AMP-activated protein kinase(AMPK)is a conserved cellular energy receptor that plays an important role in regulating cell growth,proliferation,differentiation,autophagy,phosphorylation,crosstalk,and glucose and lipid metabolism.AMPK is activated during low-energy or other extreme conditions,and it is suppressed by an excess of nutrients to maintain the energy balance.Additionally,the regulatory mechanism of the AMPK signaling pathway mediating ferroptosis reflects its unique role.AMPK plays a specialized regulatory function in various organelles,which provides a new direction for disease therapy.It is also a therapeutic target to prevent diseases such as reproductive system diseases,aging,cancer,inflammation and cardiac dysfunction.This article reviews cellular energy imbalance.AMPK stimulates its potential therapeutic potential in diseases and drugs through diverse signal regulatory mechanisms.It provides a new treatment for different system diseases.This review summarizes the diverse regulatory mechanisms of the AMPK signaling pathway and provides a theoretical reference for cancer therapy and other disease therapies targeting AMPK.

Objective:To explore the potential of integrating virtual surgery with three-dimensional (3D) printed guides in the surgical management of mandibular benign tumors and subsequent reconstruction of bone defects.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent computer-assisted resection and vascularized fibular flap reconstruction for benign mandibular tumors at the Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2020. According to the utilization of guide plates for mandibular and fibular osteotomy during surgical procedures or not, the patients were categorized into two cohorts: a guide plate cohort and a non-guide plate cohort. In the guide plate group, custom-designed gudie plates based on virtual surgical plans were fabricated using 3D printing technology and employed intraoperatively; In the non-guide plate group, surgery was exclusively performed based on virtual surgical plan and prebent titanium plate without any supplementary plating. The measured outcomes included fibular flap osteotomy, operation duration, and clinical flap survival. Computed tomography images obtained one week post-surgery were utilized to assess the intersegmental commissure degree between fibular segments as well as between fibular segments and mandible, commissure degree between fibular segments and prebent titanium plate, and condyle position. The satisfaction of patients with their facial appearance was evaluated 6 months after the surgery using a visual analogue scale. Statistical analysis was conducted using SPSS 21.0 software. Independent sample t-tests was utilized to compare the duration of operation and and postoperative evaluation of facial appearance, the Chi-square tests was utilized for condyle position, commissure degrees among interactions involving fibular segments, prebent titanium plates, bone segments( P<0.05 denoted statistical significance). Results:A total of 30 patients were enrolled, comprising 17 males and 13 females, with a median age of 24 years (16-64 years). The preparation process of fibular flaps proceeded smoothly. The required length of fibula was measured as (14.1 ± 1.9) cm (5.7-18.1 cm), while the number of fibular segments ranged from 2 to 4, averaging at approximately 2.9 ± 0.6. The mandibular defects were repaired using a single-layer fibula in 12 cases, a vascularized folded fibula in 7 cases and a combination of vascularized and non-vascularized fibula in 11 cases. The operation time for the guide plate group was recorded as ( 335.9 ± 64.0) min (240-433 min), while it was observed to be (470.7 ± 140.5 ) min (280-680 min) for the non-guide plate group.The postoperative follow-up duration ranged from 9 to 23 months, with an average period of 11 months. All fibular flaps demonstrated clinical survival. The number of patients with good commissure degree between fibular and mandibular segments, between prebent titanium plate and fibular and mandibular segments and the position of condyle were 15, 15 and 13 cases in guide plate group, 10, 13 and 11 cases in non-guide plate group respectively. The statistical analysis revealed a significant difference ( P<0.05) in the degree of commissure between the fibular and the mandibular segments (15/15 vs. 10/15) in the two groups. Both groups exhibited high levels of satisfaction regarding their postoperative facial appearance at the 6 months follow-up, observed to be 9.6±0.5 and 9.3±0.5 respectively, and the statisticla analysis revealed non-significant difference ( P>0.05). Conclusion:The integration of virtual surgery with 3D printed guide plates can effectively reduce operative time and improve precision in the repair and reconstruction of free-fibular flaps following resection of benign tumors of the mandible.

Objective:To investigate the therapeutic effect of digital technology assisted design of fibula flap for the repair of maxillary tumor defect and implant denture.Methods:A retrospective analysis was performed in patients with benign maxillary tumors who were admitted to Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Zhengzhou Universityfrom March 2018 to October 2020. Before the surgery, the virtual tumor resection, fibula reconstruction and stereomodels were printed for the fabrication of fibular osteotomy guide plates.And titanium plates were prefabricated with the stereomodels. Personalized titanium meshes were prebent manually. During the operation, the tumor was removed according to the osteotomy guide plate.The fibula was reshaped according to the surgical plan and the guide plate.And maxillary defects were reconstructed using the fibular flap combined with a prebent personalized titanium mesh.Straumann implants were implanted 6-9 months after bone grafting.The upper porcelain crown was repaired 3-4 months after implantation to restore the occlusal relationship and masticatory function. The facial appearance, masticatory function and peri-implant inflammation were followed up.Results:A total of 12 cases were included in this study, 7 males and 5 females, aged 20-55 years, with a median age 36 years old. Among them, there were 3 cases of ossifying fibroma, 7 cases of ameloblastoma, and 2 cases of odontogenic myxoma.According to the James Brown classification, there were 4 cases of Type Ⅱb, 3 cases of Type Ⅱc, 3 cases of Type Ⅱd, and 2 cases of Type Ⅲb. Tumor resection and fibula reconstruction went smoothly in 12 patients and all the free fibular flaps survived 14 days after surgery. The patients had maxillofacial symmetry, good occlusal relationship after the implant repair, and normal chewing and masticatory functions, after 12-48 months of follow-up, with an average of 26 months. The mouth opening reached 2.8-3.3 cm, without obvious peri-implantitis.Conclusion:The use of digital technology to design fibula flap to repair the defect after maxillary tumor resection and implant denture can not only restore the patients’ facial contour, but also restore their occlusal relationship and masticatory function.

Objective:To explore the potential of integrating virtual surgery with three-dimensional (3D) printed guides in the surgical management of mandibular benign tumors and subsequent reconstruction of bone defects.Methods:A retrospective analysis was conducted on the clinical data of patients who underwent computer-assisted resection and vascularized fibular flap reconstruction for benign mandibular tumors at the Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Zhengzhou University, from June 2013 to December 2020. According to the utilization of guide plates for mandibular and fibular osteotomy during surgical procedures or not, the patients were categorized into two cohorts: a guide plate cohort and a non-guide plate cohort. In the guide plate group, custom-designed gudie plates based on virtual surgical plans were fabricated using 3D printing technology and employed intraoperatively; In the non-guide plate group, surgery was exclusively performed based on virtual surgical plan and prebent titanium plate without any supplementary plating. The measured outcomes included fibular flap osteotomy, operation duration, and clinical flap survival. Computed tomography images obtained one week post-surgery were utilized to assess the intersegmental commissure degree between fibular segments as well as between fibular segments and mandible, commissure degree between fibular segments and prebent titanium plate, and condyle position. The satisfaction of patients with their facial appearance was evaluated 6 months after the surgery using a visual analogue scale. Statistical analysis was conducted using SPSS 21.0 software. Independent sample t-tests was utilized to compare the duration of operation and and postoperative evaluation of facial appearance, the Chi-square tests was utilized for condyle position, commissure degrees among interactions involving fibular segments, prebent titanium plates, bone segments( P<0.05 denoted statistical significance). Results:A total of 30 patients were enrolled, comprising 17 males and 13 females, with a median age of 24 years (16-64 years). The preparation process of fibular flaps proceeded smoothly. The required length of fibula was measured as (14.1 ± 1.9) cm (5.7-18.1 cm), while the number of fibular segments ranged from 2 to 4, averaging at approximately 2.9 ± 0.6. The mandibular defects were repaired using a single-layer fibula in 12 cases, a vascularized folded fibula in 7 cases and a combination of vascularized and non-vascularized fibula in 11 cases. The operation time for the guide plate group was recorded as ( 335.9 ± 64.0) min (240-433 min), while it was observed to be (470.7 ± 140.5 ) min (280-680 min) for the non-guide plate group.The postoperative follow-up duration ranged from 9 to 23 months, with an average period of 11 months. All fibular flaps demonstrated clinical survival. The number of patients with good commissure degree between fibular and mandibular segments, between prebent titanium plate and fibular and mandibular segments and the position of condyle were 15, 15 and 13 cases in guide plate group, 10, 13 and 11 cases in non-guide plate group respectively. The statistical analysis revealed a significant difference ( P<0.05) in the degree of commissure between the fibular and the mandibular segments (15/15 vs. 10/15) in the two groups. Both groups exhibited high levels of satisfaction regarding their postoperative facial appearance at the 6 months follow-up, observed to be 9.6±0.5 and 9.3±0.5 respectively, and the statisticla analysis revealed non-significant difference ( P>0.05). Conclusion:The integration of virtual surgery with 3D printed guide plates can effectively reduce operative time and improve precision in the repair and reconstruction of free-fibular flaps following resection of benign tumors of the mandible.

Objective:To investigate the therapeutic effect of digital technology assisted design of fibula flap for the repair of maxillary tumor defect and implant denture.Methods:A retrospective analysis was performed in patients with benign maxillary tumors who were admitted to Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Zhengzhou Universityfrom March 2018 to October 2020. Before the surgery, the virtual tumor resection, fibula reconstruction and stereomodels were printed for the fabrication of fibular osteotomy guide plates.And titanium plates were prefabricated with the stereomodels. Personalized titanium meshes were prebent manually. During the operation, the tumor was removed according to the osteotomy guide plate.The fibula was reshaped according to the surgical plan and the guide plate.And maxillary defects were reconstructed using the fibular flap combined with a prebent personalized titanium mesh.Straumann implants were implanted 6-9 months after bone grafting.The upper porcelain crown was repaired 3-4 months after implantation to restore the occlusal relationship and masticatory function. The facial appearance, masticatory function and peri-implant inflammation were followed up.Results:A total of 12 cases were included in this study, 7 males and 5 females, aged 20-55 years, with a median age 36 years old. Among them, there were 3 cases of ossifying fibroma, 7 cases of ameloblastoma, and 2 cases of odontogenic myxoma.According to the James Brown classification, there were 4 cases of Type Ⅱb, 3 cases of Type Ⅱc, 3 cases of Type Ⅱd, and 2 cases of Type Ⅲb. Tumor resection and fibula reconstruction went smoothly in 12 patients and all the free fibular flaps survived 14 days after surgery. The patients had maxillofacial symmetry, good occlusal relationship after the implant repair, and normal chewing and masticatory functions, after 12-48 months of follow-up, with an average of 26 months. The mouth opening reached 2.8-3.3 cm, without obvious peri-implantitis.Conclusion:The use of digital technology to design fibula flap to repair the defect after maxillary tumor resection and implant denture can not only restore the patients’ facial contour, but also restore their occlusal relationship and masticatory function.

Objective:To provide theoretical guidance for the treatment of mandibular ameloblastoma by comparing the differences in the quality of life (QOL) of patients with mandibular ameloblastoma repaired by vascularized iliac bone flap and fibular flap.Methods:Seventy-two patients with mandibular ameloblastoma were admitted to the Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Zhengzhou University from August 2016 to April 2019. There were 38 males and 34 females, aged 18-45 years, with an average of 33 years. The patients were divided into group A (iliac bone flap) with 28 cases and group B (fibula skin flap) with 44 cases. The 14-item Oral Health Impact Profile questionnaires (OHIP-14) was used to investigate and compare the differences in the QOL of patients 6 and 24 months after surgery.Results:All the 72 cases of free flaps survived. The OHIP-14 showed that there was no difference in physiological pain between the preoperative and postoperative levels ( P>0.05). There was no difference between the two groups. The scores of psychological discomfort and psychological disorder decreased at 24 months after surgery, without significantly statistical difference compared with that at 6 months after surgery ( P>0.05). The scores of physical impairment, disability and social impairment significantly reduced at 24 months after surgery, with significantly statistical difference compared with that at 6 months after surgery (iliac bone group t=8.07, 6.01 and 23.19; fibula group t=6.56, 4.27 and 13.01, P<0.05). The scores of functional limitations significantly reduced in both groups at 24 months after surgery, but the difference was still statistically significant ( t=2.30, P<0.05) between the iliac bone group (17.68±3.44) and the fibula group (22.70±11.19). Conclusions:There is no significant difference in the QOL between the two groups of patients with mandibular defects at 24 months after surgery. The application of iliac bone flapis is recommended for patients with mandibular body defects and fibular flap for large defects or lesions involving the condyles and chin.

Objective To explore the relationship between m6A RNA methylation regulators and prognosis of prostate cancer.Methods Clinicopathological and mRNA-related data of 496 cases of prostate cancer were downloaded from the Cancer Genome Atlas(TCGA)database,and 12 m6A regulators were identified:METTL3,METTL14,WTAP,RBM15,ZC3H13,YTHDC1,YTHDC2,YTHDF1,YTHDF2,HNRNPC,FTO,and ALKBH5.The m6A regulators differentially expressed in prostate cancer samples were screened.Unsupervised clustering of prostate cancer tissues was used to compare differences in overall survival.Multivariate Cox regres-sion analysis was used to divide patients into high-and low-risk groups according to the risk scores,and survival rates were compared.The risk score of clinicopathological factors was determined,and a multivariate Cox regression analysis model was constructed to evaluate the prognostic prediction value.Immunohistochemical staining was performed to detect METTL14 and FTO expression in prostate cancer tis-sues.Results Eight differentially expressed regulators were screened from 12 m6A regulators.Unsupervised cluster analysis divided the samples into Clusters 1,2,and 3 and found significant differences in survival time in all three groups.Multivariate Cox regression analyses revealed that METTL14and FTOwere strongly associated with the prognosis of patients with prostate cancer.A Cox regression model con-structed to score the risk of prostate cancer revealed that the high-and low-risk groups had survival differences,and the risk score could be used as an independent prognostic factor.The positive expression rates of METTL14 and FTO protein in prostate cancer tissues were significantly higher than those in adjacent tissues(P<0.05).Conclusion In this study,a prognostic prediction model based on m6A regulators of prostate cancer was constructed,in which the risk score could be used as an independent prognostic factor.METTL14and FTOcould be used as molecular markers for the diagnosis of prostate cancer and as potential targets for treatment.

Objective:To explore the application of of virtual surgical planning combined with intraoperative navigation in the accurate resection of maxillary tumor and simultaneous reconstruction.Methods:From October 2015 to December 2016, the patients with maxillary tumor treated at the First Affiliated Hospital of Zhengzhou University were included in this study. Before the surgery, the virtual surgical planning was used to complete tumor identification, virtual tumor resection, fibula reconstruction, and then stereomodel was printed for the fabrication of fibular osteotomy guide plate and prebent of personalized titanium mesh. During the operation, navigation technology was used to determine the position of the designed osteotomy line for the accurate resection of maxillary tumor. The bone defect reconstruction was performed using fibular flap guided by osteotomy plate and prebent personalized titanium mesh. Histopathological examination was conducted to evaluate the safety of the surgical boundary. The postoperative color gradient map, self evaluation of facial appearance satisfaction, mouth opening degree and jaw vertical distance were used to evaluate the reconstruction of maxillary defects.Results:A total of 5 patients were enrolled in this study, 3 males and 2 females, with a median age of 39 years old (ranged 27 to 50). Among these cases, 2 were benign tumors and 3 were malignant. The operation of 5 cases was successful and all the fibular flaps were survived. There were 27 frozen pathological examinations, 25 were negative. One patient was treated with both adjuvant biological therapy and radiotherapy. Two patients were treated with only radiotherapy. The color gradient map showed that the position of fibular flap was highly consistent with the pre-operative surgical design. Four patients reported their facial appearance were excellent and one was good postoperatively. The mouth opening degree of the patients was 2.8-3.2 cm. The vertical jaw distance between mandible and fibula repair area was 6.5-10.0 mm. After 14-28 months follow-up, one patient with positive surgical boundary had local recurrence.Conclusions:Virtual surgical planning combined with simultaneous intraoperative navigation can improve the accuracy of maxillary tumor resection and reconstruction, and so as to improve the the quality of life of patients after surgery.

Objective:To explore the application of of virtual surgical planning combined with intraoperative navigation in the accurate resection of maxillary tumor and simultaneous reconstruction.Methods:From October 2015 to December 2016, the patients with maxillary tumor treated at the First Affiliated Hospital of Zhengzhou University were included in this study. Before the surgery, the virtual surgical planning was used to complete tumor identification, virtual tumor resection, fibula reconstruction, and then stereomodel was printed for the fabrication of fibular osteotomy guide plate and prebent of personalized titanium mesh. During the operation, navigation technology was used to determine the position of the designed osteotomy line for the accurate resection of maxillary tumor. The bone defect reconstruction was performed using fibular flap guided by osteotomy plate and prebent personalized titanium mesh. Histopathological examination was conducted to evaluate the safety of the surgical boundary. The postoperative color gradient map, self evaluation of facial appearance satisfaction, mouth opening degree and jaw vertical distance were used to evaluate the reconstruction of maxillary defects.Results:A total of 5 patients were enrolled in this study, 3 males and 2 females, with a median age of 39 years old (ranged 27 to 50). Among these cases, 2 were benign tumors and 3 were malignant. The operation of 5 cases was successful and all the fibular flaps were survived. There were 27 frozen pathological examinations, 25 were negative. One patient was treated with both adjuvant biological therapy and radiotherapy. Two patients were treated with only radiotherapy. The color gradient map showed that the position of fibular flap was highly consistent with the pre-operative surgical design. Four patients reported their facial appearance were excellent and one was good postoperatively. The mouth opening degree of the patients was 2.8-3.2 cm. The vertical jaw distance between mandible and fibula repair area was 6.5-10.0 mm. After 14-28 months follow-up, one patient with positive surgical boundary had local recurrence.Conclusions:Virtual surgical planning combined with simultaneous intraoperative navigation can improve the accuracy of maxillary tumor resection and reconstruction, and so as to improve the the quality of life of patients after surgery.

Objective:To investigate the clinical efficacy of budesonide formoterol combined with tiotropium bromide in the treatment of asthma chronic obstructive pulmonary disease(COPD) overlap (ACO).Methods:From January 2016 to December 2018, 160 ACO patients who met the inclusion criteria in the Department of Respiratory Medicine, Linxi Hospital, Kailuan General Hospitalwere selected as the observation objects.Prospective cohort study was used for observation and analysis.The patients were divided into study group and control group with 80 cases in each group by random number table.Both groups received conventional treatment, on this basis, control group received budesonide and formoterol powder inhalation, 1 inhalation/time, 2 times/d, study group received tiotropium bromide 1 granule/time, once a day based on the control group.Both groups were treated for 12 months.The clinical efficacy, lung function, blood gas analysis, inflammatory factors and T lymphocyte levels were compared between the two groups.Results:The total control rate in study group was 87.5%(70/80), significantly higher than that in control group (70.0%(56/80)), the difference was statistically significant (χ 2=7.32, P<0.05). After treatment, the asthma control test (ACT) scores in both groups increased significantly, while ACT scores in study group((23.12±3.12) point )was significantly higher than that in control group ((20.45±4.28) point, t=4.51, P<0.05). After treatment, the COPD assessment test (CAT) scores in both groups decreased significantly, while CAT scores in study group ((14.25±3.03) point ) was significantly lower than that in control group ((18.69±3.52) point, t=8.55, P<0.05). After treatment, the forced expiratory volume in 1s (FEV1), FEV1%, FEV1 /Forced vital capacity (FEV1/ FVC) and Inspiratory capacity / total lung capacity (IC/TLC) levels in both groups increased significantly, while FEV1((2.20±0.47)L), FEV1%((68.62±7.89)%), FEV1/ FVC((67.63±7.59)%)and IC/TLC levels(48.84±4.86)%) in study group were significantly higher than those in control group ((1.93±0.49)L, (61.88±7.65)%, (62.88±8.41)%, (43.22±5.15)%)(t value were 3.56, 5.49, 3.75, 7.10, all P<0.05). After treatment, the level of partial pressure of oxygen (PaO 2) in both groups increased significantly, while PaO 2 level in study group((78.12±6.45) mmHg) was significantly higher than that in control group ((72.45±7.52) mmHg)( t=5.12, P<0.05). After treatment, the arterial partial pressure of carbon dioxide (PaCO 2) level in both groups decreased significantly, while PaCO 2 level in study group((46.73±7.13) mmHg) was significantly lower than that in control group((49.81±8.02) mmHg) ( t=2.57, P<0.05). After treatment, the levels of IL-6, hs CRP and TNF-α in the two groups were decreased significantly, while IL-6, hs-CRP and TNF-α levels in study group((15.35±6.72) ng/L, (18.14±7.62) mg/L, (56.84±4.92) ng/L) were significantly lower than those in control group((21.42±5.35) ng/L, (23.35±8.64) mg/L, (69.45±8.51) ng/L) (t value were 6.32, 4.05, 11.47, all P<0.05). After treatment, the levels of CD4 + and CD4 +/CD8 + levels in both groups increased significantly, while CD4 + and CD4 +/CD8 + levels in study group((44.20±6.02)%, (1.82±0.31)) were significantly higher than those in control group((38.52±5.56)%, (1.43±0.29)) ( t=6.20, 8.22, all P<0.05). CD8 + level in both groups decreased significantly, while CD8 + level in study group((23.62±7.89)%) was significantly lower than that in control group((27.42±7.65)%)( t=3.09, P<0.05). Conclusion:Budesonide and formoterol combined with tiotropium bromide in the treatment of ACO has good clinical efficacy, reduce the level of inflammation, relieve the clinical symptoms of COPD and asthma, improve the respiratory function and lung function of patients, and have a good effect on improving the cellular immune function.