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

To evaluate the clinical safety of four CD19-targeted and two BCMA-targeted chimeric antigen receptor T-cell (CAR-T) therapies.

OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

Rescue vehicles and nursing unit drug stock are important in the clinical rescue process.Strengthening the management of rescue vehicles and nursing unit drug stock is conducive to ensuring the safety of clinical medication and impro-ving the quality of medical services.Based on scientificity,universality,guidance,and operability principles,the standard prepa-ration team revealed relevant national policy documents,domestic and foreign standards specifications,and literature.It sorted the key contents of rescue vehicles and base drug management.After several rounds of opinion collection and expert argumentation,the social organization standard Pharmacy administration and pharmacy practice in healthcare institutions—Part 3-7-3:Pharma-ceutical supply services—Key drugs management—Rescue vehicle and nursing unit drug stock management was proved.The main content of the standard includes 10 elements from 3 key parts:basic requirements,management processes,and quality manage-ment and evaluation improvement,to provide guidance in allocating,storing,and managing rescue vehicles and nursing unit drug stock.

Objective To investigate the clinical characteristics and traditional Chinese medicine(TCM)syndrome types of colorectal polyp(CP)and to explore their correlation with hyperlipidemia and other related risk factors.Methods From January 2022 to December 2023,174 patients with CP(polyp group)and 87 patients without intestinal abnormalities(non-polyp group)who underwent colonoscopy or treatment at the Endoscopy Center of Dongguan Hospital of Guangzhou University of Chinese Medicine were selected.Their data of medical records were collected,including gender,age,body mass index(BMI),history of diabetes mellitus,history of hypertension,blood lipid indicators[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and arteriosclerosis index(AI)],the presence of fatty liver or not,and the foci,number,size,and pathological types of polyps.Moreover,TCM syndrome differentiation of patients in the polyp group was carried out,and then the clinical characteristics and TCM syndrome types of CP as well as their correlation with hyperlipidemia were statistically analyzed.Results(1)The age group of 41-60 years old accounted for a higher percentage in patients of the polyp group and non-polyp group,59.8％in the polyp group and 49.4％in the non-polyp group,and the comparison of ages between the two groups showed statistically significant difference(P＜0.05).(2)The polyp foci of CP were mostly located in the left colon,accounting for 63.2％;single polyp was common,accounting for 69.0％;the size of polyps was usually 1-10 mm,accounting for 90.2％;the polyps were predominated by non-adenomatous polyps,accounting for 51.1％.(3)In the polyp group,spleen deficiency and dampness retention syndrome was the predominated syndrome type,accounting for 44.8％,and then followed by syndrome of damp-heat in large intestine,which accounted for 30.5％.(4)Comparison of the distribution of BMI and history of diabetes mellitus among various TCM syndrome types showed statistically significant differences(P＜0.05),while no statistically significant differences were presented in the comparison of gender,age,history of hypertension,and history of fatty liver,as well as the polyp foci,number,size,and pathological types among patients with various TCM syndrome types(P＞0.05).(5)The percentage of complication of hyperlipidemia in the polyp group was significantly higher than that in the non-polyp group,and the difference was statistically significant(P＜0.01).The levels of TC,TG,LDL-C,and Al in the polyp group were significantly higher than those in the non-polyp group,the differences being statistically significant(P＜0.05 or P＜0.01).However,the difference of the HDL-C level between the two groups was not statistically significant(P＞0.05).(6)Comparison of TC and LDL-C levels among the patients with different polyp foci and LDL-C level among the patients with various TCM syndrome types showed statistically significant differences(P＜0.05 or P＜0.01),while no statistically significant differences of blood lipid indicators were presented among the patients with various foci,number,sizes,and pathological types of the polyp and among the patients with various TCM syndrome types(P＞0.05).Conclusion Age is a risk factor for CP.CP patients are usually differentiated as the syndrome of spleen deficiency and dampness retention and the syndrome of damp-heat in large intestine,and the distribution of TCM syndrome types exert a certain correlation with BMI and history of diabetes mellitus.Hyperlipidemia is also a risk factor for the onset of CP,and abnormal levels of TC,TG,LDL-C,and Al exert certain correlation with the occurrence of polyps.TC and LDL-C have a certain correlation with the polyp foci,and LDL-C may also be related to the distribution of TCM syndrome types.

Rescue vehicles and nursing unit drug stock are important in the clinical rescue process.Strengthening the management of rescue vehicles and nursing unit drug stock is conducive to ensuring the safety of clinical medication and impro-ving the quality of medical services.Based on scientificity,universality,guidance,and operability principles,the standard prepa-ration team revealed relevant national policy documents,domestic and foreign standards specifications,and literature.It sorted the key contents of rescue vehicles and base drug management.After several rounds of opinion collection and expert argumentation,the social organization standard Pharmacy administration and pharmacy practice in healthcare institutions—Part 3-7-3:Pharma-ceutical supply services—Key drugs management—Rescue vehicle and nursing unit drug stock management was proved.The main content of the standard includes 10 elements from 3 key parts:basic requirements,management processes,and quality manage-ment and evaluation improvement,to provide guidance in allocating,storing,and managing rescue vehicles and nursing unit drug stock.

OBJECTIVE To investigate the effects of clopidogrel on the pharmacokinetics and pharmacodynamics of ciprofol in rats.METHODS Eighteen male SD rats were randomly divided into control group,clopidogrel normal-dose group and clopidogrel high-dose group,with 6 rats in each group.Among them,rats in the normal-dose group and high-dose group were given 7.5 mg/kg and 15 mg/kg clopidogrel by gavage,respectively,and rats in the control group were given the same volume of 0.5％sodium carboxymethyl cellulose solution,once a day,for 14 consecutive days.Afterward,2.4 mg/kg ciprofol was injected by tailvein and blood samples were collected from the inner canthus of the eye at 2,4,8,12,16,20,30,45 and 60 min after the end of the administration.During this period,the duration of the loss of righting reflex(LORR)in rats was counted.After the proteins were precipitated by acetonitrile,the rat plasma sample was analyzed by LC-MS/MS using deuterated ciprofol as the internal standard,Symmetry C18 as the chromatographic column,and acetonitrile-0.01％ammonia solution containing 5 mmol/L ammonium acetate(gradient elution)as the mobile phase to detect the concentration of ciprofol in the plasma.The pharmacokinetic parameters in rats were calculated by using DAS 2.0 software.RESULTS Compared with control group,area under the drug concentration-time curve and mean residence time of ciprofol increased or prolonged significantly,while plasma clearance decreased significantly in clopidogrel normal-dose and high-dose groups;the duration of LORR in rats was prolonged by 19.5％and 23.9％,with statistical difference(P＜0.05).However,there was no statistically significant difference in the pharmacokinetic parameters or LORR duration of ciprofol between the different dose groups of clopidogrel(P＞0.05).CONCLUSIONS Clopidogrel could inhibit the metabolism of ciprofol in rats and prolong the duration of LORR.

Objective To investigate the effect of esketamine on perioperative pain and depression in patients with thoracoscopic pulmonary nodule resection. Methods A total of 120 patients with selective thoracoscopic pulmonary nodule resection were randomly divided into low-dose esketamine group (group L), high-dose esketamine group (group H) and saline control group (group C), with 40 cases in each group. Before skin incisionafter anesthetic induction, 0.25 mg/kgesketamine, 0.50 mg/kg esketamine and the equivalent amount of saline were separately administered for patients in the three groups. Visual Analogue Scale (VAS) score for pain and the Self-rating Depression Scale (SDS) score were compared among the three groups at the time points of one day before surgery (T₀), one day after surgery (T₁), three days after surgery (T₂), and the day of discharge (T₃), and postoperative analgesia within 24 h and perioperative adverse reactions were also recorded. Results The VAS scores for rest and coughing at T₁ were significantly lower in group L and group H than group C (P < 0.05); compared with group C, the total press number of analgesic pump with in 24 h and effective press number were significantly decreased in group L and group H, and the dosage of sufentanil was also significantly decreased(P < 0.05). There were no significant differences in depression scores at different time points among the three groups (P>0.05). There were no significant differences in the incidence rates of nausea, vomiting, dizziness, hallucinations, and nightmares among the three groups (P>0.05). Conclusion Esketamine can effectively alleviate pain on the first day after operation and reduce the dosage of opioid analgesics without increasing the incidence of adverse reactions in patients with thoracoscopic pulmonary nodule resection; compared with 0.25 mg/kg esketamine, 0.50 mg/kg esketamine doesn't demonstrate better postoperative analgesia or improvement in perioperative depression.

Objective:To explore the value of dual-layer detector spectral CT quantitative parameters in evaluating the treatment response of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).Methods:The study was a cross-sectional study. From May 2021 to March 2023, a total of 52 patients with LARC who received complete nCRT and were pathologically confirmed rectal adenocarcinoma at the Guangdong Province Hospital of Traditional Chinese Medicine were retrospectively enrolled. Each patient underwent spectral CT examination before and after nCRT, including plain scan, arterial phase (AP), and venous phase (VP) scans. According to the tumor regression grade, the patients were divided into the good response ( n=20) and the poor response group ( n=32). Measurements of the primary tumor′s spectral CT parameters, including effective atomic number (Z eff) at plain scan, iodine concentration (IC), CT values of 40 keV and 100 keV virtual monochromatic image (VMI) at dual-enhanced phases, were taken before and after nCRT. Additionally, the normalized iodine concentration (NIC), spectral curve slope (λHU), and the change rate of the above parameters before and after nCRT were calculated. The independent sample t-test or Mann-Whitney U test was used to compare the differences between the two groups. The receiver operating characteristic (ROC) curve was used to assess the efficacy of various metrics in evaluating the tumor treatment response of nCRT. A binary logistic regression analysis of combined parameter results was performed for the parameters with the areas under curve (AUC)>0.75, and the AUC of the combined parameter was evaluated. Results:There were significant differences in NIC AP and λHU VP before nCRT, NIC VP and λHU VP after nCRT, and the change rates of Z eff, NIC AP, NIC VP and λHU AP between the good response group and the poor response group ( P<0.05). The remaining parameters showed no statistically significant difference ( P>0.05). The ROC curve results showed that the AUCs of the above 8 parameters for evaluating tumor treatment response of nCRT were 0.702, 0.655, 0.695, 0.769, 0.738, 0.807, 0.791, and 0.677, respectively. The AUC of the combined model of the three parameters with AUC>0.75 (λHU VP after nCRT, the change rate of NIC AP and NIC VP) was 0.869, with 80.0% sensitivity and 84.4% specificity. Conclusion:The quantitative parameters derived from spectral CT may provide new markers for evaluating the response to nCRT treatment in patients with LARC. The multi-parameter combined model can improve diagnostic efficacy.

Objective:To identify the risk factors, and develop and validate a risk prediction model for abnormal bone mass in end-stage renal disease (ESRD) patients.Methods:It was a retrospective cross-sectional study. The clinical and laboratory data of ESRD patients who were hospitalized in the Department of Nephrology, Zhongda Hospital Affiliated to Southeast University from January 2022 to May 2023 were collected retrospectively. The patients were randomly divided into training and validation cohorts at a ratio of 7∶3. They were further divided into normal and abnormal bone mass groups according to the T value measured by dual-energy X-ray absorptiometry (DXA). Then, backward stepwise regression and least absolute shrinkage and selection operator (LASSO) were respectively used to develop the risk prediction model for abnormal bone mass in ESRD patients. Akaike information criterion (AIC), bayesian information criterion (BIC), and accuracy were used to evaluate the performance of these two models, after which the preferable model was selected. Moreover, the receiver operating characteristic (ROC) curve, calibration curve, Hosmer-Lemeshow test, and decision curve analyses (DCA) were applied to evaluate the diagnostic performance of the preferable model. Finally, a dynamic nomogram for individual assessment was constructed based on the preferable model.Results:A total of 254 ESRD patients were enrolled, including 160 (63.0%) males, 161 (63.4%) hemodialysis patients, and 202 (79.5%) patients with abnormal bone mass. There was no significant difference in the prevalence of abnormal bone mass between training group ( n=178) and validation group ( n=76) (79.2% vs. 80.3%, χ2=0.036, P=0.849). The final variables and variable parameters included in the LASSO and stepwise regression models were the same, which were five variables: age, body mass index, hypertension, diabetes, and osteocalcin. Both models also had the same AIC, BIC, and accuracy in the training group, which were 113.45, 132.54, and 0.837, respectively. Therefore, the LASSO model and the stepwise regression model performed consistently in this study and could be considered as the same model, hereafter referred to as the Model. The Model's area under the ROC curve in the training and validation groups was 0.923 (95% CI 0.884-0.963) and 0.809 (95% CI 0.675-0.943), respectively. The optimal cutoff for the training group was 0.858, with a sensitivity of 0.801, a specificity of 0.973 and an accuracy of 0.837; when this cutoff value was taken, the validation group's sensitivity was 0.689, specificity was 0.800, and accuracy was 0.711. The Model demonstrated excellent performance in the calibration curve, Hosmer-Lemeshow test ( P>0.05), and DCA. Finally, based on the five predictors of the Model, a dynamic nomogram was created for clinicians to enter baseline clinical parameters for early identification of high-risk patients with abnormal bone mass. Conclusions:A dynamic nomogram for abnormal bone mass in ESRD patients is constructed with good predictive performance based on the prediction model, which can be used as a practical approach for the personalized early screening and auxiliary diagnosis of the potential risk factors and assist physicians in making a personalized diagnosis for patients.