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*

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: To analyze the efficacy and access safety of extracorporeal membrane oxygenation (ECMO) in series with continuous renal replacement therapy (CRRT) access for critically ill patients using propensity score matching analysis, and to explore the potential influencing factors of infection. METHODS: A total of 200 critically ill patients who received both ECMO and CRRT treatment in the intensive care unit (ICU) of Huai'an Second People's Hospital from December 2020 to December 2024 were retrospectively selected as the research subjects. They were divided into the independent operation group (72 cases) and the series system group (128 cases) according to the access connection mode of ECMO and CRRT. Propensity score matching analysis was used to perform 1 : 1 matching for patients of the two groups. The general data [age, gender, body mass index (BMI), clinical diagnosis, underlying disease, intubation method, intubation position, disease severity, ECMO support duration, catheter indwelling duration, oxygenation index (PaO₂/FiO₂) at 48 hours after ECMO initiation, serum creatinine (SCr), procalcitonin (PCT), hemoglobin (Hb), white blood cell count (WBC), platelet count (PLT)], treatment status [ECMO initiation duration, ECMO operation duration, ECMO flow, left ventricular ejection fraction (LVEF), CRRT initiation duration, CRRT catheter indwelling duration, inflow and outflow volume of replacement fluid], clinical outcome indicators (28-day survival rate, length of ICU stay, renal function recovery, fluid balance compliance rate), and access safety indicators (incidence of ECMO access thrombosis, incidence of infection, and incidence of bleeding events) of all the patients were collected. Subgroup analysis was conducted based on the occurrence of infection, and multivariate Logistic regression analysis was used to screen the potential risk factors for infection in critically ill patients receiving both ECMO and CRRT treatment. RESULTS: Finally, a total of 120 patients were successfully matched, with 60 patients in both the independent operation group and the series system group. No statistically significant differences were observed in the general data between the two groups, indicating comparability. Compared with the independent operation group, the ECMO flow at 48 hours after ECMO initiation, SCr, and alanine transaminase (ALT) of the patients in the series system group were significantly decreased, while the LVEF at 48 hours after ECMO initiation was significantly increased, additionally, the CRRT initiation duration, CRRT catheter indwelling duration, and the length of ICU stay were significantly shortened, and the inflow and outflow volume of replacement fluid were significantly increased. The incidence of infection and bleeding events in the series system group was significantly lower than that in the independent operation group [infection incidence: 11.67% (7/60) vs. 36.67% (22/60), bleeding event incidence: 8.33% (5/60) vs. 48.33% (29/60), both P < 0.05]. No significant difference was found in the other general data, treatment status, clinical outcome indicators, or access safety indicators between the two groups. Among the 120 patients, 29 cases developed infection (accounting for 24.17%), and 91 cases had no infection (accounting for 75.83%). Compared with the non-infection group, the catheter indwelling duration was significantly prolonged and PCT was significantly increased in the infection group, while the PLT and the proportion of patients with ECMO and CRRT access connected via the series system were significantly decreased. Multivariate Logistic regression analysis showed that catheter indwelling duration [odds ratio (OR) = 1.277, 95% confidence interval (95%CI) was 1.001-1.629, P = 0.049], PCT (OR = 1.529, 95%CI was 1.222-1.914, P < 0.001], PLT (OR = 0.953, 95%CI was 0.926-0.981, P = 0.001), and access connection mode (OR = 0.289, 95%CI was 0.090-0.930, P = 0.037) were potential risk factors for infection in critically ill patients. CONCLUSIONS The ECMO-in-series CRRT access can accelerate the initiation of CRRT, avoid local bleeding, stabilize patients' cardiac, hepatic and renal functions, reduce potential infection risks, and improve the prognosis of patients.
Humans ; Extracorporeal Membrane Oxygenation/adverse effects* ; Critical Illness/therapy* ; Retrospective Studies ; Continuous Renal Replacement Therapy ; Male ; Female ; Intensive Care Units ; Propensity Score ; Middle Aged ; Renal Replacement Therapy ; Adult ; Aged ; Risk Factors

Objective:To compare the efficacy and safety of azacitidine combined with venetoclax or CAG regimen in the treatment of newly treated elderly patients with acute myeloid leukemia (AML).Methods:A retrospective cohort study was conducted. The clinical data of 34 newly treated elderly patients with AML treated in the Fifth People's Hospital of Datong from May 2018 to August 2023 were retrospectively analyzed. According to the treatment regimen, all patients were divided into venetoclax group (azacitidine + venetoclax, 17 cases) and CAG group (azacitidine + CAG regimen, 17 cases). The clinicopathological characteristics, efficacy, adverse reactions and survival of the both groups were compared.Results:There were no statistically significant differences in the clinical data of both groups (all P > 0.05). The complete remission (CR) rate and the objective response rate (ORR) in venetoclax group were higher than those in CAG group [CR: 70.6%(12/17) vs. 47.1% (8/17); ORR: 82.4% (14/17) vs. 64.7% (11/17)],while the differences in CR and ORR were not statistically significant (χ 2 = 2.00, P = 0.163; χ 2 = 2.00, P = 0.244). The follow-up time[ M ( Q1, Q3)] was 25.4 months (7.2 months, 60.3 months). At the end of follow-up, 19 of 34 patients survived (13 cases in venetoclax group and 6 cases in CAG group); 15 died (4 cases in venetoclax group and 11 cases in CAG group). The median overall survival (OS) time was 14.22 months (95% CI: 8.2-60.3 months) and 10.56 months (95% CI: 7.2-50.2 months), respectively in venetoclax group and CAG group;the median progression-free survival (PFS) time was 9.97 months (95% CI: 5.4-40.5 months) and 6.82 months (95% CI: 5.0-36.2 months), respectively, and there were no statistically significant differences in OS and PFS between the two groups (all P > 0.05). Grade 3-4 hematological adverse reactions occurred in 16 and 14 patients in venetoclax group and CAG group, respectively. There were no significant differences in granulocyte deficiency time, platelet deficiency time, infection and bleeding incidence between the two groups (all P > 0.05). Conclusions:Azacitidine combined with venetoclax or CAG regimen have better clinical efficacy and safety for newly treated elderly patients with AML.

Objective To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation(LDH)by finite element analysis.Methods Lumbar CT image of a 48-year-old female patient with LDH(heighted 163 cm,weighted 53 kg)was collected.Mimics 20.0,Geomagic Studio,Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments.Compression techniques under horizon-tal position,30° forward bending and 10° backward extension were simulated respectively.After applying the pressure,the ef-fects of compression techniques under different positions on stress,strain and displacement of various tissues of intervertebral disc and nerve root were observed.Results L4,5 segment finite element model was successfully established,and the model was validated.When compression manipulation was performed on the horizontal position,30° flexion and 10° extension,the annular stress were 0.732,5.929,1.286 MPa,the nucleus pulposus stress were 0.190,1.527,0.295 MPa,and the annular strain were 0.097,0.922 and 0.424,the strain sizes of nucleus pulposus were 0.153,1.222 and 0.282,respectively.The overall displace-ment distance of intervertebral disc on Y direction were-3.707,-18.990,-4.171 mm,and displacement distance of nerve root on Y direction were+7.836,+5.341,+3.859 mm,respectively.The relative displacement distances of nerve root and interverte-bral disc on Y direction were 11.543,24.331 and 8.030 mm,respectively.Conclusion Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend,by increasing the distance between herniated interverte-bral disc and nerve root,to reduce symptoms of nerve compression,to achieve purpose of treatment for patients with LDH,in which the compression manipulation is more effective when the forward flexion is 30°.

Objective:To investigate distribution and drug resistance of pathogens of bloodstream infection in patients with hematological malignancies,in order to provide reference for clinical infection control and treatment.Methods:The clinical information of blood culture patients in the hematology department of our hospital from January 2016 to December 2021 was reviewed.They were divided into transplantation group and non-transplantation group according to whether they had undergone hematopoietic stem cell transplantation.The types of pathogens and their drug resistance were analyzed.Results:Two hundred and ninety-nine positive strains of pathogenic bacteria were detected.In the transplantation group,Gram-negative bacteria accounted for 68.5％(50/73),Gram-positive bacteria accounted for 6.8％(5/73),and fungi accounted for 24.7％(18/73).The resistance rate of Escherichia coli to the third-generation cephalosporins was 77.8％,and 11.5％to carbapenems.The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 50.0％,and 56.2％to carbapenems.In the non-transplantation group,Gram-negative bacteria accounted for 64.1％(145/226),Gram-positive bacteria accounted for 31.0％(70/226),and fungi accounted for 4.9％(11/226).Gram-positive bacteria were mainly Enterococcus faecium(6.6％,15/226)and Coagulase-negative Staphylococci(6.2％,14/226).The fungi were all Candida tropicalis.The resistance rate of Escherichia coli to the third-generation cephalosporins was 63.8％,and 10.3％to carbapenems.The resistance rate of Klebsiella pneumoniae to the third-generation cephalosporins was 46.3％,and 26.8％to carbapenems.Conclusion:The types of pathogenic bacteria in bloodstream infection in patients with hematological malignancies are varied.Gram-negative bacteria is the main pathogenic bacteria.The resistance of pathogenic bacteria to antibiotics is severe.Antibiotics should be used scientifically and reasonably according to the detection and resistance of pathogenic bacteria.

Objective:To investigate the expression of miR-1247-5p(miR-1247-5p)in breast cancer tissues,and to analyze its predicted target genes by bioinformatics.Methods:The cancerous tissues and adjacent tissues were collected from 104 patients with breast cancer who received surgical treatment in our unit from June 2019 to December 2020.The relative expression of miR-1247-5p was detected by RT-PCR.The expression of miR-1247-5p in cancer tissues of patients with different clinicopathological characteristics was compared.The target genes of miR-1247-5p were predicted.The DAVID database was used for function and pathway enrichment of miR-1247-5p target genes.The String database was utilized to analyze the interactions of miR-1247-5p target genes.Results:The expression level of miR-1247-5p in breast cancer tissue was lower than that in adjacent tissue(P＜0.05).There were 38 potential target genes of miR-1247-5p,and the functions of its target genes are mainly concentrated in transcriptional regulation of RNA polymerase Ⅱ promoter,gene expression/transcriptional regulation,plasma membrane portion,synaptosome,protein binding,and poly(A)RNA binding,etc.The involved pathways were mainly enriched in cancer pathway,interaction between cytokines and cytokine receptors,and Phosphatidylinositol 3 kinase(PI3K)-protein kinase B(Akt)signal pathway,etc.Phosphatase and tensin homology(PTEN),epithelial growth factor receptor(EGFR),pseudouridine synthase 1(PUS1)encoding protein were found in the key node positions of miR-1247-5p gene target gene protein-protein interaction networks(PPI).Conclusion:miR-1247-5p is down-regulated in breast can-cer tissues,and its target genes are enriched in multiple biological processes and tumor-related signal transduction pathways.miR-1247-5p may participate in the occurrence and development of breast cancer by regulating the expression of its target genes.

Objective:To analyze the status quo of intelligent health management services in health examination institutions in Shanxi Province.Methods:This study is a cross-sectional study. In October 2023, 292 health examination institutions in 11 cities of Shanxi Province were surveyed by convenient sampling with the help of “Questionnaire star” to investigate the health examination (management) institutions to carry out smart health management services from January to December 2022. It was mainly divided into three aspects: pre-inspection, in-inspection and post-inspection, including 6 dimensions, with a total of 21 items. A total of 300 questionnaires were distributed in this survey, and 292 were effectively collected, with an effective recovery rate of 97.33%. The 292 questionnaires were divided and compared according to four regions: the north of Shanxi Province, the middle of Shanxi Province, the south of Shanxi Province and the southeast of Shanxi Province.Results:The health examination (management) institutions were distributed in 11 prefectures and cities in Shanxi Province, and there were 56 (19.2%) tertiary health examination (management) institutions. There were 178 government organizations (61.0%) and 114 social organizations (39.0%). There were 256 (87.7%) that carried out smart health management services; among them, 229 (78.4%) had smart management service systems, and 58 (19.9%) had physical examination centers with smart health management clinics. A total of 108 institutions (36.99%) carried out follow-up visits after intelligent screening. The prevalence of intelligent referrals were 63.3%, 59.6%, 78.0% and 85.2% in the north of Shanxi Province, the middle of Shanxi Province, the south of Shanxi Province and the southeast of Shanxi Province, respectively ( χ2=14.02, P<0.05). The prevalence of self-service in the north of Shanxi Province, the middle of Shanxi Province, the south of Shanxi Province and the southeast of Shanxi Province were 39.2%, 52.3%, 62.0% and 37.0%, respectively ( χ2=9.75, P<0.05). Conclusions:The development of intelligent health management in health examination (management) institutions in Shanxi Province is good, and the service scale continues to grow, but the problem of uneven development among regions is severe. In addition, the proportion of institutions providing services through information technology is not high, and the rate of intelligent management outpatient service, intelligent post-examination follow-up and intelligent physical examination service satisfaction is low.