Objective:To observe any ability of pulsed electromagnetic field (PEMF) stimulation to regulate inflammation in degenerate nucleus pulposus cells.Methods:Primary nucleus pulposus cells from rats were cultured and divided into a control group, a model group, an A2AR-small interfering RNA group (A2AR-siRNA group), and a PEMF group. The control and model group cells were stimulated with tumor necrosis factor-α (TNF-α) in phosphate-buffered saline solution, those in the A2AR-siRNA and the PEMF groups were transfected with A2AR siRNA and given TNF-α stimulation. The PEMF group cells had four hours daily of PEMF irradiation beginning within 24 hours after the TNF-α stimulation for 2 days. After 48 hours, cell proliferation was detected by CCK8 assay, while the positive expression of A2AR in the nucleus pulposus cells was measured using immunofluorescence staining. The expression of A2AR, cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element binding protein (CREB), nuclear factor-κB (NF-κB), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and interleukin-6 (IL-6) in the cells was observed using western blotting and real-time fluorescence quantitative polymerase chain reactions.Results:The rate of cell proliferation among the model group was approximately 60%, significantly lower than that of the control group (100%), but significantly higher than that of the A2AR-siRNA group (approximately 34%). The cell proliferation rate of the PEMF group was approximately 80%, significantly higher than that of the model and A2AR-siRNA groups. Compared with the control group, the positive expression of A2AR in the nucleus pulposus cells, A2AR protein and mRNA in the model group increased significantly in response to stress. The expression of A2AR protein and mRNA in the A2AR-siRNA group and the PEMF group was significantly lower than in the model group. Compared with the control group, the cAMP level in the nucleus pulposus cells of the model group had decreased significantly. The cAMP content in the A2AR-siRNA group further decreased compared with the model group, and that in the PEMF group increased compared with the model and the A2AR-siRNA groups. The average expression of PKA and CREB in the model group was significantly higher than among the control group, while that of PKA and CREB in the A2AR-siRNA group was significantly lower. The PKA and CREB protein levels in the PEMF group were slightly higher than in the A2AR-siRNA group, but the difference was not statistically significant. The expression of NF-κB, NLRP3, and IL-6 protein and mRNA in the cells of the model group was significantly higher than in the control group, but those of the A2AR-siRNA group were significantly higher than in the model group. The levels in the PEMF group were significantly lower than among the model and A2AR-siRNA groups, on average.Conclusions:Down-regulation of A2AR content further aggravates the inflammatory injury of degenerated nucleus pulposus cells. The mechanism may be related to the down-regulation of CREB activity, activation of the NF-κB signaling pathway, and subsequent up-regulation of inflammatory factors NLRP3 and IL-6. PEMF stimulation cannot significantly increase the A2AR level in degenerated nucleus pulposus cells, but it can promote the expression of cAMP and inhibit the downstream NF-κB signaling pathway, thereby exerting an anti-inflammatory effect.

OBJECTIVE: To compare the effectiveness of a zero-profile three-dimensiaonal (3D)-printed microporous titanium alloy Cage and a conventional titanium plate combined with a polyether-ether-ketone (PEEK)-Cage in the treatment of single-segment cervical spondylotic myelopathy (CSM) by anterior cervical discectomy and fusion (ACDF). METHODS: The clinical data of 83 patients with single-segment CSM treated with ACDF between January 2022 and January 2023 were retrospectively analyzed, and they were divided into 3D-ZP group (35 cases, using zero-profile 3D-printed microporous titanium alloy Cage) and CP group (48 cases, using titanium plate in combination with PEEK-Cage). There was no significant difference in gender, age, disease duration, surgical intervertebral space, and preoperative Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) score, neck disability index (NDI), vertebral height at the fusion segment, Cobb angle, and other baseline data between the two groups (P>0.05). The operation time, intraoperative blood loss, hospital stay, complications, interbody fusion, and prosthesis subsidence were recorded and compared between the two groups. VAS score, NDI, and JOA score were used to evaluate the improvement of pain and function before operation, at 3 months after operation, and at last follow-up, and the vertebral height at the fusion segment and Cobb angle were measured by imaging. The degree of dysphagia was assessed by the Bazaz dysphagia scale at 1 week and at last follow-up. RESULTS: The operation was successfully completed in all the 83 patients. There was no significant difference in intraoperative blood loss and hospital stay between the two groups (P>0.05), but the operation time in the 3D-ZP group was significantly shorter than that in the CP group (P<0.05). Patients in both groups were followed up 24-35 months, with an average of 25.3 months, and there was no significant difference in the follow-up time between the two groups (P>0.05). The incidence and grade of dysphagia in CP group were significantly higher than those in 3D-ZP group at 1 week after operation and at last follow-up (P<0.05). There was no dysphagia in 3D-ZP group at last follow-up. There was no complication such as implant breakage or displacement in both groups. The intervertebral fusion rates of 3D-ZP group and CP group were 65.71% (23/35) and 60.42% (29/48) respectively at 3 months after operation, and there was no significant difference between the two groups [OR (95%CI)=1.256 (0.507, 3.109), P=0.622]. The JOA score, VAS score, and NDI significantly improved in the 3D-ZP group at 3 months and at last follow-up when compared with preoperative ones (P<0.05), but there was no significant difference between the two groups (P>0.05). There was no significant difference in the improvement rate of JOA between the two groups at last follow-up (P>0.05). At 3 months after operation and at last follow-up, the vertebral height at the fusion segment and Cobb angle significantly improved in both groups, and the two indexes in 3D-ZP group were significantly better than those in CP group (P<0.05). At last follow-up, the incidence of prosthesis subsidence in 3D-ZP group (8.57%) was significantly lower than that in CP group (29.16%) (P<0.05). CONCLUSION The application of zero-profile 3D-printed Cage and titanium plate combined with PEEK-Cage in single-segment ACDF can both reconstruct the stability of cervical spine and achieve good effectiveness. Compared with the latter, the application of the former in ACDF can shorten the operation time, reduce the incidence of prosthesis subsidence, and reduce the incidence of dysphagia.
Humans ; Spinal Fusion/instrumentation* ; Titanium ; Cervical Vertebrae/surgery* ; Diskectomy/instrumentation* ; Bone Plates ; Male ; Printing, Three-Dimensional ; Female ; Retrospective Studies ; Middle Aged ; Treatment Outcome ; Benzophenones ; Adult ; Spondylosis/surgery* ; Aged ; Polymers ; Ketones ; Polyethylene Glycols

Objective:To observe any ability of pulsed electromagnetic field (PEMF) stimulation to regulate inflammation in degenerate nucleus pulposus cells.Methods:Primary nucleus pulposus cells from rats were cultured and divided into a control group, a model group, an A2AR-small interfering RNA group (A2AR-siRNA group), and a PEMF group. The control and model group cells were stimulated with tumor necrosis factor-α (TNF-α) in phosphate-buffered saline solution, those in the A2AR-siRNA and the PEMF groups were transfected with A2AR siRNA and given TNF-α stimulation. The PEMF group cells had four hours daily of PEMF irradiation beginning within 24 hours after the TNF-α stimulation for 2 days. After 48 hours, cell proliferation was detected by CCK8 assay, while the positive expression of A2AR in the nucleus pulposus cells was measured using immunofluorescence staining. The expression of A2AR, cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element binding protein (CREB), nuclear factor-κB (NF-κB), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), and interleukin-6 (IL-6) in the cells was observed using western blotting and real-time fluorescence quantitative polymerase chain reactions.Results:The rate of cell proliferation among the model group was approximately 60%, significantly lower than that of the control group (100%), but significantly higher than that of the A2AR-siRNA group (approximately 34%). The cell proliferation rate of the PEMF group was approximately 80%, significantly higher than that of the model and A2AR-siRNA groups. Compared with the control group, the positive expression of A2AR in the nucleus pulposus cells, A2AR protein and mRNA in the model group increased significantly in response to stress. The expression of A2AR protein and mRNA in the A2AR-siRNA group and the PEMF group was significantly lower than in the model group. Compared with the control group, the cAMP level in the nucleus pulposus cells of the model group had decreased significantly. The cAMP content in the A2AR-siRNA group further decreased compared with the model group, and that in the PEMF group increased compared with the model and the A2AR-siRNA groups. The average expression of PKA and CREB in the model group was significantly higher than among the control group, while that of PKA and CREB in the A2AR-siRNA group was significantly lower. The PKA and CREB protein levels in the PEMF group were slightly higher than in the A2AR-siRNA group, but the difference was not statistically significant. The expression of NF-κB, NLRP3, and IL-6 protein and mRNA in the cells of the model group was significantly higher than in the control group, but those of the A2AR-siRNA group were significantly higher than in the model group. The levels in the PEMF group were significantly lower than among the model and A2AR-siRNA groups, on average.Conclusions:Down-regulation of A2AR content further aggravates the inflammatory injury of degenerated nucleus pulposus cells. The mechanism may be related to the down-regulation of CREB activity, activation of the NF-κB signaling pathway, and subsequent up-regulation of inflammatory factors NLRP3 and IL-6. PEMF stimulation cannot significantly increase the A2AR level in degenerated nucleus pulposus cells, but it can promote the expression of cAMP and inhibit the downstream NF-κB signaling pathway, thereby exerting an anti-inflammatory effect.

A review was undertaken of the operation process and development of transcutaneous electrical acupoint stimulation (TEAS) and related devices for TEAS, with the aim to offer a reference for developing an international standard for the basic safety and essential performance of the devices. The articles related to TEAS and instruction of devices for TEAS were searched using the EMBASE, MEDLINE, and Web of Science databases with the time period from inception to July 18, 2023. In the absence of a parameter description of the stimulators, a multimeter was used to measure the output voltage, resistance, and current. Thirty-two related devices for TEAS were obtained. The safety parameters of most devices were neither clearly defined, nor stand ardized, and in some cases were missing. There was a noticeable disparity in the upper safety limits of the output current among the devices. The sizes of the skin electrode pads as well as the lengths of the electrode connecting wires of most devices were not clearly indicated. Acupoints on different parts of the human body, including the upper limbs, head, auricle, chest, abdomen, trunk, and lower limbs, required different maximum tolerable current intensities and current densities. It is important to indicate comprehensive output/safety parameters and essential performance for devices for TEAS to meet the need of global distribution, achieve precise stimulation parameters at different acupoints across the human body, and allay any safety concern of national therapeutic device authorities, the regulators, manufacturers, and end users.

Objective To analyze the prognostic value of preoperative peripheral blood inflammatory markers neutrophil to lymphocyte ratio(NLR)combined with tumor markers carcinoembryonic antigen(CEA)and glycoprotein antigen CA19-9 in patients with colon cancer.Methods A retrospective study was conducted on 158 cases of colon cancer patients who visited the 1st Affiliated Hospital of Kunming Medical University from May 2018 to October 2020.The receiver operating characteristic curve(ROC)was used to determine the critical values of various indicators and group them.The Kaplan Meier method was used to analyze the relationship between NLR,CEA,CA19-9,and combined detection of different groups and patient survival prognosis.Multivariate Cox regression analysis was used to analyze the factors affecting patient prognosis.Results The preoperative NLR level(P=0.035),combined testing group(P=0.008),and postoperative pathological N stage(P＜0.001)were independent risk factors for OS,and the joint testing group had the highest risk ratio among preoperative indicators(P=0.008,HR=2.664,95％CI 1.503～4.315).Conclusion The combined detection of NLR,CEA,and CA19-9 in peripheral blood before surgery has independent prognostic value for patients with colon cancer.

Objective:To document any effect of a pulsed electromagnetic field (PEMF) on the regulation of neuropeptide Y (NPY) in nucleus pulposus (NP) tissue, NP cell apoptosis and matrix degradation using rats with intervertebral disc degeneration (IDD).Methods:Eighteen Sprague-Dawley rats were randomly divided into a control group, an IDD model group (the model group), and a PEMF group. IDD was induced in both the model and PEMF groups. Right after the modeling, the PEMF group received 14 days of PEMF treatment, while the control group and model group were given no special treatment. Meanwhile, the primary rat nucleus pulposus cells (NPCs) were cultured using Dulbecco′s Modified Eagle Medium at 37℃ and 5% CO 2. When the fusion rate reached 90% after passage, the NPCs were divided into a control group, a TNF-α model group (referred to as model group) and TNF-α + PEMF group (referred to as PEMF group) and treated accordingly. Eight weeks after the modeling, safranin-o/fast green staining was used to assess any pathological morphology changes. The expression of NPY, neuropeptide Y receptor Y2 (NPY2R), bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), collagen type II (Col-II) and matrix metalloproteinase-3 (MMP3) in the intervertebral disc and the cultivated nucleus pulposus cells of the 3 groups were determined. Results:The intervertebral disc cells in the model group were ruptured and folded, with significantly increased polysaccharide and protein components, and significantly increased bone fibers. In the PEMF group the cell boundaries were clearer, with less fibrin fracture and increased cartilage tissue. NPY was expressed in the fibrous annulus and the nucleus pulposus of the intervertebral disc in the model group. The average expression levels of NPY and NPY2R were significantly higher than in the control group and the model group. Compared with the control group, there was a significant increase in the level of Bax and a significant decrease in the expression of Bcl-2 in the model group, and there was a significant decrease in the level of Bax in the PEMF group. Compared with the control group, there was a significant decrease in the Col-II level but a significant increase in the MMP3 protein expression in the model group. The average Col-II mRNA expression was significantly higher in the PEMF group compared with the model group, but the average MMP3 protein expression was significantly less. Those results are consistent with observations in vivo.Conclusion:PEMF may reverse the imbalance of ECM metabolism and delay IDD degeneration by up-regulating the expression of NPY and Bcl-2, as well as blocking the Bax/Bcl-2 signaling pathway to inhibit apoptosis of nucleus pulposus cells.

Humans ; Thyrotoxicosis/chemically induced* ; Amiodarone

Objective:To investigate the application value of the diagnostic and surgical method for asymmetric prominent mandibular angle assisted by digital surgical design.Methods:The data of the females in Han nationality with prominent mandibular angle from December 2010 to December 2020 in the Department of Digital Plastic Surgery of Plastic Surgery Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively. ProPlan CMF 3.0 software was used to preoperatively mirror the patient’s three-dimensional(3D) model to obtain a diagnosis. The characteristics of bilateral differences of asymmetry of mandible were evaluated, and the surgical method were analyzed. The effect of surgery was objectively evaluated by indicators such as gonion point width (Go-W), condyle apex height (Co-H), and mandibular angle(Ag). SPSS 18.0 was used for statistical analysis, and the data were tested by Kolmogorov-Smirnov test, and the result were in line with the normal distribution. The data were expressed in Mean±SD, and the paired t-test was used to compare the measurement result of the indicators on both sides of the mandible, and P<0.05 was a statistically significant difference. Results:A total of 30 female patients, aged from 18 to 39 years, were included. Preoperative 3D model measurements showed a longer mandibular ascending branch on one side of the mandible (long side) and a more extrusion of the mandibular angle on the other side (prominent side), which was treated with a modified surgical method of mandibular angle osteotomy. The height of the osteotomy line on the long side was the height of the exuberant osteotomy line + the height difference between the two sides, and the thickness of the outer plate grinding on the protrusion side was the thickness of the outer plate grinding on the long side + the width difference between the two sides. Both the preoperative pogonion and menton points were far from the long side of the mandible and biased towards the prominent side. The height, width and mandibular angle of the marker points on both sides of the mandible were compared, and the differences were statistically significant ( P<0.01). Among them, the asymmetrical difference between Go-W, Co-H and Ag was the largest, which could be used to evaluate the effect of surgery. The differences between Go-W, Co-H and Ag before and after surgery on the long side of the mandible were (1.10±2.05) mm, (12.84±2.96) mm, (-17.75±5.16)°, and the differences between the three indicators on the prominent side were (4.24±1.64) mm, (10.95±3.25) mm, (-14.87±5.14)°, respectively, and the differences between preoperative and postoperative comparisons were statistically significant ( P<0.01). The asymmetric differences between the three indicators on both sides of the mandible after surgery were (-0.32±2.30) mm, (-0.02±0.37) mm, (-0.01±1.87)°, respectively, and the differences were not statistically significant ( P>0.05). All patients had no complications such as hematoma and infection after surgery, and the patients were satisfied with the result of the operation. Conclusions:Asymmetric hypertrophy mandibular angle can be reconstructed by the patient’s preoperative 3D model to accurately measure the differences between the two sides of the mandible. This design can effectively guide the surgical method, improve the symmetry of the patient’s bilateral mandible, and achieve better aesthetic effects on the face.

Objective:To investigate the application value of the diagnostic and surgical method for asymmetric prominent mandibular angle assisted by digital surgical design.Methods:The data of the females in Han nationality with prominent mandibular angle from December 2010 to December 2020 in the Department of Digital Plastic Surgery of Plastic Surgery Hospital, Chinese Academy of Medical Sciences were analyzed retrospectively. ProPlan CMF 3.0 software was used to preoperatively mirror the patient’s three-dimensional(3D) model to obtain a diagnosis. The characteristics of bilateral differences of asymmetry of mandible were evaluated, and the surgical method were analyzed. The effect of surgery was objectively evaluated by indicators such as gonion point width (Go-W), condyle apex height (Co-H), and mandibular angle(Ag). SPSS 18.0 was used for statistical analysis, and the data were tested by Kolmogorov-Smirnov test, and the result were in line with the normal distribution. The data were expressed in Mean±SD, and the paired t-test was used to compare the measurement result of the indicators on both sides of the mandible, and P<0.05 was a statistically significant difference. Results:A total of 30 female patients, aged from 18 to 39 years, were included. Preoperative 3D model measurements showed a longer mandibular ascending branch on one side of the mandible (long side) and a more extrusion of the mandibular angle on the other side (prominent side), which was treated with a modified surgical method of mandibular angle osteotomy. The height of the osteotomy line on the long side was the height of the exuberant osteotomy line + the height difference between the two sides, and the thickness of the outer plate grinding on the protrusion side was the thickness of the outer plate grinding on the long side + the width difference between the two sides. Both the preoperative pogonion and menton points were far from the long side of the mandible and biased towards the prominent side. The height, width and mandibular angle of the marker points on both sides of the mandible were compared, and the differences were statistically significant ( P<0.01). Among them, the asymmetrical difference between Go-W, Co-H and Ag was the largest, which could be used to evaluate the effect of surgery. The differences between Go-W, Co-H and Ag before and after surgery on the long side of the mandible were (1.10±2.05) mm, (12.84±2.96) mm, (-17.75±5.16)°, and the differences between the three indicators on the prominent side were (4.24±1.64) mm, (10.95±3.25) mm, (-14.87±5.14)°, respectively, and the differences between preoperative and postoperative comparisons were statistically significant ( P<0.01). The asymmetric differences between the three indicators on both sides of the mandible after surgery were (-0.32±2.30) mm, (-0.02±0.37) mm, (-0.01±1.87)°, respectively, and the differences were not statistically significant ( P>0.05). All patients had no complications such as hematoma and infection after surgery, and the patients were satisfied with the result of the operation. Conclusions:Asymmetric hypertrophy mandibular angle can be reconstructed by the patient’s preoperative 3D model to accurately measure the differences between the two sides of the mandible. This design can effectively guide the surgical method, improve the symmetry of the patient’s bilateral mandible, and achieve better aesthetic effects on the face.