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

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

In the earliest days,the idea that surviving a single infection often resulted in lifelong immunity to the infecting pathogen was recorded and then led to the discovery of vaccination.We have now confirmed that such protection is primarily based on the generation of immunological memory in antibody response.With the wide implementation of more and more vaccines around the world,it is well documented that different vaccines have different potential regarding to the duration of antibody response.In clinical observations,live-attenuated vaccines often elicit long-term immunity but are also accompanied with risks in safety that are hard to avoid.In order to develop novel vaccines with both excellent potential in eliciting antibody memory and low safety risk,it is critical to further investigate the mechanism of antibody memory in the perspective of immunology.Antibody memory is mediated by certain long-lived B cells:long-lived plasma cell can secret antibody to maintain serum antibody titer while memory B cell contributes to the rapid immune response during the secondary encounter of pathogens.Cellular and molecular processes that drive the production of long-lived plasma cells and memory B cells are subjects of intensive research and have important implications for global health.Several factors in the vaccine would indeed affect and regulate these processes,including the antigen valency,vaccine kinetics and the signal integration of both antigen and danger molecules.Many studies have focused on strategies to manipulate these factors to improve or develop new vaccines.Here,we will summarize our current knowledge on how the component in vaccines will affect their potential in generating and sustaining antibody memory,and also point out the challenges we face in the route of developing a"perfect"vaccine.

Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.

Objective The evaluation of lymph node properties before lung cancer surgery has a great impact with the choice of surgical methods.Although there are various examination methods,many methods have invasive or accuracy problems.In order to improve the accuracy of diagnosis,we mainly discuss the value of wide-body spectral CT in the differential diagnosis of mediastinal metastatic lymph nodes,non-metastatic lymph nodes in lung cancer patients and reactive hyperplastic lymph nodes.Methods The clinical and imaging data of 64 patients with lung cancer and 28 patients with pulmonary inflammatory lesions were retrospectively analyzed.All patients underwent plain scan and enhanced dual-phase spectral CT scan.The size,density,three-phase IC,NIC,and λHU of lymph nodes in metastatic,non-metastatic and inflammatory reactive hyperplasia groups were measured on 70 keV single-energy images and iodine-based images,respectively.The single-factor variance and Kruskal-Wallis H rank sum test were used to analyze and compare the differences.Results The short diameter of metastatic lymph nodes was larger than that of non-metastatic lymph nodes and reactive hyperplastic lymph nodes(P<0.001).The plain scan density of reactive hyperplastic lymph nodes was higher than that of metastatic lymph nodes(P<0.001),but there was no significant difference between non-metastatic lymph nodes(P=0.325).The CT values of reactive hyperplastic lymph nodes in arterial phase and venous phase were higher than those of metastatic and non-metastatic lymph nodes(P<0.05).Except for NIC in arterial phase,IC,NIC and λHU in plain scan,IC and λHU in arterial phase,IC,NIC and λHU in venous phase of reactive hyperplastic lymph nodes and metastatic lymph nodes were statistically significant(all P<0.05).There was no significant difference in IC,NIC and λHU between reactive hyperplastic lymph nodes and non-metastatic lymph nodes in plain scan,arterial phase and venous phase(all P>0.05).Conclusion The quantitative and spectral curve slope of iodine in mediastinal metastatic lymph nodes of lung cancer were basically lower than those in reactive hyperplastic lymph nodes.The quantitative parameters of spectral CT had certain diagnostic efficacy in differentiating metastatic lymph nodes and reactive hyperplastic lymph nodes,while the spectral parameters of non-metastatic lymph nodes and reactive hyperplastic lymph nodes were not statistically significant.

OBJECTIVES: The excretion of urinary vitamin D-binding protein (uVDBP) is related to the occurrence and development of early-stage renal damage in patients with Type 2 diabetes (T2DM). This study aims to explore the significance of detecting uVDBP in T2DM patients and its relationship with renal tubules, and to provide a new direction for the early diagnosis of T2DM renal damage. METHODS: A total of 105 patients with T2DM, who met the inclusion criteria, were included as a patient group, and recruited 30 individuals as a normal control group. The general information and blood and urine biochemical indicators of all subjects were collected; the levels of uVDBP, and a marker of tubular injury [urine kidney injury molecule 1 (uKIM-1), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine retinol-binding protein (uRBP)] were detected by enzyme-linked immunosorbent assay. The results were corrected by urinary creatinine (Cr) to uVDBP/Cr, uKIM-1/Cr, uNGAL/Cr and uRBP/Cr. The Pearson's and Spearman's correlation tests were used to analyze the correlation between uVDBP/Cr and urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and markers of tubular injury, and multivariate linear regression and receiver operating characteristic curve were used to analyze the correlation between uVDBP/Cr and UACR or eGFR. RESULTS: Compared with the normal control group, the uVDBP/Cr level in the patient group was increased (P<0.05), and which was positively correlated with UACR (r=0.774, P<0.01), and negatively correlated with eGFR (r=-0.397, P<0.01). There were differences in the levels of uKIM-1/Cr, uNGAL/Cr, and uRBP/Cr between the 2 groups (all P<0.01). The uVDBP/Cr was positively correlated with uKIM-1/Cr (r=0.752, P<0.01), uNGAL/Cr (r=0.644, P<0.01) and uRBP/Cr (r=0.812, P<0.01). The sensitivity was 90.0% and the specificity was 82.9% (UACR>30 mg/g) for evaluation of uVDBP/Cr on T2DM patients with early-stage renal damage, while the sensitivity was 75.0% and the specificity was 72.6% for evaluation of eGFR on T2DM patients with early-stage renal damage. CONCLUSIONS The uVDBP/Cr can be used as a biomarker in early-stage renal damage in T2DM patients.
Humans ; Diabetes Mellitus, Type 2/complications* ; Creatinine ; Vitamin D-Binding Protein/urine* ; Lipocalin-2/urine* ; Kidney/metabolism* ; Glomerular Filtration Rate ; Biomarkers

Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer. However, the specific effective components and the potential mechanism of Poria remain largely unknown. To identify the effective components and the mechanism of Poria water extract (PWE) to treat dampness stagnancy due to spleen deficiency syndrome (DSSD), a rat model of DSSD was established through weight-loaded forced swimming, intragastric ice-water stimulation, humid living environment, and alternate-day fasting for 21 days. After 14 days of treatment with PWE, the results indicated that PWE increased fecal moisture percentage, urine output, D-xylose level and weight; amylase, albumin, and total protein levels; and the swimming time of rats with DSSD to different extents. Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS. Mechanistic studies revealed that PWE significantly increased the expression of serum motilin (MTL), gastrin (GAS), ADCY5/6, p-PKAα/β/γ cat, and phosphorylated cAMP-response element binding protein in the stomach, and AQP3 expression in the colon. Moreover, it decreased the levels of serum ADH, the expression of AQP3 and AQP4 in the stomach, AQP1 and AQP3 in the duodenum, and AQP4 in the colon. PWE induced diuresis to drain dampness in rats with DSSD. Eleven main effective components were identified in PWE. They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach, MTL and GAS levels in the serum, AQP1 and AQP3 expression in the duodenum, and AQP3 and AQP4 expression in the colon.
Animals ; Rats ; Poria ; Spleen ; Albumins ; Chromatography, Liquid ; Cyclic AMP Response Element-Binding Protein

Objective:The purpose of this study was to investigate the clinical value of CT-guided localization of pulmonary nodules with soft wire hook-wire by trailing technique.Methods:The clinical data of 211 pulmonary nodules of 185 patients from November 2020 to March 2022 in Beijing Aerospace General Hospital were retrospectively analyzed. The pulmonary nodules were localized with soft wire hook-wire by trailing technique before video-assisted thoracic surgery (VATS). The success rate, complications, pathological results and localization operations related data were statistically analyzed.Results:The success rate of localization was 97.63% (206/211), and the success rate of VATS removal was 99.53% (210/211). The average operation time was (7.19 ± 2.62) min, and the average time required for resection of lesions was 27 min (10 to 126 min). During the surgery, the soft wire hook-wire of two patient was found to be dislocated and retracted into the chest wall. The pulmonary nodules were successfully located and removed according traces left by puncture points on the lung surface. It was found that the hook-wire was located in the interlobar fissure in 3 patients. The pulmonary nodules were successfully removed by the hook-wire position and appropriately expanding the resection range. A minor pneumothorax occurred in 49 patients, but no closed drainage was needed; 12 patients developed intrapulmonary hematoma; 15 patients with chest pain were treated with analgesia.Conclusions:For small pulmonary nodules requiring thoracoscopic surgery, the computed tomography-guided pulmonary nodule localization with soft wire hook-wire by trailing technique is more convenient, safe and effective, and is worthy of promotion to use.

Ischemic stroke is a common neurological disorder that can lead to neuronal death and neurological dysfunction. Microglia is the main immune cells in the central nervous system, involved in post-stroke inflammation and tissue repair. Triggering receptor expressed on myeloid cells 2 (TREM2), a receptor expressed on the surface of microglia, plays a multifaceted role in neuronal survival and nerve repair after ischemic stroke, including promoting the phagocytosis of microglia, inhibiting excessive inflammatory response, maintaining the proliferation and survival of microglia, protecting neurons from damage, and promoting the recovery of nerve function. Therefore, elucidating the immunoregulatory mechanism of TREM2 on microglia after cerebral ischemia is of great significance for exploring new therapeutic directions for ischemic stroke.

Objective To investigate whether the semen quality of men undergoing conventional semen analysis from this center has changed over time in 10 years.Methods The data of 231 519 semen samples provided by males undergoing conventional seminal anal-ysis in outpatient department of Reproductive Medicine Affiliated to Shandong University from January 2013 to December 2022 were ret-rospectively analyzed.The sperm concentration,motility,percentage of progressively motile sperm and percentage of normal morphology sperm were analyzed according to the World Health Organization(WHO)Laboratory Manual for the Examination and Treatment of Hu-man Semen(5th edition)and the changes of these parameters in 10 years were compared.Results From 2013 to 2022,there were no significant changes in the proportions of men with different sperm concentration,motility,percentage of progressively motile sperm in reproductive clinics.Approximately 27％of infertile male patients had low sperm concentration each year,approximately 34％of infer-tile male patients had low sperm motility each year,approximately 10％of infertile male patients was not found sperm in semen samples each year,and the percentages of normal morphology sperm of approximately 57％of infertile male patients were lower than the refer-ence value.The semen routine analysis results of approximately 50％of infertile male patients were in the normal range.The proportion of normal semen population did not change significantly.Conclusion The semen quality of infertile men does not change significantly in recent 10 years.