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

BACKGROUND: The mechanisms distinguishing metabolically healthy from unhealthy phenotypes within the same BMI categories remain unclear. This study aimed to investigate the associations between regional fat distribution and metabolically unhealthy phenotypes in Chinese adults across different BMI categories. METHODS: This cross-sectional study involving 11833 Chinese adults aged 20 years and older. Covariance analysis, adjusted for age, compared the percentage of regional fat (trunk, leg, or arm fat divided by whole-body fat) between metabolically healthy and unhealthy participants. Trends in regional fat percentage with the number of metabolic abnormalities were assessed by the Jonckheere-Terpstra test. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated by logistic regression models. All analyses were performed separately by sex. RESULTS: In non-obese individuals, metabolically unhealthy participants exhibited higher percent trunk fat and lower percent leg fat compared to healthy participants. Additionally, percent trunk fat increased and percent leg fat decreased with the number of metabolic abnormalities. After adjustment for demographic and lifestyle factors, as well as BMI, higher percent trunk fat was associated with increased odds of being metabolically unhealthy [highest vs. lowest quartile: ORs (95%CI) of 1.64 (1.35, 2.00) for men and 2.00 (1.63, 2.46) for women]. Conversely, compared with the lowest quartile, the ORs (95%CI) of metabolically unhealthy phenotype in the highest quartile for percent arm and leg fat were 0.64 (0.53, 0.78) and 0.60 (0.49, 0.74) for men, and 0.72 (0.56, 0.93) and 0.46 (0.36, 0.59) for women, respectively. Significant interactions between BMI and percentage of trunk and leg fat were observed in both sexes, with stronger associations found in individuals with normal weight and overweight. CONCLUSIONS Trunk fat is associated with a higher risk of metabolically unhealthy phenotype, while leg and arm fat are protective factors. Regional fat distribution assessments are crucial for identifying metabolically unhealthy phenotypes, particularly in non-obese individuals.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Adipose Tissue ; Body Fat Distribution ; Body Mass Index ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Phenotype

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Objective To explore the application value of fractional anisotropy(FA)analysis of RGB component transformation in different directions of fibers in substantia nigra in Parkinson's disease(PD).Methods There were 35 cases of PD and 37 cases of normal control group.After being performed by brain diffusion tensor imaging(DTI)scanning,the sequence was imported into 3DSlicense 5.6.0,and the diffusion module was used to implement pseudo color mapping based on FA,locate and segment substantia nigra,and use the substantia nigra mask as the tracking starting point.After forming tracing,fibers were imported into DTIANALYSIS 1.51,converting the RGB components into FA values for analysis,and visualized the analysis result.At the same time,fiber length,fiber density,and segmented FA point cloud percentage were compared.Results Compared with the normal group,the length of substantia nigra fibers in the PD group was shorter[(95.14±19.85)mm vs(115.99±21.39)mm,P＜0.01],and there was a statistical difference between the two groups.There was no statistical difference in fiber density[(0.07±0.05)/mm3 vs(0.10±0.12)/mm3,P＞0.05]between control group and PD group.The percentage of FA segment point clouds in the PD group was lower than that in the normal group at 0.9-1,but the principal component characteristics of the point cloud ratios in each FA segment were not significant.Conclusion Based on the transformation of RGB components into FA analysis,the length,density,and FA values of substantia nigra nerve fibers in PD patients can be quantified and visualized,providing a basis for the study of PD neural pathways.

Objective To explore the visualization effect of different walking fibers and anatomical positions of the basal nucleus in the postcentral gyrus based on the diffusion tensor imaging(DTI)fiber bundle of the precentral gyrus and internal capsule reconstruction model.Methods A set of diffusion tensor volume(DTV)data was used to visualize and export a mesh model by a 3DSlicense 5.6.2 software.The basal nucleus were reconstructed by 3DSlicense through T1W1 data from the same scan,and exported the mesh model,and thus imported the above model into DTIANALYSIS 1.51 software for visualization.By adjusting the RGB component threshold,the fiber bundles were screened to obtain fiber bundles that mainly run left and right,front and back,and up and down.The anatomical relationship between the fiber bundles and the basal nucleus was observed.Results The fiber bundles originating from the precentral gyrus were mainly distributed in the inner and lower parts,and run above and outside the basal nucleus;The fiber bundles that mainly run forward and backward are distributed on the outer side and run on the outer side of the basal nucleus;The fiber bundles that mainly run up and down were distributed in the upper and middle parts of the precentral gyrus,with some fibers running towards the hypothalamus.They intersect in the corpus callosum and ventral pons,and run along the posterior part of the space between the lentiform nucleus and the dorsal thalamus.Conclusion Based on the RGB components in DTI,fibers with different walking directions in the precentral gyrus can be screened to display their anatomical position relationship with the basal ganglia.

Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.

Objective To compare the dosimetric effects of volume modulated arc therapy(VMAT)and intensity modulated radiation therapy(I M RT)on the anal sphincter(AS)and its sub-structures in neoadjuvant radiotherapy for rectal cancer to facilitate the selection of radiotherapy techniques.Methods Fifty rectal cancer patients receiving neoadjuvant radiotherapy were selected,and 2 types of radiotherapy plans,including coplanar double full-arc VMAT and coplanar seven-field homo-geneous IMRT,were designed based on the CT images of the patients,respectively.Under the premise of ensuring that the irradiated doses to the target area and the major organs at risk reached the standard and met the clinical requirements,AS and its substructures were added as the organs at risk for dosimetric evaluation.The absolute dose parameters and relative dose parameters of AS and its substructures were counted by dose-volume histograms.Statistical analysis was performed using IBM SPSS 22.0 software.Results The VMAT plan had the relative dose parameters V20,V30,and V40 of AS and its substructures lower those of the IMRT plan,the differences were statistically significant(P＜0.05),while the differences in V5 and V 10 were not statistically significant(P＞0.05).The VMAT plan had the absolute dose parameterDmeanlower while the D2％slightly higher than those of the IMRT plan,the differences were statistically significant(P＜0.05).The difference in D98％between the two plans was not statistically significant(P＞0.05).Conclusion During rectal cancer radiotherapy VMAT generally behaves better than IMRT in protecting AS and its sub-structures and decreasing injuries of AS and its sub-structures dosimetrically.[Chinese Medical Equipment Journal,2024,45(8):63-67]

This study explores the effect of apigenin(APG), oxymatrine(OMT), and APG+OMT on the proliferation of non-small cell lung cancer cell lines and the underlying mechanisms. Cell counting kit-8(CCK-8) assay was used to detect the vitality of A549 and NCI-H1975 cells, and colony formation assay to evaluate the colony formation ability of the cells. EdU assay was employed to examine the proliferation of NCI-H1975 cells. RT-qPCR and Western blot were performed to detect the mRNA and protein expression of PLOD2. Molecular docking was carried out to explore the direct action ability and action sites between APG/OMT and PLOD2/EGFR. Western blot was used to study the expression of related proteins in EGFR pathway. The viability of A549 and NCI-H1975 cells was inhibited by APG and APG+OMT at 20, 40, and 80 μmol·L~(-1) in a dose-dependent manner. The colony formation ability of NCI-H1975 cells was significantly suppressed by APG and APG+OMT. The mRNA and protein expression of PLOD2 was significantly inhibited by APG and APG+OMT. In addition, APG and OMT had strong binding activity with PLOD2 and EGFR. In APG and APG+OMT groups, the expression of EGFR and proteins in its downstream signaling pathways was significantly down-regulated. It is concluded that APG in combination with OMT could inhibit non-small lung cancer, and the mechanism may be related to EGFR and its downstream signaling pathways. This study lays a new theoretical basis for the clinical treatment of non-small cell lung cancer with APG in combination with OMT and provides a reference for further research on the anti-tumor mechanism of APG in combination with OMT.
Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; Apigenin ; Molecular Docking Simulation ; Alkaloids ; Quinolizines ; RNA, Messenger ; ErbB Receptors

OBJECTIVE: To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12. RESULTS: In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred. CONCLUSIONS GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).
Humans ; Percutaneous Coronary Intervention/adverse effects* ; Quality of Life ; Depression ; Coronary Disease/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Angina Pectoris/drug therapy* ; Prognosis ; Anxiety ; Treatment Outcome ; Double-Blind Method