Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

Objective To investigate extended high-frequency hearing in young adults and to analyse its char-acteristics.Methods A total of 230 freshmen(101 males and 129 females,aged 17-19 years old)from the class of 2023 at the Air Force Medical University underwent audiometric tests,including acoustic impedance,conventional frequency and extended high-frequency audiometry,and distortion product otoacoustic emissions(DPOAE).Ac-cording to the results of extended high-frequency audiometry,the students were divided into normal and abnormal groups,and the hearing thresholds at conventional frequencies were compared between the two groups.Results Of the 230 students,47.83％(110/230)showed abnormal extended high-frequency hearing.The hearing thresholds of the right ear were 1 to 3 dB higher than those of the left ear at most frequencies.The hearing thresholds of the ab-normal group were higher than those of the normal group in the conventional frequencies(P＜0.05).The difference in extended high-frequency thresholds between the two groups increased with higher frequency.Conclusion Ex-tended high-frequency hearing loss occurs earlier,and has a higher prevalence in young adults,and right ear hearing is worse than that of left ear.Extended high-frequency audiometry can be used as a predictive tool for detecting con-ventional frequency hearing loss.

Objective To investigate the expression of serum tumor-associated antigens(TAAs)in patients with rheumatoid arthritis(RA)and analyze their clinical significance for RA.Methods A total of 214 RA patients were enrolled in the RA group,while 198 age-and gender-matched healthy individuals were included in the HC group.Rheumatoid factor(RF),anti-cyclic citrullinated peptide antibody(Anti-CCP),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),interleu-kin-6(IL-6),ferritin levels,as well as gender,age,disease duration,disease activity score(DAS28)and clinical manifestations were collected from the RA group.The expression of TAAs in RA patients and the clinical characteristics of TAA-positive patients were analyzed.Spearman correla-tion analysis was used to evaluate the relationships between TAAs and clinical indicators in RA pa-tients.Results The positive rate of carbohydrate antigen 125(CA125)in the RA group was 8.88％,which was significantly higher than 1.01％ in the HC group(P＜0.001).Serum CA125 and cytok-eratin fragment 19(CYFRA21-1)levels in the RA group were significantly higher than those in the HC group,whereas alpha-fetoprotein(AFP),carcinoembryonic antigen(CEA),carbohydrate anti-gen 199(CA199)and neuron-specific enolase(NSE)levels were significantly lower(P＜0.001).TAA-positive patients had significantly older age and higher rates of pulmonary interstitial lesions compared to TAA-negative patients(P＜0.05).Patients with DAS28 scores＞5.1 had significantly higher CA125 levels than those with DAS28 scores ≤5.1(P＜0.05).CA125 levelswere positively corre-lated with DAS28 scores,ESR,RF,and anti-CCP antibodies(r=0.142,0.140,0.268,0.183;P＜0.05).Conclusion In RA patients,the positivity rate and levels of some serum TAAs are ele-vated,and TAA-positive patients tend to be older and have higher incidence of pulmonary interstitial lesions.CA125 levels are positively correlated with RA disease activity.

Objective To study the clinical features and treatment outcomes of otitis media caused by antineu-trophil cytoplasmic antibody ANCA-associated vasculitis[otitis media with AAV(OMAAV)].Methods A total of 19 cases of OMAAV diagnosed between September 2015 to September 2022 were studied.OMAAV was defined using the criteria introduced by Japan Society of Otology.Results Median age of all patients was 61.8 years old,predominantly proteinase 3(PR3)positive(47.3％).Averaged score of vasculitis activity was 6.6.Disease also in-volved lung(84.2％),nose(73.7％)and facial nerve(21.0％).Pathological biopsy was performed in nine pa-tients,and two reports indicated ANCA-related disease.Fourteen affected ears of eight patients showed mixed hear-ing loss.The administration of corticosteroid together with an immunosuppressant significantly improved hearing,from averaged air conduction of 75.1±23.2 dB HL to 50.5±22.1 dB HL after treatment(P＜0.05).Conclusion Otologists shall be aware of OMAAV when handling intractable otitis media in elderly patients if bone conduction hearing gets worse and there are other affected organs.Immunological serum test is an important diagnostic basis.Most patients were misdiagnosed for certain time,and hearing level might not be improved unless early diagnose and proper treatment.

Objective To establish normal reference values for the sensory organization test(SOT)for flight crews of different ages from 20 to 50 years old,and to investigate the effect of age on the results of the SOT.Meth-ods A total of 122 flight crew members were divided into three groups of 20～29(n=57),30～39(n=44),and 40～50 years old(n=21).The EquiTest Dynamic Balance System was applied to test the SOT of 122 flight crew members.Equilibrium score,composite equilibrium score,the sensory weighting score of somatosensory,visual,vestibular,and visual preference,the strategy analysis scores,and the center of gravity alignment under six condi-tions were analyzed.Results The equilibrium scores for conditions 1 to 6 were 94.41±1.47,93.27±1.96,92.57±2.74,85.01±5.43,70.62±7.23,and 69.08±7.84,respectively,and the composite equilibrium score was 81.31±3.38.The sensory weighting scores of somatosensory,visual,vestibular,and visual preference were 98.97±2.08,89.57±5.14,73.89±7.95,and 98.84±5.78,respectively.The strategy analysis scores for conditions 1 to 6 were 95.57±1.23,94.87±1.58,93.93±5.12,88.21±4.01,79.49±7.90,and 80.55±6.57,respectively.There were significant differences in equilibrium score and somatosensory sensory weighting scores for condition 2 across age groups in this study,and the differences in other parameters between age groups were not statistically significant.Conclusion This study establishes normal reference values of SOT for flight crews of different ages to provide an objective reference for the selection of flight cadets and the medical evaluation of flight crews'sensory organization ability of balance function.

Objective To explore the ArcCHECK system-based methods for dose verification of ultra-long target for cervical cancer VMAT so as to assure the precision of cervical cancer radiotherapy.Methods A total of 33 patients with ultra-long target(target length≥26 cm)admitted to some hospital for cervical cancer VMAT from 2021 to 2023 were selected retrospectively,and radiotherapy plans were designed for the patients with VMAT technology and verified dosimetrically with different methods.Firstly,the dose distribution data were collected respectively at 5 and 8 cm away from the center of the ArcCHECK system along the bed exit direction,and enrolled into Group Test 1 and Test 2 respectively.Then the ArcCHECK system was flipped 180°,and the dose distribution data were acquired at 8 cm away from the center along the bed exit direction and included into Group Test 3.Dose merging between Group Test 2 and Test 3 with the Merge function was carried out to obtain the dose distribution data which were divided into Group Test 4.The monitor units of Group Test 1,2 and 4 were summarized,and difference analyses were performed on the length of the target area,detection point and irradiation time.Group Test 1,2 and 4 were compared in terms of γ pass rate,normalized dose deviation,confidence limit(CL)of pass rate and acceptance rate(γ pass rate≥95%and γ pass rate≥90%).Spearman's correlation coefficient was used to correlate the parameters such as maximum transverse diameter,length,volume and monitor unit of the target area and expected execution time of the plan.SPSS 19.0 software was used for statistical analysis.Results Group Test 1,2 and 4 had the monitor unit being(758.76±107.63)MU,and had statistically significant differences in length of the target area,detection point and irradiation time(P<0.01).In Group Test 4 γ pass rate under 2%/2 mm criterion did not reach 90%,and in Group Test 1 and 2 γ pass rates under 3%/3 mm and 3%/2 mm criteria both amounted to 95%.Group Test 1,2 and 4 had statistically significant differences in γ pass rate and normalized dose deviation(all P<0.05).In Group Test 1 there were more than 90%of the verification results where γ pass rate≥95%and more than 95%where γ pass rate≥90%under 3%/3 mm criterion.The monitor unit was positively correlated with the maximum transverse diameter,length and volume of the target area,respectively(0.337≤r≤0.568,P<0.05),and the expected execution time of the plan was positively correlated with the volume and monitor unit of the target area,respectively(0.457≤r≤0.517,P<0.01).Conclusion The dose verification method with the target at 5 cm away from the center along the bed exit direction can be applied clinically with high feasibility to the dose verification during the radiotherapy of the cervical cancer VMAT patients with ultra-long target,with the safety of the verification devices ensured effectively.

Objective To investigate extended high-frequency hearing in young adults and to analyse its char-acteristics.Methods A total of 230 freshmen(101 males and 129 females,aged 17-19 years old)from the class of 2023 at the Air Force Medical University underwent audiometric tests,including acoustic impedance,conventional frequency and extended high-frequency audiometry,and distortion product otoacoustic emissions(DPOAE).Ac-cording to the results of extended high-frequency audiometry,the students were divided into normal and abnormal groups,and the hearing thresholds at conventional frequencies were compared between the two groups.Results Of the 230 students,47.83％(110/230)showed abnormal extended high-frequency hearing.The hearing thresholds of the right ear were 1 to 3 dB higher than those of the left ear at most frequencies.The hearing thresholds of the ab-normal group were higher than those of the normal group in the conventional frequencies(P＜0.05).The difference in extended high-frequency thresholds between the two groups increased with higher frequency.Conclusion Ex-tended high-frequency hearing loss occurs earlier,and has a higher prevalence in young adults,and right ear hearing is worse than that of left ear.Extended high-frequency audiometry can be used as a predictive tool for detecting con-ventional frequency hearing loss.

Objective To study the clinical features and treatment outcomes of otitis media caused by antineu-trophil cytoplasmic antibody ANCA-associated vasculitis[otitis media with AAV(OMAAV)].Methods A total of 19 cases of OMAAV diagnosed between September 2015 to September 2022 were studied.OMAAV was defined using the criteria introduced by Japan Society of Otology.Results Median age of all patients was 61.8 years old,predominantly proteinase 3(PR3)positive(47.3％).Averaged score of vasculitis activity was 6.6.Disease also in-volved lung(84.2％),nose(73.7％)and facial nerve(21.0％).Pathological biopsy was performed in nine pa-tients,and two reports indicated ANCA-related disease.Fourteen affected ears of eight patients showed mixed hear-ing loss.The administration of corticosteroid together with an immunosuppressant significantly improved hearing,from averaged air conduction of 75.1±23.2 dB HL to 50.5±22.1 dB HL after treatment(P＜0.05).Conclusion Otologists shall be aware of OMAAV when handling intractable otitis media in elderly patients if bone conduction hearing gets worse and there are other affected organs.Immunological serum test is an important diagnostic basis.Most patients were misdiagnosed for certain time,and hearing level might not be improved unless early diagnose and proper treatment.

Objective To explore the ArcCHECK system-based methods for dose verification of ultra-long target for cervical cancer VMAT so as to assure the precision of cervical cancer radiotherapy.Methods A total of 33 patients with ultra-long target(target length≥26 cm)admitted to some hospital for cervical cancer VMAT from 2021 to 2023 were selected retrospectively,and radiotherapy plans were designed for the patients with VMAT technology and verified dosimetrically with different methods.Firstly,the dose distribution data were collected respectively at 5 and 8 cm away from the center of the ArcCHECK system along the bed exit direction,and enrolled into Group Test 1 and Test 2 respectively.Then the ArcCHECK system was flipped 180°,and the dose distribution data were acquired at 8 cm away from the center along the bed exit direction and included into Group Test 3.Dose merging between Group Test 2 and Test 3 with the Merge function was carried out to obtain the dose distribution data which were divided into Group Test 4.The monitor units of Group Test 1,2 and 4 were summarized,and difference analyses were performed on the length of the target area,detection point and irradiation time.Group Test 1,2 and 4 were compared in terms of γ pass rate,normalized dose deviation,confidence limit(CL)of pass rate and acceptance rate(γ pass rate≥95%and γ pass rate≥90%).Spearman's correlation coefficient was used to correlate the parameters such as maximum transverse diameter,length,volume and monitor unit of the target area and expected execution time of the plan.SPSS 19.0 software was used for statistical analysis.Results Group Test 1,2 and 4 had the monitor unit being(758.76±107.63)MU,and had statistically significant differences in length of the target area,detection point and irradiation time(P<0.01).In Group Test 4 γ pass rate under 2%/2 mm criterion did not reach 90%,and in Group Test 1 and 2 γ pass rates under 3%/3 mm and 3%/2 mm criteria both amounted to 95%.Group Test 1,2 and 4 had statistically significant differences in γ pass rate and normalized dose deviation(all P<0.05).In Group Test 1 there were more than 90%of the verification results where γ pass rate≥95%and more than 95%where γ pass rate≥90%under 3%/3 mm criterion.The monitor unit was positively correlated with the maximum transverse diameter,length and volume of the target area,respectively(0.337≤r≤0.568,P<0.05),and the expected execution time of the plan was positively correlated with the volume and monitor unit of the target area,respectively(0.457≤r≤0.517,P<0.01).Conclusion The dose verification method with the target at 5 cm away from the center along the bed exit direction can be applied clinically with high feasibility to the dose verification during the radiotherapy of the cervical cancer VMAT patients with ultra-long target,with the safety of the verification devices ensured effectively.

Objective To establish normal reference values for the sensory organization test(SOT)for flight crews of different ages from 20 to 50 years old,and to investigate the effect of age on the results of the SOT.Meth-ods A total of 122 flight crew members were divided into three groups of 20～29(n=57),30～39(n=44),and 40～50 years old(n=21).The EquiTest Dynamic Balance System was applied to test the SOT of 122 flight crew members.Equilibrium score,composite equilibrium score,the sensory weighting score of somatosensory,visual,vestibular,and visual preference,the strategy analysis scores,and the center of gravity alignment under six condi-tions were analyzed.Results The equilibrium scores for conditions 1 to 6 were 94.41±1.47,93.27±1.96,92.57±2.74,85.01±5.43,70.62±7.23,and 69.08±7.84,respectively,and the composite equilibrium score was 81.31±3.38.The sensory weighting scores of somatosensory,visual,vestibular,and visual preference were 98.97±2.08,89.57±5.14,73.89±7.95,and 98.84±5.78,respectively.The strategy analysis scores for conditions 1 to 6 were 95.57±1.23,94.87±1.58,93.93±5.12,88.21±4.01,79.49±7.90,and 80.55±6.57,respectively.There were significant differences in equilibrium score and somatosensory sensory weighting scores for condition 2 across age groups in this study,and the differences in other parameters between age groups were not statistically significant.Conclusion This study establishes normal reference values of SOT for flight crews of different ages to provide an objective reference for the selection of flight cadets and the medical evaluation of flight crews'sensory organization ability of balance function.