BACKGROUND: Neuroticism has been associated with numerous health outcomes. However, most research has focused on a single specific disorder and has produced controversial results, particularly regarding mortality risk. Here, we aimed to examine the association of neuroticism with morbidity and mortality and to elucidate how neuroticism affects trajectories from a healthy state, to one or more neuroticism-related disorders, and subsequent mortality risk. METHODS: We included 483,916 participants from the UK Biobank at baseline (2006-2010). Neuroticism was measured using the Eysenck Personality Questionnaire. Three clusters were constructed, including worry, depressed affect, and sensitivity to environmental stress and adversity (SESA). Cox proportional hazards regression and multistate models were used. Linear regression was used to examine the association between neuroticism and immune parameters and neuroimaging measures. RESULTS: High neuroticism was associated with 37 non-overlapping diseases, including increased risk of infectious, cardiometabolic, neuropsychiatric, digestive, and respiratory diseases, and decreased risk of cancer. After adjustment for sociodemographic variables, physical measures, healthy behaviors, and baseline diagnoses, moderate-to-high neuroticism was associated with a decreased risk of all-cause mortality. In multistate models, high neuroticism was associated with an increased risk of transitions from a healthy state to a first neuroticism-related disease (hazard ratio [HR] [95% confidence interval (CI)] = 1.09 [1.05-1.13], P  <0.001) and subsequent transitions to multimorbidity (1.08 [1.02-1.14], P  = 0.005), but was associated with a decreased risk of transitions from multimorbidity to death (0.90 [0.84-0.97], P for trend = 0.006). The leading neuroticism cluster showing a detrimental role in the health-illness transition was depressed affect, which correlated with higher amygdala volume and lower insula volume. The protective effect of neuroticism against mortality was mainly contributed by the SESA cluster, which, unlike the other two clusters, did not affect the balance between innate and adaptive immunity. CONCLUSION This study provides new insights into the differential role of neuroticism in health outcomes and into new perspectives for establishing mortality prevention programs for patients with multimorbidity.
Humans ; Neuroticism/physiology* ; Male ; Female ; Middle Aged ; Aged ; Proportional Hazards Models ; Surveys and Questionnaires ; Adult ; Risk Factors

BACKGROUND:For thoracolumbar spine fractures with developmental stenosis of the vertebral arch,accurate nail placement is difficult using traditional fluoroscopy-assisted techniques.O-arm navigation assistance systems offer higher precision in general vertebral arch nail placement,but there is scarce literature on the application of O-arm navigation-assisted nail placement in thoracolumbar spine fractures with developmental stenosis of the vertebral arch both domestically and abroad. OBJECTIVE:To explore the accuracy of percutaneous vertebral arch nail placement assisted by O-arm navigation in patients with thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch. METHODS:A retrospective analysis was conducted on 53 patients who underwent percutaneous vertebral arch screw fixation surgery at Department of Orthopedics,General Hospital of Central Theater Command of PLA for thoracolumbar spine fractures complicated by developmental stenosis of the vertebral arch from January 2021 to March 2023.Totally 208 cases of vertebral arch developmental stenosis were found(cases with multiple vertebral arch developmental stenosis were counted separately).Based on the surgical approach,the patients were divided into two groups:O-arm navigation group(n=98)and C-arm fluoroscopy group(n=110).Postoperative imaging data were compared between the two groups,including anatomical perforation score,functional perforation score,actual vs.expected nail trajectory in the horizontal plane,and sagittal plane angle differences. RESULTS AND CONCLUSION:(1)There was no significant difference in the narrowest width of the pedicle isthmus(pow)between the two groups of patients(P>0.05).The proportions of different degrees of narrowing(mild:6 mm≤pow<7 mm,moderate:5 mm≤pow<6 mm,severe:pow<5 mm)were also not significantly different between the two groups(P>0.05).(2)The overall grade and scores of anatomical perforation and functional perforation were lower in the O-arm group compared to the C-arm group,and these differences were statistically significant(P<0.001).In terms of the angular deviation between the actual and planned screw trajectories,the O-arm group had smaller deviations,and these differences were statistically significant(P<0.05).(3)In the mild and moderate narrowing groups,the O-arm group showed significant advantages in anatomical perforation,functional perforation,and angular deviation between actual and planned screw trajectories,and these differences were statistically significant(P<0.001).(4)The O-arm group demonstrated better performance in anatomical perforation and functional perforation,especially in the T12-L2 segment,with more significant advantages.Additionally,the O-arm group had better angular deviations in actual and planned screw trajectories in all segments compared to the C-arm group.(5)Therefore,the use of O-arm navigation-assisted percutaneous screw placement for the treatment of thoracolumbar fractures with developmental pedicle isthmal narrowing provides higher accuracy and safer surgery.

OBJECTIVE: To explore the anatomical parameters of the cervical uncinate process "inflection point" through cervical CT angiography (CTA) and MRI measurements, offering a reliable and safe anatomical landmark for anterior cervical decompression surgery. METHODS: A retrospective analysis was conducted on the cervical CTA and MRI imaging data of normal adults who met the selection criteria between January 2020 and January 2024. The CTA dataset included 326 cases, with 200 males and 126 females, aged 22-55 years (mean, 46.7 years). The MRI dataset included 300 cases, with 200 males and 100 females, aged 18-55 years (mean, 43.7 years). Based on the CTA data, three-dimensional models of C ₃-C ₇ were constructed, and the following measurements were obtained from the superior view: uncinate process "inflection point" to vertebral artery distance (UIVD), uncinate process tip to vertebral artery distance (UTVD), uncinate process "inflection point" to "inflection point" distance (UID), uncinate process long-axis to sagittal angle (ULSA), and uncinate process "inflection point" to transverse foramen-sagittal angle (UITSA). From the anterior view, the anterior uncinate process to sagittal angle (AUSA) was measured. From the posterior view, the posterior uncinate process to sagittal angle (PUSA) was measured. Based on the MRI data, uncinate process "inflection point" to dural sac distance (UIDD) and dural sac width (DSW) were measured. The trends in measurement parameters of C ₃-C ₇ were observed, and the differences in measurement parameters between genders and between the left and right sides of the same segment were compared, as well as the difference in UID and DSW within the same segment was compared. RESULTS: The measurement parameters from C ₃ to C ₇ in the CTA data showed a general increasing trend, with no significant difference between the left and right sides within the same segment ( P>0.05). The UIVD, UTVD, and UID were greater in males than in females, with significant differences observed in the UIVD and UTVD at C ₃ and C ₆ and UID at C ₃, C ₆, and C ₇ ( P<0.05). The MRI measured DSW showed a general increasing trend from C ₃ to C ₇, and the DSW at C ₆ was greater in females than in males, with a significant difference ( P<0.05). The UIDD showed a gradual decreasing trend, with the smallest value at C ₆. There was no significant difference between males and females or between the left and right sides within the same segment ( P>0.05). The UID was greater than the DSW at C ₃-C ₇, and the differences were significant ( P<0.05). CONCLUSION The uncinate process "inflection point" is a constant anatomical structure located at the anteromedial aspect of the uncinate process tip and laterally to the dural sac. It maintains a certain safe distance from the vertebral artery. As a decompression landmark in anterior cervical spine surgery, it not only ensures surgical safety but also guarantees complete decompression.
Humans ; Adult ; Male ; Female ; Middle Aged ; Retrospective Studies ; Cervical Vertebrae/surgery* ; Magnetic Resonance Imaging ; Decompression, Surgical/methods* ; Young Adult ; Adolescent ; Computed Tomography Angiography ; Imaging, Three-Dimensional ; Vertebral Artery/anatomy & histology* ; Anatomic Landmarks/diagnostic imaging*

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

BACKGROUND:Steroid-induced avascular necrosis of the femoral head is a common progressive,crippling and high incidence of non-traumatic osteonecrosis of the femoral head,but its exact pathogenesis is not clear.Internal heat acupuncture therapy has a good clinical effect in the treatment of steroid-induced avascular necrosis of the femoral head,but its specific mechanism is not clear.OBJECTIVE:To investigate the effect of internal heat acupuncture on osteoblast apoptosis and expression of Bcl-2-associated X protein(Bax)and B lymphocytoma-2(Bcl-2)in steroid-induced avascular necrosis of the femoral head in rabbits.METHODS:Totally 24 male New Zealand rabbits were randomly divided into blank group,model group,and internal heat acupuncture group(n=8).The rabbit model of steroid-induced avascular necrosis of the femoral head was made in the last two groups by methylprednisolone sodium succinate combined with Escherichia coli endotoxin.After successful model establishment for 4 weeks,the rabbits in the internal heat acupuncture group received internal heat acupuncture intervention on the buttocks of rabbits,once a week for 20 minutes each time,while the other two groups did not receive any intervention.After 4 weeks of treatment,samples were harvested.Morphological changes of femoral head and osteoblast apoptosis were observed by hematoxylin-eosin staining and TUNEL assay.Protein expression of Bcl-2 and Bax in rabbit femoral head tissue was detected by immunohistochemistry and western blot assay.RESULTS AND CONCLUSION:(1)In the blank group,there were abundant hematopoietic cells in the bone marrow cavity,clear and orderly trabecular structure,few adipocytes and few empty bone lacunae.In the model group,the number of adipocytes in the bone marrow cavity increased significantly,accompanied by hyperplasia,steatosis of some osteocytes and more empty bone lacunae.After the intervention of internal heat acupuncture,the number of adipocytes and hollow bone lacunae was less than that in the model group,but more obvious than that in the blank group.(2)Compared with the blank group,the apoptosis of osteoblasts in the model group was significantly increased,the expression of Bax was significantly increased(P＜0.001),and the expression of Bcl-2 was significantly decreased(P＜0.001).After the intervention of internal heat acupuncture,the apoptosis of osteoblasts was significantly decreased,the expression of Bax was significantly decreased(P＜0.001),and the expression of Bcl-2 was significantly increased(P＜0.001).(3)The results show that internal heat acupuncture can alleviate steroid-induced avascular necrosis of the femoral head by inhibiting osteoblast apoptosis in the femoral head.

Objective:To analyze risk factors for immune checkpoint inhibitor-related pneumonitis (CIP) in non-small cell lung cancer (NSCLC) patients based on clinical and radiological characteristics, and to develop and validate a nomogram model for predicting the risk of CIP.Methods:A retrospective case-controlled study was conducted. The clinical data of 159 patients diagnosed with NSCLC in Shanxi Province Cancer Hospital between January 2020 and December 2023 who received immune checkpoint inhibitor (ICI) therapy were retrospectively analyzed. Based on the development of CIP after immunotherapy, the patients were divided into the CIP group (30 cases) and the control group (129 cases). The clinical data of NSCLC patients, hematological indicators and the data of imaging characteristics before their first ICI treatment were collected. Quantitative assessments were performed on pretreatment chest CT images, including lung total tumor volume, number of involved lung segments, and pulmonary infection index. Logistic regression analysis was used to screen out the factors influencing the development of CIP. R 4.3.0 statistical software was used to construct a nomogram model for predicting CIP based on the statistically significant risk factors identified in the multivariate logistic regression analysis. The predictive performance of the model was evaluated by using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Calibration curves and decision curve analysis (DCA) were employed to assess the model's consistency and clinical benefit.Results:There were statistically significant differences in the proportions of patients with a history of chest radiotherapy and those receiving different immunotherapy regimens between the control group and the CIP group (both P < 0.001). The difference in the lactate dehydrogenase (LDH) [ M ( IQR)] between the both groups was statistically significant [211.00 U/L (57.00 U/L) vs. 276.00 U/L (136.00 U/L), Z = -3.41, P < 0.001]; additionally, the difference in lung status score between the 2 groups was statistically significant ( P < 0.001). Multivariate logistic regression analysis revealed that a history of chest radiotherapy (with vs. without: OR = 4.200, 95% CI: 1.466-12.036), the combination of immunotherapy (monotherapy vs. the combined therapy: OR = 0.106, 95% CI: 0.022-0.509), LDH ≥ 255.5 U/L (< 255.5 U/L vs. ≥ 255.5 U/L: OR = 0.988, 95% CI: 0.981-0.995), and severe lung status score(mild vs. moderate vs. severe: OR = 0.187, 95% CI: 0.059-0.593) were independent risk factors for CIP development in NSCLC patients after immunotherapy (all P < 0.05). A nomogram model for predicting CIP occurrence was constructed based on chest radiotherapy history, immunotherapy regimen, LDH, and lung status score. ROC curve analysis showed the AUC was 0.878 (95% CI: 0.813-0.942). The calibration curve demonstrated the good consistency between the predicted risk probability of CIP and the observed outcomes; DCA indicated that the model had favorable clinical benefits. Conclusions:The constructed nomogram prediction model shows a good predictive performance.

Objective To evaluate the efficacy of cefoperazone-sulbactam(CS)combined with ulinastatin in the treatment for stroke-associated pneumonia(SAP)after endovascular treatment of acute large vessel occlusive stroke(AIS-LVO).Methods This study retrospectively included patients who developed SAP after endovascular treatment of AIS-LVO admitted to the intensive care unit of the Department of Neurology at the First Affiliated Hospital of Xi'an Jiaotong University from March 2022 to December 2023.Patients were randomly divided into the ulinastatin group(combined application of ulinastatin and CS)and the control group(sole application of CS)using a random number table.Baseline and clinical data,including sex,age,infarct laterality,culprit vessel,trial of Org 10172 in acute stroke treatment(TOAST)classification,baseline National Institutes of Health stroke scale(NIHSS)score,baseline Glasgow coma scale(GCS)score,medical history(hypertension,diabetes,coronary heart disease,atrial fibrillation,past history of stroke),history of smoking and alcohol consumption,admission baseline blood pressure,laboratory test results at admission(including red blood cell count,white blood cell count,neutrophil count,platelet count,random blood glucose levels,albumin,creatinine,low-density lipoprotein cholesterol,uric acid,and D-dimer),and endovascular therapies(including mechanical retrieval of thrombus,stenting,balloon dilatation,arterial thrombolysis and combination therapy)were collected from both groups.After the diagnosis of SAP,patients in both groups underwent conventional treatment such as sputum expectoration and clearance,antipyretic and antitussive treatment,oxygen therapy,respiratory support,fluid and nutrition support,along with CS anti-infective therapy.In contrast to the control group,the ulinastatin group additionally received continuous ulinastatin treatment for at least 7 days.The adverse reactions of the two groups after initiating SAP treatment including allergic reactions(such as sudden dyspnea,skin redness,and shock),decrease in peripheral white blood cell count(below 4.0 × 109/L),nausea and vomiting,diarrhea,rash and/or itching,and liver enzymes(aspartate aminotransferase or alanine aminotransferase)elevation(more than twice the upper limit of normal)were compared between the two groups.The efficacy indicators encompassing arterial blood gas analysis(oxygenation index)and inflammatory factor indicators(interleukin-6[IL-6],procalcitonin)after 7 days of SAP treatment,pneumonia-related symptoms and signs before and after SAP treatment(including body temperature,heart rate,respiratory rate,sputum volume and characteristics,changes in lung rales,etc.),imaging examinations(such as head CT and chest CT).The evaluation of therapeutic efficacy is classified as(1)markedly effective:following treatment,significant relief was observed on pneumonia-related symptoms and signs,with body temperature returned to normal,and arterial blood gas analysis and inflammatory factor indicators returned to normal levels;post-treatment imaging studies reveal that over 2/3 of lung inflammation has been absorbed;(2)effective:after treatment,some improvement was observed in pneumonia-related symptoms and signs,with mild improvement in arterial blood gas analysis and inflammatory factor indicators;post-treatment imaging studies reveal some absorption of lung inflammation;(3)ineffective:no improvement or further deterioration of pneumonia-related symptoms,arterial blood gas analysis,and inflammatory factor indicators after treatment.The arterial blood gas analysis,inflammatory factor indicators and efficacy indicators were evaluated and compared between the control and the ulinastatin group.Compare the prognosis(improvement of the lesion in the chest CT after 7 days of treatment,length of stay in the intensive care unit,total length of hospital stay,and modified Rankin scale[mRS]score assessed via telephone follow-up or outpatient revisit 90 days after endovascular treatment[with an mRS score ≤2 indicating a good prognosis],as well as mortality).Results A total of 99 patients with AIS-LVO who developed SAP after endovascular treatment were included in this study,with 69 males(69.7％)and 30 females(30.3％),and an average age of(68±10)years.Among them,there were 46 cases in the ulinastatin group and 53 cases in the control group.(1)No statistically significant differences were observed in baseline or clinical characteristics between the two groups(all P＞0.05).(2)The overall effective(markedly effective and effective)rate of SAP treatment was greater in the ulinastatin group than that in the control group(89.1％[41/46]vs.69.8％[37/53],P=0.019).(3)No statistically significant differences were observed in serum IL-6 levels,procalcitonin levels,or arterial oxygenation index between the ulinastatin group and the control group before treatment(all P＞0.05).seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[64.39±52.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.31±0.20]μg/L)in the ulinastatin group were significantly lower compared to those before treatment(all P＜0.01),and the arterial oxygenation index was significantly higher than that before treatment([359.35±92.56]mmHg vs.[273.34±95.65]mmHg,P＜0.01).Seven days after treatment,the levels of serum IL-6([21.13±14.86]ng/L vs.[31.90±21.95]ng/L)and procalcitonin([0.12±0.11]μg/L vs.[0.26±0.24]μg/L)in the ulinastatin group were significantly lower than those in the control group(all P＜0.01),and the arterial oxygenation index was significantly higher than that of the control group([359.35±92.56]mmHg vs.[314.81±81.97]mmHg,P=0.020).(4)In the ulinastatin group,there was 1 case of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 6.5％(3/46).In the control group,there were 2 cases of nausea and vomiting,1 case of itching and/or rash,and 1 case of elevated liver enzymes,resulting in an adverse reaction rate of 7.5％(4/53).No statistically significant differences were observed in the adverse reaction rate between the two groups(P＞0.05).(5)After 7 days of treatment,the ulinastatin group exhibited a greater improvement rate in chest CT lesions compared to the control group(93.5％[43/46]vs.77.4％[41/53],P=0.026).No statistically significant differences were observed between the two groups in terms of the length of stay in the intensive care unit or the total length of hospital stay(both P＞0.05).Additionally,the 90-day mortality rate after intravascular treatment was lower in the ulinastatin group compared to the control group(6.5％[3/46]vs.20.8％[11/53],P=0.040).No statistically significant differences were observed in the good prognosis rate between the two groups(P=0.119).Conclusions Combined treatment with CS and ulinastatin can improve the clinical symptoms,inhibit inflammatory factors and reduce mortality rate in SAP patients after receiving endovascular treatment for AIS-LVO.The results of this study still need to be further confirmed by large-scale prospective studies.

Objective:To evaluate the safety and efficacy of early precise lower limb weight-bearing functional rehabilitation after open reduction and internal fixation of ankle fractures.Methods:A restropective multi-center study was conducted to enroll the eligible 120 patients with malleolar fracture who received the same surgical treatment from March 2023 to December 2023 at the trauma centers in 7 tertiary hospitals according to the inclusion criteria. They were assigned into a study group ( n=60) for precise lower limb weight-bearing functional rehabilitation with the assistance of intelligent lower limb walking rehabilitation crutches and a control group ( n=60) for conventional weight-bearing functional rehabilitation which was gradually increased according to their own feelings under the protection of a walking boot. All the 60 patients in the study group completed their final follow-ups. They were 25 males and 35 females, with an age of (43.8±16.6) years and a body mass index of (25.3±2.3) kg/m 2. Only 51 patients in the control group completed their final follow-ups. They were 27 males and 24 females, with an age of (45.1±16.4) years and a body mass index of (24.7±2.3) kg/m 2. When their incisions healed and their sutures were removed 2 weeks after operation, the patients were guided to start lower limb weight-bearing functional rehabilitation, and exercises for foot and ankle joint mobility and lower limb muscles. The end point of follow-up was 12 weeks after operation. The 2 groups were compared in terms of the crutch-off rates, thigh circumferences, calf circumferences, dorsiflexions, plantarflexions, ankle swellings, American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores, and visual analog scale (VAS) pain scores at 6 and 12 weeks after operation. The complications were also recorded in the 2 groups. Results:No statistically significant differences were observed in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). At 6 and 12 weeks after operation, the crutch-off rates [41.7% (25/60) and 100.0% (60/60)], dorsiflexions (69.3%±21.6% and 82.9%±26.3%) and AOFAS ankle-hindfoot scores [(68.5±7.6) points and (96.9±3.7) points] in the study group were significantly better than those in the control group [13.7% (7/51) and 39.2% (20/51), 61.5%±16.5% and 72.0%±14.3%, (61.9±9.3) points and (90.1±7.2) points] ( P<0.05). At 6 weeks after operation, the thigh circumference (97.4%±1.9%), calf circumference (97.3%±1.9%), and plantarflexion (76.6%±19.8%) in the study group were significantly higher than those in the control group (95.9%±2.5%, 94.6%±3.2%, and 63.9%±16.9%) ( P<0.05). There were no significant differences between the 2 groups in ankle swelling at 6 or 12 weeks after operation, or thigh or calf circumference, plantarflexion, or VAS pain score at 12 weeks after operation ( P>0.05). No wound complications, secondary fracture displacement, or loosening of internal fixation occurred in either group during the follow-up period. There were no cases of nonunion or delayed union. Conclusions:Early lower limb weight-bearing functional rehabilitation after open reduction and internal fixation of ankle fractures demonstrates good safety. Precise weight-bearing rehabilitation accelerates functional recovery of the ankle, enabling earlier return to normal daily activities.

Objective:To investigate the effect of triply periodic minimal surfaces (TPMS) structure and ceramic volume fraction on the mechanical properties of polymer-infiltrated ceramic network (PICN) composite and reveal its strengthening and toughening mechanism.Methods:In this study, TPMS structures with gyroid (G), primitive (P), diamond (D), and ceramic volume fraction (40%, 55%, 70%, 85%) were designed. Porous zirconia scaffolds were prepared using stereolithography technology, and resin was infiltrated into the scaffolds through a vacuum. Then, the PICN composites were obtained after curing. The bending strength, elastic modulus and fracture toughness of PICN were tested using an electronic universal testing machine, with commercial PICN as the control group. The micromorphology of PICN was observed through stereomicroscope and scanning electron microscope. The cytocompatibility of PICN was verified by using cell counting kit, live/dead cell staining and phalloidin staining.Results:The bending strength values of PICN with different ceramic volume fractions ranged from 82.0 MPa to 376.0 MPa, and they gradually increased as the ceramic volume fraction rised. The elastic modulus values of PICN with different ceramic volume fractions ranged from 12.1 GPa to 56.1 GPa. The fracture toughness values of PICN with different ceramic volume fractions ranged from 1.7 MPa·m 1/2 to 6.5 MPa·m 1/2. The bending strength of 85G PICN reached 306.0 MPa, and it had the highest fracture toughness (6.5 MPa·m 1/2) and an appropriate elastic modulus between that of the control group and that of enamel. Under scanning electron microscopy, it could be observed that the cracks branch and deflect at the interface and eventually terminate within the resin phase. After co-culture with PICN, the survival rate of mouse fibroblasts exceeded 80%, indicating that PICN had no cytotoxicity. Conclusions:The PICN composite with TPMS structure can satisfy the mechanical properties and cytocompatibility of dental prosthesis.

Objective: To explore the mechanism of action of hepatic leukemia factor (HLF) in diabetes mellitus and to construct a conditional animal model of mice with islet β ⁃cell⁃specific HLF gene knockout. Methods: At the cellular level , the effects of HLF inhibition or overexpression on the proliferation of MIN6 cells was verified by the CCK⁃8 assay. The effects of HLF inhibition or overexpression were detected at the mRNA level and protein level by Cre + / - mice (C57BL/6J) to obtain offspring mice. The genotypes of the mice were identified by the PCR method.The differences in the expression levels of the HLF gene at the mRNA and protein levels in islet β ⁃cell knockout mice (HLFflox/flox Cre + / - ) and control mice (HLFflox/flox ) were detected by RT⁃qPCR technology and Western blot technology to verify the knockout effect. At the same time , the islet tissues of the mice in two groups were taken to make paraffin sections and analyzed by hematoxylin⁃eosin (HE) staining. Results: HLF gene inhibition or overex⁃pression had no significant effect on the proliferation of MIN6 cells. When the HLF gene was inhibited in MIN6 cells , the mRNA expression level decreased by 74% compared with the control group , and the protein expression level decreased by 60% compared with the control group. After overexpressing the HLF gene , the mRNA expres⁃sion level was 2. 13 times compared with that of the control group , and the protein expression level was 1. 8 times compared with that of the control group. The mRNA expression level of the HLF gene in the knockout mice de⁃creased by 89% compared with the control group , and the protein expression level decreased by 65% compared with the control group. The results of HE staining showed that there was no significant difference in the cell mor⁃phology in the islet tissues between the knockout mice and the control mice. Inhibiting HLF increased the glycogen content in MIN6 cells by approximately 20% . Conclusion The HLF gene knockout mice are successfully con⁃structed , providing an animal model for studying the role of HLF in the pathogenesis of diabetes mellitus.