OBJECTIVE To introduce the development of an intelligent prescription review decision-support system for anti-tumor drugs and assess its clinical application outcomes. METHODS Relevant data sources， including national and local pharmaceutical administration policies， clinical practice guidelines/consensus， hospital information systems data， and genetic testing results， were integrated. Adhering to the principles of structure， standardization and dynamic updating， a knowledge base covering chemotherapeutic， targeted and immunotherapeutic agents was constructed using a dual-dimensional modeling approach that combined “drug attributes” and “clinical contexts”. This knowledge base was then embedded into the hospital’s electronic medical order system to establish the prescription review decision-support system. The application and performance of the system were evaluated at Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. RESULTS A knowledge base containing 18 318 prescription review rules for anti-tumor drugs was constructed， and a closed-loop prescription review system was successfully established， encompassing pre-prescription real-time intervention， in-process interactive review， and post-prescription evaluation and analysis. From 2021 to 2024， the system generated a total of 57 879 alerts for prescriptions of five typical categories of anti-tumor drugs. For platinum-containing prescriptions， 22 577 alerts were generated， with Cisplatin for injection （lyophilized） being the most frequently alerted drug （13 445 alerts）， and “ototoxicity risk due to combined use” alerts remained high （7 682 alerts）. For methotrexate-containing prescriptions， 3 721 alerts were recorded， primarily related to “precaution-related issues” （76.4%， 2 843/3 721）. For doxorubicin-containing prescriptions， 17 301 alerts were triggered， primarily related to “dosage and administration” （14 315 alerts）. For human epidermal growth factor receptor 2-targeted agents-containing prescriptions， 1 007 alerts were issued， mostly related to “reimbursement restrictions” （956 alerts）. For programmed death-1/programmed death-ligand 1 inhibitors-containing prescriptions， the alerts increased year by year， totaling 13 273 alerts， primarily related to “inappropriate indication” （9 118 alerts）. Over the 4 years， the physician response rates to system alerts were 21.4%， 27.1%， 33.5% and 51.6%， respectively. CONCLUSIONS An intelligent decision-support system for anti-tumor drug prescription review， encompassing a closed-loop process of “real-time pre-event intervention， interactive in-event prescription review， post-event evaluation and analysis”， has been successfully constructed and implemented throughout the entire workflow. There is a discernible trend in this hospital， where the focus on monitoring anti-tumor drugs is shifting towards immunotherapy drugs. Additionally， the acceptance rate of physicians regarding prescription review opinions has been steadily increasing year by year.

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 To investigate the effect of astragaloside Ⅳ (AS-Ⅳ) on renal ischemia-reperfusion injury (RIRI) and its specific mechanism. Methods Forty-eight rats were randomly divided into 6 groups, with 8 rats in each group: sham operation group (Sham group), RIRI group, RIRI + AS-Ⅳ (10 mg/kg) group, RIRI + AS-Ⅳ (20 mg/kg) group, RIRI + AS-Ⅳ (40 mg/kg) group and RIRI + AS-Ⅳ + Brusatol group [Brusatol is a nuclear factor E2-related factor 2 (Nrf2) inhibitor]. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels of rats were detected using an automatic biochemical analyzer; the pathological damage degree of rats kidney tissue was evaluated by hematoxylin-eosin staining and scored; the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in rats serum, and interleukin (IL)-1β and IL-18 in rats kidney tissue were detected by enzyme-linked immunosorbent assay; the degree of cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; real-time fluorescence quantitative polymerase chain reaction and Western blotting were used to determine the messenger RNA (mRNA) and protein levels of Nrf2/heme oxygenase-1 (HO-1) signaling pathway and cell pyroptosis regulatory factors in rats kidney tissue. Results Compared with the Sham group, the BUN and Scr levels in the RIRI group were increased, the renal function and tissue damage were more severe, the degree of cell apoptosis was aggravated, the MDA level was increased, and the SOD activity was decreased, the Nrf2 and HO-1 protein and mRNA levels were downregulated, the NOD-like receptor protein 3 (NLRP3), Cle-Caspase-1 (the activated form of Caspase-1) and gasdermin D (GSDMD)-N protein levels were upregulated, the NLRP3, Caspase-1 and GSDMD-N mRNA levels were increased, and the release of IL-1β and IL-18 was increased. Compared with the RIRI group, the BUN and Scr levels in rats after AS-Ⅳ treatment were decreased, the degree of renal function and tissue damage was reduced, the degree of cell apoptosis was decreased, the MDA level was decreased, and the SOD activity was increased, the Nrf2 and HO-1 protein and mRNA levels were increased, the NLRP3, Cle-Caspase-1 and GSDMD-N protein levels were decreased, the NLRP3, Caspase-1 and GSDMD-N mRNA levels were decreased, and the release of IL-1β and IL-18 was reduced. Compared with the RIRI + AS-Ⅳ (20 mg/kg) group, the MDA level and SOD activity in rats of the RIRI + AS-Ⅳ + Brusatol group were increased, the Nrf2 and HO-1 protein and mRNA levels were decreased, the NLRP3, Cle-Caspase-1 and GSDMD-N protein levels were upregulated, the NLRP3, Caspase-1 and GSDMD-N mRNA levels were increased, and the release of IL-1β and IL-18 was increased. Conclusions AS-Ⅳ may alleviate RIRI in rats by inhibiting oxidative stress response and pyroptosis, and this mechanism is related to the activation of Nrf2/HO-1 signaling pathway.

BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective In this study,the potential profile characteristics of exercise self-efficacy of patients with inflammatory bowel disease(IBD)were explored,and the influencing factors of different types of patients were an-alyzed,so as to provide a reference for nurses to formulate standardized management measures.Methods From June 2023 to May 2024,a total of 342 hospitalized patients with IBD in tertiary A hospital in Wuxi were recruited as research subjects by a convenience sampling method.The General Information Questionnaire,Exercise Self-effica-cy Scale,Exercise Behavioral Stage Distribution Scale and the Social Support Rating Scale were used for investiga-tion.The latent profile analysis was conducted to classify exercise self-efficacy levels,while multiple Logistic regres-sion analysis was utilized to evaluate the influencing factors.Results A total of 320 valid questionnaires were col-lected,and the effective questionnaire recovery rate was 93.57％.The total score of exercise self-efficacy for IBD pa-tients was(64.61±14.83)points.The exercise self-efficacy was classified into 3 latent categories:low efficacy-somatic emotion group(n=64,20.00％),medium efficacy-work conflict group(n=158,49.38％),and high efficacy-social interfer-ence group(n=98,30.62％).Occupation,recurrence times,comorbid chronic diseases,self-assessed economic pressure,and social support level were found to be influencing factors of the latent profile classification of exercise self-effi-cacy in IBD patients(P＜0.05).Conclusion The levels of exercise self-efficacy of patients with IBD are significant-ly heterogeneous,and there are several important influencing factors.Nursing staff should formulate targeted inter-vention strategies based on the characteristics of exercise self-efficacy in such patients,so as to improve patients' exercise self-efficacy and the effectiveness of disease rehabilitation.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

Objective To explore the effect of the knockdown of transmembrane 9 superfamily protein member 2 (TM9SF2) on the replication of vesicular stomatitis virus (VSV), and investigate its role in the mechanism of antiviral innate immunity. Methods Small interfering RNA (siRNA) was used to knock down the TM9SF2 gene in human non-small cell lung cancer A549 cells. The CCK-8 method was used to assess cell proliferation. A VSV-green fluorescent protein (VSV-GFP) infected cell model was established. The plaque assay was used to measure the viral titer in the supernatant. RT-qPCR and Western blotting were employed to quantify the mRNA and protein levels of VSV genome replication in A549 cells following VSV infection, as well as the expression of interferon β (IFN-β) mRNA and interferon regulatory factor 3 (IRF3) protein phosphorylation following polyinosinic-polycytidylic acid (poly(I:C)) stimulation. Results Compared to the negative control, the knockdown of TM9SF2 exhibited a significant effect, with no observed impact on A549 cell proliferation. The VSV-GFP infected A549 cell model was successfully established. After viral stimulation, fluorescence intensity was reduced following TM9SF2 knockdown, and the mRNA and protein levels of VSV were significantly downregulated. The viral titer of VSV was decreased. After poly(I:C) stimulation, TM9SF2 knockdown significantly upregulated the mRNA level of IFN-β and the phosphorylation level of IRF3 protein. Conclusion The knockdown of TM9SF2 inhibits the replication of vesicular stomatitis virus, and positively regulates the type I interferon signaling pathway, thus enhancing the host's antiviral innate immune response.
Humans ; Virus Replication/genetics* ; Signal Transduction ; Membrane Proteins/metabolism* ; A549 Cells ; Vesiculovirus/physiology* ; Interferon-beta/metabolism* ; Interferon Regulatory Factor-3/genetics* ; Interferon Type I/metabolism* ; Vesicular Stomatitis/immunology* ; Gene Knockdown Techniques ; Vesicular stomatitis Indiana virus/physiology* ; RNA, Small Interfering/genetics*

Knee osteoarthritis (KOA) is a common chronic degenerative disease that not only causes pain and reduces the quality of life for patients but also imposes a significant societal burden. Clinical pathways can be developed by referencing recommendations from clinical practice guidelines to localize guidelines within the context of integrated traditional Chinese and western medical systems. However, existing clinical pathways suffer from shortcomings such as deficiencies in integrated traditional Chinese and western medical diagnosis and treatment, inadequate shared decision-making between healthcare providers and patients, and suboptimal visualization of clinical pathways. This study aimed to address and optimize the clinical pathway of KOA by comprehensively organizing and localizing the recommended guidelines. The concept of integrated traditional Chinese and western medicine was reflected through the construction of a path of joint decision-making between doctors and patients, emphasizing the coexistence of diagnosis and screening, the combination of clinical and imaging staging, joint decision-making between doctors and patients, and treatment stages. This pathway emphasizes patient-centered approach, with pain relief and functional rehabilitation running parallel, achieving the implementation of evidence-based concepts in practical medical practice. It provides a concrete basis for joint decision-making between doctors and patients in the integrated treatment of KOA with traditional Chinese and western medicine, which helps to improve diagnosis and treatment efficiency and patient quality of life.

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.