This study employed bioinformatics to screen the feature genes related to efferocytosis in diabetic kidney disease(DKD) and explores traditional Chinese medicine(TCM) regulating these feature genes. The GSE96804 and GSE30528 datasets were integrated as the training set, and the intersection of differentially expressed genes and efferocytosis-related genes(ERGs) was identified as DKD-ERGs. Subsequently, correlation analysis, protein-protein interaction(PPI) network construction, enrichment analysis, and immune infiltration analysis were performed. Consensus clustering was conducted on DKD patients based on the expression levels of DKD-ERGs, and the expression levels, immune infiltration characteristics, and gene set variations between different subtypes were explored. Eight machine learning models were constructed and their prediction performance was evaluated. The best-performing model was evaluated by nomograms, calibration curves, and external datasets, followed by the identification of efferocytosis-related feature genes associated with DKD. Finally, potential TCMs that can regulate these feature genes were predicted. The results showed that the training set contained 640 differentially expressed genes, and after intersecting with ERGs, 12 DKD-ERGs were obtained, which demonstrated mutual regulation and immune modulation effects. Consensus clustering divided DKD into two subtypes, C1 and C2. The support vector machine(SVM) model had the best performance, predicting that growth arrest-specific protein 6(GAS6), S100 calcium-binding protein A9(S100A9), C-X3-C motif chemokine ligand 1(CX3CL1), 5'-nucleotidase(NT5E), and interleukin 33(IL33) were the feature genes of DKD. Potential TCMs with therapeutic effects included Astragali Radix, Trionycis Carapax, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma, which mainly function to clear heat, replenish deficiency, activate blood, resolve stasis, and promote urination and drain dampness. Molecular docking revealed that the key components of these TCMs, including β-sitosterol, quercetin, and sitosterol, exhibited good binding activity with the five target genes. These results indicated that efferocytosis played a crucial role in the development and progression of DKD. The feature genes closely related to both DKD and efferocytosis, such as GAS6, S100A9, CX3CL1, NT5E, and IL33, were identified. TCMs such as Astragali Radix, Trionycis Carapa, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma may provide a new therapeutic strategy for DKD by regulating efferocytosis.
Humans ; Computational Biology ; Diabetic Nephropathies/physiopathology* ; Protein Interaction Maps ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Phagocytosis/genetics* ; Efferocytosis

In recent years, cancer treatment methods and means are becoming more and more diversified, and single treatment methods often have limited efficacy, while the synergistic effect of immunity combined with chemotherapy can inhibit tumor growth more effectively. Based on this, we constructed a sodium alginate hydrogel composite system loaded with chemotherapeutic agents and tumor vaccines (named SA-DOX-NA) with a view to the combined use of chemotherapeutic agents and tumor vaccines. Firstly, the tumor vaccine (named NA) degradable under acidic conditions was constructed by in situ polymerization using chicken ovalbumin (OVA), acrylamide (AAM) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Then a hydrogel composite system SA-DOX-NA co-loaded with chemotherapeutic drug doxorubicin (DOX) and NA was prepared using sodium alginate as a matrix. The results showed that SA-DOX-NA had good in situ gel-forming ability and formed a mesh structure that could realize the co-loading of DOX and NA as well as the slow drug release. The electron microscopy results showed that SA-DOX-NA had good in situ gel-forming ability with good internal connectivity, and the three-dimensional mesh structure could realize the co-loading of DOX and NA as well as the slow drug release. The antitumor and immunomodulatory results showed that SA-DOX-NA both effectively inhibited the growth of tumor cells and efficiently promoted the proliferation and activation of DC2.4 dendritic cells without additional adjuvant. In summary, SA-DOX-NA exerts the dual efficacy of chemotherapy and immunotherapy for tumor treatment, and has a good application prospect in local tumor treatment.

Twelve compounds were isolated from the rice fermentation extracts of Penicillium expansum GY618 by silica column chromatography, Sephadex gel column chromatography, ODS column chromatography and semi preparative HPLC methods. They were determined as 11-hydroxyl-penicitrinone F (1), penicitrinone F (2), betulin (3), erythrodiol (4), ergosterol (5), ergost-5α,8α-epidioxy-6,22-dien-3β-ol (6), (5α,8α-epidioxy-(22E,24R)-ergosta-6,9(11),22-trien-3β-ol) (7), 5α,8α-epidioxy-(22E,24R)-23-methylergosta-6,22-dien-3β-ol (8), 5α,8α-epidioxy- 23,24(R)-dimethylcholesta-6,9(11),22-trien-3β-ol (9), dankasterone A (10), (17R)-4-hydroxy-17-methylincisterol (11) and ergosta-4,6,8(14),22-tetraen-3-one (12), through mass spectrometer, nuclear magnetic resonance (NMR) and comparison with the literature. Compound 1 was a new compound and compounds 2-4, 6-12 were isolated from Penicillium expansum fungus for the first time. The tyrosinase inhibitory activity experiment showed that compounds 1, 3 and 12 showed certain inhibitory activity against tyrosinase with IC₅₀ values of (75 ± 9), (69 ± 8) and (64 ± 2) μmol·L^-1, respectively. The IC₅₀ of other compounds were all greater than 100 μmol·L^-1, while IC₅₀ of the positive control kojic acid was (46 ± 4) μmol·L^-1.

INTRODUCTION: Paediatric sexual assault (SA) victims should be assessed for post-exposure prophylaxis (PEP) to mitigate the risk of sexually transmitted infections (STIs). We describe the clinical characteristics of children and young persons (CYPs) presenting with SA at KK Women's and Children's Hospital in Singapore, viral PEP (human immunodeficiency virus [HIV] and hepatitis B virus [HBV]) prescribing practices, and STI evaluation at follow-up. METHOD: Medical records of CYPs ≤16 years who presented with SA between January 2022 and August 2023 were reviewed, including assault and assailant characteristics, baseline and follow-up STI screening, PEP prescription, adherence and follow-up attendance. CYPs with SA in the preceding 72 hours by HIV-positive or HIV-status unknown assailants with high-risk characteris-tics were eligible for HIV PEP. RESULTS: We analysed 278 CYPs who made 292 SA visits. There were 40 (13.7%) CYPs eligible for HIV PEP, of whom 29 (82.9%) received it. Among those tested at baseline, 9% and 34.9% of CYPs tested positive for Chlamydia trachomatis and Gardnerella vaginalis, respectively. None tested positive for Neisseria gonorrhoeae, Trichomonas vaginalis, HIV, HBV or hepatitis C. Majority of CYPs tested were HBV non-immune (n=167, 67.6%); only 77 (46.1%) received the vaccine. Out of 27 CYPs eligible for HBV PEP with immunoglobulin, only 21 (77.7%) received immunoglobulin. A total of 37 CYPs received HIV PEP, including 8 who were retrospectively deemed ineligible. Only 10 (27%) completed the course. Overall, 153 (57.7%) CYPs attended follow-up, and none seroconverted for HIV or HBV. CONCLUSION We report suboptimal rates of HBV post-exposure vaccination, and low compliance to HIV PEP and follow-up among paediatric SA victims. Factors contri-buting to poor compliance should be examined to optimise care for this vulnerable population.
Humans ; Post-Exposure Prophylaxis/methods* ; Female ; Child ; Adolescent ; Singapore/epidemiology* ; HIV Infections/prevention & control* ; Male ; Sexually Transmitted Diseases/epidemiology* ; Retrospective Studies ; Hepatitis B/prevention & control* ; Follow-Up Studies ; Child, Preschool ; Sex Offenses/statistics & numerical data* ; Child Abuse, Sexual

OBJECTIVE: To detect and analyze the expression and clinical significance of long non-coding RNA tyrosine kinase non-catalytic region adaptor protein 1-antisense RNA1 (NCK1-AS1) in patients with acute myeloid leukemia (AML). METHODS: 89 AML patients and 23 healthy controls were included from the People's Hospital Affiliated to Jiangsu University. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of NCK1-AS1 and NCK1 in bone marrow samples. The relationship between the expression of NCK1-AS1 and the clinical characteristics of patients were analyzed, as well as the correlation between NCK1-AS1 and NCK1. RESULTS: The expression level of NCK1-AS1 in all AML, non-M3 AML and cytogenetically normal AML (CN-AML) patients was significantly higher than that in the control group (P < 0.01, P < 0.05, P < 0.01, respectively). In non-M3 AML, patients with high NCK1-AS1 expression had a significantly lower hemoglobin level than those with low NCK1-AS1 expression (P =0.036), furthermore, NCK1-AS1 ^high patients had shorter overall survival than NCK1-AS1^low patients (P =0.0378). Multivariate analysis showed that NCK1-AS1 expression was an independent adverse factor in patients with non-M3 AML ( HR =2.392, 95% CI :1.089-5.255, P =0.030). In addition, NCK1 expression was also significantly upregulated in all AML, non-M3 AML and CN-AML patients compared with controls (P < 0.01, P < 0.01, P < 0.001, respectively). There was a certain correlation between NCK1-AS1 and NCK1 expression (r =0.37, P =0.0058). CONCLUSION High expression of NCK1-AS1 in AML indicates poor prognosis of AML patients.
Humans ; Leukemia, Myeloid, Acute/genetics* ; RNA, Long Noncoding/genetics* ; Oncogene Proteins/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Prognosis ; Male ; Female ; Middle Aged ; Adult ; Case-Control Studies ; Clinical Relevance

BACKGROUND: Quantitative flow ratio (QFR) holds significant value in guiding drug-coated balloon (DCB) treatment and enhancing outcomes. However, the predictive capability of post-angioplasty QFR for long-term clinical events in patients with de novo lesions who receive DCB treatment remains uncertain. The aim of this study was to explore the potential significance of post-angioplasty QFR measurements in predicting clinical outcomes in patients underwent DCB treatment for de novo lesions. METHODS: Patients who underwent DCB-only intervention for de novo lesions were enrolled. QFR was conducted after DCB treatment. The patients were then categorized based on post-angioplasty QFR. The primary endpoint was major adverse cardiac events (MACE), encompassing all-cause death, cardiovascular death, nonfatal myocardial infarction, stroke, and target vessel revascularization. RESULTS: A total of 553 patients with 561 lesions were included. The median follow-up period was 505 days, during which 66 (11.8%) MACEs occurred. Based on post-procedural QFR grouping, there were 259 cases in the high QFR group (QFR > 0.93) and 302 cases in the low QFR group (QFR ≤ 0.93). Kaplan-Meier analysis revealed a significantly higher cumulative incidence of MACE in the low QFR group (log-rank P = 0.004). The multivariate Cox proportional hazards model demonstrated a significant inverse correlation between QFR and the occurrence of MACEs (HR = 0.522, 95%CI: 0.289-0.942, P = 0.031). Landmark analysis indicated that high QFR had a significant reducing effect on the cumulative incidence of MACEs within 1 year (log-rank P = 0.016) and 1-5 years (log-rank P = 0.026). CONCLUSIONS In patients who underwent DCB-only treatment for de novo lesions, higher post-procedural QFR values (> 0.93) were identified as an independent protective factor against adverse prognosis.

Objective To report a case of tibial synovial sarcoma and review relevant literature to enhance understanding of this disease.Methods The clinical data of a patient with tibial synovial sarcoma treated at Kaifeng Central Hospital were retrospectively analyzed.A literature search was conducted in domestic and international databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,PubMed,Web of Science,and Embase,up to July 2024.Relevant literature was comprehensively reviewed to summarize the imaging and pathological characteristics,treatment,and prognosis of synovial sarcoma.Results A 29-year-old female patient was admitted with left lower extremity pain.X-ray examination revealed a proximal tibia space-occupying lesion suggestive of malignancy,and a mid-tibial space-occupying lesion considered benign.Contrast-enhanced computed tomography(CT)and plain magnetic resonance imaging(MRI)of the proximal tibial lesion also suggested malignancy.Ultrasound-guided biopsy of the proximal tibial tumor revealed a poorly differentiated malignant tumor.Immunohistochemistry results indicated monophasic synovial sarcoma,requiring genetic testing for definitive diagnosis.The patient underwent wide resection of the proximal left tibial malignancy with tumor-type artificial joint replacement,combined with curettage and bone cement filling for the left mid-tibial lesion under anesthesia.Postoperative pathology of space-occupying lesions in the proximal tibia confirmed monophasic synovial sarcoma,and fluorescence in situ hybridization(FISH)demonstrated a rupture of the synovial sarcoma translocation gene(SYT)(i.e.,SS18 positive).There was no recurrence or metastasis found in the patient during the reexamination 6 months after postoperative chemotherapy.As of July 2024,15 cases of genetically confirmed primary intraosseous synovial sarcoma have been reported internationally.Symptoms included pain and swelling,with a medical history of 1-2 years.The X-ray and CT findings showed osteolytic destruction with bone cortical discontinuity.In 13 cases,the intraosseous masses extended to the extraosseous area;in 2 cases,punctate calcifications were detected within the masses.Plain MRI scan showed iso-signal or hypo-signal on T1WI and hyper-signal,iso-signal,and hypo-signal on fat-suppressed T2WI,and enhanced MRI scan demonstrated heterogeneous enhancement.Pathological examination showed spindle-shaped cells under microscopy.Immunohistochemistry results showed positive epithelial membrane antigen(EMA),broad-spectrum cytokeratin(AE1/AE3),Ewing's sarcoma marker(CD99),and transducin-like enhancer of Split 1(TLE1).Twelve patients underwent surgical treatment;6 patients received adjuvant chemotherapy after surgery,of whom 4 developed local recurrence or distant metastasis at initial diagnosis,and 3 died during follow-up.Among the 6 patients who did not receive adjuvant chemotherapy,3 suffered from recurrence or distant metastasis.Conclusions Primary intraosseous synovial sarcoma is a rare malignant tumor with non-specific clinical manifestations.Imaging features typically include osteolytic destruction and intraosseous masses extending extraosseously,suggesting an intraosseous origin.Pathology and immunohistochemistry aid diagnosis,but definitive confirmation relies on further genetic testing.At present,the main treatment regimens for synovial sarcoma involve comprehensive therapies such as surgery and adjuvant chemotherapy,and the prognosis of patients is poor.

Humans ; Vascular Stiffness ; Coal Mining ; Occupational Diseases/epidemiology* ; Risk Factors ; Coal ; Miners

Fragment with some anti-pancreatic cancer activity was identified by screening our internal chemical library. Eighteen compounds in 4 classes were synthesized by systematic modification and their anti-pancreatic cancer activity were evaluated. Ⅱ-1 (IC₅₀ = 6.40 ± 0.34 μmol·L^-1) and Ⅱ-2 (IC₅₀ = 7.15 ± 0.51 μmol·L^-1) exhibited outstanding activity. Subsequently, the anti-migration ability and invasion ability of Ⅱ-1 was evaluated by wound healing assay and invasion assay, Ⅱ-1 exhibited good anti-migration ability and outstanding anti-invasion ability. Using molecular docking technology and molecular dynamics simulation technology, the potential target was locked on bispecific tyrosine phosphorylation regulates kinase 1A (DYRK1A). By enzyme activity testing, the inhibitory capacity of Ⅱ-1 and Ⅱ-2 was 48% and 32%, respectively.

Tablets represent the most widely used oral solid dosage form in the pharmaceutical industry. Puerarin monohydrate (PUEM), a solid form of the natural antihypertensive drug puerarin, is commercially available. However, the low solubility of PUEM poses a significant challenge for the development of its tablet dosage form. In this study, we successfully prepared the sodium chelates of puerarin (PUE-Na·7H₂O) using reactive crystallization techniques. The crystal structure of PUE-Na·7H₂O was analyzed using single crystal technology, which revealed the structural characteristics of its metal chelate. Our thermodynamic studies demonstrated that the formation of PUE-Na·7H₂O involved the simultaneous deprotonation of PUE and the chelation of PUE^- and Na⁺. This reaction process was spontaneous and exothermic (ΔG < 0, ΔH < 0), and reducing the temperature facilitated the formation of the chelate. Nucleation kinetics studies revealed that chelate molecules were more likely to nucleate and crystallize under low temperature, high concentration, and high rotational speed conditions. Compared to commercially available PUEM, PUE-Na·7H₂O showed significantly improved water solubility, with a 33.5-fold increase in solubility and a 37.6-fold decrease in intrinsic dissolution rate. Our study identified drug-sodium chelation as an effective means for improving drug solubility and elucidated the mechanisms governing its formation kinetics and thermodynamics. These findings could provide new solutions for related product development and tremendous commercial opportunities.