Purpose: Esophagojejunal anastomotic leakage (EJAL) represents a severe postoperative complication following total or proximal gastrectomy. Treatment strategies include conservative management, endoscopic interventions, and surgery; however, comparative data remain limited. This study aimed to compare clinical outcomes of different strategies to identify the optimal approach based on anastomotic defect size. Materials and Methods: This retrospective study reviewed 100 patients diagnosed with EJAL between January 2015 and October 2024. Patients were categorized into four groups:conservative management, endoscopic vacuum-assisted closure (E-VAC), other endoscopic treatments, and surgery. The primary outcomes were leakage duration and length of hospital stay after EJAL diagnosis, whereas the secondary outcome was time to C-reactive protein normalization. Subgroup analyses were performed according to defect size. Results: Among the 100 patients, 76 were male and 24 were female, with a mean age of 65.7 years. Conservative treatment was the most common modality (53%), followed by other endoscopic treatments (19%), E-VAC (14%), and surgery (14%). In patients with a defect size <1 cm, conservative treatment was associated with significantly shorter leakage duration (P=0.035) and earlier resumption of diet (P=0.029) compared with endoscopic treatment.Among those with defects ≥2 cm, E-VAC demonstrated the most favorable median outcomes across all variables; however, statistical significance was not achieved because of the small sample size. Conclusions Conservative treatment appears to be the most effective treatment strategy for EJAL with anastomotic defects <1 cm. For larger defects (≥2 cm), E-VAC may offer clinical benefit, although further studies are needed to confirm its efficacy. These findings highlight the importance of individualized treatment selection based on defect size.

This study aimed to determine the prevalence of human epidermal growth factor receptor 2 (HER2)–ultralow breast cancer among cases initially classified as HER2 immunohistochemistry (IHC) 0 and assess interobserver variability in interpreting low-level HER2 expression. Methods: In this multicenter retrospective study, all invasive breast cancer cases diagnosed between January and December 2022 across 10 Korean institutions were retrieved. Institutional pathologists reexamined HER2 IHC slides originally reported as IHC 0 according to the 2018 American Society of Clinical Oncology/College of American Pathologists guidelines and reclassified them as HER2-null (0), HER2-ultralow (0+), or HER2-low (1+). Slides from 10% of HER2-null and HER2-ultralow cases were digitized for central review and independently assessed by two pathologists, with discrepancies resolved by consensus. Results: Among 8,026 cases, 2,836 cases (35.5%) were initially reported as IHC 0. Upon re-review, 1,673 (59.0%), 1,139 (40.2%), and 24 (0.8%) cases were reclassified as HER2-null, HER2-ultralow, and HER2-low, respectively. The prevalence of HER2-ultralow breast cancer varied considerably across institutions (23.7%–78.1%). Central review of 268 digitized cases showed concordance in 193 cases (72.0%). Among the 75 discordant cases, 54 tumors (72.0%) were upgraded from HER2-null to HER2-ultralow, and 18 (24.0%) tumors were upgraded from HER2-ultralow to HER2-low. Furthermore, two tumors (2.7%) were downgraded from HER2-ultralow to HER2-null. Conclusions: Approximately 40% of cases initially categorized as IHC 0 were reclassified as HER2-ultralow. The substantial inter-institutional variability observed in interpreting low-level HER2 expression highlights the need for standardized training and quality assurance to ensure accurate identification of patients eligible for HER2-targeted antibody–drug conjugates.

The recent approval of trastuzumab deruxtecan for human epidermal growth factor receptor 2 (HER2)–low and HER2-ultralow breast cancer mandates an adequate assessment of these categories. Methods: Seven breast pathologists from the Breast Pathology Study Group of the Korean Society of Pathologists held an on-site expert consensus meeting. Fifteen sets of virtual whole slide images (WSI) of hematoxylin and eosin stain and HER2 immunohistochemistry were provided. The pathologists were given 60 minutes to submit their diagnosis of HER2 expression into null, ultralow, 1+, 2+, or 3+. Afterwards, in-depth discussion and consensus diagnoses were made by real-time visualization of the WSI. Results: After the consensus meeting, unanimous 100% agreements were seen only in five (33.3%) of the examined cases, which consisted of three 1+ cases and two 2+ cases. Two cases (13.3%) had mild disagreement, with only one pathologist’s disagreement. Of note, eight cases (53.3%) showed significant disagreement, defined by more than two pathologists’ disagreement. All HER2-null cases were reclassified as ultralow after consensus review, suggesting potential widespread underclassification of ultralow cases in clinical practice. Conclusions: Experts had significant discrepancies in interpreting HER2-low/ultralow status. It is important to assess if the distinction between HER2-low and ultralow is strictly required and if HER2-null breast cancer exists in reality.

Replicative senescence in endothelial cells is characterized by an irreversible cell cycle arrest and impaired endothelial function, contributing to vascular aging and cardiovascular disease. Natural compounds are being actively studied for their potential to delay cellular senescence and protect vascular health. Among them, rice bran has demonstrated several vascular benefits that are mainly attributed to gamma-oryzanol (γ-Orz), a major bioactive component in rice bran. However, its role in regulating endothelial replicative senescence and the underlying molecular mechanisms remain unclear. This study aimed to explore the protective effects of rice bran extract (RBE) and γ-Orz on replicative senescence in porcine coronary artery endothelial cells (PCAECs). Replicative senescence was modeled in PCAECs by serial passaging from P1 to P3 with varying concentrations of RBE and γ-Orz.Senescence was evaluated by measuring senescence-associated β-galactosidase (SA-β-gal) activity, cell proliferation, oxidative stress, and the expression of cell cycle regulatory proteins. RBE and γ-Orz significantly reduced SA-β-gal activity, improved proliferation, and decreased oxidative stress in P3 cells, along with downregulation of senescence-related proteins p53, p21, and p16. Additionally, γ-Orz suppressed sodium-glucose co-transporter 2 expression, reduced NADPH oxidase overexpression, and restored eNOS levels. These findings indicate that RBE and γ-Orz delay endothelial senescence by alleviating oxidative stress, highlighting their potential to reduce cardiovascular disease risk associated with endothelial senescence.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.

Objective:To observe the clinical efficacy and safety of Jianpi Bushen Jiedu Prescription combined with 5-fluorouracil (5-FU)-based chemotherapy and targeted therapy for the treatment of advanced colorectal cancer patients with liver and kidney yin deficiency combined with spleen deficiency pattern.Methods:A randomized controlled trial was conducted. A total of 72 hospitalized patients with advanced colorectal cancer treated at the Department of Oncology, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from October 2022 to January 2024 were enrolled as study subjects. Using a random number table method, they were allocated into two groups, with 36 patients in each group. The control group received the mFOLFOX6/FOLFIRI combined with bevacizumab regimen, while the treatment group was administered additional oral Jianpi Bushen Jiedu Prescription on the basis of the control group. Two weeks was a cycle in both groups, with a total of 6 cycles of treatment. Serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 724 (CA724) were detected using electrochemiluminescence; the Karnofsky Performance Status (KPS) scale was utilized to evaluate patients' functional status; vital signs were continuously monitored, and adverse reactions were recorded. The short-term efficacy and TCM syndrome efficacy of patients were evaluated.Results:The treatment group demonstrated higher objective response rate (ORR) [31.25% (10/32) vs. 21.88% (7/32), χ2=0.72] and disease control rate (DCR) [84.38% (27/32) vs. 71.88% (23/32), χ2=1.46] compared to the control group, without statistical significance ( P>0.05). Post-treatment levels of CEA [4.09 (3.31,8.57) μg/L vs. 10.07 (4.55,22.35) μg/L, Z=-2.10] and CA72-4 [4.54 (2.04,10.99) mU/L vs. 9.48 (4.34,18.95) mU/L, Z=-2.52] in the treatment group were significantly lower than those in the control group ( P<0.05). The total effective rate of TCM syndrome was significantly higher in the treatment group [78.13% (25/32)] compared with the control group [50.00% (16/32)], with statistical significance ( χ2=5.50, P=0.019). Post-treatment KPS scores in the treatment group [80.0 (80.0, 80.0) vs. 70.0 (62.5, 80.0), Z=-2.76] were significantly higher compared with the control group ( P<0.01). During the treatment period, the treatment group showed statistical significance compared with the control group in the incidence of hemoglobin decrease ( χ2=4.66), leukopenia decrease ( χ2=4.27), and peripheral neuropathy ( χ2=3.93), with statistical significance ( P<0.05). Conclusion:The addition of Jianpi Bushen Jiedu Prescription to 5-FU-based chemotherapy combined with targeted therapy demonstrates significant clinical benefits in advanced colorectal cancer patients, including reducing tumor marker levels, alleviating clinical symptoms, improving quality of life, and mitigating treatment-related toxicities, with a good safety.

Exposure to acceleration can have Various effects on the physiology,psychology,and performance of human.With the increasing density and complexity of China's space mission,and the significant differences between deep space exploration and near Earth orbit flight,unprecedented challenges have been posed to the emotions of astronauts and the ability of human-machine collaboration to complete complex operational tasks in special environments.Similarly,with the continuous development of high-performance fighter jets,air combat operation are becoming increasingly complex,and the payload generated by the aircraft is also increasing.The requirements for the anti-overload ability of fighter pilots are also becoming higher and higher.A review of recent studies on physiological and cognitive load of acceleration exposure on humans.The research on human physiology is relatively systematic,but there is limited research on cognitive load.The corresponding evaluation methods,assessment methods,and assessment systems are not comprehensive enough,and there is a lack of mechanistic analysis.Multimodal analysis and modeling are even rarer.Further in-depth research is needed on the cognitive load and evaluation techniques of overweight environment in the future.This article provides reference for the selection,adaptive training,and related experimental research of overweight endurance for astronauts and pilots in the future.

Objective:To assess the fall risk of hospitalized patients with cardiovascular diseases, analyze the related influencing factors, and construct a prediction model based on machine learning technology, so as to provide a basis for the fall management of hospitalized patients with cardiovascular diseases.Methods:This study was a retrospective cohort study. A total of 450 patients admitted to the Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University from June 2017 to June 2024 were selected as the research objects by convenience sampling method. By reviewing electronic medical records, trained nurses extracted the patients' general information and Activities of Daily Living Scale (ADL) scores during hospitalization. Lasso regression was used to screen risk factors, and machine learning libraries were used to construct support vector machine (SVM), decision tree, XGBoost, and neural network models. Bootstrap resampling method and area under the curve (AUC) were used to verify the model performance.Results:Among the 450 patients, there were 261 males and 189 females, with a mean age of (66.0 ± 8.4) years. Among them, 90 patients fell during hospitalization and 360 patients did not fall. The results of Lasso regression showed that ADL score ≤60 points, use of hypnotics, hypokalemia, nighttime toilet visits≥2 times, use of antihypertensive drugs, no caregiver, and history of atrial fibrillation were all risk factors for falls in hospitalized patients with cardiovascular diseases (regression coefficients ranging from 0.61 to 1.20, all P<0.01). Among the machine learning models, XGBoost had the best comprehensive performance (AUC=0.98), which was better than decision tree (AUC=0.66), SVM (AUC=0.95), and neural network (AUC=0.87). Conclusions:The fall risk of hospitalized patients with cardiovascular diseases is jointly affected by physiological, medication and behavioral factors, and the XGBoost model can effectively identify high-risk groups. In actual clinical work, nursing strategies can be optimized in combination with risk factors, and the application of intelligent fall prediction and assessment tools can be promoted.

Objective:To construct decision indicator system for the allocation of life-support equipment on the basis of hospital-based health technology assessment(HB-HTA)theory,and explore its application value in the management for life-support equipment.Methods:The decision indicators of the allocation of life-support equipment were formulated from four dimensions that included equipment safety,effectiveness,suitability and economy on the basis of HB-HTA theory,so as to assess and manage the decision for allocation of equipment.A total of 149 using life-support equipment in clinical work in West China Hospital of Sichuan University from January 2022 to December 2023 were selected,and expert review mode was adopted to conduct decision for allocation of 138 equipment received management for allocation from January to December 2022,and the decision indicator system for the allocation of life-support equipment on the basis of HB-HTA theory was adopted to conduct decision management for the allocation of 143 equipment(included 132 equipment received expert review mode for management of allocation)that received management for allocation from January to December 2023.The predictive assessment value for target,the achievement ratio of HB-HTA performance,the result of examination of management level of 46 personnel from clinical department,15 personnel from department of equipment,and 11 personnel from other department in items of allocation of equipment were compared between two kinds of management modes for allocation.Results:The predictive assessment values for target of the allocation items of heart-support equipment,respiratory-support equipment,anesthesia-support equipment and other support equipment which adopted HB-HTA management mode for allocation were respectively 0.65±0.22,0.68±0.16,0.70±0.15 and 0.58±0.20,which were higher all than those of management mode of expert review for allocation,and the differences were statistically significant(t=3.362,3.585,f4.152,3.247,P<0.05).The achievement ratio of average performance of safety,effectiveness,suitability and economy of allocation items of HB-HTA management mode were respectively(97.29±1.65)%,(96.19±2.08)%,(95.82±2.29)%and(94.92±2.29)%,all of which were higher than those of expert review management mode for allocation,and the differences were statistically significant(t=2.297,2.377,2.753,2.951,P<0.05).The results of the personnel who worked in clinical department,equipment department and other department were respectively(93.24±3.12)scores,(95.35±3.22)scores and(95.78±1.82)scores in adopting HB-HTA management mode for allocation to conduct examination for the management level about allocation items of life-support equipment with allocation decision,all of which were higher than those of expert review management mode for allocation,and the differences of them were statistically significant(t=3.220,2.435,2.404,P<0.05).Conclusion:The application of HB-HTA theory in indicator system of allocation decision of life-support equipment can comprehensively analyze the safety,effectiveness,suitability and economy of equipment allocation,and enhance the scientific nature of declaring project for allocation of life-support equipment,and improve the achievement degree of the target of implementing the project of the allocation of life-support equipment,and raise the business level of the management team for the project of allocation of life-support equipment.