Objective:To explore the application effect of integrated root cause analysis (RCA) in the analysis of approximate administration error events, and to provide reference for the management of clinical approximate administration error events.Methods:A non-synchronous pre-and post-control study was conducted. The data of 3 cases of approximate error events of drug administration in the Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University from January to September 2021 were retrospectively analyzed. The integrated RCA was used to find out the proximal causes, and the system diagram and problem tree analysis were used to determine the root causes. The improvement measures were formulated through barrier analysis, including improving the safety barrier of hospital information system (HIS), updating the database of drug instructions in the Department of Cardiology, standardizing the barrier of nurses′ treatment and examination of medical orders, and visual management barrier. The integrated RCA improvement measures were applied to the management of approximate error events of drug administration. The improvement effect was evaluated by comparing the number of adverse events of medication errors before improvement (January to September 2021) and after improvement (September 2023 to May 2024), the error rate of HIS drug orders, the number of drug interceptions in pharmacies, the processing time of doctors′ HIS orders, and the qualified rate of medical staff 's drug knowledge assessment.Results:There were 32 medical staff in the department of cardiology before improvement, including 6 males and 26 females, aged (31.03 ± 4.29) years old. After improvement, 30 medical staff, 6 males and 24 females, aged (31.20 ± 4.37) years old. After the implementation of integrated RCA improvement, the number of adverse events of medication errors decreased from 3 cases before improvement to 0 cases after improvement. The error rate of HIS drug orders decreased from 11.83%(11/93) before improvement to 2.74%(2/73) after improvement. Improve the pre-audit system without pharmacy drug delivery interception function, improve the pre-application drug information 6 990, the number of drug interception was 0; after improvement, 7 782 pieces of drug information were claimed, and the number of drug interceptions was 78. The difference before and after improvement was statistically significant ( χ2=68.54, P<0.05). After the improvement, the doctor′s HIS doctor′s order processing time including admission, discharge, preoperative, postoperative, examination and medication, and temporary doctor′s order processing time were (1.14 ± 0.41), (1.37 ± 0.30), (0.43 ± 0.11), (0.51 ± 0.11), (0.40 ± 0.10) and (0.51 ± 0.14) min, respectively. They were lower than (4.07 ± 0.70), (3.69 ± 0.60), (1.44 ± 0.24), (2.10 ± 0.45), (1.41 ± 0.28) and (1.44 ± 0.29) min before improvement, and the differences were statistically significant ( t values were 15.21-21.42, all P<0.05). The qualified rate of drug knowledge examination of medical staff increased from 81.25%(26/32) before improvement to 100.00%(30/30) after improvement, and the difference was statistically significant ( P<0.05). Conclusions:The application of integrated RCA to analyze the approximate error events of drug administration is helpful to identify the system defects in the workflow of electronic medical order administration more comprehensively, improve work efficiency and ensure the quality and safety of medical care.

Purpose To investigate the expression of POLR2M in colorectal cancer(CRC)and its effects on cell growth,apoptosis and invasion.Methods GEPIA2.0,TCGA and Kaplan-Meier Plotter databases were used to ana-lyze the differential expression of POLR2M in CRC tissues and normal adjacent tissues,and to evaluate its prognostic significance using the Log-rank test.Quantitative real-time PCR(qRT-PCR)was used to detect the expression of POLR2M in human colorectal cancer cell lines SW480,HCT-8,RKO,LOVO,DLD-1,HCT-116,SW620 and human normal colorectal cell line FHC.DLD-1 and RKO cells were stably transfected with lentivirus,and the POLR2M groups were up-regulated into the control group(LV-NC)and experimental group(LV-POLR2M),and the transient transfec-tion of SW620 and SW480 cells with interfering fragments of SiRNA was used to down-regulate the POLR2M groups into the control group(Si-NC)and experimental group(Si-POLR2M),and the transfection efficiency of each group was verified.CCK-8,plate cloning,Transwell and scratch healing assays were used to detect cell proliferation,invasion and migration.Flow cytometry was used to detect the effects of POLR2M on cell cycle and apoptosis.Results GE-PIA2.0,TCGA and Kaplan-Meier Plotter database analysis showed that the expression of POLR2M in colorectal cancer was significantly higher than in normal adjacent tissues(P＜0.05),and the expression of POLR2M was closely associ-ated with the histological type of colorectal cancer and lymph node metastasis(P＜0.05),but not with the age,gen-der,tumor grade and vascular invasion of patients(P＞0.05).The prognosis of patients with POLR2M overexpression was poor(P＜0.05).The results of qRT-PCR showed that compared with FHC cells,the mRNA expression of POLR2M in SW480,HCT-8,RKO,LOVO,DLD-1,HCT-116 and SW620 cell lines was increased(F=97.7,P＜0.05),and POLR2M stable overexpression and interference cell lines were successfully constructed.Compared with the LV-NC group,the viability,colony number,number of cells passing through the chamber and cell mobility of DLD-1 and RKO cells in the LV-POLR2M group were significantly increased(P＜0.05).Compared with the Si-NC group,the viability,colony number,number of cells passing through the chamber,and cell mobility of SW620 and SW480 cells in the Si-POLR2M group were significantly decreased(P＜0.05).Downregulation of POLR2M induced cell cycle arrest in G1 phase and promotes apoptosis(P＜0.05).Conclusion POLR2M may play a role as a pro-tumor gene in CRC,and its high expression can significantly promote the proliferation and invasion of CRC cells.

OBJECTIVE: To identify the underlying molecular mechanism of Modified Hu-Lu-Ba-Wan (MHW) in alleviating renal lesions in mice with diabetic kidney disease (DKD). METHODS: The db/db mice were divided into model group and MHW group according to a random number table, while db/m mice were settled as the control group (n=8 per group). The control and model groups were gavaged daily with distilled water [10 mL/(kg·d)], and the MHW group was treated with MHW [17.8 g/(kg·d)] for 6 weeks. After MHW administration for 6 weeks, indicators associated with glucolipid metabolism and urinary albumin were tested. Podocytes were observed by transmission electron microscopy. Kidney transcriptomics was performed after confirming therapeutic effects of MHW on DKD mice. The relevant target of MHW' effect in DKD was further determined by enzyme-linked immunosorbent assay, Western blot analysis, immunohistochemistry, and immunofluorescence staining. RESULTS: Compared with the model group, MHW improved glucose and lipid metabolism (P<0.05), and reduced lipid deposition in the kidney. Meanwhile, MHW reduced the excretion of urinary albumin (P<0.05) and ameliorated renal damage. Transcriptomic analysis revealed that the inflammation response, particularly the interleukin-17 (IL-17) signaling pathway, may be responsible for the effect of MHW on DKD. Furtherly, our results found that MHW inhibited IL-17A and alleviated early fibrosis in the diabetic kidney. CONCLUSION MHW ameliorated renal damage in DKD via inhibiting IL-17A, suggesting a potential strategy for DKD therapy.
Animals ; Diabetic Nephropathies/genetics* ; Interleukin-17/antagonists & inhibitors* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Kidney/ultrastructure* ; Podocytes/metabolism* ; Mice ; Albuminuria ; Lipid Metabolism/drug effects* ; Mice, Inbred C57BL

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Processing for deodorization is widely used in the production of animal-derived Chinese medicinal materials. In this study, Heracles Neo ultra-fast gas-phase electronic nose combined with chemometrics was employed to analyze the overall odor difference of Cervi Cornu Pantotrichum(focusing on that derived from Cervus nippon Temminck in this study) before and after processing. The results showed that the electronic nose effectively distinguished between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. HS-GC-MS was used to identify and quantify the volatile components in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum, and 35 and 37 volatile components were detected in the medicinal materials and decoction pieces, respectively. The medicinal materials and decoction pieces contained 28 common volatile components contributing to the odor of Cervi Cornu Pantotrichum. The odor activity value(OAV) of each volatile component was calculated based on the olfactory threshold and relative content. The results showed that there were 17 key odor substances such as isovaleraldehyde, 2-methylbutanal, isobutyraldehyde, hexanal, and methanethiol in the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. All of them had bad odor and were the main source of the odor of Cervi Cornu Pantotrichum. The results of principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) showed that there were significant differences in volatile components between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. Based on the thresholds of P<0.05 and Variable Importance in Projection(VIP)>1, 21 differential volatile odor components were screened out. Among them, isopentanol, isovaleraldehyde, 2-methylbutanal, n-nonanal, and dimethylamine were the key differential odor compounds between the medicinal materials and decoction pieces of Cervi Cornu Pantotrichum. The odor compounds and their relative content reduced, and some flavor substances such as esters were produced after processing with wine, which was the main reason for the reduction of the odor after processing of Cervi Cornu Pantotrichum.
Odorants/analysis* ; Electronic Nose ; Gas Chromatography-Mass Spectrometry/methods* ; Animals ; Volatile Organic Compounds/analysis* ; Deer ; Drugs, Chinese Herbal/chemistry*

To clarify the species, pathogenicity, and distribution of the pathogens causing the root rot of Atractylodes lancea in Hubei province, the tissue separation method was used to isolate the pathogens from root rot samples in the main planting areas of A. lancea in Hubei. Based on the preliminary identification of the Fusarium genus by the internal transcribed spacer(ITS) sequence, three housekeeping genes, EF1/EF2, Btu-F-FO1/Btu-F-RO1, and FF1/FR1, were amplified and sequenced. Subsequently, a phylogenetic tree was constructed based on these TEF gene sequences to classify the pathogens. The pathogenicity of these strains was determined using the root irrigation method. A total of 194 pathogen strains were isolated using the tissue separation method. Molecular identification using the three housekeeping genes identified the pathogens as F. solani, F. oxysporum, F. commune, F. equiseti, F. tricinctum, F. redolens, F. fujikuroi, F. avenaceum, F. acuminatum, and F. incarnatum. Among them, F. solani and F. oxysporum were the dominant strains, widely distributed in multiple regions, with F. solani accounting for approximately 54% of the total isolated strains and F. oxysporum accounting for approximately 34%. Other strains accounted for a relatively small proportion, totaling approximately 12%. The results of pathogenicity determination showed that there were certain differences in pathogenicity among strains. The analysis of the pathogenicity differentiation of the widely distributed F. solani and F. oxysporum strains revealed that these dominant strains in Hubei were mainly highly pathogenic. This study determined the species, pathogenicity, and distribution of the pathogens causing the root rot of A. lancea in Hubei province. The results provide a scientific basis for further understanding the root rot of A. lancea and its epidemic occurrence and scientifically preventing and controlling this disease.
Plant Diseases/microbiology* ; Atractylodes/microbiology* ; Phylogeny ; Plant Roots/microbiology* ; Fusarium/classification* ; China ; Virulence ; Fungal Proteins/genetics*