Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment， diet， and lifestyle， which is closely related to many diseases in modern medicine， such as hyperlipidemia， obesity， fatty liver， atherosclerosis， metabolic syndrome， and cardiovascular and cerebrovascular diseases， with a wide range of influence and far-reaching harm. According to the Huangdi Neijing， lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids， which has the function of nourishing， and it is the initial state and source of important substances in the human body such as brain， marrow， essence， and blood. Once the grease of the human body is abnormal， it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach， which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments， leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity， which accumulates in the body's meridians， blood vessels， skin pores， and organs， forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays， it was divided into four common pathogenesis types： ''inability to distinguish between the clear and turbid， turbid stagnation in the Ying blood''， ''spleen not rising clear， turbid accumulation in the vessels''， ''spleen dysfunction， lipid retention in the pores''， ''spleen failure to transportation and transformation， and grease accumulation in the liver''. According to the pathogenesis， it could be divided into four common syndromes， namely， turbid stagnation in the Ying blood， turbid accumulation in the vessels， lipid retention in the pores， and grease accumulation in the liver， and the corresponding prescriptions were given for syndrome differentiation and treatment， so as to guide clinical differentiation and treatment of the lipid turbidity disease.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC_50s for BD and BC were 11.63 and 11.71 μmol·L^-1, respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD's role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.
Humans ; Lung Neoplasms/metabolism* ; STAT3 Transcription Factor/metabolism* ; Antineoplastic Agents/chemistry* ; A549 Cells ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

Objective:To explore the influencing factors of AIDS-related deaths among HIV-infected patients in Shandong Province, to help reduce the risk of death and prolong survival time.Methods:The study population was HIV-infected patients in Shandong Province from 2017-2021, and Cox proportional hazards regression model was used to analyze the influencing factors of AIDS-related deaths and deaths within one year of confirmation.Results:Among 14 700 HIV- infected patients reported in Shandong Province in 2017-2021, 351 AIDS-related deaths occurred, accounting for 2.4% (351/14 700). The results of multifactorial Cox proportional hazards regression model analysis showed that the risk factors for AIDS-related deaths among HIV-infected patients included education level of junior high school, high school, and secondary school (a HR=1.37, 95% CI:1.01-1.84), sample source from healthcare institutions (a HR=1.61, 95% CI:1.22-2.12), duration of disease in AIDS stage (a HR=9.86,95% CI:6.86-14.19), baseline CD4 +T lymphocytes (CD4) undetected (a HR=3.93, 95% CI:2.69-5.75), duration of antiviral treatment (ART) <6 months (a HR=3.46, 95% CI:2.42-4.93) and no ART (a HR=1.45, 95% CI:1.02-2.07), final CD4 <200 cells/μl (a HR=3.51, 95% CI:2.18-5.65) and final CD4 undetected (a HR=10.58, 95% CI:6.15-18.19), and final viral load (VL) values of 50-999 copies/ml,≥1 000 copies/ml and undetected (a HR=2.59, 95% CI:1.07-6.26; a HR=9.50, 95% CI:5.60-16.12; a HR=15.33, 95% CI:8.91-26.36). Factors with higher risk of AIDS-related deaths within one year of confirmation of HIV-infected patients included samples originating from healthcare facilities (a HR=1.68, 95% CI: 1.19-2.36), AIDS stage of disease (a HR=10.60, 95% CI:7.13-15.75), baseline CD4 undetected (a HR=3.71, 95% CI:2.34-5.90), duration of ART <6 months (a HR=4.30, 95% CI:2.85-6.49) and no ART (a HR=2.05, 95% CI:1.35-3.13), final CD4 <200 cells/μl (a HR=5.45,95% CI:2.04-14.60) and final CD4 undetected (a HR=20.95, 95% CI: 7.69- 57.04), and final VL values of 50-999 copies/ml, ≥1 000 copies/ml and undetected (a HR=15.21, 95% CI: 2.54-91.21; a HR=42.93, 95% CI:9.64-191.20; a HR=61.35, 95% CI:13.85-271.77). Conclusions:Expanding the coverage of testing, promoting early detection and treatment, strengthening regular follow-up and the test of HIV-infected patients, grasping the progress of the disease to provide accurate management and treatment are important for reducing the disease mortality rate and prolonging the survival time of HIV-infected patients.

Objective:To investigate the clinical characteristics, diagnosis and treatment methods of children with gene mutation-negative essential thrombocytosis (ET).Methods:The clinical data of a child with gene mutation-negative ET in the Blood Diseases Hospital of Chinese Academy of Medical Sciences were collected, and the related literature was reviewed.Results:The epistaxis was the main clinical symptom of this child. He was diagnosed as ET (gene mutation-negative) by bone marrow aspiration and gene detection. After hydroxyurea treatment, the platelet count increased and the clinical symptoms were improved.Conclusions:The incidence rate of ET in children is low, and the frequency of gene mutation-negative ET in children reported in the literature is different. The large number of samples and long-term follow-up studies are needed.

With the further increase of the global cancer burden, various cancers are increasingly challenging human health status and quality of life. Thus, early screening of cancer is crucial. Urinary volatile organic compounds (VOCs) detection techniques have the advantages of easy access to samples, high acceptance of patients, non-invasive, and so on, which have been favored and concerned by researchers. In this paper, existing techniques and methods for cancer diagnosis based on urine VOCs were described, relevant studies on the use of urine VOCs for cancer diagnosis were reviewed, and the barriers and future perspectives of the technique were discussed. This paper can be a reference for researchers working in the direction of urinary VOCs detection, a multidisciplinary field that spans medicine and materials science.

Objective:To analyze clinical characteristics of patients with novel coronavirus Omicron variant of concern infection, and to provide practical data and experience for subsequent clinical treatment.Methods:A retrospective analysis was performed for the clinical data of 5 cases with novel coronavirus Omicron variant of concern infection treated in the First Hospital of Jiaxing from December 18, 2021 to January 28, 2022. The patients' clinical data were recorded, including gender, age, length of hospital stay, vaccination status, clinical symptoms, laboratory indicators [white blood cell count (WBC), lymphocyte count (LYM), eosinophil count (EOS), hypersensitivity C-reactive protein (hs-CRP), novel coronavirus antibody immunoglobulin (IgG and IgM)], chest CT, treatment course and disease outcome.Results:All 5 patients were male, aged 24-37 years old. Four patients were vaccinated with novel coronavirus vaccine (one patient received 3 doses of the vaccine and 3 patients received only the first 2 doses of the vaccine), and no infection was found in chest CT. Laboratory examination showed that WBC, LYM, EOS and hs-CRP levels were normal, and only showed mild symptoms of upper respiratory tract infection. One patient was not vaccinated with novel coronavirus vaccine, and signs of viral pneumonia could be seen in chest CT, laboratory examination showed that WBC and hs-CRP levels increased, suggesting that bacterial infection, fever, cough, sputum and other respiratory symptoms were obvious, and the treatment time was long. All 5 patients were treated with Chinese medicine Lotus antipyretic and Baihu Yinqiao decoction based on routine antiviral therapy.Conclusions:Patients with novel coronavirus Omicron variant of concern infection vaccinated with the novel coronavirus vaccine have milder clinical symptoms, with less obvious chest CT findings and faster recovery. Chinese medicine Lotus antipyretic and Baihu Yinqiao decoction has obvious therapeutic effect on such patients.

Objective:To investigate the protective effect and mechanism of Acronychia pedunculata water extracts on UV-induced light damage of human keratinocytes.Methods:The experiment was conducted from December 2018 to April 2020 in the Guangxi Medical University Laboratory of Genetics. The photoaged keratinocyte model was used, the cells were co-cultured with different concentrations of Acronychia pedunculata water extracts. The cell proliferation rate was detected by CCK-8 method. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and total antioxidant capacity (T-AOC) of cells were detected by a test kit. The levels of IL-1β, IL-6 and tumor necrosis factor-alpha (TNF-α) were determined by ELISA.Results:The proliferation of HaCaT cells was promoted by 0.5 mg/L-2.0 mg/L of the extracts. Compared with control group, the proliferation rate of HaCaT cells in the experimental group was significantly increased ( P<0.05). Compared with control group, the contents of ROS was decreased ( F=214.67, P<0.05), MDA was decreased ( F=811.88, P<0.05), SOD was increased ( F=28.95, P<0.05), CAT was increased ( F=213.31, P<0.05), GPX was increased ( F=65.10, P<0.05), T-AOC was increased ( F=305.58, P<0.05), IL-1β was decreased ( F=15.46, P<0.05), IL-6 was decreased ( F=59.2, P<0.05), and TNF-α was decreased ( F=33.13, P<0.05). Conclusions:The extracts of 0.5-2.0 mg/L of Acronychia pedunculata have protective effects on the photoaging cell model, which may be related to the increase of SOD, CAT, GPX and other antioxidant enzymes and the level of T-AOC in photoaging HaCaT cells, and the decrease of ROS, MDA content and the expression of inflammatory cytokines.