Objective:To investigate the clinical significance and inducing factors of abnormal intraoperative neurophysiological monitoring (IONM) signals during surgery for cervical degenerative diseases.Methods:A retrospective analysis was performed on 586 patients who underwent cervical degenerative disease surgery with IONM at the Department of Orthopedics, The First Affiliated Hospital of Soochow University, from April 2015 to April 2024. Surgical approaches included 380 anterior spinal canal decompression and fusion procedures, 154 posterior spinal canal decompression and fusion procedures (including single-door laminoplasty, total laminectomy, and hemilaminectomy), and 52 combined anterior-posterior surgeries. The multimodal IONM protocol employed transcranial electrical stimulation motor evoked potentials (TES-MEP) and cortical somatosensory evoked potentials (CSEP), combined with electromyography (EMG). Bilateral deltoid muscles, thenar/hypothenar muscles and abductor hallucis muscles were monitored in all patients. Intraoperative MEP, SEP, and EMG results were recorded to analyze the causes of abnormal signals, intraoperative response strategies, and postoperative neurological function and outcomes. Fourfold table chi-square tests were used to analyze factors possibly associated with IONM alerts.Results:Among the 586 cervical surgeries, 17 cases (2.9%) exhibited abnormal IONM signals. These included 4 cases of anterior cervical discectomy and fusion (ACDF), 4 cases of anterior cervical corpectomy and fusion (ACCF), and 2 cases of combined anterior-posterior surgeries for cervical spondylotic myelopathy; and 5 posterior surgeries and 2 anterior ACCF procedures for ossification of the posterior longitudinal ligament (OPLL). The rate of abnormal IONM signals was significantly higher in patients with maximum spinal cord compression (MSCC)>60% (5.8%, 12/208) than in those with MSCC≤60% (χ 2=9.417, P=0.002); in patients with intraoperative hypotension during posterior surgery (mean arterial pressure reduction>20% from baseline, cumulative duration>20 min), the abnormal IONM rate was 22.2% (6/27), which was significantly higher than that in patients without intraoperative hypotension (χ 2=33.542, P<0.001); in patients who underwent calcified tissue removal during anterior surgery, the abnormal IONM rate was 9.3% (5/54), which was significantly higher than that in patients without calcified tissue removal (χ 2=13.162, P=0.003). Thus, MSCC>60%, intraoperative hypotension during posterior surgery, and calcified tissue removal during anterior surgery may be inducing factors for abnormal IONM signals. Among the 17 patients with monitoring abnormalities, 8 cases showed no significant improvement after corresponding intraoperative treatments, and 7 of these 8 cases experienced varying degrees of muscle strength decline and sensory numbness immediately after surgery; 9 cases showed partial or complete recovery of signals, among which 8 cases had no new-onset neurological impairment after surgery, and 1 case developed unilateral upper limb grip strength decline. IONM demonstrated a sensitivity of 0.8750 and specificity of 0.8889. Conclusions:Multimodal IONM can detect electrophysiological abnormalities of spinal cord nerve function during cervical degenerative disease surgery, providing real-time warning of potential nerve damage during the operation. The proportion of abnormal IONM signals is relatively high in cases with MSCC>60%, intraoperative hypotension during posterior cervical surgery, or calcified tissue removal during anterior cervical surgery.

Objective:To investigate the effects of aerobic exercise training combined with cognitive behavioral therapy on blood pressure, exercise tolerance, and sleep quality in patients with sleep disorders complicated by high-normal blood pressure.Methods:A total of 60 individuals with sleep disorders complicated by high-normal blood pressure, who underwent community health screening and received treatment at the Third Affiliated Hospital of Wenzhou Medical University (Ruian People's Hospital) from February 2022 to February 2024, were prospectively included in this study. The patients were randomly assigned to two groups using a random number table: a cognitive therapy group and a combined intervention group, with 30 patients in each group. The cognitive therapy group received cognitive behavioral therapy, while the combined intervention group received both aerobic exercise training and cognitive behavioral therapy. Changes in blood pressure, the proportion of patients with elevated blood pressure, exercise tolerance, and Pittsburgh Sleep Quality Index (PSQI) score were compared between the two groups. Additionally, the overall effective rate of treatment for sleep disorders was evaluated for both groups.Results:Before intervention, there was no statistically significant difference in blood pressure between cognitive therapy and combined intervention groups ( P > 0.05). After intervention, the 24-hour mean systolic blood pressure was (121.63 ± 3.47) mmHg (1 mmHg = 0.133 kPa) for the cognitive therapy group and (114.56 ± 3.07) mmHg for the combined intervention group. The 24-hour mean diastolic blood pressure was (81.03 ± 2.78) mmHg for the cognitive therapy group and (77.59 ± 2.09) mmHg for the combined intervention group. Both the 24-hour mean systolic and diastolic blood pressures in each group significantly decreased when compared with the values recorded before intervention ( t = 10.54, 17.52, 5.52, 10.68, all P < 0.05). After intervention, both the 24-hour mean systolic and diastolic blood pressures in the combined intervention group were significantly lower than those in the cognitive therapy group ( t = 8.36, 5.41, both P < 0.001). Before intervention, there was no statistically significant difference in the proportion of patients with elevated blood pressure between the two groups ( P > 0.05). After intervention, the proportion of patients with elevated blood pressure was 40.00% (12/30) in the cognitive therapy group and 66.67% (20/30) in the combined group. Both groups showed a significant increase in the proportion of patients with elevated blood pressure compared with pre-intervention values ( χ2 = 4.02, 11.38, both P < 0.05). After intervention, the proportion of patients with elevated blood pressure in the combined intervention group was significantly higher than that in the cognitive therapy group ( χ2 = 4.28, P < 0.05). Before intervention, there was no significant difference in exercise tolerance between the two groups ( P > 0.05). After intervention, the combined intervention group showed significant increases in anaerobic threshold [(1 475.25 ± 415.65) mL/min] and oxygen pulse [(14.78 ± 2.86) mL/beat] compared with pre-intervention values ( t = 3.58, 7.49, both P < 0.05). However, there was no significant difference in the carbon dioxide ventilation equivalent (VE/VCO 2@VCP) at the ventilatory compensation point compared with pre-intervention levels ( P > 0.05). After intervention, the anaerobic threshold and oxygen pulse in the combined intervention group were significantly higher than those in the cognitive therapy group [(1 137.41 ± 349.86) mL/min, (9.94 ± 2.05) mL/beat] ( t = -3.40, -7.53, both P < 0.05). There was no significant difference in exercise tolerance in the cognitive therapy group between pre- and post-intervention ( P > 0.05). Before intervention, there was no significant difference in PSQI score between cognitive therapy and combined intervention groups ( P > 0.05). After intervention, score for sleep quality [(1.65 ± 0.26) points , (1.24 ± 0.23) points], sleep onset time [(1.51 ± 0.19) points, (1.33 ± 0.18) points], sleep time [(1.47 ± 0.23) points, (1.31 ± 0.20) points], sleep efficiency [(1.31 ± 0.20) points, (1.05 ± 0.19) points], sleep disturbance [(0.93 ± 0.15) points, (0.77 ± 0.20) points], hypnotic medication use [(0.96 ± 0.22) points, (0.67 ± 0.17) points], and daytime function [(1.19 ± 0.25) points, (1.02 ± 0.22) points] decreased in both groups compared with pre-intervention scores ( t = 8.21, 15.58, 9.86, 14.76, 10.02, 15.36, 8.78, 17.59, 7.84, 12.36, 5.74, 11.98, 12.03, 17.14, all P < 0.05). After intervention, PSQI score in the combined intervention group was significantly lower than that in the cognitive therapy group ( t = 6.46, 3.76, 2.87, 5.16, 3.50, 5.71, 2.79, all P < 0.05). The total effective rate for treating sleep disorders in the combined intervention group was 86.67% (26/30), which was significantly higher than that in the cognitive therapy group [63.33% (19/30), χ2 = 4.35, P < 0.05). Conclusions:Aerobic exercise training combined with cognitive behavioral therapy can improve exercise tolerance, reduce blood pressure, and enhance sleep quality in patients with sleep disorders and high-normal blood pressure.

Objective:To investigate the clinical significance and inducing factors of abnormal intraoperative neurophysiological monitoring (IONM) signals during surgery for cervical degenerative diseases.Methods:A retrospective analysis was performed on 586 patients who underwent cervical degenerative disease surgery with IONM at the Department of Orthopedics, The First Affiliated Hospital of Soochow University, from April 2015 to April 2024. Surgical approaches included 380 anterior spinal canal decompression and fusion procedures, 154 posterior spinal canal decompression and fusion procedures (including single-door laminoplasty, total laminectomy, and hemilaminectomy), and 52 combined anterior-posterior surgeries. The multimodal IONM protocol employed transcranial electrical stimulation motor evoked potentials (TES-MEP) and cortical somatosensory evoked potentials (CSEP), combined with electromyography (EMG). Bilateral deltoid muscles, thenar/hypothenar muscles and abductor hallucis muscles were monitored in all patients. Intraoperative MEP, SEP, and EMG results were recorded to analyze the causes of abnormal signals, intraoperative response strategies, and postoperative neurological function and outcomes. Fourfold table chi-square tests were used to analyze factors possibly associated with IONM alerts.Results:Among the 586 cervical surgeries, 17 cases (2.9%) exhibited abnormal IONM signals. These included 4 cases of anterior cervical discectomy and fusion (ACDF), 4 cases of anterior cervical corpectomy and fusion (ACCF), and 2 cases of combined anterior-posterior surgeries for cervical spondylotic myelopathy; and 5 posterior surgeries and 2 anterior ACCF procedures for ossification of the posterior longitudinal ligament (OPLL). The rate of abnormal IONM signals was significantly higher in patients with maximum spinal cord compression (MSCC)>60% (5.8%, 12/208) than in those with MSCC≤60% (χ 2=9.417, P=0.002); in patients with intraoperative hypotension during posterior surgery (mean arterial pressure reduction>20% from baseline, cumulative duration>20 min), the abnormal IONM rate was 22.2% (6/27), which was significantly higher than that in patients without intraoperative hypotension (χ 2=33.542, P<0.001); in patients who underwent calcified tissue removal during anterior surgery, the abnormal IONM rate was 9.3% (5/54), which was significantly higher than that in patients without calcified tissue removal (χ 2=13.162, P=0.003). Thus, MSCC>60%, intraoperative hypotension during posterior surgery, and calcified tissue removal during anterior surgery may be inducing factors for abnormal IONM signals. Among the 17 patients with monitoring abnormalities, 8 cases showed no significant improvement after corresponding intraoperative treatments, and 7 of these 8 cases experienced varying degrees of muscle strength decline and sensory numbness immediately after surgery; 9 cases showed partial or complete recovery of signals, among which 8 cases had no new-onset neurological impairment after surgery, and 1 case developed unilateral upper limb grip strength decline. IONM demonstrated a sensitivity of 0.8750 and specificity of 0.8889. Conclusions:Multimodal IONM can detect electrophysiological abnormalities of spinal cord nerve function during cervical degenerative disease surgery, providing real-time warning of potential nerve damage during the operation. The proportion of abnormal IONM signals is relatively high in cases with MSCC>60%, intraoperative hypotension during posterior cervical surgery, or calcified tissue removal during anterior cervical surgery.

Objective:To investigate the effects of aerobic exercise training combined with cognitive behavioral therapy on blood pressure, exercise tolerance, and sleep quality in patients with sleep disorders complicated by high-normal blood pressure.Methods:A total of 60 individuals with sleep disorders complicated by high-normal blood pressure, who underwent community health screening and received treatment at the Third Affiliated Hospital of Wenzhou Medical University (Ruian People's Hospital) from February 2022 to February 2024, were prospectively included in this study. The patients were randomly assigned to two groups using a random number table: a cognitive therapy group and a combined intervention group, with 30 patients in each group. The cognitive therapy group received cognitive behavioral therapy, while the combined intervention group received both aerobic exercise training and cognitive behavioral therapy. Changes in blood pressure, the proportion of patients with elevated blood pressure, exercise tolerance, and Pittsburgh Sleep Quality Index (PSQI) score were compared between the two groups. Additionally, the overall effective rate of treatment for sleep disorders was evaluated for both groups.Results:Before intervention, there was no statistically significant difference in blood pressure between cognitive therapy and combined intervention groups ( P > 0.05). After intervention, the 24-hour mean systolic blood pressure was (121.63 ± 3.47) mmHg (1 mmHg = 0.133 kPa) for the cognitive therapy group and (114.56 ± 3.07) mmHg for the combined intervention group. The 24-hour mean diastolic blood pressure was (81.03 ± 2.78) mmHg for the cognitive therapy group and (77.59 ± 2.09) mmHg for the combined intervention group. Both the 24-hour mean systolic and diastolic blood pressures in each group significantly decreased when compared with the values recorded before intervention ( t = 10.54, 17.52, 5.52, 10.68, all P < 0.05). After intervention, both the 24-hour mean systolic and diastolic blood pressures in the combined intervention group were significantly lower than those in the cognitive therapy group ( t = 8.36, 5.41, both P < 0.001). Before intervention, there was no statistically significant difference in the proportion of patients with elevated blood pressure between the two groups ( P > 0.05). After intervention, the proportion of patients with elevated blood pressure was 40.00% (12/30) in the cognitive therapy group and 66.67% (20/30) in the combined group. Both groups showed a significant increase in the proportion of patients with elevated blood pressure compared with pre-intervention values ( χ2 = 4.02, 11.38, both P < 0.05). After intervention, the proportion of patients with elevated blood pressure in the combined intervention group was significantly higher than that in the cognitive therapy group ( χ2 = 4.28, P < 0.05). Before intervention, there was no significant difference in exercise tolerance between the two groups ( P > 0.05). After intervention, the combined intervention group showed significant increases in anaerobic threshold [(1 475.25 ± 415.65) mL/min] and oxygen pulse [(14.78 ± 2.86) mL/beat] compared with pre-intervention values ( t = 3.58, 7.49, both P < 0.05). However, there was no significant difference in the carbon dioxide ventilation equivalent (VE/VCO 2@VCP) at the ventilatory compensation point compared with pre-intervention levels ( P > 0.05). After intervention, the anaerobic threshold and oxygen pulse in the combined intervention group were significantly higher than those in the cognitive therapy group [(1 137.41 ± 349.86) mL/min, (9.94 ± 2.05) mL/beat] ( t = -3.40, -7.53, both P < 0.05). There was no significant difference in exercise tolerance in the cognitive therapy group between pre- and post-intervention ( P > 0.05). Before intervention, there was no significant difference in PSQI score between cognitive therapy and combined intervention groups ( P > 0.05). After intervention, score for sleep quality [(1.65 ± 0.26) points , (1.24 ± 0.23) points], sleep onset time [(1.51 ± 0.19) points, (1.33 ± 0.18) points], sleep time [(1.47 ± 0.23) points, (1.31 ± 0.20) points], sleep efficiency [(1.31 ± 0.20) points, (1.05 ± 0.19) points], sleep disturbance [(0.93 ± 0.15) points, (0.77 ± 0.20) points], hypnotic medication use [(0.96 ± 0.22) points, (0.67 ± 0.17) points], and daytime function [(1.19 ± 0.25) points, (1.02 ± 0.22) points] decreased in both groups compared with pre-intervention scores ( t = 8.21, 15.58, 9.86, 14.76, 10.02, 15.36, 8.78, 17.59, 7.84, 12.36, 5.74, 11.98, 12.03, 17.14, all P < 0.05). After intervention, PSQI score in the combined intervention group was significantly lower than that in the cognitive therapy group ( t = 6.46, 3.76, 2.87, 5.16, 3.50, 5.71, 2.79, all P < 0.05). The total effective rate for treating sleep disorders in the combined intervention group was 86.67% (26/30), which was significantly higher than that in the cognitive therapy group [63.33% (19/30), χ2 = 4.35, P < 0.05). Conclusions:Aerobic exercise training combined with cognitive behavioral therapy can improve exercise tolerance, reduce blood pressure, and enhance sleep quality in patients with sleep disorders and high-normal blood pressure.

Objective To investigate the function of CFTR in ApoE-/- mice with HHcy-induced hepato-cellular injury. Methods Thirty six 5-week old ApoE-/- mice were divided into three groups , including the ApoE-/- group, the HHcy group and the intervention group, (n = 12). Twelve normal C57BL/6J mice were fed with regular mouse diet as the normal control (SPF grade). HL-7702 human liver cells were intervened by Hcy (100 μmol/L) and 100 μmol/L Hcy + folic acid (100 μmol/L Hcy + F). The changes of Hcy, ALT and AST in the serum and the expression of CFTR mRNA and protein in liver and liver cells were detected. The concen-trations of ALT and AST in the liver cell intervened by VX-770 agonist and CFTR(inh)-172 inhibitor were mea-sured by ELISA. Results Compared with the control group , the levels of Hcy , ALT and AST were higher and the levels of CFTR mRNA and protein were lower in the Meth group (P < 0. 05 ) , while the reverse result in the Meth + F group (P < 0.05). Compared with the control group, the levels of CFTR mRNA and protein were de-creased and the levels of ALT and AST were increased in the 100 μmol/L Hcy group (P < 0.05). Compared with the 100 μmol/L Hcy group , the levels of CFTR mRNA and protein were increased and the levels of ALT and AST were decreased in the 100 μmol/L Hcy + F group (P < 0.05). Stimulated with VX-770 can reduce the concentrations of ALT and AST and the vice versa in the CFTR (inh)-17 group the concentration was increased in liver cells. Conclusion CFTR plays an important role in the regulation of hepatocellular injury by HHcy.

Aim To investigate the role of miR-125 b and its DNA methylation in homocysteine ( Hcy )-in-duced vascular smooth muscle cells( VSMCs) prolifera-tion. Methods VSMCs were stimulated with 0,50, 100, 200, 500 μmol · L-1 Hcy respectively. Then qRT-PCR was used to detect the mRNA levels of miR-125b,and nested-touchdown methylation-specific PCR ( ntMS-PCR) was used to detect the methylation levels of miR-125b. VSMCs were transfected with miR-125b precursor or the inhibitor of miR-125b ,then 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyl tetrazolium bromide ( MTT ) assay was used to reflect the proliferation of VSMCs. The distribution of CpG islands of miR-125b promoter region was analyzed by bioinformatics meth-ods. VSMCs were stimulated with 100 μmol·L-1 Hcy and transfected with or without DNA methylation inhib-itors 5-nitrogen impurity cytidine ( AZC) , then the ex-pression of miR-125b was detected by qRT-PCR. Re-sults The mRNA levels of miR-125 b were decreased in 100,200,500 μmol·L-1 Hcy group compared with 0 μmol·L-1 Hcy group. The precursor of miR-125b could inhibit the proliferation activity and the inhibitor of miR-125 b could increase the proliferation activity of VSMCs cells. Bioinformatics analysis indicated that MiR-125 b promoter region had a CpG island whose length was 792 bp ( 1881-2672 ) . The miR-125 b pro-moter region methylation levels increased after Hcy in-tervention ( P <0. 01 ) . The expression level of miR-125 b increased after AZC intervention ( P <0. 05 ) . Conclusions ① Hcy promotes vascular smooth mus-cle cell proliferation maybe by down-regulating the ex-pression of miR-125b. ② Hcy down-regulates the ex-pression of miR-125 maybe by up-regulating the methy-lation levels of miR-125b promoter region.

Aim To investigate the possible mecha-nisms of the levels of NO decrease induced apoptosis in human placental trophoblast cells. Methods Human placental trophoblast cells ( HTR-8 ) were cultured in 5 ml DMEM-F12 culture medium with 37℃ 5% CO2 . Then, the old culture medium was discarded and re-placed with 10,100,500,1 000 μmol·L-1 L-NAME, and the group without L-NAME was set as the control group, cultured for 48h. The effects of L-NAME on the survival of cells were detected by methylthiazolyldiphe-nyl tetrazolium bromide ( MTT); the content of NO in cells was tested by nitrate reductive enzymatic;trans-mission electron microscopy, flow cytometry analysis and Annexin-V FITC dyeing were used to test the effects of L-NAME on apoptosis in HTR-8 cells;restore Fe3+ colorimetric assay was applied for detection of to-tal antioxidant capacity ( T-AOC ) , xanthine oxidase for detection of superoxide dismutase ( SOD) activity, and thiobarbituric acid colorimetry for determination of content of MDA. Results Compared with the control group, the survival rate of HTR-8 cells and the levels of NO in 100,500,1 000 μmol·L-1 L-NAME group were significantly reduced(P<0.05,P<0.01). Flow analysis and Annexin-V FITC staining showed that L-NAME could induce cell apoptosis in a dose-dependent manner. The number of cell apoptosis was negatively correlated with the content of NO ( r = -0.5210 ) in HTR-8 cells. Transmission electron microscopy results showed that compared with the control group, the ex-perimental group's cell nucleus shape was irregular, nuclear pyknosis in irregular shape, the chromatin ag-glutination or side the collection, mitochondrial swell-ing or enrichment, crest fracture or dissolved, even vanished, forming the vacuole, especially in 100 μmol ·L-1 L-NAME group, the apoptotic bodies obviously appeared. At the same time, T-AOC, SOD levels in HTR-8 cells decreased ( P <0.05 ) , and the MDA content increased ( P<0.05 ) . The number of cell ap-optosis was negatively correlated with the level of T-AOC ( r= -0.3212 ) , SOD ( r= -0.2779 ) in HTR-8 cells , while positively correlated with the content of MDA(r=0.2807). Conclusion Oxidative stress may play an important role in the levels of NO decrease in-duced apoptosis in human placental trophoblast cells.

Aim To explore the role of ERO1 αand its DNA methylation in homocysteine (Hcy)-induced in-hibition of hepatocytes proliferation.Methods The hepatocytes stimulated with 0 μmol·L -1 Hcy were set as the normal group (NC group)and the hepatocytes stimulated with 1 00 μmol·L -1 Hcy as the experimen-tal group (Hcy group).Methyl thiazolyl tetrazolium (MTT)reduction assay was used to reflect the prolifer-ation of the hepatocytes;qRT-PCR and Western blot were used to detect the mRNA and protein levels of ERO1 α;the expression of green fluorescence protein was observed in hepatocytes after the recombinant plas-mid of ERO1 α was constructed,which was used to confirm if the recombinant plasmid into hepatocytes was successful,then the mRNA and protein levels of ERO1 αwere assayed and the proliferation of the hepa-tocytes was also detected;ntMSP was used to detect the change of ERO1 αDNA methylation.Results The mRNA and protein levels of ERO1 αwere decreased in Hcy group compared with NC group,and the prolifera-tion activity of hepatocytes in Hcy group was de-creased.Sequencing result showed that the recombi-nant plasmid of ERO1 αwas constructed successfully. QRT-PCR and Western blot revealed that ERO1 αwas overexpressed. The result of MTT suggested that ERO1 αoverexpression restored hepatocyte proliferation inhibited by Hcy.Hcy caused ERO1 αDNA hyperm-ethylation.Conclusions Hcy inhibits hepatocyte pro-liferation by downregulating the expression of ERO1 α, and methylation of ERO1 αpromoter may play a role in this process.