Risk and benefit of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to assess the risks and benefits of reinitiating antiplatelet therapy after spontaneous intracerebral hemorrhage (ICH) through a systematic review and meta-analysis. The reinitiation of antiplatelet therapy is commonly used to reduce major vascular events in patients with occlusive vascular diseases, but its use in ICH patients may increase the risk of bleeding. MATERIALS AND METHODS: A comprehensive search was conducted on databases including MEDLINE, Embase, Cochrane Library, clinicaltrials.gov, and the International Standard Randomized Controlled Trial Number Register (ISRCTN). Randomized controlled trials and cohort studies that investigated the use of reinitiation of antiplatelet therapy after hemorrhagic stroke were included. Data on ICH recurrence, major bleeding events, major occlusive cerebrovascular events, ischemic stroke, and all-cause mortality were extracted and analyzed using R software. RESULTS: The study included a total of 10 studies with 6,340 participants. The control group consisted of 2,964 patients who did not receive antiplatelet therapy, while the study group included 1,285 patients who received antiplatelet therapy without restrictions on the specific drug type. The meta-analysis showed that antiplatelet therapy significantly reduced the risk of ICH recurrence (RR=0.72, 95% CI: 0.59, 0.87), had no significant impact on the risk of severe bleeding events (RR=0.93, 95% CI: 0.80, 1.08), significantly lowered the risk of major occlusive cerebrovascular events (RR=0.59, 95% CI: 0.46, 0.77), had no significant effect on the risk of ischemic stroke (RR=0.77, 95% CI: 0.53, 1.12), and did not significantly influence the risk of all-cause mortality (RR=0.75, 95% CI: 0.45, 1.15). CONCLUSIONS: Based on the findings, reinitiating antiplatelet therapy after spontaneous ICH appears to be generally safe. However, the benefits in terms of reducing the risk of all-cause mortality are not evident and require confirmation through large-scale, long-term, prospective, randomized controlled trials.

Cardiac MRI feature-tracking-derived torsion mechanics in systolic and diastolic dysfunction in systemic light-chain cardiac amyloidosis.

AIM: To describe the myocardial torsion mechanics in cardiac amyloidosis (CA), and evaluate the correlations between left ventricle (LV) torsion mechanics and conventional parameters using cardiac magnetic resonance imaging feature tracking (CMR-FT). MATERIALS AND METHODS: One hundred and thirty-nine patients with light-chain CA (AL-CA) were divided into three groups: group 1 with preserved systolic function (LV ejection fraction [LVEF] ≥50%, n=55), group 2 with mildly reduced systolic function (40% ≤ LVEF <50%, n=51), and group 3 with reduced systolic function (LVEF <40%, n=33), and compared with age- and gender-matched healthy controls (n=26). All patients underwent cine imaging and late gadolinium-enhancement (LGE). Cine images were analysed offline using CMR-FT to estimate torsion parameters. RESULTS: Global torsion, base-mid torsion, and peak diastolic torsion rate (diasTR) were significantly impaired in patients with preserved systolic function (p<0.05 for all), whereas mid-apex torsion and peak systolic torsion rate (sysTR) were preserved (p>0.05 for both) compared with healthy controls. In patients with mildly reduced systolic function, global torsion and base-mid torsion were lower compared to those with preserved systolic function (p<0.05 for both), while mid-apex torsion, sysTR, and diasTR were preserved (p>0.05 for all). In patients with reduced systolic function, only sysTR was significantly worse compared with mildly reduced systolic function (p<0.05). At multivariable analysis, right ventricle (RV) end-systolic volume RVESV index and NYHA class were independently related to global torsion, whereas LVEF was independently related to sysTR. RV ejection fraction (RVEF) was independently related to diasTR. LV global torsion performed well (AUC 0.71; 95% confidence interval [CI]: 0.61, 0.77) in discriminating transmural from non-transmural LGE in AL-CA patients. CONCLUSION: LV torsion mechanics derived by CMR-FT could help to monitor LV systolic and diastolic function in AL-CA patients and function as a new imaging marker for LV dysfunction and LGE transmurality.

[Characteristics of genioglossus neuromuscular activity in patients with obstructive sleep apnea during drug-induced sleep].

Objective: To analyze genioglossus (GG) activation responses to the negative pressure of upper airway cavity during awake and different sleep stages in patients with different obstructive sleep apnea (OSA) graduation. Methods: This prospective cohort study started from August 2019 to January 2021, recruited 42 male OSA patients aged from 21 to 59 (38.77±8.42) years. After completing whole night polysomnography (PSG) and upper airway CT, each subject underwent drug-induced sleep with simultaneous monitoring of genioglossal electromyography (GGEMG) and pressure of epiglottis (Pepi). Subjects were divided into three groups of mild OSA(7 males), moderate OSA(12 males), and severe OSA(23 males). The differences in upper airway CT measurements, parameters of GGEMG and Pepi during awake and induced sleep were compared. Statistical analysis was conducted by SPSS 21.0. Results: There was no significant difference in the GGEMG parameters between the mild and moderate groups. In wakefulness, the peak phasic GGEMG of the severe group was higher than the mild group (t=1.249, P=0.025), with no statistically difference in the corresponding Pepi. In the sleep onset, the GGEMG parameters and Pepi in severe group were higher than the other two groups. Linear regression analysis of the maximum GGEMG and maximum Pepi at the end of obstructive apnea (OA) in all moderate plus severe patients (n=35) was shown nonlinear correlation (r=0.28, P=0.694). The airway length of the glossopharyngeal cavity was linearly correlated with the maximum Pepi of OA (r=0.468, R2=0.219, P=0.005). Conclusions: The individual difference of GG activation in OSA patients is related to the severity of the disease (frequency of respiratory events) and negative pressure stimulation. In moderate and severe OSA patients, GG activity is not in harmony with the corresponding negative pressure stimulation, which may be one of the mechanisms leading to the aggravation of OSA.

[Impact of asthma action plan-based remote joint management model on asthma control in children].

Objective: To compare the effects of the China Children's Asthma Action Plan (CCAAP)-based remote joint management model with traditional management model on the control of childhood asthma. Methods: A retrospective cohort study was conducted to analyze the general data and asthma control assessment data of 219 children with asthma who attended the respiratory department of Guangzhou Women's and Children's Medical Center from April 2021 to October 2021 and were followed up for 1 year or more. According to the follow-up management model, the CCAAP-based remote joint management model was used in the observation group and the traditional management model was used in the control group, and the propensity score matching method was applied to match the data of children in the two management models for comparison. Paired-samples t-test, Wilcoxon signed-rank test, McNemar χ2-test or χ2-test or nonparametric tests were used to compare the general data and asthma control assessment data between the two matched groups of children. Results: Among 219 children with asthma, 145 were male and 74 were female, aged at consultation (7.2±2.4) years. There were 147 cases in the observation group and 72 cases in the control group, and 27 cases in each of the observation and control groups were successfully matched. The number of asthma exacerbation aura, acute exacerbations, and emergency room visits or hospitalizations for asthma exacerbations were lower in the observation group than in the control group after pairing (1 (0, 2) vs. 3 (1, 5) times, 0 (0,0) vs. 0 (0, 1) times, 0 (0,0) vs. 1 (0, 1) times, Z=-3.42, -2.58, -3.17, all P<0.05). The use of peak flowmeters was higher in children aged 5 years and older in the observation group than in the control group after pairing (100% (22/22) vs. 13% (3/23), χ2=54.00,P<0.001). The ratio of actual to predicted 1st second expiratory volume of force after follow-up in the observation group after pairing was higher than that before follow-up in the observation group and after follow-up in the control group ((95±11)% vs. (85±10)%, (95±11)% vs. (88±11)%, t=-3.40, 2.25, all P<0.05). The rate of complete asthma control after follow-up was higher in both the observation and control groups after pairing than before follow-up for 12 months in both groups (93% (25/27) vs. 41% (11/27), 52% (14/27) vs. 41% (11/27), H=56.19, 45.37, both P<0.001), and the rate of complete control of asthma in children in the observation group was higher than that in the control group at 3 and 12 months of follow-up management (56% (15/27) vs. 25% (5/20), 93% (25/27) vs. 52% (14/27), χ2=47.00, 54.00, both P<0.001). The number of offline follow-up visits, inhaled hormone medication adherence scores, and caregiver's asthma perception questionnaire scores were higher in the observation group than in the control group after pairing (6 (4, 8) vs. 4 (2,5), (4.8±0.3) vs. (4.0±0.6) score, (19.3±2.6) vs. (15.2±2.7) score, Z=6.58, t=6.57, 5.61, all P<0.05), and the children in the observation group had lower school absences, caregiver absences, asthma attack visit costs, and caregiver PTSD scores than the control group (0 (0,0) vs.3 (0, 15) d, 0 (0,0) vs. 3 (0, 10) d, 1 100 (0, 3 700) vs. 5 000 (1 000, 10 000) yuan, 1.3 (1.1, 1.9) vs. 2.0 (1.2, 2.7) score, Z=-2.89, -2.30, 2.74, 2.73, all P<0.05). Conclusion: The CCAAP-based joint management model of asthma control is superior to the traditional management model in the following aspects: it can effectively improve asthma control, self-monitoring, and lung function in children; it can improve treatment adherence and caregivers' asthma awareness; and it can reduce the duration of absenteeism from school, the cost of asthma exacerbation visits, and caregiver's negative psychology.

[Notch signaling pathway inhibitor DAPT improves alcohol-induced neuronal differentiation impairment in zebrafish].

OBJECTIVE: To explore the role of the Notch signaling pathway in regulating neuronal differentiation and sensorimotor ability in a zebrafish model of fetal alcohol spectrum disorder. METHODS: Zebrafish embryos treated with DMSO or 50 µmol/L DAPT (a Notch signaling pathway inhibitor) were examined for mortality rate, hatching rate, malformation rate, and body length at 15 days post fertilization (dpf). The mRNA expression levels of sox2, neurogenin1 and huc in the treated zebrafish embryos were detected using in situ hybridization and qRT-PCR, and their behavioral responses to strong light and vibration stimulation were observed. The zebrafish embryos were then exposed to DMSO, 1.5% ethanol, DAPT, or both ethanol and DAPT, and the changes in mRNA expression levels of sox2, neurogenin1, huc, and the Notch signaling pathway genes as well as behavioral responses were evaluated. RESULTS: Exposure to 50 µmol/L DAPT significantly increased the mortality rate of 1 dpf zebrafish embryos (P < 0.01), decreased the hatching rate of 2 dpf embryos (P < 0.01), increased the malformation rate of 3 dpf embryos (P < 0.001), and reduced the body length of 15 dpf embryos (P < 0.05). DAPT treatment significantly downregulated sox2 mRNA expression (P < 0.01) and increased neurogenin1 (P < 0.05) and huc (P < 0.01) mRNA expressions in zebrafish embryos. The zebrafish with DAPT treatment exhibited significantly shortened movement distance (P < 0.001) and lowered movement speed (P < 0.05) in response to all the stimulation conditions. Compared with treatment with 1.5% ethanol alone, which obviously upregulated notch1a, her8a and NICD mRNA expressions in zebrafish embryos (P < 0.05), the combined treatment with ethanol and DAPT significantly increased neurogenin1 and huc mRNA expression, decreased sox2 mRNA expression (P < 0.01), and increased the moving distance and moving speed of zebrafish embryos in response to strong light stimulation (P < 0.05). CONCLUSION: Ethanol exposure causes upregulation of the Notch signaling pathway and impairs neuronal differentiation and sensorimotor ability of zebrafish embryos, and these detrimental effects can be lessened by inhibiting the Notch signaling pathway.

Detection of haemodynamic obstruction in hypertrophic cardiomyopathy using the sub-aortic complex: a cardiac MRI and Doppler study.

AIM: To investigate the "sub-aortic complex (SAC)", a new cardiac magnetic resonance imaging (CMRI)-derived parameter, for the evaluation of left ventricular (LV) outflow tract (LVOT) obstruction in patients with hypertrophic cardiomyopathy (HCM), compared with conventional CMRI parameters and Doppler echocardiography. MATERIALS AND METHODS: A total of 157 consecutive patients with HCM were recruited retrospectively. The patients were divided into two groups, 87 with LVOT obstruction and 70 without obstruction. The SAC was defined as a specific anatomical SAC affecting the LVOT, which were measured on the LV three-chamber steady-state free precession (SSFP) cine image at the end-systolic phase. The relations between the existence and severity of obstruction and SAC index (SACi) were evaluated using Pearson's correlation coefficient, receiver operating characteristic (ROC) curves, and logistic regression. RESULTS: The SACs were significantly different between the obstructive and non-obstructive groups. The ROC curves indicated that the SACi was able to discriminate obstructive and non-obstructive patients with the best predictive accuracy (AUC = 0.949, p<0.001). The SACi was an independent predictor of LVOT obstruction and there was a significant negative correlation between resting LVOT pressure gradient and SACi (r=0.72 p<0.001). In the subgroup of patients with or without severe basal septal hypertrophy, the SACi was still able to predict LVOT obstruction with excellent diagnostic accuracy (AUC = 0.944 and 0.948, p<0.001, respectively). CONCLUSION: The SAC is a reliable and straightforward CMRI marker for assessing LVOT obstruction. It is more effective than CMRI two-dimensional flow in diagnosing the severity of obstruction in patients with HCM.

[Clinicopathological features of low-grade oncocytic renal tumor (CD117-negative, cytokeratin 7-positive): report of seven cases].

Objective: To explore clinicopathological features of low-grade oncocytic tumor (LOT) of the kidney and to analyze its relationship to hybrid oncocytic/chromophobe tumor (HOCT) of the kidney, renal oncocytoma (RO), and chromophobe renal cell carcinoma (chRCC). Methods: Seven LOTs were identified from the pathologic archives of two hospitals, including Xiangya Hospital (5 cases) and the Second Xiangya Hospital (2 cases) of Central South University between 2012 and 2019. Clinical data of the LOTs were collected. The tumor morphology was analyzed and immunohistochemistry was performed. Results: All LOTs occurred in adults, aged from 49 to 72 years (median 56.0 years, mean 60.7 years). The tumor size ranged from 2.5 to 6.0 cm (median 4.3 cm, mean 4.3 cm). There were three male and four female patients. Three cases occurred in the left kidney and four in the right. All the tumors were solitary lesions without the clinicopathologic background of Birt-Hogg-Dubé (BHD) syndrome or oncocytosis. Five patients had available follow-up data (follow-up period 23-95 months, median 69.0 months, mean 64.6 months) and all were alive without disease. Microscopically, all LOTs were well-circumscribed (7/7). Three LOTs were partly encapsulated. The tumors demonstrated a predominant growth pattern comprising prominently compact small nests surrounded by delicately branching thin-walled blood vessels, imparting an organoid architecture (7/7), but variable numbers of glandular or gland-like structures were often seen among the small nests (7/7). There were frequently areas with loose, edematous stroma, and the tumor cells exhibited reticular, trabecular, or single cell arrangements (6/7). Focal hemorrhage was also commonly present in both compact and loose areas (5/7). In addition, focally cystic formation and ossification occurred in the compact area of one case and in the loose area of another case. The tumor cells in LOT showed intermediate cytologic characteristics between RO and chRCC, including abundantly eosinophilic granular cytoplasm, ovoid to round nuclei with mostly smooth contours, discernable small nucleoli (RO features), frequently delicate perinuclear halos, and occasional binucleation (chRCC features). The tumors were typically CK7-positive and CD117-negative (7/7), and variable staining for PAX8 (5/7), P504s (2/7), and vimentin (1/7). They were negative for CK20, CD10 and FOXI1. All tumors retained SDHB immunostaining. Conclusions: LOT is a rare and indolent oncocytic renal tumor with homogeneously intermediate cytologic features between RO and chRCC. There are some clinicopathologic overlaps between LOT and sporadic HOCT. The distinctive morphology and immunophenotype of LOT suggest that it is potentially a distinct tumor entity.

[Soluble egg antigen of Schistosoma japonicum induces macrophage apoptosis in mice].

OBJECTIVE: To investigate the dynamic changes of macrophage numbers and apoptosis during Schistosoma japonicum infection, and to investigate the possible mechanisms of macrophage apoptosis induced by S. japonicum soluble egg antigen (SEA). METHODS: C57BL/6 mice at ages of 6~8 weeks were randomly divided into 4 groups, including three experimental groups and a normal control group. Each mouse in the experimental groups was infected with (12 ± 1) cercariae of S. japonicum via the abdominal skin, and all mice in an experimental group were sacrificed 3, 5, 8 weeks post-infection, respectively, while mice in the control group were not infected with S. japonicum cercariae and sacrificed on the day of S. japonicum infection in the experimental group. Mouse liver specimens and peritoneal exudation cells were sampled in each group, and the dynamic changes of macrophage numbers and apoptosis were detected. Mouse peritoneal macrophages were isolated, purified and treated with S. japonicum SEA, PBS and ovalbumin (OVA) in vitro, and the macrophage apoptosis was detected using flow cytometry. The mRNA and protein expression of BCL-2 protein family members were determined in macrophages using real-time quantitative PCR (qP-CR) and Western blotting assays, and the activation of caspase 3 was determined using flow cytometry and Western blotting. In addition, macrophages were in vitro treated with S. japonicum SEA in presence of a caspase inhibitor, H2O2 or N-acetyl-L-cysteine, and the apoptosis of macrophages was detected using flow cytometry. RESULTS: The total macrophage numbers continued to increase in mouse liver [(0.873 ± 0.106) × 106, (2.737 ± 0.460) × 106 and (3.107 ± 0.367) × 106 cells, respectively; F = 81.900, P < 0.01] and peritoneal specimens [(5.282 ± 1.136) × 105, (7.500 ± 1.200) × 105 and (12.800 ± 0.800) × 105 cells, respectively; F = 55.720, P < 0.01] 3, 5 and 8 weeks post-infection with S. japonicum, and the numbers of apoptotic macrophages also continued to increase in mouse liver [(0.092 ± 0.018) × 106, (0.186 ± 0.025) × 106 and (0.173 ± 0.0270) × 106 cells; F = 57.780, P < 0.01] and peritoneal specimens [(0.335 ± 0.022) × 105, (0.771 ± 0.099) × 105 and (1.094 ± 0.051) × 105 cells; F = 49.460, P < 0.01] 3, 5 and 8 weeks post-infection with S. japonicum. The apoptotic rate of SEA-treated macrophages [(24.330 ± 0.784)%] was significantly higher than that of PBS-[(18.500 ± 1.077)%] and OVA-treated macrophages [(18.900 ± 1.350)%] (both P values < 0.01). There were no significant differences in the mRNA or protein expression of Bcl-2 [Bcl - 2 mRNA expression: (1.662 ± 0.943) vs. (1.000 ± 0.000), t = 1.215, P > 0.05; BCL protein expression: (0.068 ± 0.004) vs. (0.070 ± 0.005), t = 0.699, P > 0.05], Bax [Bax mRNA expression: (0.711 ± 0.200) vs. (1.000 ± 0.000), t = 2.507, P > 0.05; BAX protein expression: (0.089 ± 0.005) vs. (0.097 ± 0.003), t = 2.232, P > 0.05] and Bak [Bak mRNA expression: (1.255 ± 0.049) vs. (1.00 ± 0.00), t = 0.897, P > 0.05; BAK protein expression: (0.439 ± 0.048) vs. (0.571 ± 0.091), t = 2.231, P > 0.05] between in SEA- and PBS-treated macrophages. S. japonicum SEA induced macrophage apoptosis in the presence of a caspase inhibitor (F = 0.411, P > 0.05); however, SEA failed to induce macrophage apoptosis in the presence of H2O2 or NAC (F = 11.880 and 9.897, both P values < 0.05). CONCLUSIONS: S. japonicum SEA may induce macrophage apoptosis through promoting reactive oxygen species expression during S. japonicum infections in mice.

Development and validation of an individualized nomogram for predicting the high-volume (> 5) central lymph node metastasis in papillary thyroid microcarcinoma.

PURPOSE: Papillary thyroid microcarcinoma (PTMC) frequently presents a favorable clinical outcome, while aggressive invasiveness can also be found in some of this population. Identifying the risk clinical factors of high-volume (> 5) central lymph node metastasis (CLNM) in PTMC patients could help oncologists make a better-individualized clinical decision. METHODS: We retrospectively reviewed the clinical characteristics of adult patients with PTC in the Surveillance, Epidemiology, and End Results (SEER) database between Jan 2010 and Dec 2015 and in one medical center affiliated to Chongqing Medical University between Jan 2018 and Oct 2020. Univariate and multivariate logistic regression analyses were used to determine the risk factors for high volume of CLNM in PTMC patients. RESULTS: The male gender (OR = 2.02, 95% CI 1.46-2.81), larger tumor size (> 5 mm, OR = 1.64, 95% CI 1.13-2.38), multifocality (OR = 1.87, 95% CI 1.40-2.51), and extrathyroidal invasion (OR = 3.67; 95% CI 2.64-5.10) were independent risk factors in promoting high-volume of CLNM in PTMC patients. By contrast, elderly age (≥ 55 years) at diagnosis (OR = 0.57, 95% CI 0.40-0.81) and PTMC-follicular variate (OR = 0.60, 95% CI 0.42-0.87) were determined as the protective factors. Based on these indicators, a nomogram was further constructed with a good concordance index (C-index) of 0.702, supported by an external validating cohort with a promising C-index of 0.811. CONCLUSION: A nomogram was successfully established and validated with six clinical indicators. This model could help surgeons to make a better-individualized clinical decision on the management of PTMC patients, especially in terms of whether prophylactic central lymph node dissection and postoperative radiotherapy should be warranted.

[Uniportal thoracoscopic decortication for stage â ¢ tuberculous empyema of 158 cases].

Objective: To examine the safety and feasibility of uniportal video-assisted thoracoscopic (VATS) decortication in patients presenting with stage Ⅲ tuberculous empyema. Methods: From August 2017 to July 2020, 158 patients of stage Ⅲ tuberculous empyema underwent uniportal VATS decortication with partial rib resection and customized periosteal stripper in Department of Thoracic Surgery, Shanghai Pulmonary Hospital. There were 127 males and 31 females, aged (M(IQR)) 32(28) years (range:14 to 78 years). Follow-up was performed in the outpatient clinic or via social communication applications, at monthly thereafter. If there was no air leak and chest tube drainage was less than 50 ml/day, a chest CT was performed. If the lung was fully re-expanded, chest tubes were removed. All patients received a follow-up chest CT 3 to 6 months following their initial operations which was compared to their preoperative imaging. Results: There was one conversion to open thoracotomy. The operative time was 2.75 (2.50) hours (range: 1.5 to 7.0 hours), and median blood loss was 100 (500) ml (range: 50 to 2 000 ml). There were no perioperative mortalities. There were no major complications except 1 case of redo-VATS for hemostasis due to excessive drainage and 1 case of incision infection, The incidence of prolonged air leaks (>5 days) was 80.3%(126/157). The postoperative hospital stay was 5.00 (2.25) days (range: 2 to 15 days). All patients were discharged with 2 chest tubes, and the median duration drainage was 21.00 (22.50) days (range: 3 to 77 days). Follow-up was completed in all patients over a duration of 20 (14) months (range: 12 to 44 months). At follow-up, 149 patients(94.9%) recovered to grade Ⅰ level, 7 patients to grade Ⅱ level, and 1 patient to grade Ⅲ level. Conclusion: Uniportal VATS decortication involving partial rib resection and a customized periosteal stripper is safe and effective for patients with stage Ⅲ tuberculous empyema.

[Improvement of CT spatial resolution brings about enormous changes in the diagnosis and treatment of otological diseases].

CT examination of temporal bone is of great value in the diagnosis and treatment of otological diseases, and improvement in spatial resolution is an inevitable demand to enhance diagnostic efficiency. In the past 40 years, the spatial resolution of temporal bone CT has been continuously improved, making great contribution to improving the diagnosis and treatment level of otological diseases. The newly reported 10 µm otology CT device has greatly improved the ability to visualize fine structures and occult lesions of temporal bone key area and effectively reduced radiation dose, therefore it is expected to bring new changes to diagnosis and treatment of otological diseases.

[Analysis of the anatomical features of vestibular nerve canal based on 10 µm otology CT].

Objective: To analysis the anatomical features of normal vestibular nerve canal based on 10 µm otology CT. Methods: Sixty-seven patients (103 ears) underwent 10 µm otology CT examinations in Department of Radiology, Beijing Friendship Hospital, Capital Medical University from September 2020 to March 2021 were retrospectively recruited. There were 24 males and 43 females, aged from 18 to 70 (40±17) years. According to the morphology of the inferior vestibular nerve canal, it can be divided into four types as follows: uniform straight type, curved type, ampullary type and direct connection. The anatomical variables of the superior vestibular nerve canal (external orifice, isthmus and internal orifice widths, canal length, angle with labyrinthine segment of the facial nerve) and inferior vestibular nerve canal (widths of the externaland internal orifice, canal length, angles with long axis of the vestibule and the modiolus) between the different sides, genders and canal morphologies were analyzed and compared, respectively. Results: 100% superior vestibular nerve canals and 75.7% (78/103) inferior vestibular nerve canals are clearly depicted by otology CT. The left-side ear presented with larger internal orifice diameter of the superior vestibular neve canal [(1.46±0.47) mm vs (1.31±0.41) mm], and a smaller angle between the inferior vestibular neve canal and the modiolus [(41.6±16.9)° vs (51.6±21.0)°] than the right-side ear (all P<0.05, respectively), respectively. Compared to females, males demonstrated larger internal orifice of the superior vestibular nerve canal [(1.55±0.37) mm vs (1.28±0.36) mm, P<0.05]. The uniform straight type of the inferior vestibular nerve canal was the most common type (62.1%, 64/103), followed by the direct connection (19.4%, 20/103), and the ampullary type was the least common type (4.9%, 5/103). There were significant differences in external diameter and angles with the long axis of the vestibule and the modiolus between the four morphologies of the superior vestibular nerve canal (all P<0.05, respectively). Conclusion: Ten µm otology CT is capable of depicting normal vestibular nerve canal clearly. Quantitative measurement of the normal vestibular nerve canal can provide references for the imaging diagnosis and preoperative evaluation of lesions in this area.

[Analysis of spatial location of the malleus in patients with chronic otitis media based on 10 µm otology CT].

Objective: To assess the changes of the spatial location of the malleus in patients with chronic otitis media (COM) using 10 µm otology CT. Methods: Forty-five patients with COM (COM group, 45 ears) and 55 patients without external and middle ear disease (control group, 89 ears), who underwent 10 µm otology CT examination in Department of Radiology, Beijing Friendship Hospital, Capital Medical University from October 2020 to March 2021, were retrospectively collected during the same period. In the COM group, there are 20 males and 25 females, aged from 20 to 78 (40±14) years. In the control group, 29 were males and 26 were females, with age of 19 to 57 (32±11) years. The shortest distance between the malleus head and the upper wall, the distance between the outer edge of the malleus neck and the scutum, the distance between the outer edge of the malleus neck and the pars flaccida of the tympanic membrane, the shortest distance between the malleus head and the anterior wall, the shortest distance between the anterior process and the anterolateral wall, the shortest distance between the tip of the malleus handle and the promontory, and the shortest distance between the malleus head and the tympanic segment of the facial nerve were measured and compared between the two groups. Results: Compared with the control group, the head-upper wall distance (M (Q1, Q3)) (0.81 (0.48, 1.21) mm vs 0.57 (0.33, 0.90) mm) and the neck-scutum distance (1.79 (1.54, 2.13) mm vs 1.65 (1.48, 1.83) mm) were larger in the COM group (all P<0.05), and the neck-tympanic membrane distance (1.32 (1.15, 1.49) mm vs 1.45 (1.31, 1.59) mm) and the handle-promontory distance (1.56 (1.33, 2.09) mm vs 2.10 (1.74, 2.43) mm) were reduced in the COM group (all P<0.05, respectively). The neck-tympanic membrane distance on the left was larger than those on the right in the COM group (1.39 (1.19, 1.51) mm vs 1.21 (0.87, 1.31) mm, P<0.05). Conclusion: There are changes in the relative position of the malleus in patients with COM, which are helpful for further understanding the imaging manifestations in patients with COM.

[Application of 10 µm otology CT on evaluation of isolated malleus fixation in patients with conductive hearing loss].

Objective: To evaluate the application of 10 µm otology CT on evaluation of isolated malleus fixation (IMF) in patients with conductive hearing loss. Methods: A total of 19 patients (25 sides) with idiopathic hearing loss, including 8 males and 11 females, aged between 4 to 50 years, who underwent 10 µm otology CT examination in Department of Radiology, Beijing Friendship Hospital, Capital Medical University from October 2020 to July 2021, were retrospectively collected. For those patients with idiopathic hearing loss, there were 5 cases (6 sides), including 2 males and 3 females, with an average age of 18-70 [65(20,68)] years, with bony connection between malleus and tympanum wall. Eighteen sex-and age-matched cases with normal hearing group, including 6 males and 12 females, with an average age of 20-68 (39±14) years, as the ratio of 1∶3, were included as the controls. The distances of the tegmen tympani between malleus head and horizontal semicircular canal, as well the distances between malleus head and horizontal semicircular canal were retrospectively measured and further compared between the two groups. Results: The incidence of IMF in patients with idiopathic conductive hearing loss without other etiologies was 24.0% (6/25). The specificity of 10 µm otology CT in diagnosing IMF was 100%. The distances of tegmen tympani between horizontal semicircular canal and malleus head in IMF patients were significantly smaller compared with the controls [-0.65(-1.21, -0.35) mm vs 1.34(0.04, 1.68) mm;0.92(0.51, 1.49) mm vs 2.82(1.76, 3.53) mm](both P<0.05, respectively). There was no significant difference in distances between malleus head and horizontal semicircular canal [-1.30 (-1.90, -0.46)mm vs -0.42 (-1.15, 0.05),P=0.057]. Conclusions: IMF is not uncommon in conductive hearing loss without other causes, which can be clearly shown by 10 µm otology CT. Its occurrence is related to the local downward shift of tegmen tympani above the malleus, without upwards displacement of the malleus.

[Study on the relationship between the morphology of the isthmus of the vestibular aqueduct and Meniere's disease based on 10 µm otology CT].

Objective: To evaluate the morphology of isthmus of the vestibular aqueduct (VA) and its relationship with the occurrence, course of Meniere's disease (MD) and the degree of hearing loss based on 10 µm otology CT. Methods: A total of 13 patients with MD in Beijing Friendship Hospital, Capital Medical University from October 2020 to July 2021, including 4 males and 9 females, age from 16 to 77 (56±16) years, were prospectively enrolled. All patients underwent 10 µm otology CT examination. The included lesion side was the MD affected group (14 sides), and the non-lesion side was the MD healthy group (12 sides). According to the 1∶2 side, 16 sex-and side matched cases (28 sides) without external and middle ear disease were included in the control group, including 4 males and 12 females, age from 16 to 77 (56±14) years. The horizontal semicircular canal showed on the largest plane was considered as the standard cross-section, and continuous observation was made on this image. According to the display type of isthmus of the VA, it was divided into Ⅰ to Ⅳ grades. Kruskal Wallis test was used to compare the morphological differences of VA isthmus among the affected group, the healthy group and the control group. The degree of hearing impairment was assessed by pure tone audiometry (PTA) results, which were divided into normal/mild/moderate/moderately severe/severe/extremely severe hearing impairment. Spearman correlation analysis was used to compare the correlation between the morphological rating of VA isthmus on the affected side and age, course of disease and the results of pure tone audiometry (PTA). Results: The proportions of VA isthmic morphology GRADE Ⅰ,Ⅱ,Ⅲ,Ⅳ in the MD affected group were 28.6% (4/14), 42.9% (6/14), 21.4% (3/14), 7.1% (1/14), those in the MD healthy group were 0 (0/12), 33.3% (4/12), 33.3% (4/12), 33.3% (4/12), and those in the control group were 0 (0/28), 7.1% (2/28), 64.2% (18/28), 28.6% (8/28). The VA isthmus scores [M (Q1, Q3)] of MD affected group was lower than that of MD healthy group [2 (1, 3) vs 3 (2, 4)] and control group [2 (1, 3) vs 3 (3, 4)] (all P<0.05, respectively). The morphology of the VA isthmus on the affected side of MD was negatively correlated with age (r=-0.81, P=0.002), and there was no correlation with the course of disease and degree of hearing impairment (r=-0.40, r=-0.26; all P>0.05, respectively). Conclusion: The stenosis of the VA isthmus in MD was a possible anatomical factor for the occurrence of MD.

[Analysis of the imaging characteristics of otosclerosis based on 10 µm otology CT].

Objective: To evaluate the imaging features of otosclerosis based on10 µm otology CT. Methods: Data of 27 patients with otosclerosis (51 sides) in Beijing Friendship Hospital, Capital Medical University from October 2020 to July 2021 were retrospectively collected, including 9 males and 18 females age ffrom 22 to 70 (42±12) years. All patients underwent 10 µm otology CT examination and surgical treatment. The types, amounts and involved sites of otosclerosis were analyzed and the sensitivity of 10 µm otology CT in diagnosing otosclerosis were evaluated. Results: Fenestral type accounted for 49.0% (25/51 sides), and diffuse type accounted for 51.0% (26/51 sides),and he retrofenestral type without fenestral lesion was not seen. Single lesions accounted for 45.1% (23/51 sides) and multiple lesions accounted for 54.9% (28/51 sides). The incidence of involvement of the fissula ante fenestram and annular ligaments were both 100%. The incidence of involvement of stapes footplate, vestibule, cochlea, round window, inner auditory canal wall, facial nerve canal, stapes muscle and semicircular canal was 60.8% (31 sides), 33.3% (17/51 sides), 21.6% (11/51 sides), 17.6% (9/51 sides), 13.7% (7/51 sides), 9.8% (5/51 sides), 7.8% (4/51 sides) and 5.9% (3/51 sides), respectively. The sensitivity of 10 µm otology CT in diagnosis of otosclerosis was 100%. Conclusion: 10 µm otology CT can fully display the imaging features of otosclerosis, and has the potential to be an effective routine method for otosclerosis.

[Experimental comparison of temporal bone imaging protocol optimization between 10 µm otology CT and multi-slice CT].

Objective: To evaluate different protocol optimization strategies for temporal bone between10 µm otology CT and multi-slice CT (MSCT). Methods: Ten adult skull specimens (20-sides temporal bones) were prospectively enrolled. From October to November 2020, the temporal bones were scanned under four different imaging conditions using 10 µm otology CT (90 kV, 120 mAs; 90 kV, 140 mAs; 100 kV, 120 mAs; 100 kV, 140 mAs) and MSCT (120 kV, 220 mAs; 120 kV, 310 mAs; 140 kV, 160 mAs; 140 kV, 220 mAs), respectively. The image quality was subjectively scored using 5-grade scores, and the contrast noise ratio (CNR) of the image was measured. The absorbed dose of tissues and organs under different imaging conditions was measured by thermoluminescence dosimeter, and the effective dose was calculated. The figure of merit (FOM) is defined as the ratio of the square of the mean CNR to the effective dose. χ2 test was used to compare the difference of subjective scores of different scanning parameter groups, and paired t test was used to analyze and compare the difference of image CNR of different scanning parameter groups. The image quality, radiation dose and FOM of the combination of recommended parameters of the two devices were analyzed and compared. Results: For 10 µm otology CT, under 100 kV condition, the CNR of 140 mAs group was better than that of 120 mAs group (11.27±1.85 vs 10.26±1.38, P<0.001). There was no significant difference in subjective scores between the two groups [5.00 (4.00, 5.00) vs 5.00 (4.25, 5.00), P=0.264]. For MSCT, under 120 kV condition, the subjective scores and CNR of 310 mAs group were better than those of 220 mAs at 120 kV [4.00(3.00, 4.00) vs 3.00(3.00, 3.00),P=0.002;5.24±0.62 vs 4.60±0.62,P<0.001]. According to the principle of image quality-radiation dose optimization, the combination of 100 kV with 120 mAs and 120 kV with 310 mAs are recommended for 10 µm otology CT and MSCT, respectively. The subjective scores and CNR of 10 µm otology CT images were better than those of MSCT (5.00 (4.25, 5.00) vs 4.00 (3.00, 4.00), 10.26±1.38 vs 5.48±0.22, P<0.001). The effective dose was 1/3 of that of MSCT (82.99 µSv vs 252.56 µSv), and the FOM was 11.16 times of that of MSCT (1 268.44 mSv-1 vs 113.71 mSv-1). Conclusion: The temporal bone image quality of newly developed 10 µm otology CT is significantly better than that of MSCT, and its effective dose is lower than that of MSCT, which has more accurate and safer application potential.

[Analysis of the performance of a multi-view fusion and active contour constraint based deep learning algorithm for ossicles segmentation on 10 µm otology CT].

Objective: To explore the performance of a deep learning algorithm that combined multi-view fusion with active contour constrained for ossicles segmentation on the 10 µm otology CT images. Methods: The 10 µm otology CT image data from 79 cases (56 cases were from volunteers and 23 cases were from specimens) were retrospectively collected in the Radiology Department of Beijing Friendship Hospital from October 2019 to December 2020. An annotation of malleus, incus, and stapes were conducted. Then the datasets were established and were divided into training set (n=55), validation set (n=8), and test set (n=16). Using the rapid localization of the region of interest combined with the precise segmentation algorithm, the malleus, incus and stapes were segmented and fused from three perspectives of coronal, sagittal and cross-sectional views. Besides, an active contour loss was designed simultaneously for the segmentation of stapes. Dice similarity coefficient (DSC) was used as the objective evaluation metric for the evaluation of the segmentation results. The inter group DSC of the proposed method was compared with that of the basic method and other methods. Results: The average DSC values of the multi-view fusion segmentation algorithm for malleus, incus and stapes reached up to 94.2%±2.7%, 94.6%±2.6% and 76.0%±5.5%, respectively. After adopting the constraint of active contour loss method, the average DSC of stapes was improved (76.4%±5.4% vs 76.0%±5.5%). The visualization results also demonstrated that the segmentation results of the stapes were more complete. Conclusions: Multi-view fusion algorithm based on 10 µm otology CT images can realize accurate segmentation of malleus and incus. Combined with the constraint of active contour loss method, the segmentation accuracy of stapes can be further improved.

Peripheral blood T-cell receptor repertoire as a predictor of clinical outcomes in gastrointestinal cancer patients treated with PD-1 inhibitor.

BACKGROUND: Identifying valid biomarkers for patient selection impressively promotes the success of anti-PD-1 therapy. However, the unmet need for biomarkers in gastrointestinal (GI) cancers remains significant. We aimed to explore the predictive value of the circulating T-cell receptor (TCR) repertoire for clinical outcomes in GI cancers who received anti-PD-1 therapy. METHODS: 137 pre- and 79 post-treated peripheral blood samples were included. The TCR repertoire was evaluated by sequencing of complementarity-determining region 3 (CDR3) in the TRB gene. The Shannon index was used to measure the diversity of the TCR repertoire, and Morisita's overlap index was used to determine TCR repertoire similarities between pre- and post-treated samples. RESULTS: Among all enrolled patients, 76 received anti-PD-1 monotherapy and 61 received anti-PD-1 combination therapy. In the anti-PD-1 monotherapy cohort, patients with higher baseline TCR diversity exhibited a significantly higher disease control rate (77.8% vs. 47.2%; hazard ratio [HR] 3.92; 95% confidence interval [CI] 1.14-13.48; P = 0.030) and a longer progression-free survival (PFS) (median: 6.47 months vs. 2.77 months; HR 2.10; 95% CI 1.16-3.79; P = 0.014) and overall survival (OS) (median: NA vs. 8.97 months; HR 3.53; 95% CI 1.49-8.38; P = 0.004) than those with lower diversity. Moreover, patients with a higher TCR repertoire similarity still showed a superior PFS (4.43 months vs. 1.84 months; HR 13.98; 95% CI 4.37-44.68; P < 0.001) and OS (13.40 months vs. 6.12 months; HR 2.93; 95% CI 1.22-7.03; P = 0.016) even in the cohort with lower baseline diversity. However, neither biomarker showed predictive value in the anti-PD-1 combination therapy cohort. Interestingly, the combination of TCR diversity and PD-L1 expression can facilitate patient stratification in a pooled cohort. CONCLUSION: The circulating TCR repertoire can serve as a predictor of clinical outcomes in anti-PD-1 therapy in GI cancers.