced by 42.6%, 80.6%, and 49.8% of model C respectively, compared with that of model D. Conclusions:The improved laminar hook is more consistent with the Chinese anatomized structure of the lamina. Compared with the traditional lamina hook system, the improved lamina hook system can effectively reduce the displacement in all directions and range of motion of lumbar spondylolysis, therefor can significantly reduce the stress of internal fixation and vertebral body and has better biomechanical performance.