ObjectiveThis study aims to compare the modeling effects of submaxillary gland antigen and salivary gland antigen in the establishment of Sjögren syndrome (SS) mouse models, and to characterize the phenotypic and immunological features of these models in comparison with spontaneous SS-prone non-obese diabetic (NOD)/LtJ mice. MethodsAdult C57BL/6J mice (equal numbers of males and females) were immunized with submaxillary gland antigen or salivary gland antigen, respectively, combined with Freund's adjuvant to induce SS models. Mice immunized with phosphate-buffered saline (PBS) combined with Freund's adjuvant served as the control group. Immunization was induced via multiple subcutaneous injections in the back with antigen combined with Freund's complete adjuvant (FCA) on Days 1 and 7. A booster immunization was administered via multiple subcutaneous injections in the back with antigen combined with Freund's incomplete adjuvant (FIA) on Day 14. Female NOD/LtJ mice were used as the spontaneous SS model group, with ICR mice as the corresponding control strain for comparative analysis. Body weight, water intake, and salivary flow rate of mice were dynamically monitored for 4 weeks. At the end of the experiment, tissue and serum samples were collected, the weights of submaxillary glands, thymus, and spleen were measured, and organ indices (organ-to-body weight ratios) were calculated. Pathological morphological analysis of the submaxillary gland and spleen was performed with hematoxylin and eosin (HE) staining. Serum interleukin-17 (IL-17) level was detected using enzyme-linked immunosorbent assay (ELISA). Real-time quantitative polymerase chain reaction was used to detect the mRNA expression levels of SS type A (SSA) and SS type B (SSB) in submaxillary gland tissues. ResultsFemale mice in the submaxillary gland antigen group exhibited significantly increased water intake (P<0.05) and reduced salivary flow rate (P<0.05) compared with the female control group. No statistically significant differences were observed in the submaxillary gland index, thymus index and spleen index (P>0.05). Focal lymphocytic infiltration was observed in the submaxillary glands, and the splenic marginal zone was enlarged. Serum IL-17 levels were significantly increased (P<0.05). There was no significant difference in submaxillary gland SSA/SSB expression levels (P>0.05). Compared with the female control group, female mice in the salivary gland antigen group showed no statistically significant differences in water intake, salivary flow rate, submaxillary gland index, and spleen index (P>0.05), whereas the thymus index was significantly reduced (P<0.01). Mild inflammatory cell infiltration and glandular atrophy were observed in the submaxillary glands, and the splenic white pulp and marginal zone were slightly enlarged. Serum IL-17 levels and submaxillary gland SSB mRNA expression levels were significantly increased (P<0.01), whereas no significant change was observed in submaxillary gland SSA expression levels (P>0.05). Compared with the male control group, mild submaxillary gland atrophy was observed in male mice in the submaxillary gland antigen group, whereas no obvious changes were found in other modeling-related indicators (P>0.05). Compared with the ICR control group, NOD/LtJ model mice exhibited elevated water intake (P<0.05), significantly reduced salivary flow rate (P<0.01), no significant differences in the submaxillary gland index or spleen index (P>0.05), but a significantly increased thymus index (P<0.05). Marked focal infiltration was observed in the submaxillary glands, the splenic marginal zone was obviously enlarged, and serum IL-17 concentrations as well as submaxillary gland SSA/SSB expression levels were significantly increased (P<0.05). ConclusionSubmaxillary gland antigen and salivary gland antigen can induce SS-related features in female C57BL/6J mice. The SS-related phenotype is more pronounced in the submaxillary gland antigen group than in the salivary gland antigen group, but weaker than that in spontaneously SS-prone female NOD/LtJ mice. Immunization of male C57BL/6J mice with submaxillary or salivary gland antigens fails to induce an obvious SS phenotype.

Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Objective To investigate the clinical features,etiological features and prognosis of patients with hematologic diseases complicated with candidemia for improving clinical diagnosis and treatment.Methods A retrospective analysis was conducted for 107 hematological patients complicated with candidemia who were treated in the First Affiliated Hospital of Zhengzhou University,Henan Cancer Hospital,Henan Provincial People's Hospital,or Zhengzhou People's Hospital from June 2022 to May 2024.The clinical data and pathogenic bacteria were analyzed by univariate and multivariate analyses.Results The Candida pathogen of the 107 cases of candidemia were mostly Candida tropicalis(73.8％),followed by Candida parapsilosis,Candida glabrata,and Candida albicans.Antifungal susceptibility testing showed that 43.9％,47.7％,and 48.6％of the Candida strains were resistant voriconazole,fluconazole and itraconazole,respectively.Logistic regression analysis found that disease not in remission(OR=7.795,95％CI:2.274-26.723),septic shock(OR=10.376,95％CI:1.129-95.388),multiple organ dysfunction syndrome(MODS)(OR=9.107,95％CI:1.789-46.361),and inappropriate antifungal treatment(OR=3.422,95％CI:1.153-10.153)were risk factors for 30-day mortality in hematological patients with candidemia.Conclusions Candidemia in patients with hematological diseases is associated with high mortality rate,the major pathogen of which is Candida tropicalis.The Candida isolates showed high resistance rates to azoles.Disease not in remission,septic shock,MODS,and inappropriate antifungal treatment are the risk factors for mortality.

Myocardial infarction(MI)is the leading cause of mortality worldwide,with heart failure(HF)af-ter MI being the main driver of this high mortality rate.Currently,no method can effectively halt the progression from MI to HF.In recent years,research on myocardial regeneration has shown promise for the treatment of HF after MI.Studies have confirmed that the regulation of myocardial amino acid metabolism can achieve myocardial regeneration,and branched-chain amino acid(BCAA)metabolism is crucial for this process.BCAA can regulate the branched-chain keto acid level through the BCAA aminotransferase(BCAT)-branched-chain keto acid dehydrogenase(BCKDH),BCKDH ki-nase(BCKDK)-BCKDH,and mitochondrial protein phosphatase 2C(PP2Cm)-BCKDH axes,thereby activating the mam-malian target of rapamycin to promote myocardial regeneration.BCAA also participates in the crosstalk between glucose and lipid metabolism,reprogramming fatty acid oxidation towards glucose metabolism and inducing cardiomyocyte prolifer-ation.However,the effects of BCAA on myocardial regeneration have not been systematically reviewed.In this review,the relationship and underlying mechanism between BCAA and myocardial regeneration are discussed extensively from the perspective of amino acid metabolic reprogramming,providing a reference for the study and treatment of post-MI HF.

Objective To investigate the achievement of early fluid resuscitation targets and factors influencing 28-day outcomes in patients with sepsis.Methods A retrospective cohort analysis was conducted.A total of 164 patients with sepsis admitted to the First Affiliated Hospital of Xinjiang Medical University between January 2022 and January 2024 were enrolled.Patients were divided into survival and death groups based on 28-day survival status,with both groups receiving early fluid resuscitation.Comparisons were made between groups for general characteristics[gender,age,body mass index(BMI),infection site,comorbidities],primary indicators[central venous pressure(CVP),mean arterial pressure(MAP),urine output],and secondary indicators[blood lactate acid(Lac),procalcitonin(PCT),heart rate,sequential organ failure assessment(SOFA)on intensive care unit(ICU)admission day,Glasgow coma scale(GCS),duration and dose of vasoactive medication use].Univariate analysis identified variables associated with prognosis,followed by multivariate Logistic regression to select independent risk factors.Receiver operator characteristic(ROC curve)were plotted to assess predictive performance of each risk factor for the 28-day prognosis of patients with sepsis.Results This study included 164 patients.The primary infection sites were mainly the lungs,abdominal cavity,and urinary system,accounting for 42.7%(70/164),38.4%(63/164),and 9.1%(15/164)respectively.The survival group comprised 141 patients,while the the death group included 23 patients.No statistically significant differences existed between groups in gender,BMI,infection site(soft tissue infection vs.others),underlying diseases,MAP,urine output(all P>0.05).Compared to the survival group,the death group showed significantly higher age,pulmonary infection rate,Lac levels,vasoactive drug duration/dose,heart rate,and SOFA scores,while the rates of abdominal,and urinary tract infection,as well as CVP,PCT,and GCS scores were significantly lower(all P<0.05).The achievement rates of early fluid resuscitation parameters:MAP target achievement was highest at 78.7%(129/164),followed by urine output compliance at 78.0%(128/164),while CVP compliance was the lowest at 39.0%(64/164).The overall compliance rate was 21.3%(35/164).Univariate analysis showed that age,pulmonary infection,Lac levels,duration and dose of vasoactive drugs,heart rate,PCT,GCS score,and SOFA score were all risk factors affecting the 28-day prognosis of patients with sepsis(all P<0.05).Multivariate Logistic regression analysis showed Lac levels,and pulmonary infection were independent risk factors affecting 28-day prognosis of patients with sepsis[odds ratio(OR)were 0.801,3.966,0.812,95%confidence interval(95%CI)were 0.711-0.903,1.149-13.696,0.674-0.979 respectively,P values were<0.001,0.029,0.029 respectively].ROC curve analysis demonstrated that age,Lac levels,and pulmonary infection all possessed predictive value for 28-day outcomes(all P<0.05).Age exhibited the highest predictive value with an AUC of 0.922.At the optimal cut-off of 76.6 years,sensitivity reached 95.7%and specificity 80.9%.Conclusion The overall achievement rate of early fluid resuscation in sepsis patients was low,with age,Lac levels,and pulmonary infection being major factors influencing poor prognosis.

Objective: To investigate the factors affecting carotid plaques among perimenopausal women, so as to provide the basis for the prevention and early intervention of cardiovascular diseases in perimenopausal women. Methods: Perimenopausal women aged 40-60 who underwent health check-ups at Xingtai People's Hospital from January 2022 to January 2023 were selected as subjects by convenient sampling method. Demographic information, lifestyle, waist-to-hip ratio, and blood biochemical indicators were collected through questionnaire surveys, physical examinations, and laboratory tests. Carotid plaques were detected using a Doppler ultrasound diagnostic instrument. Factors affecting carotid plaques among perimenopausal women were identified using a multivariable logistic regression model. Results: Totally 2 146 perimenopausal women were surveyed, with an age of (50.04±5.82) years. Carotid plaques were detected in 525 cases, with a detection rate of 24.46%. Multivariable logistic regression analysis showed that older age (45-<50 years old, OR=1.474, 95%CI: 1.062-2.047; 55-60 years old, OR=1.779, 95%CI: 1.276-2.481), residing in urban areas (OR=1.601, 95%CI: 1.079-2.376), drinking (OR=1.805, 95%CI: 1.108-2.941), hypertension (OR=1.815, 95%CI: 1.290-2.553), abnormal waist-to-hip ratio (OR=2.479, 95%CI: 1.982-3.101), and abnormal atherogenic index of plasma (OR=1.325, 95%CI: 1.064-1.650) were associated with a higher risk of carotid plaques. College degree or above (college, OR=0.659, 95%CI: 0.502-0.865; bachelor's degree or above, OR=0.517, 95%CI: 0.397-0.673), physical exercise (OR=0.621, 95%CI: 0.494-0.781) were associated with a lower risk of carotid plaques. Conclusion The carotid plaques among perimenopausal women mainly affected by age, place of residence, educational level, alcohol consumption, physical exercise, hypertension, waist-to-hip ratio and atherogenic index of plasma.

Objective:To establish a high-performance liquid chromatography method for the determination of related substances in panamivir injection.Methods:The Waters Xbridge Peptide BEH C18(250 mm×4.6 mm,3.5 μm).Phosphate buffer-acetonitrile was used as mobile phase,gradient elution,flow rate 0.8 mL·min-1,column temperature 35℃,detection wavelength 210 nm.Results:Peramivir could be effectively separated from all known impurities,with a limit of quantification of 5.29-18.02 ng and a limit of detection of 1.59-5.41 ng,with a good linear relationship(r＞0.999 0)in the range of 200%of the limit of quantification to the limit concen-tration,and the average recovery rate of each impurity was 99.6%-106.8%(n=12).The results of three batches of peramivir injection samples showed that the known impurities and other largest single impurities were less than 0.2%,and the total impurities were less than 1.0%.Conclusion:Verified by analytical methodology,the method is convenient,fast,specific,sensitive,and accurate,and can be used for the determination of peramivir injection-related substances.

Objective:This study aimed to construct a prediction model for diagnosis of proliferative lupus nephritis based on a machine learning algorithm. Additionally, a user-friendly platform was developed to propose a non-invasive method to assist the pathologic classification of lupus nephritis.Methods:A retrospective analysis was conducted on clinical and pathological data of lupus nephritis patients confirmed by renal biopsy at Zhengzhou University People′s Hospital from January 2017 to August 2023. The study population was randomly divided into training and testing sets in a 7∶3 ratio. Utilizing six machine learning algorithms, classification models were developed. The predictive performance of each model was assessed using metrics such as accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). The optimal model, once identified, was deployed as a web-based calculator for convenient model application. SPSS 25.0 and R 4.2.2 were used to analyze the data.Results:The study included a total of 212 patients, with 138 cases with proliferative lupus nephritis and 74 cases with non-proliferative lupus nephritis. The AUC values for the six models, namely logistic regression, decision tree, random forest, support vector machine, extreme gradient boosting, and light gradient boosting machine, were 0.79, 0.62, 0.79, 0.88, 0.81, and 0.77, respectively; the accuracy rates were 82.54%, 65.08%, 74.60%, 85.71%, 69.84%, 71.43%, respectively. Among them, the support vector machine model demonstrated the optimal performance. This model had deployed as a web-based calculator. Based on feature importance scores, the top 10 influencing factors were identified, including anti URNP antibody, immunoglobulin G, serum globulin, estimated glomerular filtration rate, anti Smith antibody, BMI index, anti dsDNA antibody, uric acid, anti-Rib.p antibody, and gender.Conclusion:A prediction model based on machine learning algorithms was successfully established, and a web calculator was developed to offer a simple and non-invasive method for diagnosing proliferative lupus nephritis. This can assist clinicians in evaluating the risk-benefit ratio of kidney biopsy in patients with lupus nephritis.

Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and advanced fibrosis, is a leading cause of chronic liver disease worldwide, progressing to cirrhosis and ultimately hepatocellular carcinoma (HCC). Excessive accumulation of fatty acids in the liver triggers multiple forms of hepatocyte death and exacerbates NAFLD progression, with pyroptosis and apoptosis considered key events. Recent studies show that cysteine aspartic acid specific protease-3 (caspase-3) is a central regulator of both pyroptosis and apoptosis in NAFLD. Activated caspase-3 not only directly induces apoptosis but also cleaves the N-terminal domain of gasdermin E (GSDME), disrupts cell membranes, releases inflammatory factors, and thereby mediates pyroptosis. Inhibiting caspase-3 expression in NAFLD can alleviate hepatocyte injury (such as ballooning degeneration), dampen pro-inflammatory signaling, and reduce apoptosis. Caspase-3 acts as a key node coordinating pyroptosis and apoptosis and may serve as a novel therapeutic target for the prevention and treatment of NAFLD.
Non-alcoholic Fatty Liver Disease/metabolism* ; Humans ; Pyroptosis/physiology* ; Apoptosis/physiology* ; Caspase 3/physiology* ; Animals ; Gasdermins

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization