OBJECTIVES: To investigate the effect of Scleromitrion diffusum on gastric mucosal epithelial-mesenchymal transition (EMT) in rats with gastric precancerous lesion. METHODS: Fifty SD rats were randomly divided into blank control group (n=11), model control group (n=13), Scleromitrion diffusum (SD) group (n=13) and vitase group (n=13). Gastric precancerous lesion animal model was prepared by 1-methyl-3-nitro-1-nitrosoguanidine complex polyfactor method, and the drugs were administrated by gavage once a day for 6 weeks. The pathological changes of gastric mucosa were observed with hematoxylin and eosin staining, the expression of EMT marker proteins were detected with immunohistochemical staining and Western blotting. RESULTS: Compared with the model control group, the gastric mucosal injury was significantly attenuated in the Scleromitrion diffusum group, the mucosal tissue structure gradually recovered, the saccular expansion area was reduced, and the inflammatory infiltration was ameliorated. The expression of epithelial cadherin was higher, and the expression of neural cadherin and vimentin in the Scleromitrion diffusum group were lower than those of model control group (all P<0.05). CONCLUSIONS Scleromitrion diffusum can ameliorate gastric mucosal injury in rats with gastric precancerous lesion by reversing the EMT.
Animals ; Rats ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition/drug effects* ; Precancerous Conditions/metabolism* ; Gastric Mucosa/metabolism* ; Stomach Neoplasms/drug therapy* ; Male ; Cadherins/metabolism*

OBJECTIVE: To explore the clinical significance of 26 circulating tumor DNA (ctDNA) associated with multiple myeloma (MM) in peripheral blood of new diagnosed patients. METHODS: We conducted a study to detect 26 ctDNA mutations in the peripheral blood of 31 newly diagnosed multiple myeloma (NDMM) patients. RESULTS: Among the 31 NDMM patients, the ctDNA detection rate was 93.55%, significantly higher than that of FISH and chromosome screening methods. The most frequently mutated genes in NDMM were ACTG1 and GNAS. Notably, ACTG1 mutations were exclusive to NDMM patients, furthermore, resulted from the missense mutation of the exon 4. ACTG1 was the gene most frequently co-mutated with others. All patients with ACTG1 mutations were surviving, and there was a positive correlation between ACTG1 mutation and the survival of patients. GNAS mutations were confined to exon 1. CONCLUSION The detection rate of ctDNA sequencing in peripheral blood of NDMM patients was higher than that in bone marrow. ACTG1 and GNAS genes have a guiding role in the prognosis of newly diagnosed patients.
Humans ; Multiple Myeloma/blood* ; Circulating Tumor DNA/genetics* ; Mutation ; Prognosis ; GTP-Binding Protein alpha Subunits, Gs/genetics* ; Chromogranins ; Male ; Female ; Middle Aged

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVE To investigate the ultrasound characteristics of category 4 thyroid nodules in the Chinese version of the Thyroid Imaging Reporting and Data System(C-TI-RADS),and to analyze the value of ultrasonography combined with elastography scoring in the correction of nodule properties.METHODS Data from 80 patients with 105 nodules from April 2020 to December 2023 were retrospectively analyzed.Fine-needle aspiration biopsy or surgical pathology was used as the gold standard.The Kappa test was employed to evaluate diagnostic consistency,while the receiver operating characteristic(ROC)curve was utilized to assess the differentiation and accuracy of the diagnostic methods.RESULTS Sixty-eight malignant nodules and 37 benign nodules were confirmed by surgical pathology or puncture biopsy.After enhancement by ultrasonography,the percentage of malignant nodules with low intensity,centripetal enhancement,inhomogeneous enhancement,blurred boundary of enhanced nodules,enlarged enhanced nodules,and irregular enhanced nodules was significantly higher than that of the benign group,while the percentage of circumferential enhancement was lower than that of the benign group(P<0.05).The overall compliance rate of ultrasonography scoring in diagnosing C-TI-RADS category 4 thyroid nodules was 83.81%(88/105),and when compared with the pathological gold standard,the Kappa value was 0.644.The ROC curve analysis showed that the sensitivity of ultrasonography scoring in diagnosing benign and malignant nodules was 84.51%,the specificity was 82.35%,the correctness index was 0.669,the negative likelihood ratio was 0.188,and the positive likelihood ratio was 4.789.The overall compliance rate of elastography score in diagnosing C-TI-RADS category 4 thyroid nodules was 85.71%(90/105),and when compared with the pathological gold standard,the Kappa value was 0.689.The ROC curve analysis revealed that the sensitivity of elastography score in diagnosing benign and malignant nodules was 88.24%,the specificity was 81.08%,the correctness index was 0.693,the negative likelihood ratio was 0.145,and the positive likelihood ratio was 4.664.Ultrasonography enhancement features,along with the combination of ultrasonography score and elastography score,had an AUC=0.922(0.876-0.968),with an accuracy of 92.91%,demonstrating a strong ability to identify truly malignant nodules versus benign nodules.CONCLUSION Ultrasonography combined with elastography scoring is valuable in the correction of C-TI-RADS category 4 nodules in the thyroid gland and helps to improve diagnostic accuracy.

Non-steroidal anti-inflammatory drugs(NSAIDs),commonly utilized analgesics,are extensively employed for managing pain associated with musculoskeletal disorders or injuries.Recent clinical studies have demonstrated a heightened risk of bone stress injuries(BSI)in soldiers and athletes,particularly during high-intensity training,due to NSAID usage.Furthermore,the impact of NSAIDs on fracture healing is well-documented;however,the precise mechanism by which their use during training contributes to an increased incidence of stress bone injuries remains unclear.This article aims to summarize potential mechanisms through an extensive review of domestic and international literature in order to standardize the utilization and clinical management of NSAIDs,optimize pain management strategies,and prevent stress bone injuries or fractures in specific populations such as soldiers and elite athletes.

Child ; Humans ; Granulomatous Disease, Chronic/complications* ; Pneumonia

Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Inertial microfluidics,as a microfluidic technology with the ability to precisely manipulate particles and cells with high throughput,has attracted widespread attention.However,challenges remain in achieving particle focusing with insensitivity to flow rates in large-scale channels,mainly due to the instability of secondary flows within the inertial microfluidic chip.This study developed a microstructure-assisted ultra-low aspect ratio spiral microchannel,which utilized the stability and acceleration of secondary flows to achieve inertial particle focusing.The research results demonstrated successful particle focusing within a 1 mm-wide spiral channel chip,for different diameter sizes(7.3 μm and 15.5 μm),within a wide range of flow rates(0.5-3 mL/min).The focusing efficiencies for these particles were measured to be above 94%and 99%,respectively.Additionally,it was observed that the particle focusing position was approximately 100 μm away from the channel walls,significantly larger than other inertial focusing chips.Consequently,by incorporating ordered microstructures within the spiral channel chip,the stability and enhancement of secondary flows were achieved,resulting in flow rate and particle size-insensitive inertial focusing.Compared to traditional methods of inertial focusing,this design had advantages of not requiring additional sheath flow operations,and boasted high throughput and ease of manufacturing.This innovative structure opened up vast prospects for the development of portable inertial microfluidic chips,and could be used in the fields such as cell analysis and detection,flow cytometry,and online sample processing.