ObjectiveTo investigate the effects of Huangqi Jianzhongtang （HQJZ） on macrophage polarization and fat consumption in cancer cachexia （CC） mice. MethodsUltra-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） was used to control the quality of HQJZ. （1） In vitro experiment： HQJZ-containing serum was prepared， and the optimal concentration was determined by cytotoxicity assay. Mouse monocyte-derived macrophages （RAW264.7） were cultured and randomly divided into six groups， including a blank group， a classically activated macrophages （M1） group， an alternatively activated macrophages （M2） group， a HQJZ + blank group， a HQJZ+M1 group， and a HQJZ + M2 group. The relative expression of macrophage marker genes CD86， inducible nitric oxide synthase （iNOS）， CD206， and arginase-1 （Arg1） was detected by real-time quantitative polymerase chain reaction （Real-time PCR ）. （2） In vivo experiment： Thirty-two BALB/c mice were randomly divided into a control group， a model group， a medroxyprogesterone acetate （MPA） group， and a HQJZ group. Except for the control group， the other mice were injected with CT-26 colon cancer cells to establish a CC model. Mice in the MPA and HQJZ groups were given MPA （0.13 g·kg^-1·d^-1） or HQJZ （13.13 g·kg^-1·d^-1） by gavage， respectively， while mice in the control and model groups were given an equal volume of saline by gavage， with interventions continued for 10 d. Real-time PCR was used to detect the expression of macrophage markers （iNOS， Arg1， CD86， CD206） and fat browning-related genes uncoupling protein 1 （UCP1） and peroxisome proliferator-activated receptor γ （PPARγ） in epididymal adipose tissue. Western blot （WB） was used to detect protein expression levels of UCP1 and PPARγ. Micro-computed tomography （micro-CT） was used to measure residual fat volume， and hematoxylin-eosin （HE） staining was used to assess fat browning and calculate pathological scores. ResultsIn vitro， the dominant effective concentration of HQJZ-containing serum was 12.5%. Real-time PCR results showed that， compared with the blank group， Arg1 expression decreased in the HQJZ+blank group （P<0.05）， CD206 showed a downward trend without statistical significance， while iNOS and CD86 expression were significantly increased （P<0.05）. Compared with the M1 group， Arg1 and CD206 expression decreased in the HQJZ+M1 group （P<0.05）. Compared with the M2 group， CD206 expression decreased in the HQJZ+M2 group （P<0.05）， CD86 expression increased significantly （P<0.01）. In vivo， Real-time PCR results showed that， compared with the control group， CD86 and CD206 expression levels were significantly increased in the model group （P<0.01）. Compared with the model group， CD206 expression in the MPA group was significantly decreased （P<0.01）. In the HQJZ group， CD206 was significantly decreased （P<0.01）. WB results showed that， compared with the model group， protein expression of UCP1 and PPARγ was significantly reduced in the HQJZ group （P<0.05， P<0.01）. micro-CT results showed that the total white fat volume in the HQJZ group was greater than that in the model group （P<0.05）. HE staining results showed that pathological scores in the HQJZ group were lower than those in the model group （P<0.05）. ConclusionHQJZ may inhibit white adipose tissue browning by promoting macrophage M1 polarization and suppressing M2 polarization， thereby delaying fat consumption in CC mice.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

OBJECTIVES: To analyze the molecular mechanism of Xixian Pills for treatment of rheumatoid arthritis (RA). METHODS: Forty-eight rats were randomized into 6 groups (n=8), including a normal control group, a collagen-induced arthritis (CIA) model group, 3 Xixian Pills treatment (200, 400 and 800 mg/kg) groups, and a Tripterygium glycosides tablet (TGT) treatment group. In the latter 4 groups, the rats were treated with daily gavage of Xixian Pills or TGT 2 weeks after CIA modeling for 3 consecutive weeks. The differentially expressed proteins in high-dose Xixian Pills group and the model group compared with the normal control group were screened based on the tandem mass spectrometry tag (TMT) technology, and the core targets and signaling pathways were analyzed. The immune cell infiltration and gene expression data were analyzed using ggplot2 and tidyverse packages, and the correlation coefficients between the core targets and the immune cells were calculated. RESULTS: The CIA rats showed significantly increased serum levels of TNF-α and IL-6 and lowered serum IL-10 level. Treatments with high- and medium-dose Xixian Pills and TGT all significantly reduced serum TNF‑α and IL-6 and increased IL-10 levels in CIA rats. Proteomic analysis identified 160 differential proteins between the model group and high-dose Xixian Pills group, and the core targets included CCL5, STAT1, GZMB and IL7R. The areas under the ROC curve of CCL5 and STAT1 were both greater than 0.9. Immunohistochemical and immunofluorescence staining revealed increased levels of CCL5 and STAT1 in the ankle joints of CIA rats, which were significantly decreased after treatment with Xixian Pills. CONCLUSIONS Treatment with Xixian Pills offers protection of the joints in CIA rats possibly by inhibiting joint inflammation via regulating protein expressions of CCL5 and STAT1.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Rats ; Arthritis, Rheumatoid/metabolism* ; Proteomics ; Tripterygium/chemistry* ; Arthritis, Experimental/metabolism* ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-10/blood* ; Interleukin-6/blood* ; Male ; Rats, Sprague-Dawley ; Signal Transduction

Objective To analyze the epidemiological characteristics and temporal spatial clustering of hand, foot, and mouth disease in Hubei Province from 2010 to 2023, and to provide evidence for formulating prevention and control measures. Methods Descriptive epidemiological method was used to analyze the surveillance data of hand, foot, and mouth disease of Hubei Province from 2010 to 2023, and spatial clustering analysis was conducted at the district/county level using ArcGIS 10.5 software. Results A total of 1 007 600 cases of hand, foot, and mouth disease were reported from 2010 to 2023, and the average annual incidence rate was 123.60/100 000. Overall , it exhibited a cyclical pattern of high incidence every other year. Except for a few years, two peaks of incidence were observed each year, , with the first peak occurring between April to July and the second occurring in October to December, and the popular season was concentrated from April to July. Children aged < 5 years were primarily affected, with a high incidence in male patients (1.53:1). The incidence of hand, foot, and mouth disease showed a positive spatial autocorrelation（Moran's I was between 0.15 to 0.76, P<0.05）at the district/county level. The hot spots were concentrated in the northwest and southeast of Hubei Province, and the cool spots were concentrated in the east of central Hubei Province. Conclusion The incidence of hand, foot, and mouth disease has obvious seasonality and spatial clustering in Hubei Province. The key prevention and control areas are concentrated in the northwest and southeast of Hubei. Enhanced prevention and control measures should be targeted on children under 5 years old and key areas to effectively reduce the occurrence of cases.

Objective To perform laboratory detection and molecular traceability analysis on a case of imported kala-azar in Shenzhen to determine the infection strain. Methods Bone marrow puncture fluid and blood samples from a case of kala-azar in Shenzhen were collected for laboratory tests. The patient's bone marrow puncture fluid smears were stained with Giemsa and examined under a microscope. Blood samples were examined for antibodies using the rk39 visceral leishmania rapid diagnostic reagent. Whole blood DNA was extracted, and the ITS-1 sequence was amplified by PCR, sequenced and aligned, and a phylogenetic tree was constructed based on the ITS-1 sequence. Results Microscopic examination of the patient's bone marrow smears revealed a large number of Leishmania amastigotes without flagella, confirming the diagnosis of kala-azar. The patient's blood was tested positive with the rk39 rapid diagnostic reagent, and PCR amplification yielded an ITS-1 gene product sequence that matched the expected size. Sequence alignment with the NCBI database showed 100% sequence similarity with the ITS-1 gene sequence of Leishmania infantum, confirming the infecting strain as Leishmania infantum. Phylogenetic tree construction of the amplified ITS-1 sequence revealed clustering into a clade with Leishmania infantum , and close to KC347299, one of the reference sequence selected. Conclusions The case of kala-azar in Shenzhen was caused by Leishmania infantum. Kala-azar still occurs in China, so the diagnostic technology of medical personnel in non-epidemic areas should be strengthened so that they can actively use new diagnostic technologies to assist in diagnosis, thus improving their prevention and control ability of Leishmania parasites.

Objective To use the GEO dataset and bioinformatics techniques,such as LASSO logistic regression,ssGSEA,and WGCNA,to screen for RA diagnostic markers and investigate the impact of earthly flavonoids in Smi-lax glabra Roxb.on specific immune cell infiltration,to screen for rheumatoid arthritis(RA)diagnostic markers on specific immune cell infiltration and to analyze the combination of flavonoids in Smilax glabra Roxb.and diagnostic markers.Methods The normal control group and RA gene chip were obtained from the Gene Expression Omnibus database.The R 4.3.0 WGCNA software package was used to integrate and analyze the dataset,identify co-expres-sion modules and associated trait information,and screen key modules closely related to RA.LASSO regression a-nalysis was performed using the glmnet package in R to identify characteristic genes for RA.The area under the re-ceiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of the characteristic genes in RA.The gene expression data of the normal control group and RA group were subjected to quantitative immune cell infiltration analysis using the GSVA,limma,and GSEABase packages in R.The chemical components of earth-worm flavonoids in Smilax glabra Roxb.were analyzed based on UHPLC-Q-Exactive Orbitrap MS.The correlation between flavonoids and characteristic genes was assessed through molecular docking.Results The LASSO regres-sion algorithm selected 5 characteristic genes(apolipoprotein D,zinc finger and BTB domain containing 16,C-C chemokine receptor type 5,matrix metalloproteinase 1,coronin-1A).The area under ROC curve of all 5 character-istic genes was greater than 0.85,which exhibited positive correlations with various immune cells.Twenty earth-worm flavonoids of Smilax glabra Roxb.were identified using UHPLC-Q-Exactive/MS,and Mulberrin and Neobavaisoflavone were well combined with 5 immune characteristic genes.Conclusion Flavonoids compounds of Smilax glabra Roxb.have good combination with RA immune characteristic genes,providing a scientific basis for RA immunomodulation therapy and early diagnosis.

The full implementation of the dean's responsibility system under the leadership of the Party Committee trans-forms the hospital's Party Committee from its past role as the"political core"to the"leadership core".In the process of hospital management transformation,establishing a collaborative governance system between the Party and the government is key to imple-menting the dean's responsibility system under the leadership of the Party Committee.Taking the exploratory practices of Shenz-hen Hospital,Beijing University of Chinese Medicine(Longgang)as an example,this involves a comprehensive summary from improving decision-making mechanisms,leveraging the combat fortification role of Party branches and the exemplary role of Party members,and continuously expanding the service coverage of Party-building efforts.This discussion aims to explore effective im-plementation strategies for the dean's responsibility system under Party Committee leadership,to promote high-quality develop-ment of hospitals,and to provide meaningful references for the implementation of this system in public hospitals.

Objective To culture and expand primary rat aortic vascular stem cells in vitro and evaluate their characteristics as mesenchymal stem cells.Methods The thoracic and abdominal aortas isolated from 2-to 3-week-old Sprague-Dawley rats were cut into vascular segments 2.0 mm in length and cultured in culture flasks till adhesion and solidification of the outer membranes.The primary cells were further cultured to 80%-90%confluence before passaging.The morphology and growth characteristics of the cells were observed under a microscope,and the expressions of surface marker CD molecules on the cells was analyzed using flow cytometry.Adipogenic and osteogenic differentiation assays were performed to assess the capacity of the cells for multilineage differentiation.Results After 3 days of culture,a small number of spindle,star-shaped or polygonal cells migrated out from the peripheral of the vascular segments.At 5-6 days,island-like cell clusters occurred and the cells began to proliferate rapidly.The cell clusters expanded radially and showed signs of cell cloning.At 7-8 days,the cells fused into sheets and displayed a vortex-like distribution.The cells in the third passage presented with a uniform morphology,showing a typical fibroblast-like arrangement.Flow cytometry showed that the cells expressed predominantly CD44(80.3%),CD73(62.2%)and CD90(46.8%)with low expressions of CD34(1.1%),CD45(0.2%)and CD11b/c(0.2%).Adipogenic and osteogenic differentiation experiments demonstrated that the cells were capable of lipogenic and osteogenic differentiation in vitro.Conclusion Rat aortic vascular stem cells with mesenchymal stem cell characteristics can be successfully isolated and cultured by adherent culture of the segmented outer membrane.

Background::Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD.Methods::In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort.Results::In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone.Conclusion::ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE.Trial Registration::Chictr.org.cn: ChiCTR2200059599.