ObjectiveTo investigate the effects of Simiaowan on intestinal barrier function and adenosine triphosphate （ATP） binding cassette transporter G2 （ABCG2） expression in hyperuricemic （HUA） rats， and elucidate its therapeutic mechanisms. MethodsForty male Sprague Dawley （SD） rats were randomized into a normal group， a model group， low-dose （282.6 mg·kg^-1） and high-dose （565.2 mg·kg^-1） Simiaowan groups， and a Benzbromarone （4.7 mg·kg^-1） group. The HUA model was established via intraperitoneal injection of potassium oxonate （ip） combined with oral gavage of hypoxanthine （ig） for 14 days. Following modeling， treatments were administered for 14 days. Samples were collected and weighed 4 h after final dosing. Blood uric acid and hepatic function were analyzed. Histopathological changes were evaluated by hematoxylin-eosin （HE） staining， and Chiu's scoring was conducted. Enzyme-linked immunosorbent assay （ELISA） quantified tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， lipopolysaccharide （LPS）， diamine oxidase （DAO）， and D-lactic acid （D-LA） levels. Real-time polymerase chain reaction （Real-time PCR）， Western blot， and immunohistochemistry assessed the expression of Claudin-1， Occludin， occludens-1 （ZO-1）， and ABCG2 mRNAs and proteins. 16S rDNA amplicon sequencing characterized ileal microbiota. ResultsCompared with the normal group， the model group exhibited epithelial shedding in the ileal villus， structural disruption， infiltration of extensive inflammatory cells， and significantly elevated Chiu's scores （P<0.01）. The DAO， TNF-α， IL-6， IL-1β， LPS， and D-LA levels in the ileum were markedly increased （P<0.01）， while mRNA and protein expressions of Claudin 1， Occludin， ZO-1， and ABCG2， as well as positive staining area and proportion， were significantly reduced （P<0.01）. Compared with the model group， the Simiaowan groups at all doses showed improved epithelial damage in the ileal villus， significantly lowered Chiu's scores （P<0.01）， significantly reduced DAO， TNF-α， IL-6， IL-1β， LPS， and D-LA levels in the ileum （P<0.01）， and upregulated mRNA and protein expressions of Claudin 1， Occludin， ZO-1， and ABCG2， as well as positive staining area and proportion （P<0.01）. The 16S rDNA results showed that in the model group， the α-diversity index of the ileal microbiota was increased， and species diversity and richness were enhanced， with microbiota dysfunction observed. The community structure of the gut microbiota was significantly different from that of the normal microbiota. The abundance of probiotics was decreased， and the abundance of pathogenic bacteria was increased， with butyrate-producing bacteria showing a low abundance. In contrast， Simiaowan at all doses reduced species diversity and richness， regulated microbiota dysfunction， and promoted the shift of the structure of the gut microbiota community towards a normal one. This increased the abundance of beneficial bacteria， decreased the abundance of harmful bacteria， and restored the abundance of butyrate-producing bacteria. ConclusionSimiaowan enhances ileal uric acid excretion and further alleviates HUA by modulating the gut microbiota composition to improve the intestinal barrier and upregulate the expression of the urate transporter ABCG2 in HUA rats.

ObjectiveTo investigate the current situation of mutual recognition for ethical review outcomes in multicenter clinical research across 10 contracting medical institutions in Guangdong Province， analyze existing issues and propose improvement recommendations， thereby promoting the standardized management of mutual recognition for ethical review outcomes in medical institutions. MethodsData from 381 multicenter clinical studies conducted in these 10 medical institutions from January 24 to October 31， 2024， were collected. Text visualization was performed using Python and the WordCloud library， and statistical analyses were conducted with SPSS 25.0. ResultsOf the 381 studies investigated， industry-sponsored clinical trials （ISTs） accounted for 51.71%， while investigator-initiated clinical trials （IITs） constituted 48.29%. The proportions of ethical committees serving as primary reviewers and collaborative reviewers were 33.33% and 66.67%， respectively. The confirmation methods of mutual recognition outcomes were primarily expedited reviews （50.66%） and meeting reviews （49.34%）， and no cases of “direct confirmation” were found. The Chi-square test revealed statistically significant differences in review confirmation methods based on project type （χ²=14.851， P<0.001） and ethics committee role （χ²= 69.435， P<0.001）. The frequency distribution trend of the contingency table showed that IST projects and primary ethics committees preferred to employ meeting review （58.88% and 79.53% respectively， both higher than the average level of 49.34%）， while IIT projects and the collaborative ethics committees more frequently utilized expedited review （60.87% and 65.75% respectively， both higher than the average level of 50.66%）. ConclusionThe confirmation methods of mutual recognition for ethical review outcomes in multicenter clinical research are significantly associated with the role of the ethics committee and the type of project. It is recommended to improve management systems， enhance information construction and personnel training， as well as clarify mutual recognition responsibilities and strengthen supervision. This aims to ensure review quality while improving mutual recognition efficiency， thereby safeguarding the rights and interests of research participants.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

ObjectiveTo compare the differences in fungal community composition between lesional and non-lesional scalp areas in patients suffering from severe alopecia areata （AA）， and compare these with healthy scalp areas in control subjects. Additionally， to preliminarily explore the changes in scalp fungal communities in severe AA patients and their potential underlying immunological mechanisms. MethodsA total of 20 severe AA patients and 18 healthy controls were enrolled. Skin swab samples were collected from lesional and non-lesional scalp areas of severe AA patients， as well as from the normal scalp of healthy controls. The fungal internal transcribed spacer （ITS） region was amplified and analyzed using high-throughput sequencing. ResultsThe lesional scalp areas of severe AA patients exhibited higher α-diversity and species richness in fungal communities. Notably， the relative abundance of Ascomycota， along with genera such as Mycosphaerella， Aspergillus， Penicillium， and Wallemia， significantly increased in the bald regions. In contrast， Acremonium and Schizophyllum were more predominant in the non-lesional areas of severe AA patients. ConclusionDistinct region-specific differences in scalp fungal microbiota in severe AA patients suggests that fungal dysbiosis may play a potential role in the pathogenesis of alopecia areata. These findings provide new insights into the disease characteristics of severe AA from the perspective of scalp microecology.

OBJECTIVE To investigate the correlation of serum P-Tau protein and β-amyloid protein expression levels with obstructive sleep apnea syndrome(OSAS)and mild cognitive impairment(MCI)patients,and their diagnostic value.METHODS From December 2020 to December 2023,120 patients with OSAS admitted to Third Hospital of Shijiazhuang were collected as the case group.According to the diagnostic criteria for MCI,patients were grouped into OSAS without MCI group(40 cases)and OSAS with MCI group(80 cases).ELISA method was applied to detect the levels of serum P-Tau protein and β-amyloid protein.Spearman method was applied to analyze the correlation between serum P-Tau protein,β-amyloid protein,and MCI.Multivariate logistic regression was applied to analyze the influencing factors of OSAS patients with MCI.ROC curve was applied to evaluate the diagnostic efficacy of serum P-Tau protein and β-amyloid protein in OSAS patients with MCI.RESULTS The Montreal Cognitive Assessment(MoCA)score in the OSAS with MCI group was obviously lower than that in the OSAS without MCI group(P<0.05).The expression levels of P-Tau protein and β-amyloid protein in the OSAS with MCI group were obviously higher than those in the OSAS without MCI group(P<0.05).The expression levels of serum P-Tau protein and β-amyloid protein in OSAS patients were negatively correlated with MoCA score(r=-0.346,-0.565,P<0.001).Serum P-Tau protein and β-amyloid protein were risk factors for OSAS with MCI(P<0.05).The AUC of the expression levels of serum P-Tau protein,β-amyloid protein,and their combination for OSAS with MCI was 0.751,0.848,and 0.928,respectively.The combined evaluation of the two showed better results(Zcombination-P-Tau protein=4.102,P<0.001;Zcombination-β amyloid protein=2.147,P=0.032).CONCLUSION The expression of serum P-Tau protein and β-amyloid protein is upregulated in OSAS patients with MCI,they are risk factors for the development of MCI in OSAS patients.The combined detection of the two has higher diagnostic efficacy.

Objective:To evaluate the clinical efficacy of Huaiqi Huang Granules combined with conventional Western medicine therapy for the treatment of Kawasaki disease in children.Methods:A randomized controlled trial study was conducted. A total of 96 children with Kawasaki disease admitted to Hebei Children's Hospital from August 2022 to July 2024 were selected as the research objects and divided into the observation group and the control group by the random number table method, with 48 cases in each group. The control group received conventional Western medicine treatment on the basis of symptomatic treatment, while the observation group took Huaiqi Huang Granules on the basis of the control group. The treatment for both groups lasted 7 d. TCM symptoms scores of both groups were evaluated. ELISA was used to detect the levels of TNF-α, MCP-4, and IL-8, while fluorescence immunoassay was used to detect the levels of von Willebrand factor (vWF), endothelin-1 (ET-1), and nitric oxide (NO); flow cytometry was used to detect CD4 +, CD3 +, CD8 + levels and calculate CD4 +/CD8 +ratio; adverse reactions were recorded during treatment and clinical efficacy was evaluated. Results:The total effective rate was 93.75% (45/48) in the observation group and 77.08% (37/48) in the control group, with statistical significance ( χ2=5.35, P=0.021). After treatment, the scores of persistent high fever, skin macules, red throat and eyes, and fatigue in the observation group were lower than those in the control group ( t values were 5.66, 5.45, 5.03, and 5.42 respectively, P<0.01). After treatment, the levels of serum TNF-α, MCP-4 and IL-8 in the observation group were lower than those in the control group ( t values were 4.10, 5.97 and 3.82 respectively, P<0.01). After treatment, the levels of serum vWF [(19.43±3.85) μg/L vs. (23.02±4.13) μg/L, t=4.41] and ET-1 [(38.54±5.12) μg/L vs. (43.90±5.26) μg/L, t=5.06] in the observation group were lower than those in the control group ( P<0.01); the level of NO [(81.23±8.44) μg/L vs. (74.42±8.13) μg/L, t=4.03] was higher than that of the control group ( P<0.01); after treatment, the levels of serum CD4 + and CD3 + and the ratio of CD4 +/CD8 + in the observation group were higher than those in the control group ( t values were 4.91, 4.23, and 3.81 respectively, P<0.01); the CD8 + level was lower than that of the control group ( t=4.19, P<0.01). During the treatment period, the incidence of adverse reactions was 10.42% (5/48) in the observation group and 8.33% (4/48) in the control group, without statistical significance ( χ2=0.12, P=0.726). Conclusion:Huaiqi Huang Granules combined with conventional Western medicine therapy can effectively reduce the TCM syndrome score of children with Kawasaki disease, inhibit the levels of inflammatory factors, improve vascular endothelial function, enhance the body's immunity, and have good medication safety.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Background Fine particulate matter (PM_2.5) monitoring stations may generate missing data for a certain period of time due to various factors. This data loss will adversely affect air quality assessment and pollution control decision-making. Objective To propose an inverse distance weighted (IDW) spatiotemporal interpolation method based on particle swarm optimization (PSO) to interpolate and fill missing PM_2.5 spatiotemporal sequence data and increase interpolation accuracy. Methods An interpolation experiment was designed into two parts. The first part used hourly PM_2.5 observational data from four moments on January 1, 2017 in the Yangtze River Delta region. The second part employed daily PM_2.5 observational data from the first 10 d of January 2017 in the Beijing-Tianjin-Hebei region. Interpolation accuracy was evaluated using four metrics: root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and mean relative error (MRE). Results IDW spatiotemporal interpolation method optimized with PSO significantly improved the accuracy of filling missing PM_2.5 spatiotemporal sequence data. In the hourly-scale experiment conducted in the Yangtze River Delta region, compared to a distance index of 2, the accuracy metrics RMSE, MAE, MAPE, and MRE generated by the proposed method improved on average by 0.17 μg·m⁻³, 0.27 μg·m⁻³, 0.17%, and 0.01%, respectively. The PM_2.5 spatial field maps generated for four moments based on this method clearly illustrated the spatiotemporal distribution characteristics of hourly PM_2.5 concentrations in the Yangtze River Delta region. In the daily-scale experiment conducted in the Beijing-Tianjin-Hebei region, the PSO-optimized distance index outperformed the traditional method, with interpolation accuracy improvements of approximately 0.215 μg·m⁻³, 0.283 μg·m⁻³, 0.174%, and 0.014%, respectively. Furthermore, the seasonal PM_2.5 spatial field maps generated by this method revealed the spatiotemporal distribution characteristics of PM_2.5 concentrations in the Beijing-Tianjin-Hebei region across different seasons, further validating the effectiveness and applicability of this method. Conclusion The IDW spatiotemporal interpolation method optimized with PSO is highly accurate and reliable for interpolating the missing data in the Yangtze River Delta region and the Beijing-Tianjin-Hebei region, providing valuable insights for air pollution control and public health protection.

The ultra-high performance liquid chromatography( UPLC) characteristic fingerprints of Angelica dahurica and A. dahurica var. formosana were established. The compounds corresponding to common peaks were identified by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). The results were combined with chemometrics and quantitative analysis of multi-components with a single-marker method(QAMS) to study the quality control of A. dahurica and A. dahurica var. formosana. The separation was performed on a Titank C_(18) column(2. 1 mm × 150 mm, 1. 8 μm)with a mobile phase of acetonitrile-0. 2% formic acid at a flow rate of 0. 3 m L·min~(-1). The column temperature was 35 ℃ and the injection volume was 1. 2 μL. Seven batches of A. dahurica and 11 batches of A. dahurica var. formosana were injected and analyzed. The UPLC characteristic fingerprints of A. dahurica and A. dahurica var. formosana were established according to the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine( version 2012), and 19 and 20 characteristic peaks were matched respectively. The common peaks were identified by reference substance comparison and UPLC-Q-TOF-MS/MS. Cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA)were performed to analyze the chemical pattern recognition of A. dahurica and A. dahurica var. formosana. The results of CA and PCA could distinguish Angelicae Dahuricae Radix from different producing areas, and the differential quality markers of A. dahurica and A. dahurica var. formosana were obtained by OPLS-DA. With imperatorin as the internal reference, the relative correction factors of oxypeucedanin hydrate, byakangelicin, bergapten, isopimpinellin, oxypeucedanin, and isoimperatorin were 1. 310, 1. 069, 0. 729, 0. 633, 0. 753, and 1. 010, respectively. There was no significant difference between the QAMS and external standard method(ESM)results of each component, indicating that the QAMS established with imperatorin as the internal reference was accurate and reliable. The characteristic fingerprints, chemometrics, and QAMS established in this study can quickly and efficiently control the quality of A. dahurica and A. dahurica var. formosana.
Quality Control ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Angelica/chemistry* ; Chemometrics/methods* ; Tandem Mass Spectrometry/methods* ; Principal Component Analysis

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*