Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

OBJECTIVE: CRISPR-Cas protects bacteria from exogenous DNA invasion and is associated with bacterial biofilm formation and pathogenicity. METHODS: We analyzed the type I-F CRISPR-Cas system of Legionella pneumophila WX48, including Cas1, Cas2-Cas3, Csy1, Csy2, Csy3, and Cas6f, along with downstream CRISPR arrays. We explored the effects of the CRISPR-Cas system on the in vitro growth, biofilm-forming ability, and pathogenicity of L. pneumophila through constructing gene deletion mutants. RESULTS: The type I-F CRISPR-Cas system did not affect the in vitro growth of wild-type or mutant strains. The biofilm formation and intracellular proliferation of the mutant strains were weaker than those of the wild type owing to the regulation of type IV pili and Dot/Icm type IV secretion systems. In particular, Cas6f deletion strongly inhibited these processes. CONCLUSION The type I-F CRISPR-Cas system may reduce biofilm formation and intracellular proliferation in L. pneumophila.
Legionella pneumophila/pathogenicity* ; CRISPR-Cas Systems ; Biofilms/growth & development* ; Phenotype ; Bacterial Proteins/metabolism* ; Gene Deletion

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Bone grafting is a primary method for treating bone defects. Among various graft materials, xenogeneic bone substitutes are widely used in clinical practice due to their abundant sources, convenient processing and storage, and avoidance of secondary surgeries. With the advancement of domestic production and the limitations of imported products, an increasing number of bone filling or grafting substitute materials isentering clinical trials. Relevant experts have drafted this consensus to enhance the management of medical device clinical trials, protect the rights of participants, and ensure the scientific and effective execution of trials. It summarizes clinical experience in aspects, such as design principles, participant inclusion/exclusion criteria, observation periods, efficacy evaluation metrics, safety assessment indicators, and quality control, to provide guidance for professionals in the field.
Humans ; Bone Substitutes/therapeutic use* ; Randomized Controlled Trials as Topic/methods* ; Consensus ; Bone Transplantation ; Research Design

OBJECTIVE: To explore prevalence, incidence and possible factors of immediate herniated discs after posterior cervical expansive open-door laminoplasty (EODL). METHODS: Totally 29 patients with cervical spinal stenosis and intervertebral disc herniation who underwent EODL from October 2020 to December 2021 were collected, including 24 males and 5 females, aged from 43 to 81 years old with an average of (61.3±9.0) years old;the courses of disease ranged from 1 to 120 months with an average of (36.4±37.0) months. Three or more intervertebral discs on C₃-C₇ were observed. The clinical efficacy was evaluated according to Japanese Orthopaedic Association (JOA) score before operation, 3 days and 1, 3, 6 and 12 months after operation, respectively. The changes of herniated disc before and after operation were measured by multipoint area method and two-dimensional distance method, and incidence and percentage of herniated disc regression were further calculated. Cervical imaging parameters such as Cobb angle (C₃-C₇), intervertebral angle, T₁ slope (T₁S), spinal canal sagittal diameter, K-line angle, dural sac sagittal diameter were measured and compared before and after operation. Pearson correlation was used to analyze correlation between cervical sagittal imaging parameters and disc herniation changes before and after operation. RESULTS: All patients obtained grade A wound healing, and 14 of them were followed up for 3(1.00, 5.25) months. There were no immediate or long-term postoperative complications. Totally 101 herniated intervertebral discs were measured, of which 79 regression numbers were obtained by area measurement. The number of intervertebral disc regressions by distance measurement was 77. There was no statistically significant difference in Cobb angle, intervertebral angle, T₁S and K-line angle of C₃-C₇ (P>0.05), however, there were statistically significant differences in sagittal diameter of spinal canal, sagittal diameter of dural sac, and JOA score before and after operation(P<0.05). The regression ratio of disc herniation ranged from 5% to 50%, and regression ratio of disc herniation was greater than 25% in 45.57%(36/79). Disc herniation in C_4,5 was positively correlated with sagittal plane diameter in C₅(r=0.423, P=0.028). There was a negative correlation between changes of C_3,4 and C_3,4 intervertebral angle (r=-0.450, P=0.041). The improvement rate of cervical JOA score immediately after operation was (59.54±15.07) %, and postoperative follow-up improved to (76.57±14.66) %. CONCLUSION Herniated disc regression immediately after EODL is a common occurrence, and EODL should be selected as far as possible under the premise of satisfying surgical indications. The regression of disc herniation is positively correlated with spinal canal sagittal diameter, and spinal canal should be enlarged as far as possible in the appropriate scope during EODL, so as to create more opportunities and conditions for disc regression and achieve better clinical results.
Humans ; Female ; Male ; Intervertebral Disc Displacement/diagnostic imaging* ; Spinal Stenosis/diagnostic imaging* ; Laminoplasty/methods* ; Middle Aged ; Aged ; Cervical Vertebrae/diagnostic imaging* ; Adult ; Aged, 80 and over ; Intervertebral Disc/surgery*

OBJECTIVE: To explore the current research status and hotspots in the field of biomechanics of diabetic foot by bibliometric analysis methods. METHODS: Literatures related to biomechanics of diabetic foot published in the Web of Scienc Core Collection (WoSCC) from 1981 to 2024 were searched. CiteSpace software and R language bibliometrics plugin were used to conduct a visual analysis of annual publication volume of the literature, including publication volume of each country and region, the publication situation of authors and institutions, the citation situation of individual literature, and the co-occurrence network of keywords. RESULTS: Totally 996 literatures were included, and the number of published papers increased steadily. The United States (261 papers) and China (89 papers) were the top two countries in terms of the number of published papers. The mediating centrality of the United States was 0.94, and that of China was 0.01. Scholars such as Cavanagh and institutions like the Cleveland Clinic were at the core of research in this field. High-frequency keywords include plantar pressure (plantar pressure), diabetic foot (diabetic foot), ulceration (ulcer), etc. The research focuses on plantar pressure, ulcer formation and prevention, etc. CONCLUSION Biomechanical research on diabetic foot mainly focuses on the pressure distribution on the sole of the foot, callus formation, mechanical analysis of soft tissues on the sole of the foot, and the study of plantar decompression caused by Achilles tendon elongation. The research trend has gradually shifted from focusing on joint range of motion to gait and the design of braces and assistive devices, and has begun to pay attention to muscle strength, gait imbalance and proprioception abnormalities.
Humans ; Diabetic Foot/physiopathology* ; Biomechanical Phenomena ; Bibliometrics

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Objective:To investigate the application of the parameters of multimodal ultrasound elastography in differential diagnosis for thyroid nodules of patients with diffuse thyroid lesions.Methods:A total of 103 patients with diffuse thyroid lesions who underwent treatment at Affiliated Baoji Hospital of Xi′an Medical University from January 2023 to January 2024 were retrospectively selected,whose thyroid nodules were confirmed by fine needle aspiration biopsy or surgical pathology.They were grouped according to the benign or malignant nodules.56 patients with benign nodules were included in the benign nodule group,while the other 47 patients were included in the malignant nodule group.All patients were examined by conventional ultrasound and multimodal ultrasound elastography,and the relevant parameters were recorded to compare the differences between the two groups.The value of each indicator in diagnosing benign and malignant thyroid nodules was investigated.Results:There were no statistically significant differences between the benign and malignant nodule groups in terms of gender,length diameter of nodule,nodule location,functional abnormalities of thyroid,exposure history of radiation,and the presence of acoustic halos(P＞0.05),the age of patients in the malignant nodule group was lower than that of the benign nodule group(t=-3.121,P＜0.05),and the percentage of nodules with blood flow(14.89%),the percentage of aspect ratio＜1(74.47%),and the percentage of nodules with clear boundary(27.66%)in the malignant nodule group were all lower than those of the benign nodule group,with statistically significant differences(x2=25.634,5.112,12.465,P＜0.05).The ratio of lymphatic metastasis(27.66%)and that of calcification(65.96%)in the malignant nodule group were lower than those in the benign nodule group,and the differences were all statistically significant(x2=11.917,9.350,P＜0.05).The ratios of centripetal enhancement(76.60%),inhomogeneous enhancement(68.09%),low/equal enhancement(87.23%),early obvious discharge(63.83%),unclear boundary after enhancement(91.49%),and fast discharge(59.57%)in the malignant nodule group were higher than that of the benign nodule group,and the differences were statistically significant(x2=33.409,26.695,9.079,12.853,17.798,12.649,P＜0.05),respectively.The intensity and time to peak of the malignant nodule group were respectively lower and long than these of the benign nodule group,and the differences were statistically significant(t=-12.381,4.958,P＜0.05).However,the mean passage time of the two groups was not statistically significant(P＞0.05).The maximum value,minimum value and mean value of Young's modulus,the maximum value of vertical section,mean value of vertical section,maximum value of cross section,mean value of cross section in the malignant nodule group were all higher than those in the benign nodule group,and the differences were statistically significant(t=13.997,9.100,12.191,7.616,6.310,4.679,5.355,P＜0.05).The result of receiver operating characteristic(ROC)curve analysis indicated that both ultrasonography parameters and shear wave elastography(SWE)parameters had higher diagnostic value for the benign and malignant nature of thyroid nodules in patients.The area under curve(AUC)values of intensity to peak,time to peak,and the maximum value,minimum value and mean value of Young's modulus,and the maximum value of vertical section,mean value of vertical section,maximum value of cross section,mean value of cross section were respectively 0.976,0.759,0.974,0.837,0.989,0.872,0.805,0.732 and 0.749.Conclusion:Multimodal ultrasound elastography parameters has significant application value in differential diagnosis for thyroid nodules in patients with diffuse thyroid lesions.In these parameters,the diagnostic AUC values of intensity to peak,time to peak,and the maximum value and mean value of Young's modulus are higher for malignant thyroid nodules of patients,which have higher diagnostic efficiency.It can effectively help clinical doctor to accurately identify the benign and malignant nodules for patients with diffuse thyroid lesions.

Objective:To explore the application value of Superb microvascular imaging(SMI)technique in diagnosing diffuse thyroid disease with thyroid nodules,and the assessment for treatment efficacy.Methods:A total of 100 patients with diffuse thyroid disease with thyroid nodules(132 nodules),who were treated at the Baoji Hospital Affiliated to Xi'an Medical University from March 2020 to November 2024,were selected.The dual examination of SMI and conventional Color Doppler Flow Imaging(CDFI)were conducted on them.The nature of the nodules was confirmed by pathological examination.The diagnostic sensitivity,specificity and predictive value of SMI and CDFI were analyzed by using the receiver operating characteristic(ROC)curve.A series of conventional indicators,including blood flow volume,blood flow velocity,pattern of blood flow distribution,and vascular morphology,between the two imaging techniques were compared and analyzed.Results:In the 132 thyroid nodules that were detected by pathological examination,SMI identified 94 benign lesions(71.21%)and 38 malignant lesions(28.79%).The sensitivity and specificity of SMI were respectively 94.68%and 89.47%in diagnosing diffuse thyroid disease with thyroid nodules,both of them were higher than those(84.05%and 78.95%)of CDFI,and the sensitivity of SMI diagnosis was significantly higher than that of CDFI diagnosis,and the difference was statistically significant(x2=5.595,P<0.05).The nodule size as SMI diagnosis was(14.62±2.36)mm,which was significantly smaller than(16.35±4.45)mm as CDFI diagnosis,and the difference was statistically significant(x2=3.330,P<0.05).Blood flow velocity and blood flow volume of SMI diagnosis were significantly higher than those of CDFI diagnosis,and the differences were statistically significant(t=5.718,6.567,P<0.05).The detection rates of blood flow distribution mode and vascular morphology of SMI mode were significantly higher than those of CDFI mode,and the differences were statistically significant(x2=9.192,4.776,P<0.05).However,there were not statistically significant differences were observed between the two imaging techniques in terms of the shape,echo type and internal calcification of nodules(P>0.05).Conclusion:SMI technique has a significant advantage in diagnosis and assessment for diffuse thyroid disease with thyroid nodules.It can more accurately assess the hemodynamic changes of the nodules,and provide more reliable diagnostic information for clinical treatment.