BACKGROUND: Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq). METHODS: Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR. CONCLUSIONS Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.
Animals ; Mice ; Chronic Kidney Disease-Mineral and Bone Disorder/genetics* ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; Sphingolipids/metabolism* ; Transcriptome/genetics* ; Signal Transduction/genetics* ; X-Ray Microtomography ; Adenine

OBJECTIVE: To compare the diagnostic accuracy of supraspinatus muscle outlet X-ray film, oblique sagittal multislice helical CT (MSCT), and oblique sagittal MRI in the diagnosis of subacromial impingement syndrome (SIS). METHODS: A retrospective analysis was conducted on the imaging data of 106 patients diagnosed with SIS between January 2023 and December 2024. The cohort consisted of 32 males and 74 females, with ages ranging from 43 to 70 years (mean, 60.19 years). All patients underwent supraspinatus muscle outlet X-ray film, MSCT, and MRI scans, with MSCT further subjected to three-dimensional reconstruction. Two experienced radiologists independently evaluated the acromion morphology in each imaging modality using the Bigliani classification system. Inter-observer reliability was assessed via Kappa statistics. The CT three-dimensional reconstructions were used as the "gold standard". The overall consistency, Kappa values, sensitivity, and specificity of the three imaging modalities were calculated. Receiver operating characteristic (ROC) curves were plotted, and the area under the curve (AUC) was computed. RESULTS: The inter-observer reliability for supraspinatus muscle outlet X-ray film, oblique sagittal MSCT, and oblique sagittal MRI was moderate, with Kappa values of 0.62, 0.63, and 0.55, respectively. When compared to the CT three-dimensional reconstructions as the "gold standard", the overall consistency was 88.7% (94/106), 62.3% (66/106), and 58.5% (62/106), respectively. The supraspinatus muscle outlet X-ray film showed excellent consistency (Kappa=0.77), whereas the consistency of MSCT and MRI was lower (Kappa=0.34 and 0.29, respectively). In terms of diagnostic sensitivity and specificity, the supraspinatus muscle outlet X-ray film outperformed oblique sagittal MSCT and oblique sagittal MRI in distinguishing various acromion types. ROC analysis demonstrated that the AUC for the supraspinatus muscle outlet X-ray film was consistently higher than for oblique sagittal MSCT and oblique sagittal MRI, with the highest diagnostic performance observed for type Ⅲ hooked acromion (AUC=0.939). CONCLUSION Supraspinatus muscle outlet X-ray film provides the highest diagnostic accuracy for acromion classification in SIS patients, particularly in identifying type Ⅲ hooked acromion, which is strongly associated with SIS. Given its superior sensitivity and consistency, it should be considered the primary screening tool. MSCT and MRI serve as valuable supplementary modalities for complex cases and preoperative evaluation.
Humans ; Middle Aged ; Male ; Female ; Shoulder Impingement Syndrome/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Retrospective Studies ; Aged ; Adult ; Imaging, Three-Dimensional ; Sensitivity and Specificity ; Tomography, Spiral Computed/methods* ; Multidetector Computed Tomography/methods* ; Reproducibility of Results

Objective To investigate the effects of Amanita caojizong on cardiomyocyte apoptosis and the expression of apoptosis-related factors Bcl-2 and Bax,thereby providing experimental evidence for the prevention and treatment of Amanita caojizong poisoning.Methods Mouse cardiomyocytes(HL-1 cells)cultured in vitro were divided into an experimental group(treated with Amanita caojizong extract)and a control group(treated with PBS).After treatment with Amanita caojizong extract,apoptosis of HL-1 cells was observed using TUNEL staining,and the protein expression levels of Bax,Bcl-2,Caspase-3,and Cleaved Caspase-3 in HL-1 cardiomyocytes were detected by Western blot.Results Compared with the control group,the TUNEL staining showed significantly increased apoptotic fluorescence intensity in the Amanita caojizong extract-treated group.The protein expressions of Bax,Caspase-3,and Cleaved Caspase-3 in HL-1 cells in the Amanita caojizong-treated group were upregulated,while the expression of Bcl-2 was downregulated.Conclusion Amanita caojizong can promote apoptosis of mouse cardiomyocytes,and its mechanism may be associated with the Bcl-2/Bax pathway.

Objective To investigate the effects of Amanita caojizong on cardiomyocyte apoptosis and the expression of apoptosis-related factors Bcl-2 and Bax,thereby providing experimental evidence for the prevention and treatment of Amanita caojizong poisoning.Methods Mouse cardiomyocytes(HL-1 cells)cultured in vitro were divided into an experimental group(treated with Amanita caojizong extract)and a control group(treated with PBS).After treatment with Amanita caojizong extract,apoptosis of HL-1 cells was observed using TUNEL staining,and the protein expression levels of Bax,Bcl-2,Caspase-3,and Cleaved Caspase-3 in HL-1 cardiomyocytes were detected by Western blot.Results Compared with the control group,the TUNEL staining showed significantly increased apoptotic fluorescence intensity in the Amanita caojizong extract-treated group.The protein expressions of Bax,Caspase-3,and Cleaved Caspase-3 in HL-1 cells in the Amanita caojizong-treated group were upregulated,while the expression of Bcl-2 was downregulated.Conclusion Amanita caojizong can promote apoptosis of mouse cardiomyocytes,and its mechanism may be associated with the Bcl-2/Bax pathway.

BACKGROUND:Sarcopenia refers to age-related progressive,systemic muscle mass reduction and/or muscle strength decline or muscle physiological function decline,which is related to the occurrence of a variety of adverse outcomes in older adults.Exercise is considered to be one of the main strategies for combating sarcopenia in older adults,but there is a lack of specific intervention methods of different exercise patterns to intervene in sarcopenia. OBJECTIVE:To elaborate the main influencing factors of sarcopenia and the research progress of different exercise methods to improve sarcopenia in older adults,providing reference and basis for combating sarcopenia in older adults. METHODS:Web of Science,PubMed,CNKI,VIP,WanFang databases were retrieved for relevant literature published from January 2000 to October 2023 using the keywords of"sarcopenia,sport,exercise intervention,resistant training,aerobic exercise,whole body vibration training,mixed training,physical performance,muscle strength,muscle mass"in Chinese and English,respectively.A total of 126 articles were included for review. RESULTS AND CONCLUSION:Resistance exercise is still the most effective way to prevent and treat senile sarcopenia,and the effect of high-intensity resistance exercise is more significant.However,in practical application,we should pay attention to the gradual increase of training load intensity.Aerobic exercise combined with resistance exercise is more effective to improve muscle mass and function in the elderly than a single exercise mode.It is suggested that older adults can carry out the transition of low-intensity aerobic exercise in the early stage and increase resistance exercise individually in the late stage.Whole body vibration training is a new treatment method for the prevention and treatment of senile sarcopenia,but particular attention should be paid to the effects of frequency,amplitude,and duration on patients during practical application.Multicomponent exercise combines different exercise modes,which can give full play to their respective advantages,so as to personalize exercise interventions.

OBJECTIVE: To analyze the association between pulmonary surfactant protein C (SP-C) gene polymorphisms and the risk of Neonatal respiratory distress syndrome (NRDS). METHODS: Clinical data from 168 neonates diagnosed with NRDS (NRDS group) admitted between August 2020 and June 2023 were collected. Additionally, 168 neonates without respiratory distress, born during the same period, were included as the control group. Peripheral venous blood samples (2 mL each) were collected from both groups. PCR-restriction fragment length polymorphism technique was employed to detect the polymorphisms at the SP-C gene loci p.Thr138Asn (rs4715) and p.Ser186Asn (rs1124). Hardy-Weinberg equilibrium tests were conducted for genotyping, and genotypic and allelic frequencies were compared. The association between SP-C gene polymorphisms and NRDS risk was evaluated. Furthermore, genotypic and allelic frequencies at the rs4715 and rs1124 loci were compared among NRDS cases with varying degrees of disease severity. The study was approved by the Medical Ethics Committee of Shangqiu First People's Hospital (Ethics No. 2020-031). RESULTS: The frequency of the variant allele (A) at the rs4715 locus was significantly higher in the NRDS group compared to the control group (32.14% vs. 24.11%, P = 0.001). The frequency of the variant genotype (AA + AC) was also higher in the NRDS group (47.02% vs. 39.29%, P = 0.043). The frequency of the variant allele (A) at the rs1124 locus was higher in the NRDS group compared to the control group (34.23% vs. 23.51%, P = 0.027), with a higher frequency of the variant genotype (AA + AG) in the NRDS group (49.40% vs. 39.29%, P = 0.019). No significant correlation was observed between the rs4715 polymorphism and the severity of NRDS (P > 0.05). Among NRDS children with grade III severity, the frequency of the variant allele (A) at the rs1124 locus was higher than in grade I and grade II children (47.62% vs. 29.22%, P = 0.020). The frequency of the variant genotype (AA + AG) was also higher in grade III children (64.28% vs. 43.84%, P = 0.040). CONCLUSION SP-C gene polymorphisms are associated with the susceptibility to NRDS. Neonates carrying the AA genotype and the A allele at the rs1124 locus are at a higher risk of severe NRDS. These findings have provided further evidence for early screening, diagnosis, and treatment of NRDS.
Humans ; Respiratory Distress Syndrome, Newborn/genetics* ; Infant, Newborn ; Gene Frequency ; Genotype ; Polymorphism, Single Nucleotide ; Pulmonary Surfactant-Associated Protein C/genetics* ; Genetic Predisposition to Disease ; Female ; Male ; Alleles

Objective:To analyze the association between pulmonary surfactant protein C ( SP- C) gene polymorphisms and the risk of Neonatal respiratory distress syndrome (NRDS). Methods:Clinical data from 168 neonates diagnosed with NRDS (NRDS group) admitted between August 2020 and June 2023 were collected. Additionally, 168 neonates without respiratory distress, born during the same period, were included as the control group. Peripheral venous blood samples(2 mL each) were collected from both groups. PCR-restriction fragment length polymorphism technique was employed to detect the polymorphisms at the SP- C gene loci p. Thr138Asn (rs4715) and p. Ser186Asn (rs1124). Hardy-Weinberg equilibrium tests were conducted for genotyping, and genotypic and allelic frequencies were compared. The association between SP- C gene polymorphisms and NRDS risk was evaluated. Furthermore, genotypic and allelic frequencies at the rs4715 and rs1124 loci were compared among NRDS cases with varying degrees of disease severity. The study was approved by the Medical Ethics Committee of Shangqiu First People′s Hospital (Ethics No. 2020-031). Results:① The frequency of the variant allele (A) at the rs4715 locus was significantly higher in the NRDS group compared to the control group (32.14% vs. 24.11%, P=0.001). The frequency of the variant genotype (AA + AC) was also higher in the NRDS group (47.02% vs. 39.29%, P=0.043). ② The frequency of the variant allele (A) at the rs1124 locus was higher in the NRDS group compared to the control group (34.23% vs. 23.51%, P=0.027), with a higher frequency of the variant genotype (AA + AG) in the NRDS group (49.40% vs. 39.29%, P=0.019). ③ No significant correlation was observed between the rs4715 polymorphism and the severity of NRDS ( P>0.05). ④ Among NRDS children with grade Ⅲ severity, the frequency of the variant allele (A) at the rs1124 locus was higher than in grade Ⅰ and grade Ⅱ children (47.62% vs. 29.22%, P=0.020). The frequency of the variant genotype (AA + AG) was also higher in grade Ⅲ children (64.28% vs. 43.84%, P=0.040). Conclusion:SP- C gene polymorphisms are associated with the susceptibility to NRDS. Neonates carrying the AA genotype and the A allele at the rs1124 locus are at a higher risk of severe NRDS. These findings have provided further evidence for early screening, diagnosis, and treatment of NRDS.

Sleep disorders,a common concern in modern society,seriously affect people's physical and mental health.Reported findings suggest that both acute exercise intervention and long-term regular exercise intervention can improve the disrupted sleep structure and normalize the duration and proportion of the different phases of sleep.Moreover,exercise intervention has a positive effect on the endocrine functions,the metabolic functions,the immune response,the autonomic nervous system,and cardiac functions during sleep.It is a non-medicative therapeutic strategy for improving sleep disorders.The specific type of exercise intervention(aerobic exercise,resistance exercise,or meditative movement)adopted is one of the moderating variables of exercise intervention programs.Different types of exercise improve sleep disorders by way of different mechanisms.Exercise volume and intensity are another moderating variable of exercise intervention programs.The optimal amount and intensity of exercise for different individuals to improve sleep disorders may vary.Exercise interventions implemented at the different times throughout a day can also have varying degrees of impact on sleep disorders and there is no consensus on the optimal exercise time for improving sleep quality at present.Herein,we summarized the mechanisms by which exercise intervention improves sleep disorders from four perspectives,including epigenetics,hyperarousal,human circadian rhythm,and body temperature regulation.In addition,we discussed the current gaps and prospects of research in this field,aiming to provide a theoretical basis for the development of exercise prescriptions for sleep disorders.

Objective:To identify early predictors of factors influencing the efficacy of infliximab (IFX) treatment in patients with Crohn's disease (CD) .Methods:This study is a nested case-control study, including CD patients treated with IFX at the Second Affiliated Hospital of Soochow University from November 2015 to April 2021 and at the First Affiliated Hospital of Nanjing Medical University from November 2015 to December 2022. All the patients were followed up until June 2023 and categorized into IFX non-response and treatment-effective groups based on changes in clinical symptoms and endoscopic image during the follow-up. Laboratory data of inflammatory markers, post-induction trough IFX concentration and antibody levels in both groups were retrospectively collected and compared. Logistic regression models were employed to identify potential factors associated with the risk of IFX non-responsiveness. Machine learning using random forest analysis was utilized to quantitatively assess the predictive features for IFX treatment efficacy and ROC curves was used to evaluate the model's accuracy.Results:This study included 147 CD patients undergoing IFX treatment, with 58 from the Second Affiliated Hospital of Soochow University and 89 from the First Affiliated Hospital of Nanjing Medical University. Among them, 38 were classified as the IFX non-response group, and 109 as the effective group. Patients in the IFX non-response group had lower trough concentration ( P < 0.001), higher antibody levels ( P < 0.001), and a less pronounced reduction in ESR during the induction therapy ( P < 0.001). Univariate and multi-variate Logistic regression models demonstrated that IFX trough concentration and the ratio of ESR before and after induction therapy was associated with the risk of non-responsiveness. After the induction period, for each unit increase in IFX trough concentration (1 μg/ml), the risk of IFX non-response decreased by 23% ( RR = 0.77, 95% CI = 0.68-0.89), while each doubling of the ESR ratio after induction was associated with a 1.43-fold increase in the risk of non-response ( RR = 2.43, 95% CI = 1.48-4.00). Random forest machine learning analysis revealed that IFX trough concentration below 1.5 μg/ml could predict IFX non-response, with area under the ROC curve was 0.722. Conclusion:Lower post-induction IFX trough concentrations is predictive of IFX non-response, while a lack of significant decrease in ESR during the induction phase is also significantly associated with IFX non-response.

An antibody-drug conjugate(ADC)is a targeted therapeutic drug composed of a monoclonal antibody linked to a small-molecule cytotoxic drug via a linker.Once administered,ADCs bind to tumor-specific antigens,forming ADC-antigen complexes,which are internalized through endocytosis.The linkers are then cleaved via endosomal-lysosome pathway and the cytotoxic drug is released,which induces apoptosis in the target cells.ADCs combine the advantages of monoclonal antibody drugs and cytotoxic drugs.They are able to reduce damage to normal cells while killing target cells,thus exhibiting higher anti-tumor efficiency.As the treatment of hematological malignancies gradually advances into the era of targeted immunotherapy,ADCs,as one of the hot spots,have shown broad prospects and also face many challenges in drug development and clinical application.Currently marketed ADCs in China include brentuximab vedotin(anti-CD30),inotuzumab ozogamicin(anti-CD22)and polatuzumab vedotin(anti-CD79B),while those marketed abroad include gemtuzumab ozogamicin(anti-CD33)and loncastuximab tesirine(anti-CD19),all demonstrating good efficacy and safety in clinical practice.Additionally,ADCs targeting different antigens such as CD123,CD19,CD20,receptor tyrosine kinase-like orphan receptor 1(ROR1),and CD38 are undergoing clinical studies.Globally,there are over a hundred ADCs in development,and it is hoped that more breakthroughs will be achieved in the future to further optimize the treatment strategies for hematologic malignancies.