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.

Juvenile dermatomyositis(JDM) is the most common idiopathic inflammatory myopathy in children, characterized by symmetric proximal muscle weakness and characteristic skin rashes, which may be accompanied by involvement of major organs. Aberrant upregulation of the interferon signaling pathway has been confirmed as the core pathological mechanism of JDM, and is closely associated with mitochondrial dysfunction, peripheral blood immune cell dysregulation, muscle damage and repair dysfunction, as well as cutaneous and pulmonary lesions. Interferon-related biomarkers and interferon scores can serve as evaluation indicators for disease activity. Type Ⅰ interferon inhibitors and Janus kinase inhibitors provide new therapeutic options for refractory JDM. This review systematically summarizes the role of the interferon signaling pathway in the pathogenesis of JDM and its potential therapeutic targets, aiming to provide references for the mechanistic research and precise treatment of JDM.

Objective To evaluate the clinical efficacy and safety of bumetanide in comparison with other diuretics for the prevention and management of postoperative pleural effusion in patients undergoing hepatobiliary surgery.Methods A total of 168 patients undergoing routine hepatobiliary surgery were randomly assigned to either the bumetanide group or the control group(other diuretics).Patients in the bumetanide group received bumetanide injection at a dose of 1 mg intravenously once daily.In contrast,the control group received one of the following treatments:furosemide injection at 20 mg intravenously once daily,furosemide tablets at 40 mg orally twice daily,or a combination of furosemide tablets(40 mg orally twice daily)and spironolactone tablets(60 mg orally twice daily).All treatments were administered for three days postoperatively.The incidence of postoperative pleural effusion,length of hospital stay,and drug-related adverse reactions were compared between the two groups.Additionally,multivariate logistic regression analysis was conducted to identify independent risk factors for moderate-to-severe pleural effusion after surgery.Results A total of 82 patients were enrolled in the bumetanide group and 86 in the control group.No significant differences were observed in the general demographic and clinical characteristics between the two groups(P>0.05),except for sex and ALT levels(P<0.05).The incidence of moderate-to-severe pleural effusion was higher in the control group than in the bumetanide group,with rates of 9.3％and 1.2％,respectively(all P<0.05).Additionally,the length of hospital stay was significantly longer in the control group(19.94±0.90 days)compared to the bumetanide group(17.15±1.06 days)(all P<0.05).Thora-centesis was performed in 2 cases in the bumetanide group and 8 cases in the control group,but this difference was not statistically significant(P>0.05).The primary adverse drug reactions in both groups included hypokalemia,hypochloremia,hyponatremia,and hypocalcemia.The overall incidence of adverse drug reactions was 35.4％in the bumetanide group and 34.9％in the control group,showing no significant difference(P>0.05).Multivariate regression analysis revealed that a history of hepatitis B,cirrhosis,and the use of bumetanide were independent predictors of moderate-to-severe pleural effusion during routine hepatobiliary surgery(all P<0.05).Conclusions Bumetanide demonstrates superior efficacy compared to other conventional diuretics in the prevention and manage-ment of postoperative pleural effusion in hepatobiliary surgery,suggesting potential clinical application value.

Objective To evaluate the clinical efficacy and safety of bumetanide in comparison with other diuretics for the prevention and management of postoperative pleural effusion in patients undergoing hepatobiliary surgery.Methods A total of 168 patients undergoing routine hepatobiliary surgery were randomly assigned to either the bumetanide group or the control group(other diuretics).Patients in the bumetanide group received bumetanide injection at a dose of 1 mg intravenously once daily.In contrast,the control group received one of the following treatments:furosemide injection at 20 mg intravenously once daily,furosemide tablets at 40 mg orally twice daily,or a combination of furosemide tablets(40 mg orally twice daily)and spironolactone tablets(60 mg orally twice daily).All treatments were administered for three days postoperatively.The incidence of postoperative pleural effusion,length of hospital stay,and drug-related adverse reactions were compared between the two groups.Additionally,multivariate logistic regression analysis was conducted to identify independent risk factors for moderate-to-severe pleural effusion after surgery.Results A total of 82 patients were enrolled in the bumetanide group and 86 in the control group.No significant differences were observed in the general demographic and clinical characteristics between the two groups(P>0.05),except for sex and ALT levels(P<0.05).The incidence of moderate-to-severe pleural effusion was higher in the control group than in the bumetanide group,with rates of 9.3％and 1.2％,respectively(all P<0.05).Additionally,the length of hospital stay was significantly longer in the control group(19.94±0.90 days)compared to the bumetanide group(17.15±1.06 days)(all P<0.05).Thora-centesis was performed in 2 cases in the bumetanide group and 8 cases in the control group,but this difference was not statistically significant(P>0.05).The primary adverse drug reactions in both groups included hypokalemia,hypochloremia,hyponatremia,and hypocalcemia.The overall incidence of adverse drug reactions was 35.4％in the bumetanide group and 34.9％in the control group,showing no significant difference(P>0.05).Multivariate regression analysis revealed that a history of hepatitis B,cirrhosis,and the use of bumetanide were independent predictors of moderate-to-severe pleural effusion during routine hepatobiliary surgery(all P<0.05).Conclusions Bumetanide demonstrates superior efficacy compared to other conventional diuretics in the prevention and manage-ment of postoperative pleural effusion in hepatobiliary surgery,suggesting potential clinical application value.

Objective:To investigate the effect of nourishing yin and tonifying yang method on inflammatory response and bone metabolism in patients with T2DM complicated with osteoporosis (OP).Methods:A randomized controlled trial. From January 2022 to December 2023,80 patients with T2DM and OP in our hospital were selected as the observation objects, and they were divided into two groups by random number table method, with 40 cases in each group.On the basis of conventional treatment, the control group chewed vitamin D calcium chewable tablets, and the observation group added nourishing yin and tonifying yang Chinese medicine.Both groups were treated for 6 months. TCM syndrome scores were performed before and after treatment ;the levels of fasting blood glucose (FPG), 2 hPG and HbA1c were detected by intelligent blood glucose monitor;the levels of serum neutrophils and lymphocytes were detected by automatic blood analyzer, and the neutrophil/lymphocyte ratio (NLR) was calculated;the levels of serum IL-1β and TNF-α were detected by automatic chemiluminescence analyzer, the levels of type I procollagen amino terminal propeptide (PINP), type I collagen carboxy terminal peptide β special sequence (β-CTX) and 25-hydroxy vitamin D3 [25-(OH)D3] were detected by ELISA;Bone mineral density (BMD) was detected by bone mineral density detector. The adverse reactions during treatment were observed and recorded, and the clinical efficacy was evaluated.Results:The total effective rate was 92.5 %(37/40) in the observation group and 75.0 % (30/40) in the control group,the difference between the two groups was statistically significant ( χ2=4.50, P=0.034).After treatment, the scores of soreness and weakness of waist and knees, soreness and pain of waist and back, clear and long urine, pale tongue and white coating in the observation group were lower than those in the control group ( t=3.11, 3.75, 3.51, 3.74, P<0.01);the levels of serum FPG, 2 hPG and HbA1c in the observation group were lower than those in the control group ( t=3.11,3.20,3.39, P<0.01).The levels of serum NLR (2.63 ± 0.68 vs. 3.24 ± 0.79, t=3.70), IL-1β [(81.65 ± 8.30) ng/L vs. (89.03 ± 8.98) ng/L, t=3.82] and TNF-α [(35.14 ± 5.11) μg/L vs. (39.96 ± 5.38) μg/L, t=4.11] in the observation group were lower than those in the control group ( P<0.01). After treatment, the levels of PINP [(29.83 ± 3.92) ng/L vs. (34.02 ± 4.03) ng/L, t=4.71] and β-CTX [(21.30 ± 3.95 ) ng/L vs. (25.32 ± 4.18) ng/L, t=4.42] in the observation group were lower than those in the control group ( P<0.01), the levels of 25-(OH)D3 [(42.86 ± 5.12) μg/L vs. (38.08 ± 4.55) μg/L, t=4.41] and BMD [(0.90 ± 0.18) g/cm 3vs. (0.78 ± 0.16) g/cm 3, t=3.15] were higher than those in the control group ( P<0.01).During the treatment, the incidence of adverse reactions was 12.5% (5/40) in the observation group and 10.0 % (4/40) in the control group,there was no significant difference between the two groups ( χ2=0.13, P=0.723). Conclusion:The method of nourishing yin and tonifying yang can effectively improve the TCM syndromes of T2DM patients with OP, reduce the levels of blood glucose and inflammatory factors, improve bone metabolism, improve clinical efficacy and have good treatment safety.

Objective:To explore the current situation of the intrinsic capacity of elderly people in the community and analyze its influencing factors.Methods:From September 2022 to March 2023, convenience sampling was used to select 360 elderly community residents from Xicheng District, Beijing, and Xingtai City, Hebei Province, as the research subjects. The subjects were surveyed using the Intrinsic Capacity Assessment Questionnaire, Intrinsic Capacity Influencing Factors Questionnaire, Barthel Index, and Lawton Instrumental Activities of Daily Living Scale.Results:A total of 360 questionnaires were distributed, and 360 valid questionnaires were collected, with an effective response rate of 100.0% (360/360). The overall impairment rate of intrinsic capacity among 360 elderly people in the community was 90.3% (325/360), and the impairment rates in various fields from high to low were sensation, psychology, vitality, cognition, and exercise. Multiple linear regression analysis showed that age, gender, residential pattern, education level, work status, grip strength, number of geriatric syndrome, self-rated health status, adverse life events, number of social activities, transportation conditions, and social security were the influencing factors of the intrinsic capacity of elderly people in the community, and the difference was statistically significant ( P<0.05) . Conclusions:The impairment rate of intrinsic capacity among elderly people in the community is relatively high. Grassroots medical and nursing staff should assess the intrinsic capacity of elderly people in the community in health promotion work, identify elderly people with decreased intrinsic capacity early and carry out effective interventions to prevent elderly people from becoming disabled and dependent on care.

Objective:To investigate the association of peripheral axial lengths and retinal curvatures with refractive status.Methods:A cross-sectional study was conducted out.Two hundred and eighty-seven eyes of 287 consecutive children aged 6-15 years old who recieved eye examinations at Beijing Tongren Hospital from July to October 2021 were enrolled, including 154 males and 133 females.Uncorrected and best corrected visual acuity were tested with a standard logarithmic visual acuity chart.Spherical equivalent (SE) was measured via an auto refractometer after cycloplegia with tropicamide.The hyperopic, emmetropic and myopic groups were defined with a SE >+ 0.5 D, SE >-0.5 D to ≤+ 0.5 D and SE≤-0.5 D, respectively.Central and 30° peripheral eye lengths (nasal, temporal, superior, inferior) were obtained using the Lenstar LS900.Retinal coordinates were derived from partial coherence interferometry modeling and converted to retinal curvatures.According to the median horizontal peripheral eye length differences (absolute difference between nasal and temporal), participants were assigned to H1 group (absolute difference <0.35 mm) or H2 group (absolute difference ≥0.35 mm). According to the median vertical peripheral eye length differences (absolute difference between superior and inferior), participants were assigned to V1 group (absolute difference <0.32 mm) or V2 group (absolute difference ≥0.32 mm). Four groups of V1H1, V1H2, V2H1 and V2H2 were constructed according to the grouping methods in both directions above.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2021-162). Written informed consent was obtained from guardians of each subject prior to any medical examination.Results:The central axial length was 23.53(22.93, 24.10)mm.Peripheral eye lengths of temporal, nasal, superior and inferior were 22.75(22.11, 23.22)mm, 22.99(22.32, 23.45)mm, 23.24(22.58, 23.75)mm and 23.12(22.52, 23.56)mm, respectively.Temporal eye length was shorter than nasal, showing a statistically significant difference ( Z=-3.58, P<0.01). Compared with H2 group, H1 group had shorter central, nasal, superior and inferior eye lengths, showing statistically significant differences (all at P<0.05). Compared with V2 group, V1 group had shorter central, nasal and superior eye lengths, showing statistically significant differences (all at P<0.05). SE of H1 group was + 0.06 (-1.06, + 0.75) D, which was significantly greater than -0.32 (-1.64, + 0.56) D of H2 group ( Z=-2.10, P=0.04). SE of V1 group was + 0.13 (-0.81, + 0.80) D, which was significantly greater than -0.56 (-1.83, + 0.48) D of H2 group ( Z=-3.39, P<0.01). The myopia ratio of V1 group was 33.5% (58/173), which was significantly lower than 50.5% (53/105) of V2 group ( χ2=7.83, P<0.01). There was a significant overall difference in SE among VIH1, V1H2, V2H1 and V2H2 groups ( H=24.79, P<0.01). SE was greater in V1H1 group than V1H2, V2H1 and V2H2 groups (all at P<0.01). There was a significant difference in both horizontal and vertical retinal curvatures among different refractive groups ( H=22.34, 19.30; both at P<0.01). The retical curvature in both directions of hyperopic and emmetropic groups were significantly larger than those of myopic group (both at P<0.01). Conclusions:Peripheral eye lengths are asymmetric in school-aged children.Higher asymmetry is associated with myopic shifts.Myopic children have a steeper retina than the hyperopic and emmetropic children.

Objectives: . Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods: . We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results: . A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion . We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Salt stress may cause primary osmotic stress and ion toxicity, as well as secondary oxidative stress and nutritional stress in plants, which hampers the agricultural production. Salt stress-responsive transcription factors can mitigate the damage of salt stress to plants through regulating the expression of downstream target genes. Based on the soil salinization and its damage to plants, and the central regulatory role of transcription factors in the plant salt stress-responsive signal transduction network, this review summarized the salt stress-responsive signal transduction pathways that the transcription factors are involved, and the application of salt stress-responsive transcription factors to enhance the salt tolerance of plants. We also reviewed the transcription factors-regulated complex downstream gene network which is formed by forming homo- or heterodimers between transcription factors and by forming complexes with regulatory proteins. This paper provides a theoretical basis for understanding the role of salt stress-responsive transcription factors in the salt stress regulatory network, which may facilitate the molecular breeding for improved stress resistance.
Gene Expression Regulation, Plant ; Osmotic Pressure ; Plant Proteins/metabolism* ; Plants, Genetically Modified ; Salt Stress ; Salt Tolerance ; Stress, Physiological ; Transcription Factors/metabolism*

Dementia with Lewy bodies(DLB)is the second most common neurodegenerative dementia after Alzheimer's Disease(AD). This article will mainly elaborate the relationship between DLB and blood-brain barrier(BBB)from the following five aspects: (1)The structure and function of BBB; (2)In vivo assessment methods for the blood-brain barrier damage; (3)Evidence for the damage of blood-brain barrier in DLB; (4)The relationship between α-synuclein and the blood-brain barrier; (5)The relationship between APOE and the blood-brain barrier.Future research should focus on the pathogenesis of BBB damage in DLB patients, by which new drug targets for disease diagnosis and treatment may be found.