[摘 要] 目的：探究伴有肾损害（RI）的多发性骨髓瘤（MM）患者与无RI患者间是否存在免疫学指标差异。方法：用2017年1月至2023年8月在兰州大学第二医院收治的134例首次确诊为MM的患者相关信息进行回顾性分析，研究对比RI组和非RI组及Durie⁃Salmon（DS）分期和危险分层两个亚组的10种免疫学指标和6个常规血液学参数的差异。结果：RI组外周血中性粒细胞/淋巴细胞比值（NLR）、外周血单核细胞/淋巴细胞比值（MLR）、CD8+ T细胞比例、IL-10均较非RI组高（均P<0.05），淋巴细胞绝对值、CD4/CD8比值均较非RI组低（均P<0.05）。DS-Ⅲ分期患者中，RI组NLR、MLR、CD8+ T细胞比例、IL-8、IL-10均较非RI组升高（均P<0.05），而DS-Ⅰ和DS-Ⅱ患者中，RI组和非RI组患者免疫指标无明显差异。高危MM患者RI组淋巴细胞数、NLR、IL-10均较非RI有明显差异（均P<0.05）。结论：伴RI的MM患者免疫相关指标异常更为明显，DS-Ⅲ分期和高危险度分层表现出明显的免疫指标异常，本研究结果对进一步阐明MM伴有RI患者预后较差的原因及个体化治疗提供参考依据。

Objective To clarify the characteristics of shock wave sources generated at different medium interfaces.Methods The experiment used an in vitro adjustable impact pressure shock wave generation and signal acquisition system combined with a flexible PVDF sensor.The waveform of the shock wave generated by the applicator at the interface of different media(soft tissue-mimicking phantom,water and air)was explored.The characteristics of the shock wave source in the time and frequency domains were analyzed.Results When the same impact pressure was applied,shock waveforms generated at the interfaces of the phantom and water exhibited similar characteristics from a time-domain perspective.At the same time,both differed significantly from those generated at the air interface,where the absolute values of the positive and negative pressures were noticeably reduced.The characteristics of the shockwave spectra in various media revealed three distinct peak frequencies,with the modulation frequencies varying in the phantom(12.2 kHz),water(8.5 kHz),and air(7.2 kHz).In contrast,the carrier frequency remained relatively constant(between 82 and 83 kHz).When different impact pressures were applied,there was little influence on the waveform at the same medium interface,indicating that the impact pressure affected only the shockwave amplitude and not the peak frequency.As the impact pressure increases,the absolute values of the positive and negative pressures at the medium interface increase linearly.Conclusions Shockwave sources can be effectively measured using a flexible PVDF sensor.Shock waves generated at different medium interfaces exhibit temporal and spectral differences,indicating that the characteristics of shock wave propagation in air or water cannot be substituted for those in biological soft tissues.These findings provide crucial information for evaluating shockwave devices and formulating treatment protocols in the clinic.

Objective To investigate the clinical value of uric acid(UA)to albumin(Alb)ratio(UAR)in predicting the prognosis of the patients with heart failure.Methods A total of 1 893 patients with heart failure and complete clinical data in the Chinese Heart Failure Database were selected as the clinical research subjects for conducting the retrospective cohort analysis.The general clinical data,coagulation routine,tropo-nin Ⅰ(cTnⅠ),cardiac enzyme profile,liver function,B-type brain natriuretic peptide(BNP),uric acid(UA)and left ventricular ejection fraction in echocardiography in the study subjects were collected to calculate UAR.Ac-cording to the receiver operating characteristic(ROC)curve,the optimal cut-off value of UAR was selected as 17.48.Then the subjects were divided into the low UAR group(UAR＜17.48,n=1 525)and high UAR group(UAR≥17.48,n=368).The clinical data were compared between the two groups,and the effect of UAR on the all-cause mortality in the patients with heart failure was evaluated by the binary logistic regres-sion analysis.Results The follow up time in the patients was 90 d,and 37 cases(2.0％)of all-cause death oc-curred during the follow up period.The proportion of males,proportion of cardiac function grade Ⅳ,propor-tion of myocardial infarction,levels of uric acid,D-dimer,creatine kinase(CK),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),alanine aminotransferase(ALT),glutamyl transpeptidase(GGT),alkaline phosphatase(AKP)and BNP in the high UAR group were higher than those in the low UAR group,while the pulse,systolic pressure,diastolic pressure,proportions of heart function grade Ⅱ and grade Ⅲ and ALB level were lower than those in the UAR group,and the differences were statistically significant(P＜0.05).The ROC curve analysis results showed that the area under the curve of UAR for assessing the all-cause death occurrence in heart failure was 0.715(95％CI:0.626-0.804,P＜0.001),the sensitivity was 56.8％and the specificity was 81.4％;the binary logistic regression analysis results showed that the incidence rate of all-cause mortality in the high UAR group was 1.09 times higher than that in the low UAR group(OR=1.09,95％CI:1.02-1.20,P=0.017).Conclusion UAR could serve as an independent predictive fac-tor of all-cause death occurrence in heart failure,which needs clinic to pay attention.

Objective To compare the diagnostic performance of a multi-marker panel(copeptin,cardiac troponin T[cTnT],and heart-type fatty acid-binding protein[HFABP])with the single marker cTnT in the diagnosis of type 4a acute myocardial infarction(AMI),and explore the application value of combined detectionmodel with the multiple markers.Methods The enrolled non-AMI pa-tients underwent elective percutaneous coronary intervention(PCI)at Nanjing Medical University First Affiliated Hospital during the period from March to December 2022 and were assessed as postoperative elevation of cTnT above the 99th percentile upper reference limit(URL).According to the Fourth Universal Definition of Myocardial Infarction,the patients were divided into non-type 4a AMI group and type 4a AMI group based on whether type 4a AMI occurred after surgery.The concentrations of AMI biomarkers were meas-ured using a chemiluminescent immuno-gold nanoassembly immunosensor array(chemiluminescent immuno-Gold,ciGold).Receiver operating characteristic(ROC)curves were used to analyze the performance of the diagnostic models with single and combined cardiac biomarkers.The sensitivity and specificity were also obtained from the ROC curves,and the area under the ROC curve(AUCROC)was calculated to evaluate respective diagnostic value.Kappa analysis was used to assess the consistency between the results combined de-tection model of multiple biomarkers and the diagnosis based on the Fourth Universal Definition of Myocardial Infarction.Results In this study,a total of 65 patients were included in whom females accounted for 23.1％.The ROC curve indicated that the combined de-tection model of multiple cardiac biomarkers showed specificity of 96.5％,sensitivity of 92.3％,agreement rate of 94.6％,positive pre-dictive value of 92.3％,negative predictive value of 96.2％,and AUCROC of 0.979.The single cTnT diagnostic model showed specificity of 94.2％,sensitivity of 100％,agreement rate of 95.7％,positive predictive value of 100％,negative predictive value of 94.9％,and AUCROC of 0.987.Although the combined detection model of multiple biomarkers had lower sensitivity(P=0.011),it showed higher specificity(P=0.016).The analysis of AUCROC differences between the two diagnostic models showed P＞0.05,indicating no signifi-cantly statistical difference for the diagnostic accuracy.Kappa analysis demonstrated a strong consistency between the combined detec-tion model of multiple cardiac biomarkers and the diagnosis of type 4a AMI based on the Fourth Universal Definition of Myocardial In-farction with a Cohen's Kappa coefficient of 0.818.Conclusion The multi-marker combined detection model showed similar perform-ance of cTnT in diagnos of type 4a AMI with strong diagnostic consistency.However,the combined detection model exhibited an advan-tage of higher specificity.

Objective To explore the role of β-1,3-galactosyltransferase 2(B3galt2)in mice with cerebral ischemic injury.Methods Adult male C57BL/6J mice were randomly divided into the sham,suture-occluded middle cerebral artery occlusion(MCAO)model,MCAO model+lentiviral vector control(LV-GFP),and MCAO model+lentiviral vector overexpression B3galt2(LV-B3galt2)groups,with six mice in each group.Neurological deficit scoring and rotating rod experiments were performed 24 h after ischemia in each group,and 2,3,5-triphenyltetrazolium chloride(TTC)staining was used to determine the infarction volume.The number of neurons in the ischemic cerebral cortex was determined in each group using Nissl staining.The levels of oxidative stress-related factors in the brain tissues were detected using the relevant kits.Results Compared with the sham group,the MCAO model group showed increased infarct volume and neurological deficits(P<0.05),significantly decreased number of neurons in the ischemic cerebral cortex and levels of super-oxide dismutase(SOD)and glutathione peroxidase(GSH)(all P<0.05),and significantly increased levels of reactive oxygen species(ROS)and malondialdehyde(MDA)(all P<0.05).Compared with the MCAO model group,the LV-B3galt2 group had reduced volume of cerebral infarction,significantly improved neurological deficits(all P<0.05),significantly increased number of neurons in the ischemic cerebral cortex of mice,significantly decreased levels of ROS and MDA(P<0.05),and significantly elevated levels of SOD and GSH(all P<0.05).Conclusion B3galt2 overexpression can reduce brain injury in an ischemic damage mouse model,and its mechanism may be through the inhibition of oxidative stress reactions.

Humans ; Depressive Disorder, Major ; Motor Cortex ; Magnetic Resonance Imaging

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

Objective To investigate the effect of exposure to lead oxide nanoparticles (PbO NPs) on the polarization of microglia in mouse hippocampus. Methods i) Specific pathogen-free male C57 mice were randomly divided into control group, low-, medium- and high-dose groups, with 10 mice in each group. Mice in these three dose groups were intraperitoneally injected with PbO NPs suspension at doses of 5, 10 and 20 mg/kg per day, respectively, and mice in the control group were intraperitoneally injected with the same volume of 0.9% sodium chloride solution, five days per week for four weeks. ii) BV-2 cells were treated with PbO NPs at doses of 0.0, 2.5, 5.0 and 10.0 mg/L for 24 hours. iii) BV-2 cells were randomly divided into control group, PbO NPs group and triggering receptor expressed on myeloid cells 2 (TREM2) high expression + PbO NPs group. The cells in the control group received no treatment. The cells in PbO NPs group were exposed to 10.0 mg/L PbO NPs suspension for 24 hours. Cells in TREM2 high expression + PbO NPs group were transfected with Trem2 high expression plasmid, and then exposed to 10.0 mg/L PbO NPs suspension for 24 hours. iv) The mRNA expression of M1 markers ［nitric oxide synthase (iNos), cyclooxygenase 2 (Cox2), chemokine receptor 7 (Ccr7)］, M2 markers ［arginin-1 (Arg-1), transforming growth factor-β (Tgf-β), chemokine receptor 2 (Ccr2)］ and Trem2 of microglia was detected by real-time fluorescent quantitative polymerase chain reaction. The protein expression of iNOS, ARG-1 and TREM2 was detected by Western blotting. Results i) During the experiment, there was no significant difference in body weight of mice among these four groups (P>0.05). The relative expression of Cox2 and Ccr7 mRNA in the hippocampus of the mice increased in the low-dose group and the iNos, Cox2 and Ccr7 mRNA increased in the medium- and high-dose groups, compared with the control group (all P<0.05). The relative mRNA expression of Tgf-β in the hippocampus of the mice of low-dose group and Arg-1, Tgf-β and Ccr2 in the medium- and high-dose groups was decreased compared with the control group (all P<0.05). The mRNA relative expression of iNos, Cox2 and Ccr7 was increased (all P<0.05), while the mRNA relative expression of Arg-1, Tgf-β and Ccr2 was decreased (all P<0.05) in the hippocampus of the mice of high-dose group compared with the low-dose group. The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the medium- and high-dose groups was lower than those in the control group (all P<0.05). The relative expression of Trem2 mRNA and TREM2 protein in the hippocampus of mice of the high dose group was lower than those in the low- and the medium-dose groups (all P<0.05). With the increase of PbO NPs exposure dose, the relative expression of iNOS protein in hippocampus tissues of mice increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01). ii) With the increase of PbO NPs exposure dose, the relative expression of iNOS protein increased (P<0.01), and the relative expression of ARG-1 protein decreased (P<0.01) in BV-2 cells. The relative expression of iNOS protein in BV-2 cells of PbO NPs group and TREM2 high expression + PbO NPs group was increased (all P<0.05), and the relative expression of ARG-1 protein decreased (all P<0.05) compared with the control group. The relative expression of iNOS protein decreased (P<0.05), and the relative expression of ARG-1 protein increased (P<0.05) in BV-2 cells of TREM2 high expression + PbO NPs group compared with the PbO NPs group. Conclusion Exposure to PbO NPs could increase the M1 polarization and decrease the M2 polarization of microglia, with a dose-effect relationship. The M1 polarization of microglia decreased and M2 polarization increased after overexpression of Trem2 gene. The regulation of microglia polarization by TREM2 may be involved in the neurotoxic effects of PbO NPs.

The potential medicinal value of Ma bamboo (Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract (DLE) reduced fasting blood glucose levels, body weight, and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways. Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase 1 (PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor (IGF1R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Therefore, exploring the mechanism of CVDs and critical regulatory factors is of great significance for promoting heart repair, reversing cardiac remodeling, and reducing adverse cardiovascular events. Recently, significant progress has been made in understanding the function of protein kinases and their interactions with other regulatory proteins in myocardial biology. Protein kinases are positioned as critical regulators at the intersection of multiple signals and coordinate nearly every aspect of myocardial responses, regulating contractility, metabolism, transcription, and cellular death. Equally, reconstructing the disrupted protein kinases regulatory network will help reverse pathological progress and stimulate cardiac repair. This review summarizes recent researches concerning the function of protein kinases in CVDs, discusses their promising clinical applications, and explores potential targets for future treatments.
Cardiovascular Diseases ; Heart ; Humans ; Myocardium ; Protein Kinases