Design, synthesis and evaluation of novel prostate-specific membrane antigen-targeted aryl [18F]fluorosulfate PET tracers.

The expression of prostate-specific membrane antigen (PSMA) in prostate cancer is 100-1000 times higher than that in normal tissues, and it has shown great advantages in the diagnosis and treatment of prostate cancer. The combination of PSMA and PET imaging technology based on the principle of metabolic imaging can achieve high sensitivity and high specificity for diagnosis. Due to its suitable half-life (109 min) and good positron abundance (97%), as well as its cyclotron accelerated generation, 18F has the potential to be commercialize, which has attracted much attention. In this article, we synthesized a series of fluorosulfate PET tracers targeting PSMA. All four analogues have shown high affinity to PSMA (IC50 = 1.85-5.15 nM). After the radioisotope exchange labeling, [18F]L9 and [18F]L10 have PSMA specific cellular uptake (0.65 ± 0.04% AD and 1.19 ± 0.03% AD) and effectively accumulated in 22Rv1 xenograft mice model. This study demonstrates that PSMA-1007-based PSMA-targeted aryl [18F]fluorosulfate novel tracers have the potential for PET imaging in tumor tissues.

Fluorine-18 labeling PEGylated 6-boronotryptophan for PET scanning of mice for assessing the pharmacokinetics for boron neutron capture therapy of brain tumors.

Two tryptophan compound classes 5- and 6-borono PEGylated boronotryptophan derivatives have been prepared for assessing their aqueous solubility as formulation of injections for boron neutron capture therapy (BNCT). The PEGylation has improved their aqueous solubility thereby increasing their test concentration in 1 mM without suffering from toxicity. In-vitro uptake assay of PEGylated 5- and 6-boronotryptophan showed that the B-10 concentration can reach 15-50 ppm in U87 cell whereas the uptake in LN229 cell varies. Shorter PEG compound 6-boronotryptophanPEG200[18F] was obtained in 1.7 % radiochemical yield and the PET-derived radioradioactivity percentage in 18 % was taken up by U87 tumor at the limb of xenograft mouse. As high as tumor to normal uptake ratio in 170 (T/N) was obtained while an inferior radioactivity uptake of 3 % and T/N of 8 was observed in LN229 xenografted mouse.

A Novel Homoconjugated Propellane Triimide: Synthesis, Structural Analyses, and Gas Separation.

Rigid three-dimensional (3D) polycyclic propellanes have garnered interest due to their unique conformational spaces, which display great potential use in selectivity, separation and as models to study through-space electronic interactions. Herein we report the synthesis of a novel rigid propellane, trinaphtho[3.3.3]propellane triimide, which comprises three imide groups embedded on a trinaphtho[3.3.3]propellane. This propellane triimide exhibits large bathochromic shift, amplified molar absorptivity, enhanced fluorescence, and lower reduction potential when compared to the subunits. Computational and experimental studies reveal that the effective through-space π-orbitals interacting (homoconjugation) occurs between the subunits. Single-crystal XRD analysis reveals that the propellane triimide has a highly quasi-D3h symmetric skeleton and readily crystallizes into different superstructures by changing alkyl chains at the imide positions. In particular, the porous 3D superstructure with S-shaped channels is promising for taking up ethane (C2H6) with very good selectivity over ethylene (C2H4), which can purify C2H4 from C2H6/C2H4 in a single separation step. This work showcases a new class of rare 3D polycyclic propellane with intriguing electronic and supramolecular properties.

Mesoporous silica-based nanocarriers with dual response to pH and ROS for enhanced anti-inflammation therapy of 5-demethylnobiletin against psoriasis-like lesions.

Psoriasis is an inflammatory skin disease accompanied with chronic papulosquamous lesions and multiple comorbidities that considerably affect patients' quality of life. In order to develop an enhanced therapeutic strategy for psoriasis, 5-demethylnobiletin (5-DN), a kind of polymethoxyflavones (PMFs) with high anti-inflammatory activity, was delivered in vitro and in vivo by the nanocarrier of mesoporous silica nanoparticles (MSNs) both in the human keratinocytes HaCaT cell line and the mouse model with psoriasis-like lesions. The drug-loaded nanocarrier system (MSNs@5-DN) significantly improved the biocompatibility and bioavailability of 5-DN. Investigations at cell biological, histopathological, and molecular levels revealed the pharmacological mechanism of the drug delivery system, including the inhibition of inflammatory responses by downregulating the proinflammatory cytokine levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6). The upregulation of anti­inflammatory cytokine of transforming growth factor-ß1 (TGF-ß1) and microRNA-17-5p, a critical regulator of the PTEN/AKT pathway, was also observed. The psoriasis-like lesions were markedly ameliorated in the mouse models treated with MSNs@5-DN. The designed drug-loading system shows an enhanced therapeutic outcome for psoriasis-like lesion compared with free 5-DN. This study revealed the synergistic effect of functionalized MSNs loaded with PMFs on the clinical treatment of human psoriasis.

Spatiotemporal distribution and probabilistic health risk assessment of arsenic in drinking water and wheat in Northwest China.

Drinking water arsenic poisoning has been a health concern, however the importance of dietary arsenic exposure to health also needs to be taken into account. The aim of this study was to conduct a comprehensive health risk assessment of arsenic-contaminated substances in drinking water and wheat-based food intake in the Guanzhong Plain, China. 87 samples of wheat and 150 samples of water were randomly selected from the research region and examined. The level of arsenic in 89.33% of the water samples in the region exceeded the limit for drinking water (10 µg/L), with an average concentration of 29.98 µg/L. The arsenic in 2.13% of the wheat samples exceeded the food limit (0.5 mg/kg) with an average concentration of 0.24 mg/kg. Under the situation of different exposure pathways, two scenarios of deterministic and probabilistic health risk assessments were compared and analyzed. By contrast, the probabilistic health risk assessment can ensure a certain degree of confidence in the assessment results. The findings of this study indicated that the total cancer risk value faced by the population aged 3-79 years, except for those aged 4-6 years, was 1.03E-4-1.21E-3, which exceeded the 10E-6-10E-4 range of thresholds usually used by USEPA as guidance recommendations for determination. And the non-cancer risk experienced by the population aged 6 months to 79 years was higher than the acceptable threshold (1), with children aged 9 months to 1 year having the highest total non-cancer risk of 7.25. The potential health risks of the exposed population were mainly due to the drinking water route, and consumption of arsenic-containing wheat increased both carcinogenic and non-carcinogenic risks. Finally, the sensitivity analysis revealed that the assessment findings were most significantly influenced by exposure time. The amount of intake was the second influencing factor in the health risk assessment from drinking water and dietary intakes of arsenic, and arsenic concentration was the second influencing factor in the health risk assessment due to dermal exposure to arsenic. The findings of this study can aid in understanding the negative health consequences of arsenic pollution to local residents and in adopting focused remediation strategies to alleviate environmental concerns.

Characteristics of vestibular migraine, probable vestibular migraine, and recurrent vertigo of childhood in caloric and video head impulse tests.

Objective: Vertigo is very common in children, but the specific diagnosis and characteristics are not clear. The main objective of this study was to analyze the characteristics of caloric test (CT) and video head impulse test (vHIT) in vestibular migraine of childhood (VMC), probable vestibular migraine of childhood (PVMC), and recurrent vertigo of childhood (RVC), which can provide a reference value for their clinical diagnosis. Methods: We selected VMC, PVMC and RVC patients under 18 years of age from the outpatient Department of Otolaryngology-Head and Neck Surgery between May 2021 and August 2022. All patients underwent vestibular function examinations, including eye movement recording CT and vHIT. CT results depended on whether both canal paresis and directional preponderance were under normal limits, and vHIT results depended on the gain values of vestibulo-ocular reflex. The results of both tests were analyzed according to the disease type. Results: Among the 81 pediatric vertigo patients aged 5-17 years, 44 were females and 37 were males. According to the type of vertigo, 29 patients (25.80%) were diagnosed with VMC, 11 (13.58%) with PVMC, and 41 (50.62%) with RVC. The abnormal rates of the CT in VMC, PVMC, and RVC patients were 24.14%, 36.36%, and 17.07%, respectively. There was no significant difference in the abnormal rates among the three groups (P > 0.05). None of the patients showed abnormal vHIT results (all abnormal rates 0.00%). The abnormal CT rates were significantly higher than those of abnormal vHIT rates (P < 0.05). Conclusions: VMC, PVMC, and RVC are more likely to be diagnosed by symptoms, as neither CT nor vHIT are specific to any conditions. Due to different clinical presentations of vertigo in pediatric patients, it is critical to further clarify the diagnosis with medical history and clinical characteristics.

[The characteristics of vestibular-evoked myogenic potentials in unilateral Meniere's disease patients at different clinical stages].

Objective:This study was to retrospectively analyze the results of vestibular-evoked myogenic potentials（VEMP） in unilateral Meniere's disease（MD） patients. Methods:The clinical assessment results of MD patients who visited the department between January 2016 to February 2022 were reviewed. Unilateral MD patients who met the inclusion and exclusion criteria were divided into three groups according to clinical stages, namely, group 1（stage Ⅰ+ stage Ⅱ）, group 2（stage Ⅲ） and group 3（stage Ⅳ）. The normal value data were used to investigate the incidence of abnormal P1 and N1 latencies, abnormal P1-N1 interwave latency, and abnormal interaural amplitude asymmetry ratio（IAR）. Afterwards, considering all the above mentioned parameters, the VEMP result of each patient was graded into four levels（grade 1 means VEMP result is normal, grade 2, 3 and 4 means the VEMP result is abnormal in different degrees）. The correlation between VEMP result level and pure tone average（PTA） of MD patients in different clinical stages was examined. Results:The prevalence of cVEMP in three groups was 84.2%, 70.0% and 33.3%, respectively（P<0.05）. The prevalence of oVEMP in three groups was 63.2%, 34.0% and 16.7%, respectively（P<0.05）. The incidence of abnormal P1 latency, N1 letancy and P1-N1 interwave latency of cVEMP was 21.1%, 26.3% and 24.6%, respectively. The incidence of abnormal P1 latency, N1 latency and interwave latency of oVEMP was 15.6%, 43.8% and 3.1%, respectively. The incidence of abnormal cVEMP IAR in group 1, group 2 and group 3 was 6.7%, 21.2% and 33.3%, respectively（P>0.05）. The incidence of abnormal IAR of oVEMP in group 1, group 2 and group 3 was 16.7%, 23.1% and 0, respectively（P>0.05）. cVEMP and oVEMP result levels were significantly correlated with PTA（r=0.339, P<0.01; r=0.362, P<0.01 ）, respectively. Conclusion:With the progression of MD, the function of saccule-vestibular inferior nerve pathway and utricle-vestibular superior nerve pathway would deteriorate in the same way as hearing.

[Compensation effect of hearing aid on speech recognition in noise in patients with unilateral hearing loss].

Objective:The aim of this study was to investigate the speech recognition in noise in patients with unilateral hearing loss（UHL）, and explore the compensation effect of behind-the-ear（BTE） hearing aid on speech recognition in patients with varied degrees of UHL. Methods:Twenty-five participants with UHL were divided into two groups according to the degree of hearing loss: one group included subjects with unilateral moderate and moderately severe hearing loss and another one included subjects with unilateral severe and profound hearing loss. Fifteen healthy subjects with normal hearing were enrolled as the control group. The speech recognition thresholds and speech recognition scores at fixed signal noise ratio（SNR） in UHL participants with and without BTE hearing aid were tested in the sound field and compared with those in the control group. One-way ANOVA was used to examine the significance of the difference between UHL participants and control group, and paired t-test was used to analyze the compensation effect of hearing aid on speech recognition in noise in UHL participants. Results:The speech recognition thresholds were significantly higher in both UHL groups（P<0.01） compared with the control group, there was no significant difference between two UHL groups. And the speech recognition scores were significantly lower when the SNR was fixed（P<0.01）, and there were no significant differences between two UHL groups. When fitting BTE hearing aid, the speech recognition thresholds of the two groups significantly decreased（P<0.01）, and the speech recognition scores significantly improved（P<0.01）. Conclusion:Patients with above moderate UHL presented a significant decrease in performance of speech recognition in noise, and fitting BTE hearing aid on the affected ear had a positive compensation effect.

[Gain characteristics of three pairs of semicircular canals in video head impulse paradigm test and suppression head impulse paradigm test in healthy young Chinese population].

Objective:To summarize gain characteristics of three pairs of semicircular canals in head impulse paradigm （HIMP） and suppression head impulse paradigm （SHIMP） in healthy young Chinese population. Methods:HIMP and SHIMP tests were performed on 40 healthy young volunteers enrolled as study group, by using EyeseeCam examiantion system （Interacoustics，Denmark）. The elicitation rates and gain values of the two saccades were recorded, and the gain values were compared and analyzed. Results:The results of 40 healthy young people were as follows: in HIMP, the instantaneous gain at 60 ms of the horizontal semicircular canals were 1.11±0.07 on the left side and 1.08±0.07 on the right side; the regression gain of the horizontal semicircular canals were 1.09±0.06 on the left side and 1.10±0.06 on the right side; the regression gain of the vertical semicircular canals were 1.08±0.12 on the right anterior, 1.07±0.11 on the left posterior, 1.41±0.16 on the right posterior and 1.42±0.16 on the left anterior. So in HIMP, no significant difference could be found between left and right side in both horizontal and vertical semicircular canal conjugate plane regarding regression gain （P>0.05）, except that 60 ms instantaneous gain on the left horizontal semicircular canals was slightly higher than that on the right side （P<0.05）.The instantaneous gain values of the horizontal semicircular canal at 60 ms in SHIMP were 1.08±0.08 on the left side and 1.06±0.07 on the right side; the regression gain in horizontal semicircular canals were 1.06±0.07 on the left side and 1.07±0.06 on the right side, respectively; the regression gains of vertical semicircular canal were 1.06±0.13, 1.08±0.16, 1.49±0.16, 1.39±0.15, on the right anterior, left posterior, right posterior, and left anterior side. So in SHIMP, no significant difference could be found in 60 ms instantaneous gain in horizontal conjugate plane, regression gain in horizontal conjugate plane and regression gain in right anterior left posterior conjugate plane （P>0.05）, while the regression gain of the left anterior right posterior conjugate plane in the right was found slightly higher than that of the left （P<0.05）.Both 60 ms instantaneous gain and regression gain in horizontal conjugate plane in HIMP were slightly higher than that of SHIMP （P<0.05）, while no significant difference could be found in vertical conjugate planes （P>0.05）. In both HIMP and SHIMP tests, gains of the left anterior right posterior conjugate plane was slightly higher than that of both horizontal plane and the right anterior left posterior conjugate plane （P<0.05）, while no significant difference could be found in gains between horizontal and the right anterior left posterior conjugate plane （P>0.05）. Conclusion:Gain values of HIMP and SHIMP were slightly different among different semicircular canals conjugate planes.It is suggested that each examination center should establish normal values for their own and make correction regularly.

[The effect of different rotation modes on testing resulting of the subjective visual vertical].

Objective:To investigate the effect of different rotations modes of control rod on testing results of the subjective visual vertical （SVV）. Methods:Twenty-four normal young volunteers were selected for this study, and the control rod of SVV was rotated in clockwise, counterclockwise and any direction at the head tilt-positions of 0°, 45° left and 45° right. The differences of SVV deflection angle values at different rotation modes were analyzed. Results:①The deviation angle values of SVV obtained by rotating the control rod in clockwise, counterclockwise and any direction at the head tilt-positions of 0° were 1.56°±0.21°, 3.05°±0.24°, and 2.16°±0.22°, respectively，and the difference was statistically significant （P<0.05）,the deviation angle value of SVV in clockwise direction was smaller; ②At head tilt-positions of 45° left, the SVV deviation angle values obtained by rotating the control rod in three rotation modes were 2.59°±0.53°, 4.03°±0.51°, and 3.49°±0.54°, respectively, and the difference was statistically significant（P<0.05）,the deviation angle value in the clockwise direction was also smaller; ③At the head tilt-positions of 45° right, the SVV deviation angle values in three modes were 4.68°±0.58°, 7.23°±0.72°, and 5.93°±0.96°, respectively, and the difference was statistically significant （P<0.05）,the deviation value of SVV was also smaller when rotated in the clockwise direction; ④Comparison of SVV deviation angle values in three rotation modes at the head tilt-positions of 45° left and 45° right showed that there was no statistical difference in clockwise and in any direction （P>0.05）, while the difference was statistically significant when rotated in the counterclockwise direction （P<0.05）. Conclusion:Different rotation modes of the control rod during SVV testing will affect the test results. Rotating the control rod in clockwise direction to make the SVV values more accurate is recommended.

[Correlation between Mandarin acceptable noise level and cortical auditory evoked potential in young normal-hearing listeners].

Objective:To investigate the correlation between Mandarin acceptable noise level （M-ANL） and cortical auditory evoked potential （CAEP）, and to explore the possible mechanism leading to individual differences in M-ANL values. Methods:Thirty listeners aged 22-33 years with normal hearing were selected as the study subjects, and the M-ANL test and CAEP test were performed respectively. The most comfortable level （MCL）, maximum background noise level （BNL）, M-ANL and CAEP values of each subject were recorded. The latency of each wave of P1, N1, P2, N2, P300 and the amplitude of P1-N1, P2-N2, P300 in CAEP were recorded for each subject. SPSS 25.0 was used for statistical analysis to explore the correlation between the MCL value, BNL value and M-ANL values and the latency of P1, N1, P2, N2, P300 and P1-N1, P2-N2, P300 amplitudes of CAEP. Results:①The MCL value and M-ANL value were positively correlated with the P2 latency of CAEP, and the correlation coefficients were 0.404 and 0.400, respectively, and the differences were statistically significant （P<0.05）. There was no correlation with P1, N1, N2, and P300 latencies of CAEP （P>0.05）. ②The MCL value, BNL value and M-ANL value had no significant difference with the CAEP wave amplitudes of P1-N1, P2-N2, and P300 （P>0.05）. Conclusion:There was a certain correlation between M-ANL and CAEP in young adults with normal hearing, suggesting that the central auditory cortex might play a potential regulatory role in the background noise tolerance. Individuals with a greater background noise acceptance might have stronger central efferent mechanisms and/or less active central afferent mechanisms.

Clinical characteristics of vestibular evoked myogenic potentials in children with recurrent vertigo of childhood.

OBJECTIVE: To explore the possible pathogenesis of recurrent vertigo of childhood (RVC) and the clinical diagnosis value of vestibular-evoked myogenic potentials (VEMPs). METHODS: The clinical data of 19 children (5.95 ± 0.38 years) diagnosed with RVC and 17 normal children (5.35 ± 0.31 years) enrolled in the control (NC) group from April 2017 to February 2021 was collected and analyzed. All subjects were tested for both cervical VEMP (cVEMP) and ocular VEMP (oVEMP). The elicit rate, thresholds, N1 latency, P1 latency, interval, amplitude, and amplitude asymmetry ratio (AAR) of VEMPs were compared and analyzed between the two groups. RESULTS: (1) The elicit rates of cVEMP and oVEMP have no significant difference between the two groups (P > 0.05). (2) The thresholds of cVEMP and oVEMP in the RVC group were higher than that in the NC group (P < 0.05). (3) The N1 latency of cVEMP in the RVC group was longer than that in the NC group (P < 0.05). The P1 latency of cVEMP and latencies of oVEMP have no significant difference between the two groups (P > 0.05). (4) The interval of cVEMP in the RVC group was longer than that in the NC group (P < 0.05), while the interval of oVEMP has no significant difference between the two groups (P > 0.05). (5) The amplitude of cVEMP in the RVC group was higher than that in the NC group (P < 0.05), while the amplitude of oVEMP was similar in the two groups (P > 0.05). (6) The AAR values of oVEMP and cVEMP were similar in the two groups (P > 0.05). CONCLUSIONS: The elicit rates of VEMPs in children with RVC did not differ from that of normal children, but the thresholds were all increased, suggesting reduced sensitivity of the otolith organ and vestibular nerve conduction pathways. The P1 latency of cVEMP was normal in children with RVC, but N1 latency and interval of cVEMP were increased, we finally reached a conclusion that there might be potential impairment in the inferior vestibular nerve and the subsequent nerve conduction pathway in RVC.

[Myotonia-rectified bone-conducted vibration vestibular evoked myogenic potential in normal adults].

Objective:To study the characteristics of bone-conducted vibration vestibular evoked myogenic potential（BCV-VEMP） in normal adult with and without myotonia rectification, and to provide accurate reference for clinical vestibular function evaluation. Methods:Thirty normal adults（60 ears） aged 20-32 years old were selected to receive BCV-VEMP in a sitting position. BCV-VEMP were induced by B-81 bone-conducted vibrator at 129.5 FL, the P1 latency, N1 latency, P1-N1interval, amplitude, and amplitude asymmetry ratios were recorded in two test conditions. Results:Clear and repeatable waveforms of BCV-cVEMP and BCV-oVEMP were obtained in all normal adults. The P1 and N1 latencies of BCV-cVEMP were（16.00±2.02） ms and（25.04±2.57） ms, respectively, P1-N1 interval was（9.04±1.78） ms. The N1 and P1 latencies of BCV-oVEMP were（10.39±0.81） ms and（15.85±1.00） ms, respectively, iand interval was（5.46±0.86） ms. The amplitudes of BCV-cVEMP and BCV-oVEMP in two test conditions were statistically significant（P<0.05）. The amplitude asymmetry ratios of BCV-cVEMP and BCV-oVEMP after rectification were （17.03±9.14）% and （20.43±11.65）%, respectively. Conclusion:BCV-VEMP is a feasible and reliable tool for vestibular function assessment. The establishment of a normal values such as amplitude and amplitude asymmetry ratio after rectification can provide a more reliable and accurate reference.

Establishment and Validation of a Novel MRI Radiomics Feature-Based Prognostic Model to Predict Distant Metastasis in Endemic Nasopharyngeal Carcinoma.

Purpose: We aimed to establish a prognostic model based on magnetic resonance imaging (MRI) radiomics features for individual distant metastasis risk prediction in patients with nasopharyngeal carcinoma (NPC). Methods: Regression analysis was applied to select radiomics features from T1-weighted (T1-w), contrast-enhanced T1-weighted (T1C-w), and T2-weighted (T2-w) MRI scans. All prognostic models were established using a primary cohort of 518 patients with NPC. The prognostic ability of the radiomics, clinical (based on clinical factors), and merged prognostic models (integrating clinical factors with radiomics) were identified using a concordance index (C-index). Models were tested using a validation cohort of 260 NPC patients. Distant metastasis-free survival (DMFS) were calculated by using the Kaplan-Meier method and compared by using the log-rank test. Results: In the primary cohort, seven radiomics prognostic models showed similar discrimination ability for DMFS to the clinical prognostic model (P=0.070-0.708), while seven merged prognostic models displayed better discrimination ability than the clinical prognostic model or corresponding radiomics prognostic models (all P<0.001). In the validation cohort, the C-indices of seven radiomics prognostic models (0.645-0.722) for DMFS prediction were higher than in the clinical prognostic model (0.552) (P=0.016 or <0.001) or in corresponding merged prognostic models (0.605-0.678) (P=0.297 to 0.857), with T1+T1C prognostic model (based on Radscore combinations of T1 and T1C Radiomics models) showing the highest C-index (0.722). In the decision curve analysis of the validation cohort for all prognostic models, the T1+T1C prognostic model displayed the best performance. Conclusions: Radiomics models, especially the T1+T1C prognostic model, provided better prognostic ability for DMFS in patients with NPC.

Circulating T-Cell Repertoires Correlate With the Tumor Response in Patients With Breast Cancer Receiving Neoadjuvant Chemotherapy.

PURPOSE: Neoadjuvant chemotherapy (NAC) has been widely used in patients with breast cancer to minish tumor burden and increase resection rate of cancer. T-cell repertoire has been believed to be able to monitor antitumor immune responses. This study aimed to explore the dynamic change of T-cell repertoire and its clinical value in evaluating the tumor response in patients with breast cancer receiving NAC. MATERIALS AND METHODS: Ninety-four patients who underwent NAC before surgery were recruited, and peripheral blood samples were collected at multiple time points during NAC. High-throughput T-cell receptor (TCR)-ß sequencing was used to characterize the T-cell repertoire of every sample and analyzed the changes in circulating T-cell repertoire during NAC. RESULTS: We found that the diversity of TCR repertoires was associated with age and clinical stage of the patients with breast cancer. The distribution of Vß and Jß genes in TCR repertoires was skewed in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Vß20.1 and Vß30 expression levels before NAC correlate with tumor response after all cycles of NAC in HER2- and HER2+ patients, respectively. Some CDR3 motifs that correlated with clinical response in either HER2+ or HER2- patients were identified. Besides, TCR repertoire evolved during NAC and the diversity of TCR repertoire decreased more after two cycles of NAC in patients with good tumor response after all cycles of NAC (P = .0061). CONCLUSION: Our results demonstrated that TCR repertoire correlated with the characteristics of the tumor, such as the expression status of HER2. Moreover, some characteristics of TCR repertoires that correlated with clinical response were identified and they might provide useful information to tailor therapeutic regimens at the early cycle of NAC.

[Effect of the course of posterior semicircular canal benign paroxysmal positional vertigo on residual symptoms after successful canalith repositioning procedure].

Objective:To investigate the effect of the course of posterior semicircular canal benign paroxysmal positional vertigo（BPPV） on residual symptoms after successful canalith repositioning procedure（CRP）. Methods:A total of 56 patients with posterior semicircular canal BPPV were selected from July 2020 to March 2021. They were divided into the short course group and the long course group according to the duration of disease from symptom onset to CRP treatment. All patients were treated with mechanical Epley repositioning procedure with rotary chair assistance. After successful repositioning treatment, they were followed up for seven to ten days. All patients were assessed using the vertigo disorder scale （DHI） before and after treatment,the differences of each dimension score and total score of DHI before and after successful CRP were compared between these two groups. Results:① After successful CRP, in patients with mild residual symptoms, the ratio between short course group and long course group were 68.6% and 31.4%, respectively. While in patients with moderate to severe residual symptoms,the ratio between short course group and long course group was 20% and 80%, respectively. The difference was statistically significant（P<0.05）. ②Before CRP, there was no significant difference in Physical dimension（DHI-P, 7 items） and in Function dimension（DHI-F, 9 items） between the two groups（P>0.05）, but there was significant difference in Emotion dimension（DHI-E, 9 items） and in total DHI score between the two groups（P<0.05, respectively）. After treatment, there was no significant difference in DHI-P score between the two groups（P>0.05）, but there were significant differences in DHI-F, DHI-E and DHI total score between the two groups（P<0.05,respectively）. Compared with the scores of DHI-P, DHI-F, DHI-E and DHI total score before and after successful CRP, the significant differences were found between the short course group and long course group（P<0.05,respectively）. ③There was no significant difference in the difference of DHI dimensions and total score between the short course group and the long course group before after reduction（P>0.05,respectively）. Conclusion:The duration of posterior semicircular canal BPPV（P-BPPV） does not affect the short-term efficacy of P-BPPV repositioning treatment, but patients with long course of P-BPPV are more likely to have moderate to severe residual symptoms after successful CRP，mainly in social function and emotional psychology.

The Diagnostic and Prognostic Potential of the B-Cell Repertoire in Membranous Nephropathy.

Membranous nephropathy (MN), an autoimmune glomerular disease, is one of the most common causes of nephrotic syndrome in adults. In current clinical practice, the diagnosis is dependent on renal tissue biopsy. A new method for diagnosis and prognosis surveillance is urgently needed for patients. In the present study, we recruited 66 MN patients before any treatment and 11 healthy control (HC) and analyzed multiple aspects of the immunoglobulin heavy chain (IGH) repertoire of these samples using high-throughput sequencing. We found that the abnormalities of CDR-H3 length, hydrophobicity, somatic hypermutation (SHM), and germ line index were progressively more prominent in patients with MN, and the frequency of IGHV3-66 in post-therapy patients was significantly lower than that in pre-therapy patients. Moreover, we found that the IGHV3-38 gene was significantly related to PLA2R, which is the most commonly used biomarker. The most important discovery was that several IGHV, IGHD transcripts, CDR-H3 length, and SHM rate in pre-therapy patients had the potential to predict the therapeutic effect. Our study further demonstrated that the IGH repertoire could be a potential biomarker for prognosis prediction of MN. The landscape of circulating B-lymphocyte repertoires sheds new light on the detection and surveillance of MN.

[The analysis of the characteristics of hearing loss in patients with cochlear nerve aphasia identified by MRI].

Objective:To explore the characteristics of hearing loss in patients with cochlear nerve aphasia（CNA） and to provide evidences for diagnosis and treatment of cochlear nerve aphasia. Methods:A retrospective study was performed. A total of 51 cases were included in the study. The data of hearing test, inner auditory canal MRI and temporal HRCT were analyzed. Results:77.19% of the affected ears had extremely severe hearing loss, and 7.02% of the affected ears had moderate hearing loss. The residual hearing was concentrated in low-medium frequency. A CNA ear with bone cochlear nerve canal atresia can exhibited moderate hearing loss. Conclusion:The patient with CNA may still present residual hearing function. CNA could not be excluded in patients with moderate hearing loss. The "three-dimensional integration" comprehensive evaluation system, which includesinternal auditory canal MRI, temporal thin-layer CT scan and audiology evaluation, could be helpful to the diagnosis of cochlear nerveaphasia.

Single-cell transcriptome analysis revealed the heterogeneity and microenvironment of gastrointestinal stromal tumors.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the human gastrointestinal tract. In this study, we performed single-cell RNA sequencing (RNA-seq) on intra- and peri-tumor tissues from GIST patients with the aim of discovering the heterogeneity of tumor cells in GIST and their interactions with other cells. We found four predominating cell types in GIST tumor tissue, including T cells, macrophages, tumor cells, and NK cells. Tumor cells could be clustered into two groups: one was highly proliferating and associated with high risk of metastasis, the other seemed "resting" and associated with low risk. Their clinical relevance and prognostic values were confirmed by RNA-seq of 65 GIST samples. T cells were the largest cell type in our single-cell data. Two groups of CD8+ effector memory (EM) cells were in the highest clonal expansion and performed the highest cytotoxicity but were also the most exhausted among all T cells. A group of macrophages were found polarized to possess both M1 and M2 signatures, and increased along with tumor progression. Cell-to-cell interaction analysis revealed that adipose endothelial cells had high interactions with tumor cells to facilitate their progression. Macrophages were at the center of the tumor microenvironment, recruiting immune cells to the tumor site and having most interactions with both tumor and nontumor cells. In conclusion, we obtained an overview of the GIST microenvironment and revealed the heterogeneity of each cell type and their relevance to risk classifications, which provided a novel theoretical basis for learning and curing GISTs.

Changes in Alternative Splicing in Response to Domestication and Polyploidization in Wheat.

Alternative splicing (AS) occurs extensively in eukaryotes as an important mechanism for regulating transcriptome complexity and proteome diversity, but variation in the AS landscape in response to domestication and polyploidization in crops is unclear. Hexaploid wheat (AABBDD, Triticum aestivum) has undergone two separate allopolyploidization events, providing an ideal model for studying AS changes during domestication and polyploidization events. In this study, we performed high-throughput transcriptome sequencing of roots and leaves from wheat species with varied ploidies, including wild diploids (AbAb, Triticum boeoticum) and tetraploids (AABB, Triticum dicoccoides), domesticated diploids (AmAm, Triticum monococcum) and tetraploids (AABB, Triticum dicoccum), hexaploid wheat (AABBDD, T aestivum), as well as newly synthesized hexaploids together with their parents. Approximately 22.1% of genes exhibited AS, with the major AS type being intron retention. The number of AS events decreased after domestication in both diploids and tetraploids. Moreover, the frequency of AS occurrence tended to decrease after polyploidization, consistent with the functional sharing model that proposes AS and duplicated genes are complementary in regulating transcriptome plasticity in polyploid crops. In addition, the subgenomes exhibited biased AS responses to polyploidization, and ∼87.1% of homeologs showed AS partitioning in hexaploid wheat. Interestingly, substitution of the D-subgenome modified 42.8% of AS patterns of the A- and B-subgenomes, indicating subgenome interplay reprograms AS profiles at a genome-wide level, although the causal-consequence relationship requires further study. Conclusively, our study shows that AS variation occurs extensively after polyploidization and domestication in wheat species.