Myocardial fibrosis （MF）， characterized by decreased cardiac function and myocardial compliance， is a pathological process and a progression factor in various cardiovascular diseases. The nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） inflammasome is closely related to the development of MF. Recent studies have shown that traditional Chinese medicine （TCM） can regulate the NLRP3 inflammasome to alleviate MF. Based on this， this article systematically summarizes the research progress on the mechanisms by which TCM regulates the NLRP3 inflammasome to improve MF. It is found that active ingredients of TCM， such as alkaloids （lycorine，vincristine，bufalin）， saponins （astragaloside Ⅳ， diosgenin，ginsenoside Rg3）， terpenoids （celastrol，oridonin）， and phenols （polydatin，curcumin，phloridzin） as well as TCM formulas （Zhachong shisanwei pills，Zhilong huoxue tongyu capsules， Luqi formula） can inhibit the activation of the NLRP3 inflammasome， thereby suppressing the release of inflammatory factors such as interleukin-1β and IL-18， reducing inflammatory damage to myocardial tissue， alleviating excessive deposition of the extracellular matrix， and thus exerting the effect of improving MF.

Multiple system atrophy (MSA) is a rare neurodegenerative disease with complex clinical manifestations, presenting substantial challenges in clinical diagnosis and treatment. Its symptoms and the eight extraordinary meridians are potentially correlated; therefore, this article explores the association between MSA symptom clusters and the eight extraordinary meridians based on their circulation and physiological functions, as well as their treatment strategies. The progression from deficiency to damage in the eight extraordinary meridians aligns with the core pathogenesis of MSA, which is characterized by "the continuous accumulation of impacts from the vital qi deficiency leading to eventual damage". Liver and kidney deficiency and the emptiness of the eight extraordinary meridians are required for the onset of MSA; the stagnation of qi deficiency and the gradual damage to the eight extraordinary meridians are the key stages in the prolonged progression of MSA. The disease often begins with the involvement of the yin and yang qiao mai, governor vessel, thoroughfare vessel, and conception vessel before progressing to multiple meridian involvements, ultimately affecting all eight extraordinary meridians simultaneously. The treatment approach emphasizes that "the direct method may be used for joining battle, but indirect method will be needed in order to secure victory" and focuses on "eliminate pathogenic factors and reinforce healthy qi". Distinguishing the extraordinary meridians and focusing on the primary symptoms are pivotal to improving efficacy. Clinical treatment is aimed at the target, and tailored treatment based on careful clinical observation ensures precision in targeting the disease using the eight extraordinary meridians as the framework and core symptoms as the specific focus. Additionally, combining acupuncture, daoyin therapy, and other method may help prolong survival. This article classifies clinical manifestations based on the theory of the eight extraordinary meridians and explores treatment.

Objective To investigate the effect of diosgenin on the proliferation and apoptosis of breast cancer cells and its potential molecular mechanism. Methods The breast cancer cell line MCF-7 was treated with low, medium, and high doses of diosgenin, and cell proliferation was detected through the MMT method. Flow cytometry was used to detect cell apoptosis. Nuclear-cytoplasmic-protein separation method was applied to detect the subcellular localization of death associated protein (DAXX). qRT-PCR and Western blot were used to detect the expressions of DAXX and c-Jun N-terminal kinase pathway (JNK)-related proteins. Results Diosgenin considerably inhibited the proliferation of MCF-7 cells and promoted cell apoptosis in a concentration-dependent manner. Diosgenin can promote the movement of DAXX from nucleus into the cytoplasm. Diosgenin upregulated the expression of cell surface death receptor (Fas), increased the phosphorylation levels of JNK and mitogen activated protein kinase (p38), and activated the JNK/p38 signaling pathway with concentration dependence. Conclusion Diosgenin inhibits the proliferation and promotes the apoptosis of the breast cancer cell line MCF-7, whose mechanism may be related to the regulation of DAXX subcellular localization and the activation of JNK/p38 signaling pathway.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

OBJECTIVE To improve the efficiency and quality of dispensed oral drug management in the inpatient pharmacy， and ensure the safety of drug use in patients. METHODS SWOT （strength， weakness， opportunity， threat） analysis method was used to analyze the internal strengths and weaknesses， as well as the external opportunities and threats in the construction of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy of our hospital， and propose improvement strategies. RESULTS & CONCLUSIONS A refined， full-process， closed-loop traceability management system for dispensed oral drugs in the inpatient pharmacies was successfully established， which is traceable in origin， trackable in destination， and accountable in responsibility. After the application of this system， the registration rate of dispensed drug information and the correctness rate of registration content both reached 100%. The proportion of overdue drug varieties in the same period of 2024 decreased by 77.78% compared to March 2020， the inventory volume decreased by 29.50% compared to the first quarter of 2020， the per-bed medication volume decreased by 32.14% compared to the first quarter of 2020； the average workload per post in the same period of 2023 increased by 49.09% compared to 2019， the dispensing accuracy rate reached 100%， and the improvement rate of quality control problem increased by 25.25% compared to 2021. This system effectively improves the safety and accuracy of dispensed oral drug management in the inpatient pharmacy.

Objective: To investigate the urban and rural differences in adverse outcomes of pulmonary tuberculosis (PTB) in patients with pulmonary tuberculosis-diabetes mellitus comorbidity (PTB-DM), so as to provide insights into improving the prevention and treatment measures for PTB-DM. Methods: Patients with PTB-DM who were admitted and discharged from 14 designated tuberculosis hospitals in Hangzhou City from 2018 to 2022 were selected. Basic information, and history of diagnosis and treatment were collected through hospital information systems. The adverse outcomes of PTB were defined as endpoints, and the proportions of adverse outcomes of PTB in urban and rural patients with PTB-DM were analyzed. Factors affecting the adverse outcomes of PTB were identified using a multivariable Cox proportional hazards regression model. Results: A total of 823 patients with PTB-DM were enrolled, including 354 (43.01%) urban and 469 (56.99%) rural patients. There were 112 (13.61%) patients with adverse outcomes of PTB. The proportions of adverse outcomes of PTB in urban and rural patients were 14.41% and 13.01%, respectively, with no statistically significant difference (P>0.05). Multivariable Cox proportional hazards regression analysis identified first diagnosed in county-level hospitals or above (HR=2.107, 95%CI: 1.181-3.758) and drug resistance (HR=3.303, 95%CI: 1.653-6.600) as the risk factors for adverse outcomes of PTB in urban patients with PTB-DM, while the treatment/observed management throughout the process (HR=0.470, 95%CI: 0.274-0.803) and fixed-dose combinations throughout the process (HR=0.331, 95%CI: 0.151-0.729) as the protective factors for adverse outcomes in rural patients with PTB-DM. Conclusions There are differences in influencing factors for adverse outcomes of PTB in urban and rural patients with PTB-DM. The adverse outcomes of PTB are associated with first diagnosed hospitals and drug resistance in urban patients, and are associated with the treatment/observed management and fixed-dose combinations throughout the process in rural patients.

ObjectiveIn order to provide a reference for the optimization of preparation process of stir-fried Glycyrrhizae Radix et Rhizoma（sf-GRR）， the quality changes during the processing was studied. MethodsGlycyrrhizae Radix et Rhizoma was processed by stir-frying for 17 min， and samples were collected every 1 min during the processing. The appearance color of the samples was determined by visual analysis technology， the moisture and extract of the process samples were detected by the drying method and the hot extraction method of alcohol-soluble extract in the general rules of the 2020 edition of Chinese Pharmacopoeia（part Ⅳ）， and the contents of liquiritin apioside， liquiritin， isoliquiritin apioside， isoliquiritin， licoricesaponin G₂ and glycyrrhizic acid in the process samples were determined by high performance liquid chromatography（HPLC）. Then principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and Spearman correlation analysis were used for clustering， discrimination and correlation analysis of the appearance color， moisture， extract and the contents of six internal components. Based on artificial neural network and random forest algorithm， the prediction model of processing degree of sf-GRR was established. On this basis， based on the five principles of quality marker（Q-Maker）， explore the monitoring Q-Maker of sf-GRR. ResultsThe color of Glycyrrhizae Radix et Rhizoma deepened after stir-frying， and the appearance color of the sample changed from light yellow to dark yellow during processing. During the stir-frying process， the moisture content showed a decreasing trend with the extension of processing time， while the extract content showed an increasing trend with the extension of processing time. After stir-frying， the contents of liquiritin apioside， liquiritin and licoricesaponin G₂ showed an overall decreasing trend， while the contents of isoliquiritin apioside and isoliquiritin increased， and the content of glycyrrhizic acid increased slightly. The correlation analysis showed that moisture was positively correlated with brightness（L^*） and red/green value（a^*）， and negatively correlated with yellow/blue value（b^*） and total color difference（E^*ab）. Isoliquiritin apioside and isoliquiritin had negative correlation with L^* and a^*， and positive correlation with b^* and E^*ab. The processing process of sf-GRR could be divided into two stages of the early stage（0-14 min） and the late stage（15-17 min）， and could be divided into three stages of the early stage（0-6 min）， the middle stage（7-14 min） and the late stage（15-17 min） by combining the moisture， extract， the contents of 6 components and color values. Based on artificial neural network analysis and random forest algorithm， isoliquiritin apioside， isoliquiritin， liquiritin and glycyrrhizic acid were selected as monitoring markers for sf-GRR. ConclusionBased on the analysis of the exterior-interior indicators of process samples of sf-GRR， this paper ultimately identifies four processing monitoring markers， which can provide a basis for optimizing the processing technology of sf-GRR.

OBJECTIVE To provide reference for improving the pre-prescription review system and reducing the occurrence of medication error by analyzing the drug-related problems （DRPs） in the pre-prescription review orders of pediatric outpatient clinics using the Pharmaceutical Care Network Europe （PCNE） classification system. METHODS The data of pre-prescription review orders were retrospectively collected from outpatient department of Shanghai Children’s Medical Center， Shanghai Jiao Tong University School of Medicine from July 2022 to June 2023； DRPs in the pre-prescription review orders were classified and summarized by using the PCNE classification system （version 9.1）， and then analyzed in terms of types and causes of issues， and the acceptance of interventions. RESULTS A total of 66 017 DRPs orders were included， involving 41 165 patients. The proportion of DRPs orders in children aged ≤5 years old was the highest （58.25%）， followed by children aged 6-12 years old （33.52%）； the department with the highest proportion of DRPs was internal medicine of pediatrics department （71.41%）； the department with the highest incidence of DRPs was thoracic surgery department （9.73%）； top three drug categories of DRPs orders were systemic anti- infective drugs （25.26%）， Chinese patent medicines （24.74%） and respiratory drugs （22.38%）. Referring to PCNE classification system， the types of DRPs mainly focused on treatment safety （64.86%）； the reasons of DRPs orders mainly focused on dose selection （82.09%）， of which 41.26% were due to excessive drug dosage； 92.13% of interventions could be accepted and fully executed by doctors. CONCLUSIONS DRPs orders identified by the pre-prescription review system can be effectively analyzed by using PCNE classification system. Pharmacists should focus on medication use in children aged ≤5 years old， update and develop personalized prescription review rules timely， and meet the rational needs of clinical medication for children.