OBJECTIVE To establish a whole-process quality management index system for traditional Chinese medicine （TCM） reserved in the department of medical institutions， providing a reference for standardized management. METHODS An initial indicator framework was determined by collecting and analyzing relevant laws， regulations， policy documents， group standards， and literature on TCM management. Two rounds of Delphi expert consultation involving 20 experts were conducted to refine and optimize the indicator system. The analytic hierarchy process was used to construct judgment matrices and convert the indicator weights into a percentage-based system； an assessment was conducted on 14 departments with reserved TCM among the affiliated units of the Quality Management and Control Center for Traditional Chinese Medicine in Hebei Province. RESULTS The response rate for both rounds of consultation was 100%， with an expert authority coefficient of 0.89. The final quality management system of TCM reserved in the department included four first-level indicators： management （composite weight： 0.366 3）， processing （composite weight： 0.119 7）， storage （composite weight： 0.291 7） and usage （composite weight： 0.222 3）， and twenty-four second-level indicators， such as establishing an organizational structure for hospital drug quality management and having dedicated regulations for backup drugs in clinical departments. Kendall’s coefficient of concordance confirmed consistency across all levels of indicators. Based on the application of the indicator system for evaluation， the average score for the standardized management of reserved TCM in the department of medical institutions increased from 67.01 points to 85.15 points over three months. CONCLUSIONS The constructed indicator system meets the standardized management requirements for reserved TCM， enabling closed-loop management across the entire process of management， processing， storage and usage. It provides a reference for medical institutions to enhance the precision and standardization of reserved TCM management.

ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer（PEG-PLGA） nanoparticles（FA-Cre@PEG-PLGA NPs， hereinafter referred to as NPs） combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming（KM） mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells， then mice were randomly divided into model group， placebo group， hydroxycamptothecin group（8 mg∙kg^-1）， low， medium and high dose crebanine raw material groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose crebanine groups， respectively）， low， medium and high dose NPs groups（2， 2.5， 3 mg∙kg^-1）， and low， medium and high dose NPs combined with ultrasonic irradiation groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose combination groups， respectively）. The corresponding doses of drugs were administered via tail vein injection， the model group received no treatment， while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored， and parameters such as body mass change rate， thymus index， spleen index， tumor volume， tumor weight， relative tumor growth rate（T/C）， and tumor inhibition rate（TGI） were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin（HE） staining. Additionally， the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， blood urea nitrogen（BUN） and creatinine（CREA） in serum of mice were detected by biochemical method. Furthermore， the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods， the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group， the body mass growth rates of mice in the medium and high combination groups decreased， while the thymus index and spleen index increased， but there was no statistically significant difference in serum AST， ALT， BUN and CREA levels， indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body， oth groups had TGI>40% and T/C<60%， indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups， the combination groups exhibited varying degrees of necrosis in tumor cells， accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group， the high dose combination group had stronger tumor targeting ability（P<0.01）. ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site， inhibit the subcutaneous tumor growth of mouse liver cancer， but also decrease damage to liver and kidney tissues.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

OBJECTIVE To provide references for further improving the management level of Chinese herbal pieces covered by the healthcare security drug catalog （hereinafter referred to as “healthcare security covered Chinese herbal pieces”）. METHODS Policy documents related to healthcare security covered Chinese herbal pieces were retrieved from official websites of National Healthcare Security Administration and medical insurance bureaus of various provinces （autonomous regions， municipalities directly under the central government）. Using text analysis， the current management status of healthcare security covered Chinese herbal pieces in various provinces was analyzed from two dimensions： management regulations and catalog formats. RESULTS In terms of the management regulations for healthcare security covered Chinese herbal pieces， some provinces implemented both national and provincial standards for Chinese herbal pieces， while a small number of provinces adopted national standards alongside their own provincial standards. Regarding the payment categories of healthcare security covered Chinese herbal pieces， most were classified as category A， though some provinces managed them as category B， and others included both categories A and B or category C. In terms of applicants， there were three kinds： only medical institutions， only herbal piece enterprises， or both medical institutions and herbal piece enterprises being allowed to apply. During the application process， some provinces required preliminary evaluations by local healthcare security departments with recommended lists submitted， while some provinces omitted preliminary evaluations and relied solely on unified evaluation by provincial healthcare security departments. Regarding the methods for catalog formulation and adjustment， there was little variation among the provinces. In terms of the catalog format for healthcare security covered Chinese herbal pieces， some provinces had supplemented the catalog fields based on the national medical insurance catalog. In contrast， some provinces had relatively simple catalogs. Regarding the sorting of the herbal pieces catalog， some catalogs were arranged by the number of Chinese character strokes in the names of the herbal pieces， but most catalogs lacked clear sorting rules. CONCLUSIONS Significant resultshave been achieved in formulating management measures and the catalog of healthcare security covered Chinese herbal pieces. However， there is still a great necessity to develop targeted and adaptable management clauses based on local conditions and the characteristics of Chinese herbal pieces. The content and format of healthcare security drug catalog of Chinese herbal pieces should be improved； in addition， continuous tracking of the latest management policies is also essential to improve the accuracy and operability of formulated catalog.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Objective To investigate the impact of Qizhi Jiangtang Capsule (QZJT) on renal damage in diabetic nephropathy (DN) mice via NOD like receptors family pyrin domain containing 3/caspase-1/ Gasdermin D (NLRP3/caspase-1/GSDMD) signaling pathway. Methods Mice were randomly allocated into six experimental groups: a normal control group (NC), a diabetic nephropathy model group (DN), a low-dose QZJT treatment group (L-QZJT), a high-dose QZJT treatment group (H-QZJT), a positive control group administered Shenqi Jiangtang Granules (SQJT), and an ML385 group (treated with an inhibitor of nuclear factor erythroid 2-related factor 2, Nrf2). Upon successful model induction, therapeutic interventions were commenced. Renal function impairment in the mice was evaluated through quantification of fasting blood glucose (FBG), 24-hour urinary albumin (UAlb), serum creatinine (SCr), blood urea nitrogen (BUN), and the kidney-to-body mass ratio (K/B). Renal tissue pathology was evaluated using HE and PAS staining. Serum levels of inflammatory cytokines IL-1β and IL-18 were quantified by ELISA. Levels of podocyte markers and proteins involved in relevant pathways were assessed using Western blot analysis. Results Compared with the NC group, FBG, 24 h UAlb, SCr, and BUN were increased in the DN group, and the K/B mass ratio was also increased. In contrast, compared with the DN group, FBG, 24 h UAlb, SCr, and BUN in both the low-dose (L-QZJT) and high-dose Quanzhou Jintang (H-QZJT) groups were decreased, and the K/B mass ratio was decreased as well. The therapeutic efficacy of H-QZJT was comparable to that of Shenqi Jiangtang Granules. QZJT ameliorated renal histopathological injury in DN mouse, increased the protein levels of Nephrin (a podocyte marker), and decreased the protein levels of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), pro-caspase-1, and GSDMD-N. After ML385 treatment, renal cells exhibited swelling and morphological changes, the inflammatory infiltrate area was enlarged, the protein levels of NLRP3, ASC, pro-caspase-1, and GSDMD-N were up-regulated, and the levels of IL-1β and IL-18 were increased. Conclusion QZJT may inhibit podocyte pyroptosis by acting on the Nrf2 to regulate the NLRP3/caspase-1/GSDMD pathway, thus improving renal damage in DN mouse.
Animals ; Diabetic Nephropathies/pathology* ; Podocytes/pathology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Pyroptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Caspase 1/genetics* ; Signal Transduction/drug effects* ; Mice ; Phosphate-Binding Proteins/genetics* ; Male ; Intracellular Signaling Peptides and Proteins/metabolism* ; Mice, Inbred C57BL ; Kidney/pathology* ; Gasdermins

OBJECTIVES: To analyze the differences in the prognosis of gastric signet ring cell carcinoma (SRCC) among different races using the US Surveillance Epidemiology and End Results (SEER) database and The Cancer Genome Atlas (TCGA) database. METHODS: We analyzed the data of patients with gastric SRCC from the SEER database from 2000 to 2020, and divided the patients into cohorts of whites, blacks, Asians or Pacific Islanders, American Indians/Alaska Natives according to their race. The prognosis and treatment of the cohorts were evaluated using baseline demographic analysis, Kamplan-Meier survival curve, and nomogram analysis. RESULTS: We analyzed the data of a total of 2058 patients, including 8.6% blacks, 72.4% whites, 16.6% Asians or Pacific Islanders, 1.0% American Indians/Alaska Natives, and 1.4% other races. The tumor grade varied among different races, and the prevalence and survival rates of patients differed significantly across races. The differences in the white cohort were the most prominent, and all the differences were statistically significant (P<0.05). Racial differences were also noted in patient management and prognosis. CONCLUSIONS There are racial differences in tumor grades and prognosis of gastric SRCC, and these differences provide evidence for optimizing clinical diagnosis and treatment strategies for this malignancy.
Aged ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Signet Ring Cell/therapy* ; Databases, Factual ; Prognosis ; Racial Groups ; SEER Program ; Stomach Neoplasms/therapy* ; Survival Rate ; United States/epidemiology* ; White ; Asian American Native Hawaiian and Pacific Islander ; American Indian or Alaska Native ; Black or African American

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: To investigate the prevalence of hyperactivity behavior in children aged 3-6 in Yunnan Province, to explore its relationship with neuropsychological development, so as to provide clues for early prevention and intervention of attention deficit hyperactivity disorder (ADHD) in children. Methods: A total of 1 321 children aged 3 to 6 from 10 kindergartens in 5 prefectures (cities) of Yunnan Province were selected by stratified random sampling method from October 2022 to May 2023. Teacher Rating Scale (TRS) was used to investigate childrens hyperactive behavior and coexistent behavior. A qualified evaluator applied the Developmental Scale for Children Aged 0-6 Years to assess the development of 5 ability areas of gross motor movement，fine movement，adaptive ability，language and social behavior. Statistical analysis was performed using Wilcoxon rank sum test and χ2 test. Binary Logistic regression was applied to analyze the score of their hyperactivity behavior and its relationship with other behavior problems and neuropsychological development. Results: The detection rate of hyperactivity behavior was 8.6% in children aged 3 to 6 years, 12.8% in boys and 4.1% in girls (χ2=31.53, P<0.01). The detection rate of hyperactivity in 3yearold children was 13.9%, which was higher than that in 4yearold (9.2%) and 5yearold children (7.0%) (χ2=8.73, P<0.05). The detection rate of inattentionpassivity of rural children (14.6%) was higher than that of urban children (5.9%) (χ2=22.23, P<0.01). Binary Logistic regression analysis showed that the higher the level of adaptive development, the lower the risk of hyperactivity (OR=0.58, 95%CI=0.39-0.86), the higher the risk of hyperactivity (OR=0.57, 95%CI=0.35-0.91), the higher the risk of conduct problems (OR=0.57, 95%CI=0.37-0.87), inattentionpassivity (OR=0.49, 95%CI=0.33-0.74) were also at lower risk (P<0.05). Children with higher levels of fine motor development had a lower risk of inattentionpassivity (OR=0.59, 95%CI=0.37-0.93, P<0.05). Conclusions Hyperactivity in boys and inattentionpassivity in rural children requires more attention. It is necessary to strengthen childrens early adaptive ability and fine motor training to prevent hyperactive behavior and inattention.