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.

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*

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 To explore the clinical application value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB-DTPA)enhanced MRI T1 mapping in the evaluation of liver function.Methods Sixty-four patients who underwent enhanced MRI T1 mapping with Gd-EOB-DTPA and completed the laboratory examination of liver function within one week were prospectively enrolled.All patients were divided into normal control group(NCG),cirrhosis Child-Pugh A(CCA)group,cirrhosis Child-Pugh B(CCB)group,and cirrhosis Child-Pugh C(CCC)group.CCB+CCC groups were defined as a moderate and severe abnormal liver function group.The T1 mapping images of pre-enhanced,post-enhanced 10 min and 20 min were collected,and the T1 mapping val-ues of liver and spleen were measured.The ΔT1 and hepatocyte enhancement fraction(HEF)were calculated.The differences of parameters in different liver function groups were analyzed and compared,and the diagnostic efficacy of each index in distinguishing different liver function groups was evaluated.Results There were significant differences in T1plain scan,T110 min,T120 min,ΔT110 min,ΔT120 min,HEF10 min and HEF20 min among the three groups(P<0.05).The difference of T1plain scan between NCG and CCA groups,and between NCG and CCB+CCC groups was statistically significant(P<0.05).The area under the curve(AUC)of differentiating normal liver function group from abnormal liver function group was 0.761.There were significant differences in T110 min,T120 min,ΔT110 min,ΔT120 min,HEF10 min and HEF20 min between CCA and CCB+CCC groups.The AUC of differentiating the two groups was 0.757,0.820,0.735,0.820,0.790 and 0.853,respectively,and HEF20 min had the highest diagnostic efficacy.Conclusion Gd-EOB-DTPA enhanced MRI T1 mapping can be used as an effective method to evaluate liver function.

Objective To evaluate the clinical efficacy and safety of bumetanide in comparison with other diuretics for the prevention and management of postoperative pleural effusion in patients undergoing hepatobiliary surgery.Methods A total of 168 patients undergoing routine hepatobiliary surgery were randomly assigned to either the bumetanide group or the control group(other diuretics).Patients in the bumetanide group received bumetanide injection at a dose of 1 mg intravenously once daily.In contrast,the control group received one of the following treatments:furosemide injection at 20 mg intravenously once daily,furosemide tablets at 40 mg orally twice daily,or a combination of furosemide tablets(40 mg orally twice daily)and spironolactone tablets(60 mg orally twice daily).All treatments were administered for three days postoperatively.The incidence of postoperative pleural effusion,length of hospital stay,and drug-related adverse reactions were compared between the two groups.Additionally,multivariate logistic regression analysis was conducted to identify independent risk factors for moderate-to-severe pleural effusion after surgery.Results A total of 82 patients were enrolled in the bumetanide group and 86 in the control group.No significant differences were observed in the general demographic and clinical characteristics between the two groups(P>0.05),except for sex and ALT levels(P<0.05).The incidence of moderate-to-severe pleural effusion was higher in the control group than in the bumetanide group,with rates of 9.3％and 1.2％,respectively(all P<0.05).Additionally,the length of hospital stay was significantly longer in the control group(19.94±0.90 days)compared to the bumetanide group(17.15±1.06 days)(all P<0.05).Thora-centesis was performed in 2 cases in the bumetanide group and 8 cases in the control group,but this difference was not statistically significant(P>0.05).The primary adverse drug reactions in both groups included hypokalemia,hypochloremia,hyponatremia,and hypocalcemia.The overall incidence of adverse drug reactions was 35.4％in the bumetanide group and 34.9％in the control group,showing no significant difference(P>0.05).Multivariate regression analysis revealed that a history of hepatitis B,cirrhosis,and the use of bumetanide were independent predictors of moderate-to-severe pleural effusion during routine hepatobiliary surgery(all P<0.05).Conclusions Bumetanide demonstrates superior efficacy compared to other conventional diuretics in the prevention and manage-ment of postoperative pleural effusion in hepatobiliary surgery,suggesting potential clinical application value.

Objective This study aimed to evaluate the interaction between antiretroviral drug efavirenz and anti-tuberculosis 1H3P3(isoniazid plus rifapentine)in people living with HIV.Methods HIV-positive individuals on efavirenz-containing(600 mg)antiretroviral therapy(ART)received 1H3P3 regimen containing rifapentine(450 mg)plus isoniazid(400 mg)3 times a week for 1 month.Efavirenz concentrations were measured at weeks 0,2,4,8.Rifapentine concentration was determined at weeks 2 and 4.HIV RNA load was determined at weeks 0 and 8.Treatment target was efavirenz concentration＞1 mg/L.The anti-TB prevention was considered acceptable if the target of efavirenz concentration was achieved in more than 80％of participants.The participants were followed up for 18 months to evaluate the efficacy of treatment.Results Thirty-one participants living with HIV were enrolled in the study.Two participants were excluded from PK analysis because his/her baseline efavirenz concentration＜1 mg/L,suggesting poor treatment adherence.Evaluable PK data were available for 29 participants,including 23(79.3％)males.The median[interquartile range(IQR)]age of the participants was 43.0(32.5,53.5)years.The median(IQR)efavirenz plasma concentration was 2.33(1.96,2.34)mg/L at week 0,2.32(1.90,3.28)mg/L at week 2,2.07(1.83,3.09)mg/L at week 4,and 2.71(2.14,3.33)mg/L at week 8.Efavirenz concentration did not show significant difference between the 4 time points(P＞0.05).Median(IQR)rifapentine concentration was 9.36(6.23,16.47)mg/L at week 2,and 9.36(6.41,15.56)mg/L at week 4.Rifapentine concentration did not show significant difference between week 2 and week 4(P＞0.05).Efavirenz concentrations was＞1 mg/L in all participants at weeks 2,4,and 8.Furthermore,efavirenz concentration was significantly higher in females and patients with body weight＜60 kg compared with males and those with body weight ≥60 kg(P＜0.05).None of the participants had symptoms or signs of active tuberculosis during 18-month follow-up.Conclusions Isoniazid plus rifapentine(1H3P3 regimen)did not have significant effect on the plasma concentrations of efavirenz.

Objective To evaluate the clinical efficacy and safety of bumetanide in comparison with other diuretics for the prevention and management of postoperative pleural effusion in patients undergoing hepatobiliary surgery.Methods A total of 168 patients undergoing routine hepatobiliary surgery were randomly assigned to either the bumetanide group or the control group(other diuretics).Patients in the bumetanide group received bumetanide injection at a dose of 1 mg intravenously once daily.In contrast,the control group received one of the following treatments:furosemide injection at 20 mg intravenously once daily,furosemide tablets at 40 mg orally twice daily,or a combination of furosemide tablets(40 mg orally twice daily)and spironolactone tablets(60 mg orally twice daily).All treatments were administered for three days postoperatively.The incidence of postoperative pleural effusion,length of hospital stay,and drug-related adverse reactions were compared between the two groups.Additionally,multivariate logistic regression analysis was conducted to identify independent risk factors for moderate-to-severe pleural effusion after surgery.Results A total of 82 patients were enrolled in the bumetanide group and 86 in the control group.No significant differences were observed in the general demographic and clinical characteristics between the two groups(P>0.05),except for sex and ALT levels(P<0.05).The incidence of moderate-to-severe pleural effusion was higher in the control group than in the bumetanide group,with rates of 9.3％and 1.2％,respectively(all P<0.05).Additionally,the length of hospital stay was significantly longer in the control group(19.94±0.90 days)compared to the bumetanide group(17.15±1.06 days)(all P<0.05).Thora-centesis was performed in 2 cases in the bumetanide group and 8 cases in the control group,but this difference was not statistically significant(P>0.05).The primary adverse drug reactions in both groups included hypokalemia,hypochloremia,hyponatremia,and hypocalcemia.The overall incidence of adverse drug reactions was 35.4％in the bumetanide group and 34.9％in the control group,showing no significant difference(P>0.05).Multivariate regression analysis revealed that a history of hepatitis B,cirrhosis,and the use of bumetanide were independent predictors of moderate-to-severe pleural effusion during routine hepatobiliary surgery(all P<0.05).Conclusions Bumetanide demonstrates superior efficacy compared to other conventional diuretics in the prevention and manage-ment of postoperative pleural effusion in hepatobiliary surgery,suggesting potential clinical application value.

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.