[A study of the correlation between gray matter atrophy in multiple sclerosis and impairment of cognitive function domains].

Objective: To quantify cerebral cortical and deep gray matter atrophy in patients with multiple sclerosis (MS) and explore its correlation with impairment in domains of cognitive function. Methods: Twenty patients with MS and 16 healthy controls (HC) matched for age, sex, and education level were included. Using FreeSurfer software, based on 3D-MRI technology, the differences in cortical thickness and deep gray matter volume between the two groups were comparatively analyzed. A neuropsychological scale that included six domains of cognitive function was scored on both study groups to analyze the correlation between cortical thickness and volume of deep gray matter in MS patients with impairment in cognitive function domains. Results: Impairment in domains of cognitive function: cognitive impairment was present in 60% MS patients in this study, mainly manifesting as impairment of verbal memory, verbal fluency, visuospatial memory, and information processing speed function (all P<0.05). Of these, the majority had impaired visuospatial memory function (55.0%), and the least number of patients had impaired information processing speed (15.0%). Changes in cortical thickness: compared with the HC group, the MS group showed that cortical atrophy was mainly concentrated in the frontoparietal region, including significant thinning of cortical thickness in the left inferior parietal gyrus, right superior frontal gyrus, and the right superior parietal gyrus (all P<0.05). Among them, atrophy of the left inferior parietal gyrus was significantly positively correlated with the impairment of verbal memory, verbal fluency, and information processing speed (all P<0.05). There was a significant positive correlation between the right superior frontal gyrus atrophy and verbal memory, verbal fluency, and visuospatial memory impairment (all P<0.05). Changes in deep gray matter volume: compared with the HC group, deep gray matter volume in the MS group decreased significantly in the bilateral thalamus, bilateral putamen, bilateral pallidum (all P<0.01), and right nucleus accumbens (P<0.05). Among them, left thalamus atrophy was significantly positively correlated with visuospatial memory impairment (r=0.45, P=0.046), and left putamen atrophy was both significantly positively correlated with visuospatial memory (r=0.45, P=0.047) and information processing speed impairment (r=0.50, P=0.026). Conclusions: Early structural brain changes in MS are dominated by gray matter atrophy. Deep gray matter is more prominent than cortical atrophy.

Imagined eating - An investigation of priming and sensory-specific satiety.

While obesity remains a pressing issue, the wider population continues to be exposed to more digital food content than ever before. Much research has demonstrated the priming effect of visual food content, i.e., exposure to food cues increasing appetite and food intake. In contrast, some recent research points out that repeated imagined consumption can facilitate satiate and decrease food intake. Such findings have been suggested as potential remedies to excessive food cue exposure. However, the practically limitless variety of digital food content available today may undermine satiation attempts. The present work aims to replicate and extend prior findings by introducing a within-subjects baseline comparison, disentangling general and (sensory-) specific eating desires, as well as considering the moderating influence of visual and flavour stimulus variety. Three online studies (n = 1149 total) manipulated food colour and flavour variety and reproducibly revealed a non-linear dose-response pattern of imagined eating: 3 repetitions primed, while 30 repetitions satiated. Priming appeared to be specific to the taste of the exposed stimulus, and satiation, contrary to prior literature, appeared to be more general. Neither colour nor flavour variety reliably moderated any of the responses. Therefore, the results suggest that a more pronounced variety may be required to alter imagery-induced satiation.

[Effect of sleep spindle density on memory function in patients with obstructive sleep apnea hypopnea syndrome].

Objective: To explore the characteristics of sleep spindle density in nonrapid eye movement (NREM) stage 2 (N2) sleep and its effect on memory function in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: Patients who underwent polysomnography (PSG) examination due to snoring in the Second Affiliated Hospital of Soochow University from January to December 2021 were prospectively collected. A total of 119 male patients, aged 23-60 (37.4±7.3) years, were enrolled finally. According to the apnea hyponea index (AHI), the subjects were divided into a control group (AHI<15 times/h) of 59 cases and an OSAHS group (AHI≥15 times/h) of 60 cases. The basic information, general clinical data and PSG parameters were collected. Memory function scores were evaluated by using logical memory test (LMT), digit ordering test (DOT) and pattern recognition memory (PRM), spatial recognition memory (SRM) and spatial working memory (SWM) in CANTAB test. The number of N2 sleep spindles in leads left central area (C3) and right central area (C4) was counted by hand and the sleep spindle density (SSD) was calculated. The differences in the above indexes and N2 SSD were compared between the two groups. Shapiro-Wilk method, chi-squared test, Spearman correlation analysis and stepwise multivariate logistic regression analysis were used to investigate the influencing factors of memory scores in patients with OSAHS. Results: Compared with the control group, the proportion of the slow-wave sleep, the minimum blood oxygen saturation, the SSD in C3 of NREM2 stage and the SSD in C4 of NREM2 stage were lower in the OSAHS group. The body mass index (BMI), proportion of N2 sleep, oxygen reduction index, percentage of time with oxyhemoglobin saturation below 90% (TS90), maximum duration of apnea and respiratory effort-related arousal(RERA) were higher in the OSAHS group (all P<0.05). Compared with the control group, the immediate LMT score was lower, while the time for immediately completing PRM test, the total time for immediately completing SRM test and the time for delayed completing PRM test were longer in the OSAHS group, suggesting that the immediate logical memory, immediate visual memory, spatial recognition memory and delayed visual memory were worse in the OSAHS group. Stepwise multivariate logistic regression analysis revealed that the number of years of education (OR=0.744, 95%CI 0.565-0.979, P=0.035), maximum duration of apnea (OR=0.946, 95%CI 0.898-0.997, P=0.038) and N2-C3 SSD (OR=0.328, 95%CI 0.207-0.618, P=0.012) and N2-C4 SSD (OR=0.339, 95%CI 0.218-0.527, P=0.017) were independent factors affecting the immediate visual memory. The AHI (OR=1.449, 95%CI 1.057-1.985, P=0.021), N2-C3 SSD (OR=0.377, 95%CI 0.246-0.549, P=0.009), and N2-C4 SSD (OR=0.400, 95%CI 0.267-0.600, P=0.010) were independent factors affecting delayed visual memory. Conclusions: The decrease in SSD is associated with impaired memory function in patients with moderate-severe OSAHS, which is manifested as impairment of immediate visual memory and delayed visual memory. This suggests that changes of sleep spindle wave in N2 may be an electroencephalographic biomarker for assessing cognitive impairment in OSAHS patients.

[Learning curve and short-term clinical outcomes of Mako robotic-assisted direct anterior approach total hip arthroplasty].

Objective: To explore the learning curve and short-term clinical outcomes of Mako robotic-assisted direct anterior approach total hip arthroplasty (THA). Methods: The preoperative basic data, surgical information and postoperative rehabilitation of 50 patients who underwent Mako robotic-assisted THA for hip diseases in Department of Orthopedic Surgery of the 6th People's Hospital Affiliated to Shanghai Jiao Tong University from December 2018 to December 2020 were analyzed retrospectively, included operation time, intraoperative blood loss, postoperative complications, postoperative imaging parameters (abduction angle, anteversion angle, lower limb length difference, eccentricity difference) and postoperative hip joint Harris score (hip Harris score, HHS). There were 16 males and 34 females, with a mean age of 50-79(67±10) years. The postoperative clinical results of Mako robotic-assisted total hip arthroplasty was analyzed. A cumulative sum analysis (CUSUM) was performed on the operation time (OT). The CUSUM learning curve was modeled by curve fitting and R² was used to testify the goodness. The different phase of the learning curve was compared with several observation indicators. Results: All patients were followed up for more than 6 months. Two patients had poor wound healing and 5 patients had symptoms of lateral femoral cutaneous nerve injury, which disappeared within 1-2 months. No serious complications such as dislocation, aseptic loosening, periprosthetic infection or revision occurred in all the patients. The average operation time was (81±16) min, and the intraoperative blood loss was (456±84) ml. The average Harris hip score at the last follow-up was 88.6±2.5. The radiological evaluation showed that the positions of the acetabular cups were all in the Lewinnnek safety zone; the limb length discrepancy was (0.15±0.50) cm, the offset was (-0.11±0.72) cm. The OT decreased with the accumulation of the cases. The CUSUM learning curve was best modeled as cubic curve,the fitting curve reached the top at the 19th case. As a cut-off point, the 19th point divided the learing curve into two phases. There were statistical differences in OT, pelvic array installation time, acetabular registration time, acetabular reaming time (all P<0.05), but there was no significant differences in Harris hip score, acetabular prosthesis anteversion angle and abduction angle between the two groups (all P>0.05). Conclusions: The learning curve of Mako robot-assisted DAA-THA is about 19 cases. Mako robot-assisted DAA-THA can ensure the accuracy of prosthetic placement and the safety of the operation during the learning curve, and the short-term clinical results after surgery is excellent.

[Clinical characteristics of patients with obstructive sleep apnea hypopnea syndrome combined with alveolar hypoventilation].

Objective: To evaluate the clinical characteristics of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with alveolar hypoventilation. Methods: This retrospective study included patients who were diagnosed as OSAHS by polysomnography (PSG) and underwent daytime awake transcutaneous carbon dioxide (PtcCO2) monitoring from November 2019 to February 2021 at the Sleep Center of the Second Affiliated Hospital of Soochow University. A total of 177 patients were enrolled in the analysis, including 167 males and 10 females, aged (40±8) years old. Patients with daytime awake PtcCO2>45 mmHg (1 mmHg=0.133 kPa) were diagnosed as daytime alveolar hypoventilation, with which participants were divided into the daytime alveolar hypoventilation group and non-daytime alveolar hypoventilation group. Body mass index (BMI) cut-off value predicting daytime alveolar hypoventilation was calculated and the patients were divided into the high BMI group and low BMI group. The continuous nocturnal PtcCO2 data was available for a subset of 128 patients, and the patients were divided into two groups according the daytime alveolar hypoventilation or not. Across-group differences were compared, respectively. Results: Compared with the non-daytime alveolar hypoventilation group (n=125), the BMI [27.57 (26.55, 30.33) vs 26.60 (25.06, 28.09) kg/m2], Epworth sleepiness score(ESS) score [9.50 (6.25, 12.00) vs 7.00 (4.00, 10.75)], higher oxygen desaturation index (ODI) [38.00 (15.23, 64.93) vs 26.80 (11.30, 44.30) events/h] and percentage of total time with oxygen saturation level<90% (TS90%) [11.24% (1.88%, 32.44%) vs 4.35% (0.72%, 9.87%)] of the daytime alveolar hypoventilation group(n=52) were significantly higher (P<0.05), and lowest arterial oxygen saturation (LSaO2) [74.50% (60.25%, 82.00%) vs 79.00% (73.00%, 84.50%)], mean arterial oxygen saturation (MSaO2) [94.00% (91.00%, 95.00%) vs 95.00% (94.00%, 96.00%)] were significantly lower (P<0.05). The BMI cut-off value for predicting daytime alveolar hypoventilation was 27.04 kg/m2. Of the 177 enrolled patients, 90 were in the high BMI group and 87 were in low group. Compared with the low BMI group, the proportion of daytime sleepiness, the ESS score, the prevalence of hypertension, AHI and daytime awake PtcCO2 in the high BMI group were significantly higher (P<0.05). Among the subset of 128 patients with nocturnal PtcCO2 data available, the BMI, daytime PtcCO2 level, the nocturnal CO2 level and the prevalence of sleep related alveolar hypoventilation in the daytime alveolar hypoventilation group (n=40) were significantly higher than those in the non-daytime alveolar hypoventilation group (n=88) (P<0.05). Conclusions: The OSAHS patients with alveolar hypoventilation have higher BMI and more severe nocturnal hypoxia. OSAHS patients with BMI>27.04 kg/m2 are more likely to develop sleep related alveolar hypoventilation disorder.

[Effects of moderate dose rosuvastatin on carotid plaque in patients with diabetes mellitus evaluated by magnetic resonance imaging].

Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group (P<0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups (P<0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P<0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm3 vs. 75.76 (48.20, 115.64) mm3, P>0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P>0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm3 vs. 72.49 (51.91, 199.59) mm3, P<0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P<0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm3) and (12.71% (8.39%, 24.41%)) at 24 months (both P<0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups(P>0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months (P>0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.

[Effects of daytime hypercapnia on logical memory and working memory in patients with obstructive sleep apnea hypopnea syndrome].

Objective: To investigate the effects of daytime hypercapnia on logical memory and working memory in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: This prospective study recruited patients complaining of snoring and diagnosed with OSAHS at the Sleep Center of the Second Affiliated Hospital of Soochow University from January to November 2020. Patients were assessed clinically and scored for their memory function. All patients underwent daytime transcutaneous carbon dioxide (PtcCO2) test, and overnight polysomnography (PSG). Logical memory was scored using the Logical Memory Test (LMT), while working memory was evaluated by Digit Span Test (DST) and Cambridge Neuropsychological Test Automated Battery (CANTAB) which included Pattern Recognition Memory (PRM), Spatial Span (SSP), and Spatial Working Memory (SWM). Patients were divided into the normocapnic group and the hypercapnic group using the daytime PtcCO2 test. The clinical and PSG parameters and the memory test scores between the two groups were compared. Binary logistic stepwise regression was conducted to identify risk factors of memory impairment in OSAHS patients. Results: Among the 123 enrolled OSAHS patients, 79 were normocapnic and 44 were hypercapnic. There was no significant difference in the general clinical parameters between the two groups. The snoring history in years in the hypercapnic group was longer than that in the normocapnic group (P<0.05). Compared with the normocapnic group, the apnea-hyponea index (AHI), oxygen desaturation index (ODI) and percentage of total sleep time with oxygen saturation level<90% (TS90) of the hypercapnic group were higher (all P<0.05), while other PSG parameters exhibited no statistically significant differences. There was no statistically significant difference in the immediate logical memory and PRM immediate accuracy rate between the two groups, while the delayed logical memory, verbal and spatial working memory, and executive function were worse in the hypercapnic group, as shown by lower total LMT scores, lower DST, lower SSP scores (all P<0.05), and higher between errors and strategy scores (P<0.01) of SWM in the hypercapnic group. Binary logistic stepwise regression showed that PtcCO2 ≥45 mmHg (1 mmHg=0.133 kPa, OR=3.055, 95%CI 1.359-6.868, P=0.007) and higher body mass index (BMI) (OR=1.132, 95%CI 1.005-1.275, P=0.041) were risk factors for poor performance in Digit Span Backwards Test. Therefore, PtcCO2 ≥45 mmHg was an independent risk factors for poor performance in delayed LMT, SSP, and between errors and strategy scores in SWM (OR=3.109, 3.941, 3.238 and 2.785, respectively, all P<0.05). Conclusion: Hypercapnia had negative impacts on logical memory and working memory of OSAHS patients, especially on the delayed logical memory, verbal working memory and spatial working memory impairment.

[Relationship between insomnia phenotype and mild cognitive impairment in young and middle-aged patients with obstructive sleep apnea hypopnea syndrome].

Objective: To explore the relationship between insomnia phenotype and mild cognitive impairment (MCI) in young and middle-aged patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: Those patients admitted due to snoring and examined by polysomnography (PSG) in the Sleep Center of the Second Affiliated Hospital of Soochow University from January 2014 to January 2019 were screened. They were between 30 and 60 years old, and their cognitive function was assessed by the Montreal cognitive assessment (MoCA) and their sleep quality was assessed by the Pittsburgh sleep quality index (PSQI). According to the sleep apnea hypopnea index (AHI), the patients were divided into three groups: snoring group (AHI<5 times/h), mild/moderate OSAHS group (5≤AHI≤30 times/h) and severe OSAHS group (AHI>30 times/h). According to the results of PSQI score, the patients were further divided into non-insomnia group (PSQI total score<8) and insomnia group (PSQI total score≥8). The differences of parameters in different groups were compared, and the relationship between OSAHS insomnia phenotype and MCI was analyzed by binary logistic regression model. Results: A total of 2 098 patients with the average age of (42.7±8.4) years old and the average BMI of (26.3±3.6) kg/m(2) were enrolled in the study, including 398 cases in snoring group (including 254 cases in non-insomnia group and 144 cases in insomnia group), 754 cases in mild/moderate OSAHS group (including 446 cases in non-insomnia group and 308 cases in insomnia group) and 946 cases in severe OSAHS group (including 722 cases in non-insomnia group and 224 cases in insomnia group). In the mild/moderate OSAHS group, compared with the non-insomnia group, the proportion of women in the insomnia group was higher with lighter degree of obesity, lighter severity of illness and lighter degree of hypoxia (all P<0.05). In the severe OSAHS group, the general characteristics of insomnia patients were similar to those of the mild/moderate OSAHS group, and the MoCA score of the insomnia group was lower than that of the non-insomnia group [(26.3±2.7) vs (25.5±2.9) points] (P=0.001). In the evaluation of each item of PSQI, the total score and daytime dysfunction score of insomnia patients in mild/moderate OSAHS group and severe OSAHS group was higher than those in snoring group [(11.2±1.9) points, (12.8±2.2) points vs (10.9±2.1) points and (1.5±0.4) points, (1.9±0.8) points vs (0.5±0.5) points], but the score in sleep latency was lower than that in snoring group [(1.5±0.5) points, (1.5±0.5) points vs (2.1±0.8) points] (all P<0.05). After correcting the effects of OSAHS disease severity, hypoxia, awake times, education, age, gender, hypnagogue, BMI, smoking and drinking history, the risk of MCI in insomnia group of severe OSAHS patients was significantly higher than that of non-insomnia group by 49% (OR=1.49, 95%CI: 1.05-2.11). Conclusion: Insomnia phenotype is a common clinical phenotype of OSAHS, and it is a risk factor for MCI in young and middle-aged patients with severe OSAHS.

[Cluster analysis and significance of clinical subtypes in patients with obstructive sleep apnea hypopnea syndrome].

Objective: To study the clinical subtypes of obstructive sleep apnea hypopnea syndrome (OSAHS) by cluster analysis, and to discuss the characteristics and clinical significance of these subtypes. Methods: A retrospective analysis was done among patients who were diagnosed with OSAHS in the Sleeping Center of the Second Affiliated Hospital of Soochow University from January 2010 to June 2018. In this cluster analysis, 16 main symptoms, 7 comorbidities and 3 assessment scales were included. After selecting the best model, the parameters and characteristics of different subtypes were compared and analyzed. Results: A total of 2 592 patients with complete data were included in this study. After cluster analysis, they were divided into 4 groups: sleep apnea group (1 173 cases, 45.3%), daytime sleepiness group (518 cases, 20.0%), insomnia and memory loss group (212 cases, 8.2%), mild symptom group (689 cases, 26.6%). In the sleep apnea group, the patients were found to be younger [(40.2±10.4) years old], with higher body mass index (BMI) [(27.7±3.7) kg/m(2)] when compared to the other groups. In addition, the prevalence of comorbidities of this group was found to be lower, whereas the probability of sleep apnea symptom was the highest (94.7%). In daytime sleepiness group, the Epworth Sleepiness Scale (ESS) score was the highest [(12.4±5.5) points], and the probability of daytime sleepiness symptom was also found to be the highest (88.0%). The age of patients in the insomnia and memory loss group was the highest [(51.1±13.0) points], with the highest percentage of women (19.3%). The probability of insomnia was found to be 70.3%, and memory loss symptoms was 88.2% which were the highest when compared to the other groups. The prevalence of comorbidities was the highest, and the scores of short mental state scale (MMSE) and Montreal cognitive assessment (MoCA) were the lowest with a mean of [(28.5±2.4) points] and [(25.4±3.2) points], respectively, among the 4 groups. The probability of most symptoms and comorbidities were found be the lowest in the mild symptom group. There were significant differences in the main symptoms among the 4 groups (P<0.05). Symptoms like sleep apnea, daytime sleepiness, insomnia, memory loss, headache and dry mouth upon awakening were found significantly different in pairwise comparisons among the groups (P<0.002). Conclusion: The patients with OSAHS can be divided into four clinical subtypes by cluster analysis, each of which is significantly heterogeneous, and this is helpful to evaluate the condition and guide individualized treatment.

[Evaluation of the effect of electrical stimulation combined with biofeedback therapy for postpartum pelvic organ prolapse: a static and dynamic magnetic resonance imaging study].

Objective: To explore the clinical value of static and dynamic magnetic resonance imaging (MRI) in evaluating the effect of electrical stimulation combined with biofeedback in the treatment of pelvic organ prolapse postpartum. Methods: A total of 50 primiparas diagnosed as pelvic organ prolapse postpartum from February 2016 to November 2017 were randomly divided into treatment group (24 cases) and control group (26 cases). The control group recovered spontaneously, and the treatment group received electric stimulation combined with biofeedback therapy (6 weeks). All subjects underwent static and dynamic MRI before and after treatment. The thickness of bilateral puborectal muscles, levator ani hiatus area (LHA), H line, M line and levator ani plate angle (LPA) were respectively measured in rest state and strain state at 42 days and 12 weeks postpartum, and the differences of parameters were compared between two groups. Results: (1) Compared with 42 days postpartum, the effective rate of pelvic organ prolapse was 15.4% (4/26) in the control group and 62.5% (15/24) in the treatment group, which was significantly higher than that of the control group (P<0.01). (2) Compared with 42 days postpartum, the thickness of bilateral puborectal muscles in the treatment group increased at 12 weeks postpartum, while that of the H line, LHA, M line and LPA in strain state decreased. (3) At 12 weeks postpartum, the thickness of the bilateral puborectal muscle in the treatment group was greater, and LHA, M line, and LPA in strain state were less than that in the control group (all P<0.05). Conclusion: Electrical stimulation combined with biofeedback therapy can improve pelvic organ prolapse due to vaginal delivery, and the static and dynamic MRI can objectively evaluate the effect of pelvic floor rehabilitation therapy on improving the pelvic floor supporting structure and function, providing an important support and guidance for restoration of postpartum pelvic organ prolapse.

[Dynamic features of tumefactive demyelinating lesions in different clinical stages by contrast-enhanced magnetic resonance imaging].

Objective: To explore the dynamic features of tumefactive demyelinating lesions (TDLs) in different clinical stages by contrast-enhanced magnetic resonance imaging (MRI). Methods: Thirty-five patients with TDLs proven by pathological studies were prospectively recruited from January 2015 to January 2017.Brain contrast-enhanced MRI of the patients in different clinical stages including acute phase, subacute phase and chronic phase were completed after enrollment.The characteristics of contrast-enhanced MRI in different clinical stages were compared and the evolutional characteristics were summarized. Results: (1) Acute phase (35/35): the patterns of enhancement were patchy (74.3%, n=26), nodule (34.3%, n=12), closed ring (14.3%, n=5) and open ring (11.4%, n=4). (2) Subacute phase (32/35): the patterns of enhancement were open ring (40.6%, n=13), closed ring (31.3%, n=10), patchy (25.0%, n=8) and irregular edge of enhancement (21.9%, n=7). (3) Chronic phase (15/35): the patterns of enhancement were pale patchy (10/15), open ring (5/15) and closed ring (2/15). (4) The proportions of enhancement patterns including patchy, nodule, edge enhancement and pale patchy were significantly different among different clinical stages: ① The patchy and nodule were the more common enhancement patterns in acute phase. ② The edge enhancement was found mostly in subacute phase. ③ The pale patchy was found mostly in chronic phase. Conclusions: The manifestation of the lesions on contrast-enhanced MRI may have some characteristics of dynamic evolution according to different clinical stages.The dynamic observation may be helpful for the diagnosis and differential diagnosis of TDLs.

Short communication: Comparative proteomic analysis of the lactating and nonlactating bovine mammary gland.

The objective of this study was to determine how bovine mammary protein profiles vary during lactation and the dry period. Three lactating and 3 nonlactating cows were selected for mammary gland tissue sampling. Compared with the mammary proteins in nonlactating cows, a total of 60 differentially expressed proteins (DEP, including 57 upregulated and 3 downregulated) were identified in lactating cows using 2-dimensional difference gel electrophoresis combined with mass spectrometry. These DEP included enzymes and proteins associated with various macromolecular metabolic processes, and appeared to promote the increased metabolic activity associated with milk synthesis and secretion. The increased DEP were primarily related to initiation, maintenance, and involution of lactation, and included proteins involved in glycolysis/gluconeogenesis, the tricarboxylic acid cycle, the pentose phosphate pathway, oxidative phosphorylation, aminoacyl-transfer RNA biosynthesis, and fatty acid biosynthesis. Identified DEP were further validated by real-time, reverse-transcription PCR and Western blot. Five new DEP associated with lactation were uniquely identified. This work provided some protein-associated insights to facilitate further investigation of the mechanisms underlying lactation in dairy cows.

[Effects of preconditioning with hypertonic saline solution on postoperative delirium in the aged].

Objective: To evaluate and explore the mechanism of the effect of hypertonic pre-injection on postoperative delirium in the aged. Methods: From June 2016 to February 2017, participants scheduled hip arthroplasty surgery were randomly divided into four groups: Group 1 (H1) 30 patients pre-injected 4 ml/kg hypertonic solution were proceeded general anesthesia; Group 2 (H2) 30 patients pre-injected 4 ml/kg hypertonic solution were proceeded spinal canal anesthesia; Group 3 (C1) 30 patients pre-injected 4 ml/kg isotonic saline were proceeded general anesthesia; Group 4 (C2) 30 patients pre-injected 4 ml/kg isotonic saline were proceeded spinal canal anesthesia in Department of Anesthesiology, Third Hospital of Hebei Medical University.All these patients were operated after anesthesia.To avoid electrolyte disorder, the level of Na(+) , Ca(2+) , K(+) in the artery blood was analyzed.Peripheral venous blood was extracted to detect the concentration of inflammatory factors IL-1ß, IL-6, IL-10, TNF-α and nerve injury factor S100ß.In order to evaluate the relationship of these inflammatory fators with monocyte, we used flow cytometry to detect the number of mononuclear in peripheral venous blood.After operation 1 to 3 days, all these patients were assessed cognitive function by Nu-DESC. Results: Electrolytes fluctuationed in the normal range in four groups at different time points.Compared with before infusion, IL-6, IL-1ß and TNF-α of four groups were significantly increased in postoperative.Compared with group H(H1 or H2), IL-1ß, IL-6 and TNF-α were increased and IL-10 was decreased in group C(C1 or C2) after the surgery.S100ß of group C(C1 and C2) was higher than before infusion.No significant changes were found in the cotykines mentioned above between group H1 and H2. The expression of monocytes CD14(+) CD16(+) /CD14(+ +) was decreased and the incidence of postoperative delirium was lower in group H than group C(13.3%, 10.0% vs 33.3%, 36.7%, P<0.05). Conclusion: Hypertonic saline can improve postoperative delirium of the aged and the mechanism may be related to the inhibition of monocyte cells secreting inflammatory factors.

High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder.

Auditory neuropathy spectrum disorder (ANSD) is one of the most common diseases leading to hearing and speech communication barriers in infants and young children. The OTOF gene is the first gene identified for autosomal recessive non-syndromic ANSD, and patients with OTOF mutations have shown marked improvement of auditory functions from the cochlear implantation, but the true involvement of OTOF mutations in Chinese ANSD patients is still unknown which precludes the effective management of this disease. Here, we investigated the contribution of OTOF mutations to congenital ANSD patients in China. In all, 37 infants and young Children with ANSD were screened for all the exons of OTOF gene, of them 34 patients had no neonatal risk factors who were considered as congenital ANSD. The clinical manifestation and audiometric features were also investigated and compared in patients with and without OTOF mutations. In all, 14 of these subjects were shown to carry two or three mutant alleles of OTOF with the high frequency of 41.2% in congenital ANSD patients. In total, 15 novel pathogenic mutations and 10 reported mutations were identified. Our results confirmed that mutations in OTOF gene were a major cause of congenital ANSD in China. Identification of OTOF mutations can facilitate diagnosis, clinical intervention and counseling for congenital ANSD.

[Expression and significance of serum microRNA-135a-5p level in colorectal cancer].

Objective: To explore the expression level of serum miR135a-5p and its diagnostic value in colorectal cancer (CRC). Methods: Serum samples were randomly collected from 60 primary CRC patients, 40 patients with intestinal polyps and 50 healthy controls, and the serum concentrations of miR135a-5p, CEA and CA199 were detected. The relationships between serum miR135a-5p level and clinicopathological parameters were analyzed by Mann-Whitney U test. The correlation of serum miR135a-5p level and serum concentrations of CEA or CA199 was analyzed by Pearson's correlation test.Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to evaluate the diagnostic efficacy of miR135a-5p, CEA and CA199 as diagnostic indicators. Results: The serum level of miR135a-5p in CRC patient was 2.451 (1.107, 4.413), significantly higher than 0.946 (0.401, 1.942) in the patients with intestinal polyps and 0.949 (0.194, 1.415) in the healthy controls (U = 351.0 and U = 313.0, respectively, P<0.001). The serum level of miR135a-5p in CRC patients was associated with both histological differentiation and clinical stage (P<0.05 for both), however, not correlated with the serum concentration of CEA (r2 = 0.023, P = 0.293) or CA199 (r2 = 0.067, P = 0.068). The AUC of serum miR135a-5p level in CRC patients was 0.832 (0.730-0.930) when compared to the patients with intestinal polyps and was 0.875 (0.800-0.950) when compared with the healthy controls. Conclusions: The serum level of miR135a-5p in CRC patients is significantly higher than that in patients with intestinal polyps and healthy controls, and might be an important diagnostic marker of CRC.

Monolithic high-index contrast grating: a material independent high-reflectance VCSEL mirror.

In this paper we present an extensive theoretical and numerical analysis of monolithic high-index contrast grating, facilitating simple manufacture of compact mirrors for very broad spectrum of vertical-cavity surface-emitting lasers (VCSELs) emitting from ultraviolet to mid-infrared. We provide the theoretical background explaining the phenomenon of high reflectance in monolithic subwavelength gratings. In addition, by using a three-dimensional, fully vectorial optical model, verified by comparison with the experiment, we investigate the optimal parameters of high-index contrast grating enabling more than 99.99% reflectance in the diversity of photonic materials and in the broad range of wavelengths.

Mechanisms of cytotoxicity induced by the anesthetic isoflurane: the role of inositol 1,4,5-trisphosphate receptors.

Isoflurane can induce widespread cytotoxicity. We hypothesized that isoflurane induces apoptosis partly by causing excessive calcium release from the endoplasmic reticulum (ER) via direct activation of inositol 1,4,5-trisphosphate receptors (IP3R). Rat pheochromocytoma cells cultured for seven days with nerve growth factor were divided into four groups: control group (C), IP3R antagonist group (X), isoflurane group (I) and isoflurane + IP3R antagonist group (I+X). Groups I and I+X were treated with 1 MAC isoflurane for 12 h. Groups X and I+X were pretreated with IP3R antagonist. Annexin V/PI apoptosis and TUNEL assays were performed to evaluate cell apoptosis. TEM was used to observe changes in cell ultrastructure. Changes in calcium concentration ([Ca(2+)]i) in the cytoplasm were measured by flow cytometry. RT-PCR was performed to evaluate IP3R mRNA expression. TEM showed that isoflurane treatment altered cell ultrastructure. Compared to group C, cell apoptosis rate and [Ca(2+)]i increased in groups I and I+X (P < 0.05). Compared to group C, IP3R mRNA expression was lower in group X and higher in group I (P < 0.05). Compared to group X, cell apoptosis rate, [Ca(2+)]i and IP3R mRNA expression increased in groups I and I+X (P < 0.05). Compared to group I, cell apoptosis rate, [Ca(2+)]i and IP3R mRNA expression decreased in group I+X (P < 0.05). These results suggest that exposure to 1 MAC isoflurane for 12 h causes excessive calcium release partly by direct activation of IP3R on the ER membrane and triggers cell apoptosis.

[The updates of the ACMG variant interpretation guidelines affect the pathogenicity determination of OTOF gene variations in patients with auditory neuropathy].

Objective: To compare the differences between the variation interpretation standards and guidelines issued by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015 (The 2015ACMG/AMP guideline) and the Deafness Specialist Group of the Clinical Genome Resource (ClinGen) in 2018 for hereditary hearing loss (Healing loss, HL) issued the expert specification of the variation interpretation guide (The 2018 HL-EP guideline) in evaluating the pathogenicity of OTOF gene variation in patients with auditory neuropathy. Methods: Thirty-eight auditory neuropathy patients with OTOF gene variant were selected as the study subjects (23 males and 15 females, aged 0.3-25.9 years). Using whole-genome sequencing, whole exome sequencing or target region sequencing (Panel) combined with Sanger sequencing, 38 cases were found to carry more than two OTOF mutation sites. A total of 59 candidate variants were independently interpreted based on the 2015 ACMG/AMP guideline and 2018 HL-EP guideline. Compared with the judgment results in 2015 ACMG/AMP guideline, the variants interpreted as lower pathogenic classifications in the 2018 HL-EP guideline were defined as downgraded variants, and the variants regarded as higher pathogenic classifications were defined as upgraded variants. Statistical analysis was conducted using SPSS 20.0. Results: The concordance rate of variant classification between the guidelines was 72.9%(43/59). The 13.6%(8/59) of variants were upgraded and 13.6% (8/59) of variants downgraded in the classifications of the 2018 HL-EP guideline. A couple of rules saw significant differences between the guidelines (PVS1, PM3, PP2, PP3 and PP5). The distribution of pathogenicity of splicing mutation was statistically different (P=0.013). Conclusions: The 2018 HL-EP guideline is inconsistent with the 2015 ACMG/AMP guideline, when judging the pathogenicity of OTOF gene variants in patients with auditory neuropathy. Through the deletion and refinement of evidence and the breaking of solidification thinking, the 2018 HL-EP guideline makes the pathogenicity grading more traceable and improves the credibility.

[Study on the clinical characteristics of auditory neuropathy patients with normal pure tone average or mild hearing loss].

Objective: The purpose of this study was to analyze the clinical characteristics of auditory neuropathy (AN) patients with normal hearing or mild hearing loss. Methods: Data from Multicenter Study on Clinical Diagnosis and Intervention of Acoustic Neuropathy (registration number: ChiCTR2100050125). According to the Chinese clinical practice guideline of auditory neuropathy (version 2022), these patients divided into two groups: the normal hearing group (PTA Normal, PTAN group, the average hearing threshold<20 dB HL) and the mild hearing loss group (PTA Mild hearing loss, PTAM group, the average hearing threshold between 20-35 dBHL). The audiology characteristics, clinical features, and follow-up were analyzed. Data analysis was conducted using GraphPad Prism 8 and SPSS 20.0 software. Results: A total of 75 AN with normal hearing or mild hearing loss were included in this study. The PTAN group consisted of 19 patients (38 ears), including 12 males and 7 females. The average onset age was (16.9±4.5) years old, while the test age was (22.1±5.8) years old for PTAN group. The PTAM group consisted of 56 patients (112 ears), including 29 males and 27 females. The average onset age was (16.2±7.9) years old, while the test age was (23.9±9.0) yeas old for PTAM group. The average hearing threshold of low frequency (0.125-0.5 kHz) was significantly decreased. ABR disappeared in 86.00% (126/150) of the patients. The speech recognition rate was 71.80±22.44% in the PTAN group and 58.08±29.28% in the PTAM group.-SP/AP was 0.98±0.47 in the PTAN and 1.07±0.63 in PTAM group; 40 (53.33%) patients had tinnitus. 29 patients (58 ears) were followed up, including 10 patients (20 ears) in the PTAN group and 19 patients (38 ears) in the PTAM group. There was no significant change in hearing threshold in short-term follow-up (<3 years). With the extension of the disease duration (>3 years), the PTAN group tended to decrease at low frequency, and the PTAM group decreased at high frequency first. The hearing threshold at 0.25 kHz in the PTAN group and 4 kHz in the PTAM group decreased significantly. Conclusions: AN patients with normal hearing or mild hearing loss exhibit abnormal results in audiological examination results, including ABR, electrocochleography and speech discrimination score. A combination of audiological tests should be used to make the diagnosis of AN. With the progression of the disease, AN with normal hearing or mild hearing loss tends to decrease.

[Research on the variation in distortion product otoacoustic emissions in patients with auditory neuropathy during the natural course of the disease].

Objective: The purpose of this study was to investigate the characteristics of distortion product otoacoustic emissions (DPOAE) in patients with auditory neuropathy (AN). The factors affecting DPOAE elicitation rate of each frequency, elicitation rate of each ear and change rate of first and last diagnosis in the natural course were analyzed. Methods: The sample was obtained from the Multicenter Study on Clinical Diagnosis and Intervention of AN (registration number: ChiCTR2100050125), and the diagnostic criteria for AN were based on the Chinese Clinical Practice Guidelines of Auditory Neuropathy (version 2022). Patients with bilateral AN who underwent 2 or more DPOAE tests were screened and divided into infant groups (≤3 years old) and non-infant groups (>3 years old) according to the age of detection, and the trend of DPOAE elicitation rate of each frequency, elicitation rate of each ear and change rate in the natural course of disease were analyzed, in order to explore the relevant influencing factors. Results: A total of 165 patients (330 ears) with AN were included in the study. The overall DPOAE elicitation rate per ear was 77.0%±29.4% at the initial diagnosis and 65.1%±35.2% at the final diagnosis, with a reduction observed in the elicitation rate of 171 ears (51.82%). In the infant group, there were 49 cases (98 ears), including 28 males and 21 females, whose found age ranged from 0 to 3 years old, with a median age of 0.7 years. DPOAE elicitation rate per ear was 57.9%±35.5% in the initial diagnosis, and 32.4%±32.1% in the final diagnosis, with a reduction observed in the elicitation rate of 69 ears (70.41%). In the non-infant group, there were 116 cases (232 ears), including 59 males and 57 females, ranging in found age from 3.9 to 40 years old, with a median age of 14 years old. DPOAE elicitation rate per ear was 84.6%±23.4% in the initial diagnosis, and 78.3%±27.1% in the final diagnosis, with a reduction observed in the elicitation rate of 102 ears (43.97%). Age was found to be correlated with DPOAE changes by multicategorical unordered logistic regression analysis (B=-0.224, OR=0.799, P<0.001). Conclusions: The elicitation rate of DPOAE in AN patients decreases or even disappears with increasing disease duration; The rate of DPOAE extraction is found to be lower in infant patients with auditory neuropathy (AN) compared to non-infant AN patients. Additionally, it is observed that the decrease in DPOAE extraction rate is more pronounced in infant AN patients as the disease progressed, as compared to non-infant AN patients. DPOAE and cochlear microphonic potentials should be fully combined for accurate diagnosis, and regular follow-up should be conducted to understand the natural course of the disease and give personalized guidance and assistance.