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.

Abstract To clarify the service targets, service contents, and safeguard mechanisms of the basic public service program for student vision health management, the study grounded in the current status of child and adolescent myopia prevention and control in China and integrated with the practical experience and innovative practices of Wuhan National Demonstration Area for Student Vision Health Management, takes education as the main thread and schools as the base, consolidating resources from multiple stakeholders including education administrative departments, schools, families, and professional technical service institutions. Centering on four core components—vision health education, monitoring and record keeping, risk prevention and control, and dynamic management, the study constructs a multi tiered basic public service system for vision health management of primary and secondary school students. It further proposes the use of an intelligent management platform and a "three tier color coded early warning" mechanism (red, yellow, blue) to prevent and control student myopia at the source, providing schools with replicable and operable implementation pathways to enhance the level of student vision health management.

ObjectiveTo investigate the regulatory mechanism of peptidylarginine deiminase 4 （PADI4） on matrix metalloproteinase （MMPs） expression and its potential role in the development of systemic lupus erythematosus （SLE）. MethodsThe mRNA expression levels of MMP-14/17/25 in SLE patients and healthy controls （HC） were measured by real-time fluorescence quantitative reverse transcription polymerase chain reaction （RT-qPCR）， and their serum protein levels were measured by enzyme-linked immunosorbent assay （ELISA）. Spearman's rank correlation analysis was used to evaluate the correlations between MMPs levels and clinical parameters in SLE patients. Primary neutrophils were treated with the PADI4 inhibitor GSK484， or MMPs expression levels were examined in PADI4-knockdown neutrophil-like HL-60 （dHL-60） cells， and cell migration ability was assessed by wound healing assay. ResultsThe mRNA expression levels of MMP-14/17/25 in neutrophils from SLE patients were lower than those in the HC （all P<0.01）. Serum levels of these three MMPs were also lower than those in the HC （all P<0.01）. MMP-14 levels were negatively correlated with immunoglobulin G （IgG） （r=-0.266）， immunoglobulin A （IgA） （r=-0.286）， and globulin （GLB）（r=-0.269） （all P<0.05）， while both MMP-17 （r=-0.269） and MMP-25（r=-0.244） levels were negatively correlated with urinary protein （UTP） （all P<0.05）. After treatment with GSK484 （10 μmol/L） to inhibit PADI4 activity， the protein expression levels of MMP-14/17/25 in neutrophils were higher than those in the Vehicle group （all P<0.05）， and the cell migration rate in wound healing assay was also greater than that in the Vehicle group （P<0.01）. Furthermore， after knockdown of PADI4 expression， the mRNA expression levels of MMP-14/17/25 were higher than those in the Vehicle group （all P<0.05）. ConclusionMMP-14/17/25 are downregulated in SLE and negatively regulated by PADI4. PADI4 may contribute to SLE progression by suppressing MMPs expression and neutrophil migration. These findings suggest that MMPs may serve as novel biomarkers and therapeutic targets for SLE.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children and adolescents, often accompanied by motor function disorders. Sarcopenia not only has skeletal muscle dysfunction but also has neurocognitive dysfunction. At present, there is no research to explore the relationship between ADHD and skeletal muscle function. The purpose of this study is to explore whether there is a causal effect between ADHD and sarcopenia. Methods: In this study, genome-wide association study data of ADHD, appendicular lean mass (ALM), hand grip strength, and walking pace (WP) were extracted from public databases. The bidirectional two-sample Mendelian randomization (MR) method was employed to investigate the correlation between ADHD and sarcopenia-related indicators, and the inverse-variance weighted analysis as the primary analysis method. Results: Based on the forward MR analysis, a potential causal relationship exists between ADHD and ALM (odds ratio [OR]=1.020, 95% confidence interval [CI]: 1.012–1.029, p<0.001). The reverse MR analysis indicates a link between WP and the risk of ADHD (OR=2.712, 95% CI: 1.609–4.571, p<0.001), with an accelerated WP increasing the likelihood of ADHD. Nevertheless, other MR analysis results did not show significant differences. Conclusion The findings of this study indicate an intricate causal relationship between ADHD and sarcopenia, suggesting the absence of a clear link. WP may be used as one of the indicators to evaluate the risk of ADHD. At the same time, we should pay more attention to the ALM of ADHD patients.

This article reports a case of extensive ocular inflammation following zoledronic acid infusion for the treatment of osteoporosis. The patient developed pain, eyelid edema, conjunctival congestion, and decreased vision in the right eye one day after receiving intravenous zoledronic acid, and was diagnosed with uveitis, scleritis, and periorbital soft tissue inflammation. The patient′s symptoms were evaluated using the clinical activity score(CAS). After high-dose corticosteroid pulse therapy combined with other comprehensive treatments, the symptoms improved markedly. This article reviews the incidence, clinical features, potential mechanisms, management, and prognosis of ocular adverse reactions induced by zoledronic acid, and highlights the importance of early recognition and timely treatment of ocular inflammation after zoledronic acid therapy.

Objective To review the diagnostic information of 3368 viral hepatitis B inpatient cases reported by some healthcare institutions in Qinghai Province in the National Notifiable Disease Report System(NNDRS)in 2021,and to analyse the consistency of their reports and influence factor.Methods The study used the typical survey method to study 3368 hospitalized cases of hepatitis B reported by 32 medical institutions in Qinghai Province in 2021 from July 2022 to April 2023.The consistency between the reported classification and the reviewed classification was evaluated by reviewing diagnostic information of the cases,combined with the Kappa consistency test,and the consistency-influencing factors were analysed in a univariate and multivariate analysis.Results The consistency between acute,chronic,and unclassified reporting classifications and review classifications was poor(Kappa＜0.40);the consistency between acute and chronic review was poor(Kappa＜0.40).The main influence factor of the consistency of review included the level of medical institution,the patient's gender,occupation,past history,and the unit of diagnosis of initial onset of illness.Provincial medical institutions reported higher consistency,and male cases and herder cases had better consistency than female cases and other occupations.Review consistency of cases with past history was better than that of cases with unclear past history.Conclusion The consistency of diagnosis and reporting of hepatitis B cases in healthcare institutions in Qinghai Province in 2021 was low,with problems of inaccurate classification and duplicate reporting.It is recommended to strengthen the training and supervision of healthcare institutions,standardise the filling of'attached card'information,and promote the hepatitis B core antibody IgM test to improve the classification and diagnosis of acute and chronic hepatitis B,so as to comprehensively improve the accuracy of the diagnosis and reporting of hepatitis B cases.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective:To observe the effect of poly-L-lactic acid injection on the improvement of periorbital aging.Methods:A retrospective study was conducted, including 95 patients who visited the Beijing Aiyue Lige Medical Aesthetic Clinic from September to November 2021 due to periorbital aging issues such as skin laxity, fine lines, and dry wrinkles. Among them, 12 were male, and 83 were female, aged 29-59 (37.3±5.7) years. All patients received poly-L-lactic acid facial injections and were followed up for 12 months post-treatment. The periorbital aging grading and global aesthetic improvement scale (GAIS) grading were compared before and after the treatment. Patient satisfaction and adverse reactions were also evaluated.Results:Before the injection, the periorbital aging grading was (2.7±0.7). After 12 months, the periorbital aging grading was (1.4±0.5), significantly lower than before the injection ( P<0.001). The GAIS improvement rate post-injection was 97% (92/95). The patient satisfaction rate was 98.9% (94/95). Five patients developed edema post-surgery, which subsided after three days. No other adverse reactions occurred during the 12-month follow-up. Conclusion:Poly-L-lactic acid injection has a good effect on improving periorbital aging.

Objective:To observe the changes in serum estradiol (E 2) levels in pregnant women of different gestational weeks and their predictive value for early intrauterine pregnancy outcomes. Methods:A retrospective study was conducted involving 375 pregnant women who were treated at the Affiliated Yangming Hospital of Ningbo University (Yuyao People's Hospital) from September 2021 to September 2023. The clinical data were categorized based on pregnancy outcomes into three groups: a normal pregnancy group ( n = 150), a threatened miscarriage with continued pregnancy group ( n = 150), and a miscarriage group ( n = 75). The serum estradiol (E 2) levels at different gestational weeks were compared among the three groups: 5 to < 6 weeks (35-41 days), 6 to < 7 weeks (42-48 days), and 7 to 8 weeks (49-55 days). The predictive value of serum E 2 levels for early intrauterine pregnancy outcomes across different gestational weeks was analyzed using Receiver Operating Characteristic (ROC) curves. Results:In the normal pregnancy group, the serum E 2 levels at different gestational weeks were as follows: (1 691.87 ± 532.21) pmol/L for 5 to < 6 weeks, (2 376.64 ± 788.36) pmol/L for 6 to < 7 weeks, and (3 576.30 ± 1,190.06) pmol/L for 7 to 8 weeks. These values were significantly higher than those in the threatened miscarriage with continued pregnancy group [(1 409.28 ± 473.49) pmol/L, (1 893.13 ± 563.15) pmol/L, (2 035.79 ± 612.47) pmol/L, t = 5.15, 11.68, 6.60, all P < 0.05] and the miscarriage group [(906.49 ± 338.09) pmol/L, (923.63 ± 365.39) pmol/L, (950.27 ± 378.89) pmol/L, t = 16.19, 15.45, 21.50, all P < 0.05]. The serum E 2 levels at different gestational weeks in the threatened miscarriage with continued pregnancy group were significantly higher than those in the miscarriage group ( t = 7.48, 10.81, 8.89, all P < 0.05). Both the normal pregnancy group and the threatened miscarriage with continued pregnancy group showed an increasing trend in serum E 2 levels with advancing gestational weeks ( t = 6.74, 18.55, 7.58, 9.82, 11.81, 2.24, all P < 0.05). In contrast, the serum E 2 levels in the miscarriage group also increased with advancing gestational weeks, but the differences were not statistically significant ( P > 0.05). The results from the receiver operating characteristic curve analysis indicated that the areas under the curve for predicting early intrauterine pregnancy outcomes based on serum E 2 levels at different gestational weeks were 0.857, 0.810, and 0.839, demonstrating excellent diagnostic efficacy. Conclusions:Dynamic monitoring of serum E 2 levels is beneficial for predicting early intrauterine pregnancy outcomes and providing guidance for clinical diagnosis and treatment.

Objective:To explore the trajectory and predictors of depressive symptoms in disabled middle-aged and elderly adults in China.Methods:Survey data from the 2013-2020 China Health and Retirement Longitudinal Study (CHARLS) data of disabled middle-aged and elderly adults were selected to analyze the trajectory categories of depressive symptom in disabled middle-aged and elderly adults and to explore their predictors.Results:A total of 1 844 disabled middle-aged and elderly adults were analyzed for survey data. The trajectory of depressive symptoms in disabled middle-aged and elderly adults was categorized into four groups, including a low-level depression group, a depression remission group, a high-level depression group, and a depression worsening group. Logistic regression analyses revealed that gender, age, place of residence, chronic disease, self-rated health, social participation, cognition, and hearing ability were predictors of trajectories of depressive symptoms in disabled middle-aged and elderly adults.Conclusions:There is group heterogeneity in the trajectory of depressive symptoms among disabled middle-aged and elderly adults. Healthcare professionals can carry out targeted health management according to the characteristics of different categories of people.