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.

ObjectiveTo develop and preliminarily validate a prediction model for brace treatment failure risk in patients with adolescent idiopathic scoliosis (AIS), based on information obtained before brace treatment and during initial brace fitting. MethodsA total of 191 patients with AIS who initiated thoracolumbosacral orthosis treatment at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from March, 2015 to August, 2024 and had determinable outcomes were retrospectively included. Patients were divided according to a prespecified scheme into a training set (n = 133) and a validation set (n = 58). Brace treatment failure was defined as progression of the major-curve Cobb angle by ≥ 5° from baseline during follow-up or at brace weaning, or a final major-curve Cobb angle > 45°. Logistic regression, random forest, support vector machine with radial basis function kernel, and extreme gradient boosting (XGBoost) models were developed using routinely available clinical and radiographic variables before brace treatment and during initial brace fitting. Stratified five-fold cross-validation was used for hyperparameter tuning in the training set. Model performance was evaluated in the validation set using the area under the receiver operating characteristic curve (AUC), area under the precision-recall curve (AUPRC), Brier score, calibration curves, and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) was used to interpret the main explanatory model. ResultsIn cross-validation of the training set, both random forest and XGBoost showed good discriminative performance, with cross-validation-AUC values of 0.871 and 0.880, respectively. In the validation set, the AUC values of random forest and XGBoost were 0.888 and 0.899, the AUPRC values were 0.678 and 0.830, and the Brier scores were 0.086 and 0.076, respectively. Random forest was selected as the primary model for interpretation, with a calibration intercept of 0.091 and a calibration slope of 0.995. SHAP analysis indicated that the in-brace correction rate and the major-curve Cobb angle measured in the brace contributed most to the model predictions. ConclusionThe random forest model developed using routinely available pretreatment and initial-fitting variables shows preliminary predictive value for brace treatment failure risk in AIS, and may provide quantitative support for follow-up scheduling, brace-fit reassessment and early adherence-oriented management.

Periodontitis leads to progressive destruction of periodontal supporting tissues, and conventional anti-infective therapies often fail to simultaneously achieve infection control and tissue regeneration. Due to the increasing threat of antibiotic resistance, the development of novel bioactive molecules with both anti-infective and pro-regenerative properties has become a focus of research. Antimicrobial peptides (AMPs), characterized by multi-target antimicrobial mechanisms and immunomodulatory functions, have attracted considerable attention in periodontal tissue regeneration. Current evidence indicates that AMPs not only inhibit periodontal pathogens and biofilm formation, but they also regulate macrophage polarization, suppress inflammatory cytokine release, and activate signaling pathways, such as Wnt/β-catenin and MAPK/ERK. These effects promote osteogenic differentiation of periodontal ligament stem cells and bone marrow mesenchymal stem cells, while enhancing angiogenesis through VEGF induction, thereby establishing a favorable immune microenvironment for periodontal regeneration. Despite these promising findings, the in vivo stability, dosage safety, and long-term mechanisms of AMPs remain to be fully elucidated. Future studies should focus on clarifying the molecular mechanisms by which AMPs regulate the periodontal immune microenvironment and angiogenesis-osteogenesis coupled regeneration. In addition, integrating structural optimization, advanced delivery systems, and artificial intelligence-assisted peptide discovery may accelerate the development and clinical translation of novel antimicrobial peptides.

ObjectiveTo develop a carbon nanoparticle-manganese dioxide (CN-MnO₂) injection integrating visually identifiable staining and magnetic resonance (MR) T₁/T₂ dual-modal imaging, and to systematically evaluate its physicochemical properties, critical quality attributes, biocompatibility, and efficacy for gastrointestinal marking and localization. MethodsCN-MnO₂ was prepared using a mild liquid-phase in situ redox deposition strategy and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD). The pH of CN-MnO₂ was directly measured using a pH meter. The osmolality pressure of CN-MnO₂ was determined by the freezing point depression method. The bacterial endotoxin was detected using the gel-clot Limulus amebocyte lysate test, which did not rely on absorbance readings. The appearance of the CN-MnO₂ injection solution stored at 4 ℃ under light shielding and sealed for 0, 5, and 10 days was observed, and its hydrated particle size, polydispersity index, zeta potential, and pH were also measured. With gadopentetate dimeglumine (Gd-DTPA) as the positive control, different concentration gradients were established, and T₁ and T₂ relaxation times were measured to construct concentration-dependent plots of the longitudinal and transverse relaxation rates (R₁ and R₂) and calculate the corresponding relaxivities (r₁ and r₂), compare relaxivity performance, and determine the working concentration for subsequent in vivo experiments. Cytocompatibility was assessed using the methyl thiazolyl tetrazolium (MTT) assay and live/dead staining. Sixteen male 6-week-old SD rats were randomly assigned to an experimental group and a control group (n=8 per group) and subcutaneously injected with CN-MnO₂ injection at a total Mn concentration of 0.80 mmol/L or an equal volume of normal saline, respectively. Short-term in vivo safety was evaluated by regular body weight monitoring, hematoxylin-eosin (HE) staining of major organs, hematological and serum biochemical analyses, inflammatory cytokine detection, and inductively coupled plasma optical emission spectrometry (ICP-OES) analysis. Eight male 5–6-month-old Bama minipigs were randomly assigned to a CN-MnO₂ group (n=6) and a carbon nanoparticle suspension injection (CNSI) group (n=2). CN-MnO₂ injection or CNSI was injected subserosally into the stomach, small intestine, and colon. Within 5 min after each injection, the maximum staining diameter at each injection site was measured and recorded. MR T1WI/T2WI scans were performed on days 3 and 7 after injection to evaluate MR visualization at the injection sites. At the end of observation, the injection sites and major organs were collected for histopathological evaluation by hematoxylin-eosin staining. ResultsCN-MnO₂ appeared as a black suspension, with no obvious aggregation or sedimentation after standing at room temperature (20-25 ℃) for 15 days. Its average hydrodynamic diameter was approximately (228.7±15.3) nm, the polydispersity index was 0.184±0.021, and the zeta potential was (-24.6±2.8) mV. XPS showed that CN-MnO₂ was mainly composed of C, O, and Mn, with oxygen accounting for approximately 68.82%. The Mn 2p spectrum exhibited two characteristic peaks at 642.4 and 653.1 eV. XRD indicated that low-crystallinity δ-MnO₂ was dispersed within the carbon matrix. The pH was 6.82±0.06, the osmolality was (298.4±6.7) mOsm/kg, and the bacterial endotoxin level was below the detection limit. In vitro MR imaging showed a clear concentration-dependent response, with r₁ and r₂ values of 9.6 L·mmol^-1·s^-1 and 17.2 L·mmol^-1·s^-1, respectively, indicating favorable T₁/T₂ contrast performance superior to that of Gd-DTPA. At 0.80 mmol/L, CN-MnO₂ showed no obvious cytotoxicity in vitro. Short-term safety evaluation in SD rats revealed no obvious inflammatory response, impairment of liver or renal function, or abnormal manganese accumulation in major organs. In Bama minipigs, the mean staining diameters of the CN-MnO₂ group in the stomach, small intestine, and colon were (0.65±0.12) cm, (0.61±0.11) cm, and (0.58±0.10) cm, respectively, with no significant difference among the three injection sites (P>0.05). The overall mean staining diameter was smaller in the CN-MnO₂ group than in the CNSI group (P<0.05). MR examinations showed that the injection sites were identifiable on both day 3 and day 7, with stronger signals observed on day 3. At the end of observation, no obvious pathological abnormalities were observed at the injection sites or in major organs. ConclusionA CN-MnO₂ injection with uniform particle size and stable physicochemical properties can be successfully prepared. This formulation integrates visible gastrointestinal staining with MR T₁/T₂ dual-modal imaging, providing a new strategy for preoperative gastrointestinal marking and localization as well as precise intraoperative resection.

INTRODUCTION: Hydroxychloroquine (HCQ), originally an antimalarial drug, is currently used to treat multiple disorders, especially rheumatic diseases. Given its good efficacy and safety, HCQ is widely administered in pregnant patients. However, the safety profile of HCQ during pregnancy remains controversial due to limited research. In addition, HCQ has been reported to reduce preeclampsia in patients with systemic lupus erythematosus (SLE) and could potentially alleviate the symptom of preeclampsia. However, the clinical profile and molecular mechanism of HCQ in preeclampsia is yet to be fully understood. METHOD: We reviewed the literature on HCQ treatment in pregnancy with rheumatic diseases and preeclamp-sia in PubMed and Web of Science. We also discussed the safety of long-term therapy with HCQ during pregnancy. RESULTS: HCQ mainly modulates autoimmune response through inhibition of lysosomal function, toll-like receptor (TLR) signalling, nicotinamide adenine dinucleotide phosphate-mediated oxidative stress and autophagy. Benefits of HCQ in treating rheumatic diseases, including antiphospholipid syndrome, rheumatoid arthritis and Sjogren's syndrome during pregnancy, has been demonstrated in clinics. In particular, multiple clinical guidelines recommend HCQ as an indispensable therapeutic drug for pregnant patients with SLE. Additionally, it may potentially function in preeclampsia to improve clinical symptoms. CONCLUSION HCQ is effectively used for rheumatic diseases during pregnancy. The benefits of HCQ treatment in rheumatic diseases outweigh the risk of adverse reactions it induces in pregnant women.
Humans ; Hydroxychloroquine/pharmacology* ; Pregnancy ; Female ; Antirheumatic Agents/pharmacology* ; Rheumatic Diseases/drug therapy* ; Pregnancy Complications/drug therapy* ; Pre-Eclampsia/prevention & control* ; Lupus Erythematosus, Systemic/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Antiphospholipid Syndrome/drug therapy* ; Sjogren's Syndrome/drug therapy*

Pain management is an important component of military medical support during wartime.Early pain management for wounded soldiers can effectively alleviate pain,which is critical to maintaining combat effectiveness,promoting physiological and psychological recovery of wounded soldiers,preventing chronic pain,and helping them return to the battle field.In recent years,the U.S.Armed Forces have increasingly emphasized prehospital pain management.They have been updating the relevant pain management guidelines to establish a practical system in order to ensure that the pain of wounded soldiers is effectively controlled.This paper reviews the current research on prehospital pain management in the U.S.Armed Forces and summarizes the advanced and practical technologies for prehospital pain management.It provides references for research on prehospital pain management,and optimization of prehospital pain management strate-gies suited to China's operational context,and for the design of related training programs.

Objective To analyze the epidemiological characteristics of acute respiratory infections(ARIs)during the autumn-winter season in Beijing,providing evidence for the prevention,control,diagnosis,and treatment of ARIs.Methods A convenience sampling method was employed,enrolling patients who visited Peking Union Medical College Hospital(PUMCH)between September 2023 and February 2024 due to ARIs.Na-sopharyngeal swabs were collected,and real-time fluorescence quantitative PCR was used to detect six common respiratory pathogens[influenza A virus(FluA),influenza B virus(FluB),human rhinovirus(HRV),Myco-plasma pneumoniae(MP),respiratory syncytial virus(RSV),and adenovirus(ADV)],as well as SARS-CoV-2 infection.The distribution patterns of pathogen infections were analyzed.Results A total of 5556 eligible patients were included.The overall positivity rate for the six common respiratory pathogens was 63.7％,with sin-gle-pathogen positivity at 54.0％,dual-pathogen positivity at 8.9％,and triple or more pathogen positivity at 0.7％.The predominant pathogens detected were FluA(16.1％)and RSV(15.7％),followed by ADV(11.1％),MP(11.1％),HRV(10.0％),and FluB(10.0％).No significant difference in overall pathogen positivity was observed between genders.However,significant differences were found between autumn and winter(x2=34.617,P＜0.001)and among pediatric,young/middle-aged,and elderly patients(x2=422.38,P＜0.001).Specifically,MP(x2=8.647,P=0.003),FluA(x2=131.932,P＜0.001),and HRV(x2=174.199,P＜0.001)exhibited significantly higher positivity rates in autumn than in winter,whereas FluB was more prevalent in winter(x2=287.894,P＜0.001).In pediatric patients,MP,RSV,HRV,and ADV positivity rates were significantly higher than in young/middle-aged and elderly patients(all P＜0.001),whereas FluB was more common in young/middle-aged patients(both P＜0.001).The positivity rates of the six common respiratory pathogens significantly declined during the SARS-CoV-2 epidemic period,exhibiting an asynchronous seasonal pattern.Conclusions The prevalence of respiratory pathogens in Beijing is associated with age and season.Tar-geted preventive measures should be implemented in different seasons and for key populations.

Objective To explore a standardized approach for indicating dosages in Chinese patent medicines(CPM)instructions.Methods A review of 1 378 classic formulas of traditional Chinese medicine in the 2020 edition of the Pharmaco-poeia of the People's Republic of China(Chinese Pharmacopoeia)was conducted,focusing on three aspects:overdose,different dosage forms,and inclusion of toxic herbs.Approximately 50 representative formulas were selected,and their daily dosage of herbal pieces and the corresponding dosage of individual herbs were calculated.These results were then compared and analyzed against the dosages stipulated in the Chinese Pharmacopoeia.Results ①Overdose:Among the 1 378 reviewed formulas,146(10.60％)were found to involve overdose.Specifically,eight formulas were identified as having an overdose of approximately 3 to 5 times the recommended dose,including Duanxueliu tablets and Zhixue Fumai mixture.②Dosage variations across dosage forms:Based on the conversion of the Ming-Qing dynasty dosage of one liang(Chinese traditional weight unit)to 36 g,the estimated dai-ly dose per component of crude herbs in Yinqiao powder was close to the upper limit specified in the Chinese Pharmacopoeia.The total daily dose of crude herbs(75.60 g)was approximately five times that of the Yinqiao powder(15 g)listed in the Chinese Pharmacopoeia and three times that of the Japanese Kampo Yinqiao powder(23.868 g).Significant differences in dosage were ob-served among Yinqiao Jiedu preparations of different dosage forms.In terms of total daily dose of crude herbs,granules(52.50 g)had the highest dose,approximately 3-5 times that of tablets/capsules(11.20 g),soft capsules(13.44 g),and powders(15.00 g),but still 30％ lower than the original prescription from ancient texts(75.6 g).Comparing the daily dose per compo-nent,granules fell within the Chinese Pharmacopoeia dose range,while tablets,capsules,soft capsules,and powders were all below the Chinese Pharmacopoeia dose.③Inclusion of toxic herbs:Among the 20 oral formulations containing Strychnos nux-vomica(Maqianzi)listed in the Chinese Pharmacopoeia,seven species exceeded the pharmacopoeial dose of 0.3-0.6 g per day.Notably,Shenjin Huoluo pill and Shufeng Dingtong pill exceeded the Chinese Pharmacopoeia dose by 1.5-2 times.The daily dose of strych-nosine in Shenjin Huoluo pill was 21.3 mg,exceeding the toxic dose range of 5-10 mg.Conclusions The dosage indications in CPM instructions must adhere to a unified format,clearly stating the daily dose per component of crude herbs,the total daily dose of crude herbs,and the total number of administrations under the"Dosage and Administration"section.For instance,"Yinqiao Jiedu granules,with a total daily dose equivalent to 60 g of crude herbs taken in four doses(including:Flos Lonicerae 10.71 g,Fructus Forsythiae 10.71 g,Radix Platycodi 6.43 g,Herba Menthae Haplocalycis 6.43 g,Fructus Arctii 6.43 g,Semen Sojae Preparatum 5.36 g,Radix Glycyrrhizae 5.36 g,Herba Lophatheri 4.29 g,Herba Schizonepetae 4.29 g)."For CPM containing tox-ic herbs,dosage indications are even more crucial,such as specifying the daily dose of Maqianzi powder/processed Maqianzi and strychnosine in formulations containing this herb.

Objective:To evaluate the application of metagenomic next-generation sequencing（mNGS）in the identification of non-tuberculous mycobacteria（NTM）.Methods:A retrospective analysis was conducted on mNGS results of 358 bronchoalveolar lavage fluid（BALF）samples positive for NTM collected at the First Affiliated Hospital of Zhejiang University School of Medicine from February 2021 to January 2024. The analysis included the distribution of NTM species，the detection of mixed pathogens，and the performance of conventional mycobacterial detection methods.Results:The results showed that 362 strains of 15 NTM species were identified from 350 specimens，8 specimens were not precise to the species level. The most frequently detected species were Mycobacterium intracellulare（37.3%，135/362）， Mycobacterium abscessus（26.8%，97/362），followed by Mycobacterium avium（11.0%，40/362）， Mycobacterium kansasii（8.0%，29/362）and Mycobacterium chelonae（7.7%，28/362）. Single NTM species were detected in 339 specimens，while two or three NTM species were simultaneously detected in 11 specimens（3.1%，11/358）. Non-NTM microorganisms co-infected were detected in 53.4%（191/358）of NTM-positive BALF samples，including common pathogens such as Pseudomonas aeruginosa， Staphylococcus aureus，and Aspergillus fumigatus；and difficult-to-identify pathogens such as Legionella pneumophila and Talaromyces marneffei. In NTM-positive patients detected by mNGS，the results supported the diagnosis of NTM infection in 298 cases（298/358，83.2%）and 105 cases（105/358，29.3%）initiated anti-NTM treatment accordingly；while in 60 cases（60/358，16.8%）the positive results were considered as colonization or unrelated to clinical infection. For samples tested with acid-fast staining，mycobacterial liquid culture，and DNA microarray，the positivity rates for NTM were 31.5%（73/232），48.7%（57/117），and 43.0%（46/107），respectively. Conclusions:mNGS demonstrates advantages in identification of NTM. However，the test may detect multiple microorganisms，in that case，the interpretation with clinical and radiological results is requried to determine the main pathogens.

Objective To explore a standardized approach for indicating dosages in Chinese patent medicines(CPM)instructions.Methods A review of 1 378 classic formulas of traditional Chinese medicine in the 2020 edition of the Pharmaco-poeia of the People's Republic of China(Chinese Pharmacopoeia)was conducted,focusing on three aspects:overdose,different dosage forms,and inclusion of toxic herbs.Approximately 50 representative formulas were selected,and their daily dosage of herbal pieces and the corresponding dosage of individual herbs were calculated.These results were then compared and analyzed against the dosages stipulated in the Chinese Pharmacopoeia.Results ①Overdose:Among the 1 378 reviewed formulas,146(10.60％)were found to involve overdose.Specifically,eight formulas were identified as having an overdose of approximately 3 to 5 times the recommended dose,including Duanxueliu tablets and Zhixue Fumai mixture.②Dosage variations across dosage forms:Based on the conversion of the Ming-Qing dynasty dosage of one liang(Chinese traditional weight unit)to 36 g,the estimated dai-ly dose per component of crude herbs in Yinqiao powder was close to the upper limit specified in the Chinese Pharmacopoeia.The total daily dose of crude herbs(75.60 g)was approximately five times that of the Yinqiao powder(15 g)listed in the Chinese Pharmacopoeia and three times that of the Japanese Kampo Yinqiao powder(23.868 g).Significant differences in dosage were ob-served among Yinqiao Jiedu preparations of different dosage forms.In terms of total daily dose of crude herbs,granules(52.50 g)had the highest dose,approximately 3-5 times that of tablets/capsules(11.20 g),soft capsules(13.44 g),and powders(15.00 g),but still 30％ lower than the original prescription from ancient texts(75.6 g).Comparing the daily dose per compo-nent,granules fell within the Chinese Pharmacopoeia dose range,while tablets,capsules,soft capsules,and powders were all below the Chinese Pharmacopoeia dose.③Inclusion of toxic herbs:Among the 20 oral formulations containing Strychnos nux-vomica(Maqianzi)listed in the Chinese Pharmacopoeia,seven species exceeded the pharmacopoeial dose of 0.3-0.6 g per day.Notably,Shenjin Huoluo pill and Shufeng Dingtong pill exceeded the Chinese Pharmacopoeia dose by 1.5-2 times.The daily dose of strych-nosine in Shenjin Huoluo pill was 21.3 mg,exceeding the toxic dose range of 5-10 mg.Conclusions The dosage indications in CPM instructions must adhere to a unified format,clearly stating the daily dose per component of crude herbs,the total daily dose of crude herbs,and the total number of administrations under the"Dosage and Administration"section.For instance,"Yinqiao Jiedu granules,with a total daily dose equivalent to 60 g of crude herbs taken in four doses(including:Flos Lonicerae 10.71 g,Fructus Forsythiae 10.71 g,Radix Platycodi 6.43 g,Herba Menthae Haplocalycis 6.43 g,Fructus Arctii 6.43 g,Semen Sojae Preparatum 5.36 g,Radix Glycyrrhizae 5.36 g,Herba Lophatheri 4.29 g,Herba Schizonepetae 4.29 g)."For CPM containing tox-ic herbs,dosage indications are even more crucial,such as specifying the daily dose of Maqianzi powder/processed Maqianzi and strychnosine in formulations containing this herb.