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: 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.

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 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.

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.

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.

BACKGROUND:Our previous research found that Tougu Xiaotong Capsules can be used not only for the treatment of osteoarthritis,but also for rheumatoid arthritis and gouty arthritis.However,the specific mechanism of action of"Same Treatment for Different Diseases"is still unclear.OBJECTIVE:To identify the main effects and mechanisms of Tougu Xiaotong Capsules in the treatment of osteoarthritis,rheumatoid arthritis and gouty arthritis with the treating principle of"Same Treatment for Different Diseases"by the methodologies of integrated pharmacology,molecular docking techniques and molecular dynamics simulation.METHODS:The active chemical components of Tougu Xiaotong Capsules and their corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Swiss Target Prediction database.The disease genes for osteoarthritis,rheumatoid arthritis and gouty arthritis were obtained from the GeneCards and OMIM databases.Cytoscape 3.7.2 software was used to construct a drug-component-disease-target network diagram and a protein-protein interaction network.Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted using the Daivd database.Molecular docking simulations were performed on the CB-DOCK2 website,and molecular dynamics simulations were carried out using the GROMACS 2020.6 software.RESULTS AND CONCLUSION:(1)A total of 50 active components of Tougu Xiaotong Capsules were screened,with 184 potential targets and 29 intersection targets across the three types of arthritis.(2)The gene ontology enrichment analysis of the intersection targets indicated that the key gene functions of Tougu Xiaotong Capsules in treating the three types of arthritis were found to be cellular response to lipopolysaccharide,inflammatory response,extracellular matrix,protein binding,and zinc ion binding.(3)Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified key pathways as interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,NOD-like receptor and Toll-like receptor signaling pathways.(4)Six core targets[interleukin-6,interleukin-1β,prostaglandin endoperoxide synthase 1,prostaglandin endoperoxide synthase 2,cytochrome P450 1A2(CYP1A2)and C-X-C chemokine ligand 8]were determined based on the protein-protein interaction network.(5)Molecular docking results confirmed that(+)-catechin,β-sitosterol,kaempferol,myricetin,and wallichilide had good structure-activity relationships.Molecular dynamics simulations further confirmed the stable binding of CYP1A2 with wallichilide,corroborating the network pharmacology and molecular docking results.Therefore,Tougu Xiaotong Capsules may regulate the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,and other signaling pathways by targeting interleukin-1β,prostaglandin endoperoxide synthase 1,prostaglandin endoperoxide synthase 2 and CYP1A2,exert an effect of"Same Treatment for Different Diseases"on osteoarthritis,rheumatoid arthritis and gouty arthritis.

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.

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.

To explore the role of the "Clinical Practice Guidelines" column and others in the Medical Joumnal of Peking Union Medical College Hospital (Med J PUMCH) in promoting diseiplinary development.