OBJECTIVE To provide references for the accurate identification and management of immune-related cutaneous adverse events （irCAEs） caused by durvalumab， and ensuring safe clinical drug use. METHODS Clinical pharmacists participated in the diagnosis and treatment process of a patient with gallbladder cancer who developed irCAEs caused by durvalumab. The clinical pharmacists systematically reviewed the patient’s past medical history and medication history， and assisted physicians in assessing the association between adverse drug reactions and administered drugs. Meanwhile， the clinical pharmacists conducted a graded assessment of the adverse reaction， proposed recommendations such as discontinuing durvalumab and adjusting the administration regimen of glucocorticoids， assisted physicians in restarting immunotherapy， and carried out medication education and other pharmaceutical care. RESULTS The occurrence of irCAEs in this patient was “highly likely” related to durvalumab and was classified as severe. The physicians adopted the clinical pharmacist’s opinion， and after symptomatic treatment， the patient’s skin symptoms improved， and discharged with medication. After the completion of glucocorticoid therapy for the patient， the physician restarted immunotherapy with tislelizumab， and no related adverse reactions occurred again in the patient. CONCLUSIONS Durvalumab can cause irCAEs such as severe skin maculopapular rash. In clinical practice， it is crucial to promptly identify and discontinue suspicious drugs， immediately implement effective symptomatic treatment measures， and actively resume immunotherapy to ensure the continuity and safety of the patient’s treatment.

OBJECTIVE: To investigate the role of telomerase reverse transcriptase (TERT) in alleviating doxorubicin (DOX)-induced cardiotoxicity. METHODS: (1) Cell experiments: rat H9c2 cardiomyocytes were divided into control group (CON group), null adenovirus transfection group (NC group), TERT overexpression adenovirus transfection group (TERT group), DOX group (treated with 1 μmol/L DOX for 12 hours), DOX+NC group, and DOX+TERT group (null adenovirus or TERT overexpression adenovirus were transfected for 24 hours and then treated with 1 μmol/L DOX for 12 hours). The mRNA expression of TERT in cardiomyocytes was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The level of mitochondrial membrane potential was detected by immunofluorescence. The expression levels of intracellular Bax, Bcl-2, microtubule-associated protein 1 light chain 3 (LC3) and p62 were detected by Western blotting. (2) Animal experiments: male C57BL/6 mice were randomly divided into a sham operation group (Sham group), DOX group (acute cardiotoxicity model was constructed by intraperitoneal injection of DOX 15 mg/kg), DOX+NC group and DOX+TERT group (modeled after transfection with airborne adenovirus or TERT overexpression adenovirus for 7 days). After 7 days of modeling, the area of myocardial fibrosis was detected by Sirius scarlet staining, and cardiac function was detected by echocardiography. RESULTS: (1) Cellular experiments: the mRNA expression level of TERT was significantly higher in the TERT group compared with the CON and NC groups. Compared with the CON group, the TERT mRNA expression level of cardiomyocytes in the DOX group and the DOX+NC group were significantly lower, the level of mitochondrial membrane potential was significantly lower, the protein expressions of Bax and LC3 were significantly increased, and the protein expressions of Bcl-2 and p62 were significantly decreased. No significant differences were found between the DOX group and DOX+NC group. Compared with the DOX group and DOX+NC group, the TERT mRNA expression level was increased in the DOX+TERT group (relative expression: 1.02±0.10 vs. 0.61±0.05, 0.54±0.03, both P < 0.05), the level of mitochondrial membrane potential was significantly increased (1.14±0.05 vs. 0.96±0.01, 0.96±0.01, both P < 0.05), the protein expressions of Bax and LC3 were significantly decreased, and the protein expressions of Bcl-2 and p62 were significantly increased (Bax/β-actin: 0.88±0.01 vs. 1.31±0.02, 1.26±0.01; LC3-II/I: 2.16±0.05 vs. 2.64±0.06, 2.58±0.02; Bcl-2/β-actin: 0.65±0.01 vs. 0.40±0.01, 0.41±0.01; p62/β-actin: 0.45±0.01 vs. 0.23±0.02, 0.29±0.01; all P < 0.05). (2) Animal experiments: compared with the Sham group, the percentage of myocardial fibrosis area was significantly increased and left ventricular ejection fraction (LVEF) and fractional shortening (FS) were significantly decreased in the DOX group and DOX+NC group. Compared with the DOX group and DOX+NC group, the percentage of myocardial fibrotic area was significantly decreased in the DOX+TERT group (%: 2.33±0.06 vs. 3.76±0.07, 3.87±0.06, both P < 0.05), and the LVEF and FS were significantly increased [LVEF (%): 67.00±1.14 vs. 54.60±1.57, 53.40±2.18; FS (%): 38.60±0.51 vs. 30.60±1.10, 30.00±0.71; all P < 0.05]. CONCLUSION Up-regulation of TERT expression can inhibit DOX-induced cardiomyocyte autophagy and apoptosis, attenuate DOX-induced myocardial fibrosis in mice, improve cardiac function, and thus alleviate DOX-induced cardiotoxicity.
Animals ; Doxorubicin/toxicity* ; Telomerase/metabolism* ; Myocytes, Cardiac/metabolism* ; Rats ; Male ; Cardiotoxicity ; Mice, Inbred C57BL ; Mice ; Membrane Potential, Mitochondrial ; Adenoviridae ; bcl-2-Associated X Protein/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Transfection ; Apoptosis

Objective:To analyze the clinical data of seven patients with a clinical diagnosis of likely sporadic Creutzfeldt-Jakob disease (sCJD) in order to improve the understanding and diagnosis of sporadic Creutzfeldt-Jakob disease.Methods:The clinical data of 7 sCJD patients admitted to the Department of Neurology of Our Hospital from 2021 to 2023 were retrospectively analyzed.Results:All seven patients had a subacute onset of disease, and the main clinical features included rapidly progressive dementia (RPD), cerebellar symptoms, pyramidal signs, myoclonus and akinetic mutism. Magnetic resonance diffusion-weighted imaging (DWI) reveals widespread asymmetrical lace-like high signal distributed along the cortex and a basal curved ball-and-stick sign. Electroencephalography (EEG) shows diffuse spiking and spiking slow waves, and periodic triphasic waves in advanced stages of the disease. Cerebrospinal fluid 14-3-3 protein testing was performed in 6 of the 7 patients, and 4 were positive. Four patients died within six months of onset of illness.Conclusions:The disease is prevalent in middle-aged and elderly patients, with a non-significant male-to-female ratio, and is dominated by the presence of Rapidly Progressive Dementia (RPD), especially the presence of cortical high signals in the DWI sequences and diffuse sharp and slow wave issuance in the electroencephalograph (EEG), which need to be alerted to the occurrence of Creutzfeldt-Jakob Disease. Dynamic review of MRI, EEG, cerebrospinal fluid 14-3-3 protein, prion protein gene (PRNP) sequence analysis and cerebrospinal fluid prion real-time vibration-induced protein amplification (RT-QuIC) monitoring whenever possible to avoid misdiagnosis, under-diagnosis, and under-recognition.

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.

Polycystic ovary syndrome(PCOS)is a complex disease that significantly impacts women's reproductive and metabolic health.The reprogramming of glucose metabolism points to fundamental changes in energy metabolism,which are central to the imbalance in energy metabolism,hormonal abnormalities,increasing insulin resistance,and chronic inflammatory states observed in PCOS.This represents a core pathological link in the pathogenesis of PCOS.The theory of"Spleen Qi to Dispersing Essence"provides a comprehensive overview of spleen function,essential for ensuring the normal operation of organs and the distribution of Qi,blood,and bodily fluids.It serves as a crucial theoretical support for the treatment of PCOS with traditional Chinese medicine.This article explores the role of regulating PCOS based on the theory of"Spleen Qi to Dispersing Essence"with a focus on the reprogramming of glucose metabolism.The mechanism of traditional Chinese medicinal treatments that assist Spleen Qi to Dispersing Essence is closely related to regulating glucose metabolism reprogramming,offering a novel research direction for the treatment of PCOS with TCM.

Objective To explore the quantitative electroencephalography(qEEG)characteristics of the prefrontal cortex in patients with mild cognitive impairment(MCI)during digital screening tasks for MCI screening.Methods A total of 592 MCI patients(MCI group)and 317 normal cognitively elderly individuals(control group)were recruited from 40 communities in Nanjing,Jiangsu Province,from July to August,2024.All participants were as-sessed using Montreal Cognitive Assessment-Beijing Version(MoCA-BJ).Prefrontal EEG data were collected using a portable EEG device,and power spectral analysis was performed via Fast Fourier Transform.An XG-Boost algorithm was employed to construct an MCI identification model based on qEEG power features,and the model's performance was evaluated using receiver operating characteristic(ROC)curve.Results Compared with the control group,prefrontal δ,α,and β band power increased during screening tasks in MCI group(P<0.05);δ power was negatively correlated with MoCA-BJ total scores,and visuospatial/executive func-tion,attention and delayed recall scores(r=-0.269,-0.169,-0.133,-0.171,P<0.001);α power was negative-ly correlated with MoCA-BJ total scores,attention and delayed recall scores(r=-0.113,-0.075,-0.091,P<0.05).The XGBoost model based on δ and α power was excellent in MCI identification,with an area under the curve of 0.91,accuracy of 0.81,precision of 0.89,F1 score of 0.84,recall of 0.80,and specificity of 0.81.Conclusion MCI patients exhibit increased power in the prefrontal δ and α frequency bands during digital screening tasks,which is associated with cognitive decline.An XGBoost model based on qEEG power features can enable early prediction of MCI.

Objective:To evaluate the efficacy of an etoposide (Vp16) -intensified conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for the treatment of relapsed/refractory acute myeloid leukemia (AML).Method:A retrospective analysis was conducted on the clinical data of 27 recipients with relapsed/refractory AML who underwent allo-HSCT using a Vp16-intensified conditioning regimen at Aerospace Center Hospital from January 2019 to January 2022. Transplantation-related complications and treatment outcomes were observed. Kaplan-Meier survival analysis was used to assess the overall survival (OS) and disease-free survival (DFS) rates.Result:Among the 27 recipients, there were 14 males and 13 females, with a median age of 41 years (range: 12~55 years). Except for one recipient who experienced primary graft failure, the remaining 26 recipients achieved hematopoietic reconstitution. The median neutrophil and platelet engraftment times were 13 days (range: 9~20 days) and 13.5 days (range: 11~33 days), respectively. Regimen-related toxicity (RRT) was mainly gastrointestinal toxicity and oral mucositis, and no deaths were attributed to RRT. A total of 12 recipients (44.44%) developed acute graft-versus-host disease (aGVHD), of whom 3 cases (11.11%) had grade III~IV aGVHD. Chronic GVHD (cGVHD) occurred in 13 recipients (48.15%), including 8 cases (29.63%) of extensive cGVHD. The median follow-up time after transplantation was 17 months (range: 1~48 months). Fifteen recipients (55.56%) survived without disease, while 12 recipients (44.44%) died— 9 due to relapse and 3 due to transplant-related complications. The 1-year overall survival and DFS rates were 74.07% and 59.26%, respectively; the 2-year overall survival and DFS rates were 59.26% and 55.56%, respectively. The 2-year relapse rate and transplant-related mortality (TRM) were 33.33% and 11.11%, respectively.Conclusion:The Vp16-intensified conditioning regimen in allo-HSCT appears to be a viable treatment option for patients with relapsed/refractory AML, offering favorable efficacy and manageable safety.

Objective:To construct a risk prediction model for early post-injury respiratory failure in patients with traumatic cervical spinal cord injury (TCSCI) and validate its efficacy.Methods:A retrospective cohort study was conducted to analyze the clinical data of 393 TCSCI patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2020 to October 2024, including 294 males and 99 females, aged 18-82 years [59(45, 72)years]. Among them, 76 patients had respiratory failure (19.3%). The patients were randomly divided into the training set ( n=275) and validation set ( n=118) at a ratio of 7∶3. According to the presence of respiratory failure within one week after admission, 275 patients in the training set were divided into respiratory failure group ( n=53) and non-respiratory failure group ( n=222). The demographic data, injury characteristics, laboratory test results, and imaging findings of the patients were collected. Risk factors were determined through univariate analysis and multivariate Logistic regression analysis and a nomogram prediction model was constructed. The area under the receiver operating characteristic (ROC) curve (AUC) and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model. Decision curve analysis (DCA) was plotted to evaluate the clinical effectiveness of the prediction model. Results:The results of the univariate analysis showed that there were significant differences in history of respiratory diseases, causes of injury, Glasgow coma scale (GCS), American Spinal Injury Association (ASIA) classification, ASIA-motor score (AMS), injury severity score (ISS), clinical pulmonary infection score (CPIS), hypoproteinemia and cervical vertebra fracture and dislocation between the respiratory failure group and non-respiratory failure group in the training set ( P<0.05). The results of multivariate Logistic regression analysis indicated that GCS, ASIA classification, CPIS, and hypoproteinemia were independent risk factors for early post-injury respiratory failure in TCSCI patients ( P<0.05). Based on the above four variables, a Logistic regression equation was constructed: Logit( P)=2.361-0.675×ASIA classification+0.419×CPIS-0.358×GCS+0.854×hypoproteinemia. In the prediction model established based on this equation, the AUC was 0.96 (95% CI 0.94, 0.99) in the training set and 0.89 (95% CI 0.82, 0.96) in the validation set. In the calibration curves of the training set and validation set, the prediction curve and reference curve were approximately overlapping, with the average absolute errors of 0.04 and 0.03. DCA results demonstrated that both the training and validation sets exhibited positive net benefits when threshold probabilities fell within ranges of 0%-78% and 0%-87%, respectively. Conclusion:The risk prediction model for early post-injury respiratory failure in TCSCI patients based on GCS, ASIA classification, CPIS and hypoproteinemia has good predictive efficacy and clinical practicability.

Objective To study the dynamic changes in the secretion of neurotransmitters glutamic acid(Glu)and γ-aminobutyric acid(GABA)in the central auditory brain area,in order to explore the effects of sodium salicy-late on different locations of the auditory pathway.Methods A total of 126 SD rats were injected intraperitoneally with salicylate,and were divided into 10 groups including injection groups for 1,2,4,8,and 24 hours,chronic in-jection groups for 3,7,and 14 days,and chronic recovery groups for 21 and 28 days with 6 rats in each group,as well as their corresponding blank control groups.Rats in each group were anesthetized and materials were collected for further use.High-performance liquid chromatography(HPLC)was performed to detect and compare the dynam-ic changes in the levels of Glu and GABA in the auditory cortex,inferior colliculus,cochlear nucleus,and hippocam-pus of the auditory center of rats in each group at different time points.Results Compared with the control group,within 24 hours of acute injection of salicylate,the Glu content in the auditory cortex reached the peak in 1 hour,and the hippocampus reached the peak at the 4th hour after injection,and then decreased slowly.The GABA con-tent in the four brain regions showed a slow upward trend in the chronic injection period,reached the peak on the 7th day,decreased and approached normal level on the 14th day,and basically returned to the normal level in the re-covery period.Conclusion These findings indicate that salicylate has a certain short-term excitatory and stimulating effect on the central auditory system.Under the mechanism of central plasticity,after long-term injection of salicy-late,the release of neurotransmitters reaches a new excitation/inhibition balance in the central area.Glu and GABA may each play a different role that may ultimately lead to the development of tinnitus.

Background and purpose:In the quality control of mammography,the signal-to-noise ratio(SNR)refers to the ratio of the useful signal intensity to the background noise in the image,which is one of the important indicators for measuring the quality of the image.The coefficient of variation(CoV)is a commonly used indicator to describe the consistency and repeatability of SNR.This study aimed to assess the stability and repeatability of mammographic device performance by analyzing the changes in SNR CoV in two-dimensional(2D)images and tomosynthesis images(referred to as Tomo images)under different exposure modes using three mammographic devices from different manufacturers.Methods:A polymethylmethacrylate(PMMA)phantom designed for mammography quality control was used to perform automatic exposure detection at PMMA thicknesses ranging from 20-80 mm,with actual compression thickness equivalent to the average density of the breast compressed to 21-103 mm under full-field digital mammography(FFDM),low-dose mammography and digital breast tomosynthesis(DBT)exposure modes.The CoV of SNR in 2D images and tomosynthesis images was calculated for different mammographic devices under different exposure modes and compression thicknesses.Results:Between the compression thicknesses equivalent to the average density of the breast from 21 mm to 103 mm under FFDM,low-dose mammography,and DBT exposure modes,the differences in SNR CoV of 2D images under different exposure modes among mammographic devices 1,2,and 3 were statistically significant only in the DBT exposure mode(P=0.003),with SNR CoV ranging from 0.188%to 0.720%,0.368%to 1.073%and 0.402%to 1.662%,respectively.There were no statistically significant differences in SNR CoV of 2D images among devices 1,2,and 3 under FFDM and low-dose exposure modes(P=0.060).Under the DBT exposure mode,there were no statistically significant differences in the SNR CoV of the first projection image and the 0° projection image of tomosynthesis among devices 1(2 angles),2,and 3(P=0.373,P=0.742,P=0.225,P=0.693,respectively).Conclusion:The SNR CoV in 2D images and tomosynthesis images varies under different mammographic devices and exposure modes,with no fixed or standard values,but all within the required range for mammographic device quality control.The stability and repeatability of 2D images of mammographic devices are better under FFDM and low-dose exposure modes;the SNR CoV values of the first projection image and the 0° projection image of tomosynthesis under the DBT exposure mode show no statistical differences,indicating good stability of the devices.