This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Objective To analyze the involvement of pharmacists in the pharmaceutical care of olfacatumumab in the treatment of elderly patients with refractory anti-metabotropic glutamate receptor 5(mGluR5)encephalitis and to provide a reference for the treatment and pharmaceutical care of patients with refractory autoimmune encephalitis(AE).Methods An 81-year-old patient with anti-mGluR5 encephalitis who had poor first-line immunotherapy effect.The key points of pharmaceutical care were determined according to the patient's condition and the characteristics of therapeutic drugs.The drug selection,administration mode,drug interaction,adverse reactions,and precautions of ofatumumab were put forward.At the same time,the patients and their families were given medication guidance and discharge education,and regular follow-up was carried out.Results With the cooperation of doctors,the patient was provided with whole-process pharmaceutical care,and the patient's condition was improved,and the patient's condition was good so far.Conclusion Clinical pharmacists pay attention to the effectiveness and safety of the treatment with ofatumumab by carrying out individualized pharmaceutical care for this patient,which fully reflects the value of clinical pharmacists and provides a reference for the treatment and pharmaceutical care of refractory AE patients.

Objective:To mine risk signals of adverse events (AE) in agalsidase beta therapy for Fabry disease and provide reference for the safe use in clinical practice.Methods:The AE reports with agalsidase beta as the primary suspect drug in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the third quarter of 2024 were collected and the clinical information of patients involved was analyzed descriptively. AEs were standardized and categorized using the preferred term (PT) and system organ class (SOC) in Medical Dictionary for Regulatory Activities version 26.0. Signal mining was performed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A PT was defined as the risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) of ROR was >1, and the information component minus two times standard deviation ( IC025) was >0. Descriptive statistical analysis were then conducted on the risk signals. The relative risk of target adverse events in gender subgroups was evaluated using the ROR method. Results:A total of 24 163 AE reports with agalsidase beta as the primary suspect drug were collected, involving 7 763 patients and 2 382 PTs. Severe adverse events accounted for 34.9% (2 712/7 763). A total of 121 risk signals (namely PTs) across 15 SOCs were obtained. The top 5 PTs ranked by number of reports were pyrexia (483 cases), chills (449 cases), infusion related reaction (282 cases), chest pain (221 cases), and cerebrovascular accident (218 cases). The top 5 PTs ranked by signal intensity were cornea verticillata ( ROR=56.44, IC025=4.59), drug specific antibody present ( ROR=54.13, IC025=5.46), cerebral calcification ( ROR=24.82, IC025=3.16), myocardial necrosis marker increased ( ROR=24.14, IC025=3.83), and infusion site rash ( ROR=20.41, IC025=3.46). Among the top 30 PTs ranked by number of reports and signal intensity, there were 4 and 13 PTs not documented in the drug label, respectively. The former included atrial fibrillation, cellulitis, neuralgia, and pallor, while the latter included cornea verticillate, cerebral calcification, auricular swelling, vein discoloration, aortic dilatation, bundle branch block, myocardial fibrosis, cardiac infection, vein rupture, sudden hearing loss, meningitis viral, deafness transitory, and corneal opacity. Subgroup analysis by sex showed that males had higher risks in developing chills, tremor, drug specific antibody detection, renal failure, and renal impairment, while females had higher risks in weight increase and dizziness. Conclusions:The main risk signals of adverse events of agalsidase beta include pyrexia, chills, and infusion related reactions, which are consistent with those documented in package inserts. In addition, potential new risk signals such as atrial fibrillation, cellulitis, neuralgia, cornea verticillate, auricular swelling, and sudden hearing loss were also detected. The relative risks of some target adverse events vary between genders, and it is recommended to strengthen targeted drug monitoring and individualized management in clinical practice.

Objective To analyze the involvement of pharmacists in the pharmaceutical care of olfacatumumab in the treatment of elderly patients with refractory anti-metabotropic glutamate receptor 5(mGluR5)encephalitis and to provide a reference for the treatment and pharmaceutical care of patients with refractory autoimmune encephalitis(AE).Methods An 81-year-old patient with anti-mGluR5 encephalitis who had poor first-line immunotherapy effect.The key points of pharmaceutical care were determined according to the patient's condition and the characteristics of therapeutic drugs.The drug selection,administration mode,drug interaction,adverse reactions,and precautions of ofatumumab were put forward.At the same time,the patients and their families were given medication guidance and discharge education,and regular follow-up was carried out.Results With the cooperation of doctors,the patient was provided with whole-process pharmaceutical care,and the patient's condition was improved,and the patient's condition was good so far.Conclusion Clinical pharmacists pay attention to the effectiveness and safety of the treatment with ofatumumab by carrying out individualized pharmaceutical care for this patient,which fully reflects the value of clinical pharmacists and provides a reference for the treatment and pharmaceutical care of refractory AE patients.

Objective:To mine risk signals of adverse events (AE) in agalsidase beta therapy for Fabry disease and provide reference for the safe use in clinical practice.Methods:The AE reports with agalsidase beta as the primary suspect drug in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the third quarter of 2024 were collected and the clinical information of patients involved was analyzed descriptively. AEs were standardized and categorized using the preferred term (PT) and system organ class (SOC) in Medical Dictionary for Regulatory Activities version 26.0. Signal mining was performed using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. A PT was defined as the risk signal if the number of reports was ≥3, the lower limit of the 95% confidence interval ( CI) of ROR was >1, and the information component minus two times standard deviation ( IC025) was >0. Descriptive statistical analysis were then conducted on the risk signals. The relative risk of target adverse events in gender subgroups was evaluated using the ROR method. Results:A total of 24 163 AE reports with agalsidase beta as the primary suspect drug were collected, involving 7 763 patients and 2 382 PTs. Severe adverse events accounted for 34.9% (2 712/7 763). A total of 121 risk signals (namely PTs) across 15 SOCs were obtained. The top 5 PTs ranked by number of reports were pyrexia (483 cases), chills (449 cases), infusion related reaction (282 cases), chest pain (221 cases), and cerebrovascular accident (218 cases). The top 5 PTs ranked by signal intensity were cornea verticillata ( ROR=56.44, IC025=4.59), drug specific antibody present ( ROR=54.13, IC025=5.46), cerebral calcification ( ROR=24.82, IC025=3.16), myocardial necrosis marker increased ( ROR=24.14, IC025=3.83), and infusion site rash ( ROR=20.41, IC025=3.46). Among the top 30 PTs ranked by number of reports and signal intensity, there were 4 and 13 PTs not documented in the drug label, respectively. The former included atrial fibrillation, cellulitis, neuralgia, and pallor, while the latter included cornea verticillate, cerebral calcification, auricular swelling, vein discoloration, aortic dilatation, bundle branch block, myocardial fibrosis, cardiac infection, vein rupture, sudden hearing loss, meningitis viral, deafness transitory, and corneal opacity. Subgroup analysis by sex showed that males had higher risks in developing chills, tremor, drug specific antibody detection, renal failure, and renal impairment, while females had higher risks in weight increase and dizziness. Conclusions:The main risk signals of adverse events of agalsidase beta include pyrexia, chills, and infusion related reactions, which are consistent with those documented in package inserts. In addition, potential new risk signals such as atrial fibrillation, cellulitis, neuralgia, cornea verticillate, auricular swelling, and sudden hearing loss were also detected. The relative risks of some target adverse events vary between genders, and it is recommended to strengthen targeted drug monitoring and individualized management in clinical practice.

OBJECTIVE To analyze the potential adverse drug interactions(pADIs)of clarithromycin,and establish refined prescription pre-review rules.METHODS Outpatient prescriptions of clarithromycin in combination with other drugs were collected from January 1,2024 to June 30,2024 through hospital information system of the Third People's Hospital of Bengbu.pADIs were identified and their risk severities were graded according to Lexicomp and Micromedex databases.Then,refined prescription pre-review rules for clarithromycin pADIs-related drugs were established according to the identification and risk level results.RESULTS Among 3 046 clarithromycin combined drug prescriptions,946 cases of pADIs occurred in 812 prescriptions.There were 6,415 and 525 cases classified as"contraindicated","major"and"moderate",respectively.The combination drugs with"contraindicated"levels were tamsulosin,rupatadine,domperidone and ticagrelor,while those with"major"levels were mainly theophylline,dexamethasone and amlodipine.Accordingly,26 refined rules were established,including 4 items of"warning information→prescription interception",11 items of"warning information→prescription double signature"and 11 items of"attention information→prescription approval".CONCLUSIONS There are"contraindicated"and"major"risks associated with clarithromycin and its combination drugs in the hospital,and refined prescription pre-review rules for clarithromycin combined drug prescription have been established successfully.

Objective:To investigate the effect of rehabilitation exercise combined with resistance training on the postoperative recovery and quality of life among patients with pulmonary nodules.Methods:A randomized controlled study was conducted on 90 patients with pulmonary nodules who underwent thoracoscopic resection of pulmonary nodules at Zhejiang Veteran Hospital between January 2022 and April 2023. Patients were randomly allocated into an observation group and a control group, with 45 patients in each group using the random number table method. The control group underwent routine rehabilitation exercise, whereas the observation group received resistance training combined with routine rehabilitation exercise. All patients were treated for 1 week. The incidence of postoperative complications and the changes in lung function, exercise endurance, and quality of life from baseline levels were compared between the two groups.Results:The incidence of postoperative complications in the observation group was significantly lower than that in the control group [6.7% (3/45) vs. 24.4% (11/45), χ2 = 5.41, P = 0.020). After intervention, the forced expiratory volume in 1 second, maximal voluntary ventilation per minute, and forced vital capacity in the observation group were (83.84 ± 4.35)%, (96.53 ± 3.45) L/min, and (2.87 ± 0.16) L, respectively, which were higher than those in the control group [(78.98 ± 4.01)%, (92.13 ± 3.08) L/min, (2.62 ± 0.19) L, t = -5.51, -6.38, -6.75, all P < 0.001]. Additionally, the modified Medical Research Council dyspnea score in the observation group was (0.42 ± 0.13) points, which was significantly lower than that in the control group [(0.87 ± 0.19) points, t = 13.11, P < 0.001). The modified Barthel index score in the observation group was significantly higher than that in the control group [(89.53 ± 3.67) points vs. (82.94 ± 4.23) points, t = -7.89, P < 0.001). Conclusion:The combination of rehabilitation exercise and resistance training can effectively enhance lung function, exercise endurance, and overall quality of life in patients with pulmonary nodules. Furthermore, this combined therapy markedly reduces postoperative complications.

Crizotinib is a multi-target small molecule tyrosine kinase inhibitor, which can act on anaplastic lymphoma kinase (ALK), cellular-mesenchymal to epithelial transition factor and c-ros oncogene 1 (ROS1). It is mainly used in patients with ALK/ROS1-positive advanced non-small cell lung cancer. Liver injury is one of the most common adverse reactions of crizotinib. The typical symptom of crizotinib-induced liver injury is asymptomatic aminotransferase elevation, and fatal liver failure can occur in very few patients. The mechanism is mainly related to mitochondrial-mediated apoptosis, excessive autophagy, oxidative stress, and anaphylaxis. The risk factors involved are history of liver diseases, hepatitis B virus infection, combined use of immune checkpoint inhibitors or H 2-antagonist/proton pump inhibitor, gene polymorphisms of signal transducer and activator of transcription 1 and cytochrome P450. It is very important to assess liver function comprehensively before treatment, and strengthen the therapeutic drug monitoring during treatment. Measures such as temporary (reduce the dose when re-use) or permanent discontinuation should be taken when necessary.

Crizotinib is a multi-target small molecule tyrosine kinase inhibitor, which can act on anaplastic lymphoma kinase (ALK), cellular-mesenchymal to epithelial transition factor and c-ros oncogene 1 (ROS1). It is mainly used in patients with ALK/ROS1-positive advanced non-small cell lung cancer. Liver injury is one of the most common adverse reactions of crizotinib. The typical symptom of crizotinib-induced liver injury is asymptomatic aminotransferase elevation, and fatal liver failure can occur in very few patients. The mechanism is mainly related to mitochondrial-mediated apoptosis, excessive autophagy, oxidative stress, and anaphylaxis. The risk factors involved are history of liver diseases, hepatitis B virus infection, combined use of immune checkpoint inhibitors or H 2-antagonist/proton pump inhibitor, gene polymorphisms of signal transducer and activator of transcription 1 and cytochrome P450. It is very important to assess liver function comprehensively before treatment, and strengthen the therapeutic drug monitoring during treatment. Measures such as temporary (reduce the dose when re-use) or permanent discontinuation should be taken when necessary.

OBJECTIVE To analyze the influential factors of cardioto xicity in patients with positive breast cancer of human epidermal growth factor receptor 2（HER-2）treated by trastuzumab combined with chemotherapy. METHODS From April 2017 to January 2021，200 HER-2 positive breast cancer patients receiving pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab were collected from our hospital. According to the presence or absence of cardiotoxicity ，the patients were divided into cardiotoxicity group and non-cardiotoxicity group. The clinical data and echocardiographic results of the patients were collected，and the influential factors of cardiotoxicity were analyzed. RESULTS Among 200 patients，43 patients suffered from cardiotoxicity with the incidence of 21.5％. The proportion of patients with cardiotoxicity during pirarubicin+cyclophosphamide therapy accounted for 5.5％（11/200），and the proportion of patients with cardiotoxicity during sequential paclitaxel+trastuzumab therapy accounted for 20.5％（41/200）；the latter was significantly higher than the former （P＜0.01）. At the same time ，the decrease of left ventricular ejection fraction during sequential therapy of paclitaxel and trastuzumab was significantly higher than that during pirarubicin+cyclophosphamide therapy [ 14％（12％，17％）vs. 7％（3％，10％），P＜0.001]. Compared with patients without cardiotoxicity ，the proportion of patients with cardiotoxicity with a history of hyperlipidemia was significantly higher （P＜ 0.01），while the proportion of patients receiving dexrazoxane was significantly lower （P＜0.01）. Results of binary Logistic regression analysis showed that the history of hyperlipidemia [OR ＝3.672，95％ CI（1.499，8.992），P＝0.004] and the use of dextrazoxane [OR ＝0.154，95％ CI（0.072，0.330）， P＜0.001] were associated with the occurrence of cardiotoxicity. CONCLUSIONS Hyperlipidemia is an independent risk factor for cardiotoxicity induced by pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab in HER 2 positive breast cancer patients ，while the use of dextrazoxane is a protective factor.