Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective To investigate the expression of SORT1 in the gastric cancer tissue and analyze its relationship with clinical prognosis of patients as well as the pathways and mechanisms involved in gastric cancer progression.Methods The Gene Expression Profiling Interaction Analysis database,Western blot,and immunohistochemistry were employed to predict and analyze the expression of SORT1 in the gastric cancer and the adjacent tissue.The clinical case information of 109 patients who underwent radical surgery for gastric cancer in the First Affiliated Hospital of Bengbu Medical University from April 2015 to April 2017 was collected to analyze the relationship of SORT1 with the clinicopathological parameters and prognosis of the patients.Cell proliferation was detected by the CCK-8 assay and colony formation assay,while cell migration and invasion were assessed by the scratch assay and Transwell assay,respectively.Western blot was employed to determine the expression of proteins related to epithelial-mesenchymal transition(EMT)in gastric cancer cells,followed by further analysis on molecular mechanism through which SORT1 regulates EMT in gastric cancer cells.Results Western blot and immunocytochemistry results showed that SORT1 was highly expressed in the gastric cancer tissue(P=0.003,P<0.001),which was positively correlated with malignant progression of tumors(all P<0.05).The Kaplan-Meier survival analysis revealed shortened postoperative survival periods for the patients with high expression of SORT1(P<0.001).The Cox regression model indicated that SORT1 expression was an independent risk factor affecting the 5-year survival rate after surgery for gastric cancer patients(P<0.001).Up-regulation of SORT1 expression promoted the proliferation,migration,invasion,and EMT of gastric cancer cells(all P<0.05),while down-regulation of SORT1 showed the opposite effects(all P<0.05).Western blot results showed that high expression of SORT1 promoted the expression of β-catenin,cyclin D1,and c-Myc(all P<0.05).Moreover,in vitro use of the Wnt/β-catenin pathway inhibitor(XAV939)effectively suppressed the EMT enhancement caused by high expression of SORT1 in gastric cancer cells(all P<0.05).Conclusions SORT1 is highly expressed in gastric cancer and affects patients' postoperative survival periods.It is involved in the proliferation,migration,and invasion of gastric cancer cells and may promote the EMT of gastric cancer cells by activating the Wnt/β-catenin pathway.
Humans ; Stomach Neoplasms/pathology* ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Cell Movement ; Prognosis ; Cell Line, Tumor ; Adaptor Proteins, Vesicular Transport/metabolism* ; Male ; Female ; Middle Aged

OBJECTIVE: To explore the relationship between the effect of acupuncture and layered localization of computed tomography (CT) in treatment of lumbar disc herniation. METHODS: Based on the CT layered localization, the herniated lumbar discs were positioned in 5 layers, A, B, C, D and E among 300 patients with lumbar disc herniation. Combined with the horizontal and the frontal planes, the three-dimensional location was formed. Acupuncture was delivered at acupoints including bilateral Shenshu (BL23), Dachangshu (BL25), and Huantiao (GB30), Weizhong (BL40) on the affected side. One intervention of acupuncture was 30 min, once daily; 1 course of treatment was composed of 10 interventions and 2 courses were required. Before and after treatment, Japanese orthopaedic association (JOA) score was recorded, and the effect was evaluated. The curative effect was classified and compared with the CT layered localization. RESULTS: Of 300 patients, 226 cases were effective and the effective rate was 75.33%. The JOA scores of all patients, and in the effective group and the non-effective group were higher compared with the scores before treatment (P<0.05). With the layered localization considered, acupuncture was more effective on the cases positioned in C layer. Regarding the horizontal plane, the effect was better on the cases with zone 1 and zone 1-2 involved. In terms of the grade of frontal plane, acupuncture was more effective on the cases graded Ⅰ and Ⅱ. CONCLUSION The clinical effect of acupuncture on lumbar disc herniation is related with the layer and the horizontal zone of herniated disc positioned, as well as to the grade of the frontal plane.
Humans ; Acupuncture Therapy ; Intervertebral Disc Displacement/diagnostic imaging* ; Male ; Female ; Middle Aged ; Adult ; Tomography, X-Ray Computed ; Lumbar Vertebrae/diagnostic imaging* ; Acupuncture Points ; Aged ; Young Adult ; Treatment Outcome

OBJECTIVE: To investigate the effects of bone density, plate bending degree and proximal screw type on the stress fracture of clavicle hook. METHODS: Three sows weighing between 45 and 50 kg were selected, from which a total of 40 rivs were collected. The 15 ribs of sows were divided into 3 groups according to bone density and bone hardness with 5 rivs in each group. And then the 3 groups were fixed with 6-hole collarbone hook plates and 3 locking screws. Measure the maximum torsion force when the ribs were fractured by force. The same size 15 rids were divided into 3 groups, named forward bending group, 0° group(the angle between the plate surface and the rib surface) and reverse bending group. All fixed with 6-hole collarbone hook plates and locking screws to measure the maximum torsion force of rib stress fracture. Then the same size 10 rids were divided into 2 groups, the normal screw group and the locking screw group with 5 ribs in each group. Both groups were fixed with 6-hole collarbone hook plates and screws. The normal screw group was a normal screw, fixed in proximal end, and two locking screws. The locking screw group was fixed by locking screws. Measure the maximum torsion force of the two groups when the ribs fracture by force. RESULTS: In the bone density experiment, the torque force of hard bone group (104.51±6.27) N was greater than the normal bone group (75.04±3.81) N(t=8.979, P<0.05). The force of normal bone group was greater than the osteoporosis group (49.99±2.12) N(t=12.832, P<0.05). In the bending collarbone hook experiment, the order of the torque force generated by each group as follow:the forward bending group (343.59±6.18) N greater than the 0° group (106.01±5.29) N(t=65.279, P<0.05) greater than the reverse bending group (95.82±4.12) N(t=3.398, P<0.05). The force of the normal screw group (98.68±0.70) N was greater than the locking screw group (50.20±0.95) N(t=91.484, P<0.05). The data comparisons of each group were statistically significant. CONCLUSION Bone density, plate bending degree and proximal screw type had an impact on stress fracture of clavicle hook plate. Higher bone density, forward bending of the steel plate, and ordinary screws in proximal end can reduce the rates of stress fractures of clavicle hooks.
Animals ; Bone Plates ; Clavicle/surgery* ; Swine ; Fractures, Stress/etiology* ; Female ; Risk Factors ; Fracture Fixation, Internal/instrumentation* ; Bone Screws ; Biomechanical Phenomena ; Bone Density

OBJECTIVE: To compare the bone cement diffusion and clinical effects between conventional percutaneous vertebroplasty(PVP) and the application of positioning reduction and targeted puncture techniques in the treatment of elderly patients with osteoporotic vertebral compression fractures. METHODS: A retrospective comparative study was conducted, analyzing the clinical data of 268 elderly patients with single-level vertebral fractures admitted between January 2021 and March 2023. The patients were divided into two groups:the conventional PVP group (138 cases) and the targeted PVP group (130 cases). Among them, 138 patients in the conventional group were treated by traditional PVP with bilateral approach including 26 males and 112 females, with a mean age of (72.9±4.0) years old. Another 130 patients in the targeted PVP group included 23 males and 107 females, with a mean age of (72.2±7.0) years old;vertebral reduction was first achieved using prone traction and compression reduction technique based on preoperative imaging examination, the operating bed was used to maintain spinal hyper-extension of the spine and puncture the fracture space target to inject bone cement. The adequacy of bone cement filling in the fracture gap was evaluated based on imaging examination. The operation time, the rate of bone cement leakage and the type of leakage, bone cement filling in the fracture area, the amount of cement injection, the thoracolumbar back pain visual analogue scale(VAS), Oswestry disability index(ODI), and the local kyphosis Cobb angle of the fractured vertebra were compared between two groups. RESULTS: The operation time (43.9±5.7) min, bone cement filling (5.3±1.5) ml in the conventional PVP group were higher than the target group (39.3±3.6) min, (4.1±1.7) ml(P<0.05). There were no statistically significant differences in bone cement leakage rate or type(P>0.05). The targeted PVP group achieved sufficient bone cement filling in the fracture area, while the conventional PVP group had 34 cases (25.0%) with insufficient filling in the fracture area(P<0.01). There was no significant difference in VAS, ODI, and local Cobb angle of the fractured vertebra before operation between two groups(P>0.05). The VAS of 3.64±0.94 and ODI of 11.50±0.38 at 3 day after operation in the target group were better than those of the conventional group 4.69±0.78 and 15.06±1.66 (P<0.05). The local Cobb angle (7.51±5.37)° was less than that of the conventional group (11.68±3.98)°(P<0.05). CONCLUSION The application of positioning reduction and targeted puncture techniques in percutaneous vertebroplasty for elderly patients with osteoporotic vertebral compression fractures can restore vertebral height using positioning reduction technique to avoid excessive tension on the intervertebral soft tissue. Targeted puncture technique effectively stabilizes vertebral fractures and achieves adequate bone cement filling, thereby improving surgical outcomes. This technique is safe and effective, representing a new treatment modality.
Humans ; Male ; Female ; Vertebroplasty/methods* ; Aged ; Fractures, Compression/surgery* ; Retrospective Studies ; Spinal Fractures/surgery* ; Osteoporotic Fractures/surgery* ; Aged, 80 and over ; Bone Cements ; Middle Aged

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Objective:To evaluate the detection rate, anatomical distribution, and influencing factors of bone marrow edema-like signal (BMELS) in the knees of amateur marathon runners.Methods:This was a cross-sectional study. This study publicly recruited amateur marathon runners through the Hangzhou Long-distance Running Association from January 2019 to December 2024. Based on knee magnetic resonance imaging (MRI) results, participants were divided into a BMELS-positive group (BMELS present in at least one knee) and a BMELS-negative group. General clinical information was collected from participants using a questionnaire. All participants underwent a knee MRI scan to screen for the presence of BMELS and to assess its severity. Logistic regression models were used to analyze the associated factors of BMELS in amateur marathon runners, while Spearman′s correlation analysis assessed the correlation between BMELS grade and these factors.Results:A total of 60 subjects (120 knee joints) were enrolled, including 39 males (65%), aged (40.0±8.4) years. Of these, 39 were in the BMELS-positive group, and 21 were in the BMELS-negative group. The BMELS detection rate for the 120 knee joints of these 60 subjects was 53.3% (64/120). BMELS were detected in 43.3%(52/120) of the femur, 34.2% (41/120) of tibia and 17.5% (21/120) of patella. Multivariate logistic regression analysis showed an independent positive correlation between monthly running volume and knee BMELS in amateur marathon runners ( OR=1.007, 95% CI: 1.000-1.013, P=0.035). Spearman′s correlation analysis showed a weak positive correlation between the BMELS grade of the knees and the monthly running volume of amateur marathon runners ( r s=0.360, P=0.005). Conclusions:The detection rate of knee BMELS is high in amateur marathon runners, and they are distributed in a way that is characteristic of the region, with a higher incidence in the medial femoral condyle. In this population, monthly running volume is independently associated with knee BMELS, with a higher grade associated with greater monthly running volume.

Objective To establish a highly sensitive and specific method for detecting human DNA based on real time quantitative PCR(qPCR)technique for the rapid detection of potential DNA con-tamination sources in DNA laboratories.Methods Primers and probes were designed with Primer Ex-pressTM software using the reference sequence of human 18S rRNA gene as a template,and the opti-mal prime-probe combination was screened by matrix method.The PCR products of the target se-quence of human 18S rRNA gene were used to construct the plasmid,and a plasmid standard was used to draw the standard curve of the qPCR system.According to the Minimum Information for Pub-lication of Quantitative Real-time PCR Experiments(MIQE)guidelines,the specificity,sensitivity,re-peatability and application effect of the qPCR system were evaluated.Results The sensitivity of the qPCR system established in this study was 5.3×10-5 ng/μL,which showed good specificity for human DNA samples.The correlation coefficient of the qPCR system was-0.999,and amplification efficiency was 100％.Both the intra-batch and inter-batch variation coefficients were less than 2％.Conclusion The established human DNA detection method based on qPCR technique has good specificity,high sen-sitivity,and robust stability.It can be used for rapid detection of DNA contamination and daily moni-toring of the accumulated human DNA in the laboratory environment.