Objective: To investigate the effect of integrin α5 on the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in periodontal ligament fibroblasts (PDLFs) within an inflammatory microenvironment. Methods: This study was approved by the Ethics Committee of Laboratory animals. After rat PDLFs were treated with LPS (0.5, 5, and 50 µg/mL) for 24 h, the primary medium was discarded and replaced with serum-free culture medium. After 24 h, the supernatant was collected and mixed with DMEM medium containing 10% exosome-free serum at a volume ratio of 1:1 to obtain conditioned medium (CM). The groups were labeled as the 0.5-CM, 5-CM, and 50-CM groups. In addition, PDLFs cultured in DMEM medium containing 10% exosome-free serum were considered the 0-CM group. PDLFs were cultured with the above CM. In the inhibitor group, PDLFs were cultured in 0-CM containing different concentrations of integrin α5 inhibitor ATN-161 (0, 0.025, 0.25, 2.5, 25, and 250 μg/mL). The effect of CM and integrin α5 inhibitor ATN-161 on cell viability was assessed using the CCK-8 assay. According to the CCK-8 results, in further inhibitor intervention experiments, PDLFs were cultured in 0-CM, 5-CM (without/with 25 μg/mL ATN-161), and 0-CM containing 25 μg/mL ATN-161, which were labeled as the 0-CM, 5-CM, ATN-161+5-CM, and ATN-161 groups, respectively. The expression changes of integrin α5 and NLRP3 were detected using Western blot and qRT-PCR techniques. For in vivo experiments, 24 rats were randomly divided into four groups (n=6). The control group contained healthy rats that received no treatment. The rats in the other three groups were injected with 40 µL of 0-CM containing 25 μg/mL ATN-161 or 5-CM (without or with 25 μg/mL ATN-161) on the palatal side of the left maxillary first molar every three days; these groups were classified as the ATN-161, 5-CM, and ATN-161+5-CM groups, respectively. On the 30th day, the left maxillary tissue of rats was used for Micro-CT, HE staining, and immunohistochemical detection. Results : The CCK-8 assay showed that CM, 25 μg/mL ATN-161, and ATN-161 concentrations below 25 μg/mL had no significant effect on cell viability at 12 h and 24 h (P > 0.05). 50-CM and 25 μg/mL ATN-161 significantly inhibited cell viability at 48 h (P < 0.05). For in vitro experiments, compared to the 0-CM group, both the protein and mRNA levels of integrin α5 and NLRP3 were significantly increased in rat PDLFs in the 5-CM group (P < 0.05). Intervention with 25 μg/mL ATN-161 significantly attenuated the enhancement of 5-CM on the expression of integrin α5 and NLRP3 (P < 0.05). For in vivo experiments, compared to the control group, alveolar bone resorption and periodontal inflammatory cell infiltration were significantly increased in the 5-CM and ATN-161+5-CM groups, and the expression of integrin α5 and NLRP3 was significantly increased (P < 0.01). However, compared to the 5-CM group, the ATN-161+5-CM group had less alveolar bone resorption and fewer periodontal inflammatory cells. Further, the expression of integrin α5 and NLRP3 was significantly reduced (P < 0.01). Conclusion In vitro and in vivo experiments showed that integrin α5 mediated NLRP3 expression in PDLFs under an inflammatory microenvironment. ATN-161 inhibited the expression of integrin α5, thus significantly downregulating the expression of NLRP3, which plays a role in inhibiting inflammation.

The study aims to elucidate the existence forms(original constituents and metabolites) of Notoginseng Radix et Rhizoma in rats and reveal its metabolic pathways. After Notoginseng Radix et Rhizoma was administered orally once a day for seven consecutive days to rats, all urine and feces samples were collected for seven days, while the blood samples were obtained 6 h after the last administration. Using the ultra high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) technique, this study identified 6, 73, and 156 existence forms of Notoginseng Radix et Rhizoma in the rat plasma, urine, and feces samples, respectively. Among them, 101 compounds were identified as new existence forms, and 13 original constituents were identified by comparing with reference compounds. The metabolic reactions of constituents from Notoginseng Radix et Rhizoma were mainly deglycosylation, dehydration, hydroxylation, hydrogenation, dehydrogenation, acetylation, and amino acid conjugation. Furthermore, the possible in vivo metabolic pathways of protopanaxatriol(PPT) in rats were proposed. Through comprehensive analysis of the liquid chromatography-mass spectrometry(LC-MS) data, isomeric compounds were discriminated, and the planar chemical structures of 32 metabolites were clearly identified. According to the literature, 48 original constituents possess antitumor and cardiovascular protective bioactivities. Additionally, 32 metabolites were predicted to have similar bioactivities by SuperPred. This research lays the foundation for further exploring the in vivo effective forms of Notoginseng Radix et Rhizoma.
Animals ; Rats ; Drugs, Chinese Herbal/pharmacokinetics* ; Rhizome/metabolism* ; Male ; Rats, Sprague-Dawley ; Chromatography, High Pressure Liquid ; Panax notoginseng/chemistry* ; Tandem Mass Spectrometry ; Feces/chemistry*

OBJECTIVE: To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC). METHODS: Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay. RESULTS: A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells. CONCLUSION C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Stomach Neoplasms/pathology* ; Humans ; Prognosis ; Lysosomes/physiology* ; RNA-Seq ; Cell Death ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Cell Proliferation ; Single-Cell Gene Expression Analysis

Purpose/Significance Taking Jiashan county's chronic disease management mode based on blockchain as an example,new strategies for chronic disease management under the integrated county medical community mode are discussed.Method/Process U-sing the PEST-SWOT analysis method,the paper analyzes the strengths,weaknesses,opportunities and threats of the chronic disease management mode based on blockchain in Jiashan county from 4 aspects:politics,economy,society,and technology.Result/Conclu-sion The chronic disease management mode based on blockchain technology can ensure seamless connection and sharing of data,guaran-tee the security and traceability of patients'personal information and health records,and promote the common development of blockchain technology and chronic disease management in Jiashan county.

Cells are the fundamental structural and functional units of biological organisms,with inherent differences in composition and interactions with exogenous substances,known as cellular heterogeneity.Single cell inductively coupled plasma-mass spectrometry(SC-ICP-MS)allows for the high-throughput introduction of individual cells,enabling the highly sensitive detection and quantification of elements within a single cell,thus effectively providing information on cellular heterogeneity.This review outlined the SC-ICP-MS sample preparation process for different types of cells(single-cell systems,aggregation-prone and adherent cell systems,animal tissues,and plant tissues),including steps such as separation,washing,and fixation,as well as the advantages and existing issues of the current sample introduction systems and quantification methods.The recent applications of SC-ICP-MS in detecting endogenous substances(endogenous elements and proteins),exogenous substances(heavy metals,metal-based drugs and nanoparticles),and the simultaneous detection of both endogenous and exogenous substances were summarized.Finally,the perspectives on the future development of SC-ICP-MS in analytical methods and application fields were presented,including the optimization of single-cell sample preparation,transport efficiency,evaluation standards of ionization efficiency,and the establishment of multiparametric cell analysis platforms.

Objective Data mining method was used to analyze the Chinese herbal prescriptions for oral use in treating venomous snake bites collected from the major domestic literature databases and the surgery volume of Zhong Hua Yi Fang(Chinese Medical Prescriptions),so as to explore their potential prescription and medication rules,and to provide references for the treatment of venomous snake bites in the primary hospitals.Methods The Chinese herbal prescriptions for oral use in treating venomous snake bites were retrieved from the CNKI,VIP and Wanfang databases,and the ancient formulas for treating venomous snake bites were screened in the surgery volume of Zhong Hua Yi Fang(Chinese Medical Prescriptions).Excel software was used to extract the relevant information of the formulas,and R language was used to analyze the medication frequency,properties,flavors and meridian tropism of the herbs as well as their association rules and clustering analysis.Results A total of 187 prescriptions for oral use in treating venomous snake bite were obtained,involving 284 Chinese herbal medicines.The top 15 Chinese herbal medicines in decreasing sequence of medication frequency were Lobeliae Chinensis Herba,Rhei Radix et Rhizoma,Angelicae Dahuricae Radix,Glycyrrhizae Radix et Rhizoma,Paridis Rhizoma,Rehmanniae Radix,Coptidis Rhizoma,Scutellariae Radix,Lonicerae Japonicae Flos,Paeoniae Radix Rubra,Moutan Cortex,Hedyotis Diffusae Herba,Imperatae Rhizoma,Plantaginis Herba,and Scutellariae Barbatae Herba.The flavor of herbs in the prescription for the treatment of venomous snakebite was usually bitter,pungent and sweet,and their property was relatively cold.Most of the herbs had the meridian tropism of the liver meridian and lung meridian.The core prescription mainly composed of Rhei Radix et Rhizoma,Lobeliae Chinensis Herba,and Paridis Rhizoma was obtained after association rule analysis and cluster analysis.Conclusion The herbs for the treatment of venomous snake bites often have the actions of clearing heat and removing toxins,and the prescription is usually composed of Rhei Radix et Rhizoma,Lobeliae Chinensis Herba,Paridis Rhizoma together with the compatibility of medicines for clearing heat and cooling blood,extinguishing wind and arresting convulsion,clearing heat and promoting urination.

BACKGROUND:Artificial intelligence-assisted bone age assessment has become a research hotspot.Domestic and foreign studies have shown that the rapid development of artificial intelligence technology in the field of medical imaging provides the possibility of more accurate and rapid assessment of bone age. OBJECTIVE:To investigate the consistency between a domestically developed artificial intelligent Greulich-Pyle(GP)bone age assessment system and an expert manually assessed GP(expert GP),and to provide a basis for the feasibility of applying an artificial intelligent GP in clinical practice or in other fields. METHODS:Wrist radiographs were sampled from children and adolescents aged 6-15 years,of whom 672 were male and 650 were female.Bone age assessment of the same wrist radiograph was performed using the artificial intelligent GP and the expert GP.The accuracy of the artificial intelligent GP reading results was assessed by the absolute value of the difference.The consistency of the bone age results was assessed by Pearson correlation and Bland-Altamn distribution;and the consistency of the assessment was checked by Kappa test. RESULTS AND CONCLUSION:The absolute value of the difference(95%confidence interval)of the difference between artificial intelligent GP and expert GP for male and female was 0.39 years(0.37-0.41 years)and 0.32 years(0.29-0.34 years),respectively.The deviation of Bland-Altamn values for male and female was(-0.096±0.482)years and(0.014±0.415)years,respectively.The correlation results between artificial intelligent GP bone age and expert GP bone age for male and female were r=0.991 and r=0.992,respectively(P<0.000 1).The median difference between all age groups for male and female was within 0.5 years.Kappa test values were greater than 0.4 for both sexes at all ages except for the 9-year age group for male.Overall Kappa values were 0.603 and 0.659 for male and female respectively.To conclude,there is a high degree of consistency between the artificial intelligence and expert evaluation results of GP bone age values in children and adolescents aged 6-15 years.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.