Objective:To evaluate the role of neuronal nitric oxide synthase (nNOS)-nitric oxide synthase 1 adaptor protein (NOS1AP) coupling in remifentanil-induced hyperalgesia in rats.Methods:Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), nNOS-NOS1AP inhibitor ZLc002 group (group C+ Z) and remifentanil + ZLc002 group (group R+ Z). Normal saline was intravenously infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C group. Remifentanil was intravenously infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R group. ZLc002 10 mg/kg was intraperitoneally injected for 3 consecutive days, and then normal saline 0.1 ml·kg -1·min -1 and remifentanil 1.0 μg·kg -1·min -1 were intravenously infused for 60 min in C+ Z group and R+ Z group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intravenous infusion and 6, 24 and 48 h after intravenous infusion (T 0-3). All the rats were sacrificed after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of nNOS, NOS1AP and Dexamethasone-induced Ras-related protein 1 (Dexras1) protein and mRNA using the real-time polymerase chain reaction. Nitrosylated proteins were extracted by biotin conversion for determination of the expression of nNOS, NOS1AP and total and nitrosylated Dexras1 (by Western blot) and co-expression of nNOS-NOS1AP (by co-immunoprecipitation). The content of NO in the spinal cord was measured. Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3, the expression of nNOS and NOS1AP protein and mRNA was up-regulated, the co-expression of nNOS-NOS1AP and NO production were increased, and the expression of nitrosylated Dexras1 was up-regulated in group R ( P<0.05), and no significant change was found in each aforementioned parameter in group C+ Z ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, the co-expression of nNOS-NOS1AP and NO production were decreased, the expression of nitrosylated Dexras1 was down-regulated ( P<0.05), and no significant change was found in the expression of nNOS and NOS1AP protein and mRNA in group R+ Z ( P>0.05). There were no significant differences in total Dexras1 protein and mRNA expression among the four groups ( P>0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia may be related to up-regulating the expression of nNOS and NOS1AP in the spinal cord, promoting interaction between nNOS and NOS1AP and mediating NO generation and Dexras1 nitrosylation modification in rats.

Objective:To investigate the clinical characteristics of circadian rhythm disorder of blood pressure and its impact on orthostatic hypotension (OH) in Parkinson′s disease (PD).Methods:A total of 165 PD patients from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from August 2019 to October 2021 were consecutively enrolled. Medical history and scores of motor and non-motor symptoms of patients were collected. Twenty-four-hour ambulatory blood pressure and OH data were collected, and the OH questionnaire was completed. The incidence of each type of circadian rhythm disorder of blood pressure was investigated. The t test, chi-square test and Mann-Whitney U test were used to determine between-group differences of circadian rhythm disorder of blood pressure. The linear trends in clinical characteristics were tested by linear regression analysis. Logistic regression analysis was used to analyze the relationship between different circadian rhythm disorders of blood pressure and OH as well as symptomatic OH (SOH). Results:In 165 PD patients, the incidence of reverse dipping pattern was 39.39% (65/165), nocturnal hypertension was 43.64% (72/165), and awakening hypotension was 31.52% (52/165). Compared with patients without reverse dipping pattern, patients with reverse dipping pattern were older [(71.72±7.81) years vs (65.29±9.68) years, t=-4.491, P<0.001], had later onset age [(66.67±9.10) years vs (62.16±10.66) years, t=-2.809, P=0.006], longer duration [36.00(20.50, 95.50) months vs 24.00(12.00, 41.75) months, Z=-3.393, P<0.001], higher dose of levodopa (LD) [(426.15±267.38) mg/d vs (284.00±235.58) mg/d, t=-3.590, P<0.001], higher levodopa equivalent dose (LED) [(514.80±360.03) mg/d vs (341.44±284.57) mg/d, t=-3.440, P=0.001], higher Unified Parkinson′s Disease Rating Scale (UPDRS)-Ⅱ scores (12.92±6.38 vs 9.54±5.59, t=-3.434, P=0.001), higher UPDRS-Ⅲ scores (28.34±11.60 vs 21.41±12.18, t=-3.508, P=0.001) and higher percentages of hallucinations [18.46% (12/65) vs 7.00% (7/100), χ2 =5.079, P=0.024]. Compared with patients without awakening hypotension, patients with awakening hypotension were older [(70.83±7.09) years vs (66.44±10.16) years, t=-2.811, P=0.006]. Compared with patients without nocturnal hypertension, patients with nocturnal hypertension had longer duration [39.50(15.00, 96.00) months vs 24.00 (12.00, 36.00) months, Z=-2.944, P=0.003], higher LD [(398.61±251.19) mg/d vs (294.62±254.25) mg/d, t=-2.619, P=0.010], higher LED [(493.28±344.02) mg/d vs (345.05±298.59) mg/d, t=-2.959, P=0.004], higher percentages of hallucinations [19.44% (14/72) vs 5.38% (5/93), χ2 =7.882, P=0.005], higher UPDRS-Ⅱ scores (12.08±6.33 vs 10.00±5.86, t=-2.086, P=0.039), higher UPDRS-Ⅲ scores (26.50±11.72 vs 22.42±12.66, t=-2.034, P=0.044), and greater blood pressure variability (BPV) (20.66±5.47 vs 17.44±5.36, t=-3.798, P<0.001). Trend analysis showed that the variety of circadian rhythm was positively correlated with age and duration, use of levodopa and monoamine oxidase B inhibitors and amantidine, morning and daily LD and LED, UPDRS-Ⅱ, UPDRS-Ⅲ and Hamilton Anxiety Scale scores, hallucinations, OH and SOH, and BPV in PD ( P<0.05). Multivariate Logistic regression analysis showed that awakening hypotension ( OR=3.35, 95% CI 1.55-7.22, P=0.002) and nocturnal hypertension ( OR=2.44, 95% CI 1.20-4.97, P=0.014) were risk factors for OH, and LED ( OR=1.21, 95% CI 1.01-1.43, P=0.035), UPDRS-Ⅲ scores ( OR=1.09, 95% CI 1.02-1.16, P=0.009) and w-BPV ( OR=1.14, 95% CI 1.01-1.29, P=0.029) were independent risk factors for SOH. Conclusions:Circadian rhythm disorder of blood pressure was correlated with age, duration, severity of motor symptoms. Awakening hypotension and nocturnal hypertension are independent risk factors for OH in PD.

Objective:To determine the evolution of gait impairment over the course of Parkinson′s disease (PD) by assessing the changes of gait characteristics in different disease stages, which could be helpful for disease monitoring.Methods:A total of 276 PD patients [PD group, Hoehn-Yahr (H-Y) stage 1-3] and 63 healthy controls (control group) enrolled in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2019 to September 2021 were included in this cross-sectional study. The gait spatiotemporal variables were recorded by a portable inertial measurement unit system. Exploratory factor analysis was performed to obtain gait domains representing different gait characteristics. One way analysis of variance was used to evaluate the differences of gait variables and gait domains among the control group and 3 different H-Y stages of the PD group, as well as the differences among the control group and 2 motor subtypes of PD in different stages. The sensitivity of different gait variables and gait domains in evaluating the severity of gait impairments at different disease stages was compared.Results:Eleven gait spatiotemporal variables were grouped in 4 gait domains: pace (step length, gait speed and stride length), rhythm/phase (cadence, stride time and double support time), pace-related variability/asymmetry [step length coefficient of variation (CV), gait speed CV and step length asymmetry] and rhythm/phase-related variability/asymmetry (swing time CV and swing time asymmetry). As the disease progresses, most evolution trends of the 4 gait domains in the tremor-dominant PD patients were consistent with those in the non-tremor-dominant subtype. Compared with the control group, PD patients at H-Y stage 1 began to show the mild impairment of rhythm/phase-related variability/asymmetry (effect size 0.42; standardized score -0.03±0.69 vs -0.33±0.49, P<0.05), especially swing time asymmetry in tremor-dominant patients; the pace domain was damaged moderately in PD patients at H-Y stage 2 (effect size 0.64; standardized score 0.12±0.80 vs 0.64±0.81, P<0.05), especially in non-tremor-dominant PD patients, but not in PD patients at H-Y stage 1 ( P>0.05). Pace-related variability/asymmetry showed great impairment in PD patients at H-Y stage 3 (effect size 0.62; standardized score 0.27±1.12 vs -0.27±0.52, P<0.05), but not in PD patients at H-Y stages 1 and 2 ( P>0.05). Conclusions:The characteristic impairments of gait in PD evolve in the process of disease progression. The rhythm/phase-related variability/asymmetry domain may be a marker to distinguish early PD from healthy controls. The pace domain and the pace-related variability/asymmetry domain are important markers to evaluate the progression of PD.

Objective:To study the risk factors for ipsilateral severe hearing impairment in patients with hemifacial spasm (HFS) after microvascular decompression (MVD).Methods:MVD was performed in 3700 patients with HFS, admitted to our hospital from October 2007 to August 2020; according to the existence of ipsilateral severe hearing impairment, these patients were divided into severe hearing impairment group and non-severe hearing impairment group. The clinical data of these patients were compared. Multivariate linear regression analysis was used to determine the independent influencing factors for ipsilateral severe hearing impairment.Results:Forty-five patients (1.2%) had ipsilateral severe hearing impairment after MVD; no one got recovery of hearing impairment during the follow-up period (0.6-11.8 years, 6.3 years in average). As compared with those in the non-severe hearing impairment group, patients in the severe hearing impairment group had significantly older age, significantly higher percentages of male patients, and patients with left HFS, hypertension, and diabetes mellitus, statistically higher percentage of patients having small posterior fossa volume, arachnoid thickening and adhesion, and vertebral artery compression, significantly lower percentage of patients with anterior inferior cerebellar artery compression, significantly higher percentage of patients with arteriosclerosis of offending arteries and difficult decompression ( P<0.05). Multivariate linear regression analysis revealed that hypertension, vertebral artery compression, arteriosclerosis of offending artery and difficult decompression were independent risk factors for severe hearing impairment in patients with HFS after MVD. Conclusion:It's difficult to get recovery for severe hearing impairment in patients with HFS after MVD; this complication is much common in patients with hypertension, vertebral artery compression, arteriosclerosis of offending artery or difficult decompression.

Objective:To analyze the value of maximum standardized uptake value (SUV max) of 18F-fluorodeoxyglucose (FDG) PET/CT in differentiating the malignant solitary pulmonary nodules (SPN) from benign ones. Methods:18F-FDG PET/CT imaging data of 84 patients (39 males, 45 females; age: 34-81(average: 61.1) years) with SPN in the First People′s Hospital of Lianyungang between September 2017 and June 2019 were retrospectively analyzed. The pathological results were taken as the gold standard. Differences of SUV max between benign and malignant SPN were analyzed with Mann-Whitney U test, and the best cut-off value for the diagnosis of benign and malignant SPN was measured by receiver operating characteristic (ROC) curve. The diagnostic efficacy was analyzed based on SUV max. Results:The pathological results confirmed 54 patients with malignant SPN, and 30 patients with benign SPN. SUV max of malignant group was significantly higher than that of benign group (5.48±4.08 vs 1.70(0.73, 3.33); U=443.50, P=0.001). The 84 SPN included 58 solid SPN and 26 subsolid SPN. SUV max of malignant subsolid SPN and benign ones were not significantly different ( U=56.00, P>0.05). The diagnostic value of SUV max in 58 cases of solid nodules were analyzed based on ROC curves, and the optimal cut-off value was 1.85. The corresponding diagnostic sensitivity, specificity, accuracy, negative predictive value and positive predictive value were 97.06%(33/34), 62.50%(15/24), 82.76%(48/58), 15/16, 78.57%(33/42), respectively. Conclusions:18F-FDG uptake of malignant SPN were higher than benign ones. The diagnosis of benign and malignant solid SPNs based on SUV max 1.85 has high sensitivity, negative predictive value and accuracy. SUV max has limited diagnostic value on subsolid SPN.

Objective:To identify and quantify spatiotemporal and kinematic gait parameters in a group of early-stage Parkinson′s disease (PD) patients compared with healthy subjects.Methods:Eight patients with PD (PD group, Hoehn-Yahr stage≤2.5) and seven age-matched healthy subjects (control group) were enrolled from the Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between May 2017 and August 2018 for the study. The spatiotemporal and kinematic gait parameters were obtained by Vicon 3D optical motion analysis system under three conditions: single-task walking, dual-task walking and turning. The linear mixed model was used to compare the gait parameters between the two groups and analyze the interactive effects.Results:Arm swing amplitude in the PD group was lower than that in the control group ((0.63±0.15) m vs (0.89±0.27) m in single-task walking, (0.64±0.16) m vs (0.99±0.22) m in dual-task walking, β=-0.353, 95% CI -0.558--0.148, P=0.002). The PD group showed significantly higher arm swing asymmetry than the control group (12.48%±5.48% vs 6.96%±4.39% in single-task walking, 17.13%±4.05% vs 7.67%±5.23% in dual-task walking, β=8.992, 95% CI 4.148-13.836, P=0.001). A notable interactive effect of groups and task factors in arm swing asymmetry was found. The arm swing asymmetry of the PD group increased more than the control group in dual-task walking than in single-task walking (β=3.916, 95% CI 1.367-6.466, P=0.003). As for the gait characteristics of the lower limbs, stride length and step length of the PD group were lower than those of the control group ((1.10±0.17) m vs (1.31±0.10) m in stride length, β=-0.169, 95% CI -0.300--0.038, P=0.015; (0.55±0.09) m vs (0.65±0.04) m in step length, β=-0.081, 95% CI -0.150--0.013, P=0.023). For both groups, statistically significant differences were not observed in step width, stride length and step length between single-task and dual-task walking ( P>0.05). The PD group completed the turning process faster than the control group ((1.66±0.30) s vs (1.37±0.23) s, β=0.302, 95% CI 0.049-0.555, P=0.023). As for the rotation-onset pattern, no statistically significant differences were found between the PD and the control group for the onset of the head, trunk and pelvic rotation ( P>0.05). Participants started to rotate their heads before the pelvis in all groups (β=-0.060, 95% CI-0.107--0.014, P=0.011). Conclusions:The quantified gait parameters can more accurately reflect the gait characteristics of early PD. Patients with PD exhibited smaller arm swing magnitude, greater arm swing asymmetry, shorter stride length, and slower turning speed compared to the controls. Arm swing asymmetry further differs between subjects with early PD and controls under dual-task walking.

Objective: To evaluate the effects of different doses of naloxone combined with dezocine on postoperative analgesia in patients with breast cancer. Methods: One hundred and twenty patients with modified radical mastectomy were enrolled in the Tianjin Medical University Cancer Institute and Hospital, between May 2018 and January 2019. The patients were randomly assigned into group L, group M, group H, and group C (n=30). Patients in each group were administered 0.15 mg/kg of dezocine. Patients in group L, group M, and group H were intravenously instilled with naloxone (0.5, 1.0, and 1.5μg/kg, respectively), while patients in group C were administered equal volumes of normal saline. We recorded the time of awakening and removing the laryngeal mask in each group, and the blood pressure and heart rate of each patient around the time of removing the laryngeal mask. We determined the visual analog scale (VAS) scores of pain, Bruggrmann comfort scale (BCS) scores, and Ramsay sedation scores at 1h (T1), 6h(T2), 12h (T3), and 24h (T4) postoperatively, and the number of remedial analgesia and postoperative adverse reactions were recorded in each group after surgery. Results: The time of awakening and removing the laryngeal mask in group L, group M, and group H were shorter than that in group C, and group M had the shortest awakening time (P<0.05). The VAS scores of the patients in group M at T1, T2, and T3 were lower than those in the other three groups (P<0.05). The number of postoperative remedial analgesia and adverse reactions in group C were higher than those in the other three groups (P<0.05). Conclusions:Naloxone (1.0 μg/kg) combined with dezocine (0.15 mg/kg) can enhance the postoperative analgesic effect of dezocine, shorten the awakening time, and reduce the adverse reactions.

Objective To analyze the characteristic changes of macular thickness in patients with Parkinson's disease by spectral-domain optical coherence tomography (SD-OCT),and find out the association between macular thickness and disease progression,cognitive dysfunction,visuospatial impairment and asymmetry of motor symptoms.Methods Seventy-one Parkinson's disease (PD) patients who were admitted to the Department of Neurology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2016 to May 2018 and sixty-one healthy controls who volunteered to participate for the same period were enrolled and underwent SD-OCT examination.The macular thickness of all retinal quadrant segments,foveal thickness,and macular volume between the two groups were comparatively analyzed.Associations between macular measurements and clinical parameters such as disease duration,Unified Parkinson's Disease Rating Scale part Ⅲ (UPDRS-Ⅲ) scores,Montreal Cognitive Assessment (MoCA) total scores,and visuospatial subscores were analyzed using generalized estimated equation fitted with linear regression models.Results Mean macular thickness in the PD group was significantly reduced compared with those in the control group ((261.94± 12.90) μm vs (270.96± 10.71) μm,B=-8.135,P＜0.01).All quadrants of macular thickness (except fovea and 1 mm central zone) in the PD group were reduced compared with those in the control group.Receiver operating characteristic (ROC) curve analysis revealed that inner superior thickness could predict the presence of PD with an area under ROC of 0.727 (95％CI 0.662-0.792,P＜0.01).UPDRS-Ⅲ scores were negatively correlated with foveal thickness (B=-9.132,P=0.034),1 mm central zone thickness (B=6.963,P=0.036) and all quadrants of the inner ring (superior (B=-7.727,P＜0.01),inferior (B=-5.169,P=0.044),nasal (B=-5.960,P＜0.01) and temporal (B=-5.905,P＜0.01)) macular thickness.The disease duration had no relationship with any quadrant of macular measurements.No statistically significant difference was found between the macula parameters of the hemiretinae corresponding to more and less severely affected cerebral hemisphere.MoCA total scores were positively correlated with all quadrants of the inner ring (superior (B=2.693,P=0.007),inferior (B=3.391,P=0.002),nasal (B=2.609,P=0.001) and temporal (B=2.115,P=0.013)) macular thickness.MoCA visuospatial subscores were positively associated with average macular thickness (B=4.368,P=0.042),macular volume (B=0.161,P=0.004),inferior (B=8.582,6.541),nasal (B=8.130,6.017) and temporal (B=5.938,5.316)quadrants of outer and inner rings macular thickness (all P＜0.05).Conclusions In PD patients,the macular thickness and macular volume were decreased.Asymmetry was not identified between hemiretinae in PD.Some quadrants of macular thickness were associated with disease progression,cognitive dysfunction,and visuospatial impairment.

Objective To investigate the efficacy and safety of intravesical instillation with Sufuning (SFN) lotion for prevention of postoperative recurrence of bladder cancer. Methods A total of 240 bladder cancer patients who were diagnosed as bladder cancer and accepted trans-urethral resection of bladder tumor from January 2010 to June 2016 in Shanxi Provincial Cancer Hospital were randomly divided into the experimental group (120 cases) and the control group (120 cases) according to the envelope method. The patients in the experimental group were treated with SFN lotion for immediate intravesical instillation(250 mg for once), and the patients in the control group were treated with pirarubicin (THP) for immediate intravesical instillation (30 mg for once). The patients of two groups were treated with intravesical chemotherapy once a week for 8 times, and the chemotherapy was performed once a month for 1 year. The recurrence rate, progression-free survival (PFS) rate, overall survival (OS) rate and recent side effects were compared between the two groups. Results The patients were followed up for 6 to 60 months. The median follow-up time was 36.5 months.In the experimental group,6 patients were lost and 8 patients were lost in the control group.The experimental group, the total recurrence rate was 26.3 % (30/114). The control group, the overall recurrence rate was 25.0 % (28/112) (χ2= 0.142, P = 0.781). Five years of PFS rate in the experimental group and the control group was 73.7 % (84/114) and 75.0 % (84/112) respectively, and there was no significant difference between the two groups (χ2= 2.011, P= 0.615). Five years of OS rate in the experimental group and the control group was 95.6 % and 92.9 % respectively, and there was no significant difference between the two groups (χ 2= 1.611, P= 0.425). The major side effects included chemical cystitis and hematuria. The incidence of chemical cystitis and hematuria in the experimental group was significantly lower than that in the control group(χ2=5.991,P=0.018;χ2=4.925,P=0.036).There was a statistically significant difference of the hematological side effects (blood routine changes) between the two groups (χ 2= 4.891, P= 0.032). Conclusion It is safe and effective for intravesical instillation of SFN lotion to prevent the recurrence of bladder cancer.