ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure （ALF） by observing its effect on a mouse model of ALF after prophylactic administration， and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group， model group， Jiedu Huayu granules group （JDHY group）， and farnesoid X receptor （FXR） agonist （GW4064） group using a random number table， with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling， those in the normal group and the model group were given 0.9% NaCl solution by gavage， and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling， and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin （TBil）， total bile acids （TBA）， gamma-glutamyl transferase （GGT）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in mice from each group； HE staining was used to observe liver pathological changes； RT-PCR was used to measure the mRNA expression levels of FXR， fibroblast growth factor 15 （FGF15）， fibroblast growth factor receptor 4 （FGFR4）， small heterodimer partner （SHP）， and bile salt export pump （BSEP） in mice， and Western blot was used to measure the protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP. A one-way analysis of variance was used for comparison between groups， and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of TBil， ALT， AST， TBA， and GGT （all P<0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil， ALT， AST， TBA， and GGT （all P <0.01）. HE staining showed that compared with the model group， the JDHY group and the GW4064 group had milder pathological injury， a reduction in the area of hepatocyte necrosis， and alleviation of cellular swelling and edema. Compared with the normal group， the model group had significant reductions in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.05）. ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.

ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia （AML） and its correlation with clinical indicators and prognosis， and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia （AML） patients. Clinical samples from non-M3 AML patients were collected， with TRIM28 expression levels measured using real-time quantitative PCR （qPCR）. The analysis focused on correlations between TRIM28 expression and various clinical indicators， treatment efficacy， and patient prognosis. Furthermore， small interfering RNA （siRNA） technology was employed to downregulate TRIM28 expression in human primary AML cells （HL60 cell line）. The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry， respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples （P<0.000 1）， TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group （P<0.01）， and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group， and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation， positively correlated with age， bone marrow blast， peripheral blood blast and white blood cell， negatively correlated with hemoglobin. In addition， interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis， and plays a key role in the proliferation and apoptosis of AML cells， suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.

Objective: To establish a real-time quality control scheme based on the median (MD-IC) of internal control cycle threshold value in negative samples (NEG-IC-CT), so as to monitor anomalies such as progressive drift in nucleic acid testing system not covered by conventional internal quality control (IQC) in blood center nucleic acid laboratories, and to verify its feasibility. Methods: The internal control CT values of 54 426 negative samples were retrospectively collected. These samples were from four reagent batches of the two new and old equipment sets during the operation of the Wantai nucleic acid testing system in our blood center. The daily median of NEG-IC-CT values was used as the research indicator. Control limits were calculated using median absolute deviation (MAD) to construct the Median-MAD quality control chart. The monitoring performance of this scheme for the operation status of the testing system was simultaneously evaluated. Results: Statistical analysis showed significant differences in NEG-IC-CT value distribution between the new and old equipment sets, as well as between the two different reagent batches of the old equipment (P<0.000 1). The NEG-IC-CT value performance of the two different reagent batches of the new equipment was no significant difference in distribution (P>0.05). This scheme identified three typies of distinct anomalies. The out-of-control events observed with the old equipment in both the O1 and O2 reagent batches suggested potential performance decay due to equipment aging. The unreported change of reagent batch in time of Phase B with new equipment caused a stepwise drift on the quality control chart. In the later stage of Phase A with the new equipment, an alert was triggered, indicating potential quality risks associated with practices such as the mixed use of the remaining reagents and extremely long operator working hours. Conclusion: The realtime quality control scheme based on NEG-IC-CT value established in this study has been preliminarily validated for its monitoring effectiveness in nucleic acid testing in our blood center. This scheme performed well in detecting differences among testing systems and reagent batches, serving as an effective supplement to routine internal quality control. It can provide an intuitive and effective evaluation method for monitoring the performance of the nucleic acid testing process at blood center.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Objective:To explore the value of contrast-enhaoced echocardiography for measuring pulmonary transit time（PTT）in assessing heart failure after percutaneous coronary intervention（PCI）in acute ST-segment elevation myocardial infarction（STEMI）patients.Methods:From September 2023 to September 2024，120 patients with STEMI undergoing PCI at Hunan Provincial People's Hospital were prospectively selected and divided into a heart failure group（ n=42）and a non-heart failure group（ n=78）according to the guidelines. The differences in general clinical data，laboratory parameters，and echocardiographic parameters between the two groups were compared. The diagnostic efficacies of PTT，normalized PTT（nPTT），and N-terminal pro-B-type natriuretic peptide（NT-proBNP）were analyzed. Consistency between them and New York Heart Association（NYHA）heart function classification was tested. Results:Compared to the non-heart failure group，the NT-proBNP，PTT，and nPTT values in the heart failure group were significantly increased（all P<0.05）. The area under the curve（AUC）of nPTT was 0.944，better than that of PTT and NT-proBNP（AUC=0.871，0.887）. After K-means clustering reclassified patients into four levels based on nPTT values，nPTT classification showed moderate consistency with NYHA classification（Kappa=0.580， P<0.001），and nPTT differed significantly across NYHA classifications（ P<0.05）. Conclusions:PTT，as an echocardiographic index for assessing cardiac function，has similar diagnostic efficacy to NT-proBNP，the nPTT is even better. It shows moderate consistency with the NYHA classification and holds potential for differentiating overlapping NYHA grades. Importantly，it offers a fresh objective way to evaluate cardiac dysfunction after PCI in STEMI patients.

Objective To evaluate the effectiveness of virtual reality technology in breast cancer chemotherapy patients.Methods Databases were searched for randomized controlled trials literature on the effects of virtual reality technology on interventions for breast cancer chemotherapy patients.The time frame of the search was from construction of the database to February 2024.After screening the relevant literature by two researchers based on predetermined inclusion and exclusion criteria,information and methodological quality assessment were extracted.Eight literature articles were included in this study.Data analysis was performed using Revman 5.4 software,and data that could not be merged were analyzed descriptively.Results Meta-analysis showed that virtual reality technology significantly improved anxiety,depression,cancer-caused fatigue,cognitive function and quality of life of breast cancer chemotherapy patients.Conclusion Virtual reality technology as a non-pharmacological intervention can effectively improve anxiety,depression,cancer-caused fatigue,cognitive function,and quality of life of breast cancer chemotherapy patients.

Objective:To explore the current therapeutic status of rhythm control versus rate control in elderly patients with atrial fibrillation(AF)and the related factors that may influence treatment decisions.Methods:A retrospective study was conducted on AF patients aged ≥75 years old who were hospitalized in the Healthcare Department of Beijing Hospital from January 2010 to May 2020.The patients were grouped and compared according to whether they underwent rhythm control or rate control.Multivariate logistic regression analysis was used to investigate the factors that may influence the treatment decision of rhythm control or rate control.Results:A total of 167 patients was included, with a median age of 90 years old.Among them, 21 patients(12.6%)received rhythm control, and 109 patients(65.3%)received rate control.Compared with the group not receiving rhythm control, the rhythm control group had a younger age, higher BMI, higher diastolic blood pressure, a higher proportion of multiple medication use, a lower proportion of chronic kidney disease stage 3 or above, and higher hemoglobin levels(all P<0.05). Compared with the group not receiving rate control, the rate control group had a lower proportion of paroxysmal AF, a faster resting ventricular rate, a higher proportion of smoking history, a higher proportion of multiple medication use, coronary heart disease, pacemaker treatment, chronic obstructive pulmonary disease and/or asthma, and a lower proportion of cognitive impairment(all P<0.05). Multivariate logistic regression analysis revealed that multiple drug use( OR=11.578, 95% CI: 1.341-99.993, P=0.026)was positively associated with rhythm control therapy, while chronic kidney disease stage 3 or above( OR=0.248, 95% CI: 0.063-0.968, P=0.045)was negatively associated with rhythm control therapy.For rate control therapy, multiple drug use( OR=5.056, 95% CI: 2.253-11.347, P<0.001), resting ventricular rate( OR =1.033, 95% CI: 1.005-1.062, P=0.021), and chronic obstructive pulmonary disease(COPD)and/or asthma( OR=2.739, 95% CI: 1.124-6.672, P=0.027)showed positive associations. Conclusions:The application rate of rhythm control therapy is low in elderly AF patients, and ventricular rate control is the main treatment.Complex clinical conditions are the main constraints, and it is urgent to optimize individualized strategies based on prospective studies and develop new treatment techniques to improve clinical practice.

Objective:To observe any therapeutic effect of repeated high-frequency transcranial magnetic stimulation (rTMS) on patients with medication overuse headache (MOH).Methods:Fifty-seven persons with MOH were divided at random into a control group of 29 cases and an rTMS group of 28 cases. Both groups of patients stopped taking analgesics and were treated with topiramate and trazodone. The rTMS group received an additional 20 minutes of rTMS treatment daily, 5 days a week for 8 consecutive weeks. The control group received sham stimulation. Before and after the treatment, both groups′ headache symptoms, disability, depression, anxiety, cognition and sleep quality were evaluated using a visual analog scale (VAS) for pain, a migraine disability assessment scale (MIDAS), the Montreal cognitive assessment (MoCA), the Hamilton depression scale (HAMD), the Hamilton anxiety scale (HAMA) and the Pittsburgh sleep quality index (PSQI). Auditory event-related potential P300 was also measured for both groups.Results:After the treatment, the average VAS, MIDAS, HAMD, HAMA and PSQI scores of both groups had decreased significantly. The HAMD, HAMA and PSQI average scores of the rTMS group were then significantly better than the control group′s averages. The average MoCA score of the rTMS group had also improved significantly. The average latency of the auditory event-related potential P300 in the rTMS group was then (368.25±9.25)ms and its amplitude was (6.62±1.40)μV, showing significant improvement compared to before the treatment and compared with the control group.Conclusions:On the basis of oral administration of topiramate and trazodone, additional high-frequency rTMS treatment can significantly alleviate anxiety and depression in MOH patients, and improve their sleep quality and the latency and amplitude of event-related potential P300.

Objective:To verify the validity of the atopic dermatitis control tool (ADCT) in assessing disease control in patients with atopic dermatitis (AD) .Methods:Based on a cross - sectional study, demographic data, comorbidities and information on disease assessment - related scales such as the ADCT, the pruritus numerical rating scale (NRS), the patient-oriented eczema measure (POEM), and the dermatological life quality index (DLQI) were collected from patients with AD at Tianjin Medical University General Hospital from June 2021 to March 2023. The reliability and validity of the ADCT were assessed using these data. The discrimination power of the ADCT total score was evaluated by comparing the differences in the mean ADCT total scores among adjacent POEM/DLQI subgroups based on POEM/DLQI response classifications (POEM: clear or almost absent, mild, moderate, severe, very severe; DLQI: no effect, mild effect, moderate effect, serious effect, very serious effect). According to the ADCT scores, the AD patients were divided into an uncontrolled AD group (ADCT scores ≥ 7 points) and a controlled AD group (ADCT scores < 7 points). Differences between the above two groups were analyzed in terms of ADCT item scores, mean pruritus NRS scores, POEM total scores, DLQI total scores, and DLQI dimension scores to evaluate the validity of the ADCT in assessing AD disease control.Results:A total of 338 patients with AD were included, comprising 170 (50.30%) males and 168 (49.70%) females, and they were aged 17 to 89 (41.36 ± 17.63) years. Reliability analysis showed that the Cronbach′s α coefficient and split-half reliability coefficient of the ADCT were 0.886 and 0.878 respectively (both > 0.70), and the test- retest reliability coefficient was 0.977 (> 0.70, P < 0.001). Content validity analysis showed that the Pearson correlation coefficients between the ADCT item scores and the ADCT total score ranged from 0.753 to 0.852 (all P < 0.001) ; confirmatory factor analysis revealed that the Chi-square to degree of freedom ratio ( χ2/df) was 2.896 (< 5), the Tucker-Lewis index was 0.976 (> 0.9), the comparative fit index was 0.991 (> 0.9), the standardized root mean square residual was 0.026 (< 0.08), and the root-mean-square error of approximation was 0.075 (< 0.08) ; convergent validity analysis showed that the standardized factor loadings of all observed variables ranged from 0.689 to 0.905 (all > 0.500), combined reliability coefficient was 0.896 (> 0.700), and the average extracted variance value was 0.591 (> 0.500) ; criterion validity analysis showed that the correlation coefficients of the ADCT total score with other patient - reported outcome measures (the mean pruritus NRS scores, peak pruritus NRS scores, POEM total scores, and DLQI total scores) and DLQI dimension scores ranged from 0.649 to 0.730 and from 0.303 to 0.647, respectively (all P < 0.001). Analysis of the discrimination power of the ADCT total score showed significant differences in the mean ADCT total scores among adjacent POEM/DLQI subgroups (all P ≤ 0.001). The uncontrolled AD group (287 cases) showed significantly increased ADCT item scores, mean pruritus NRS score, POEM total score, DLQI total score, and DLQI dimension scores compared with the controlled AD group (51 cases, all P<0.001) . Conclusion:The ADCT exhibited good reliability, validity and discriminability based on the cross-sectional study, and can efficiently and reliably assess disease control in AD patients.