Aim To analyze the anti-A549 and HI299 lung ade-nocarcinoma activities via using examples of baicalin, astragalo-side, hesperidin and cisplatin based on real time cellular analysis (RTCA) technology, and to build a new strategy for EC50 e-valuation reflecting the time-dimensional characteristic. Methods Using RTCA Software Pro for data analysis and GraphPad Prism and Origin Pro plotting, the in vitro anti-A549 and H1299 lung adenocarcinoma activities of baicalin, astragaloside, hesperidin, and cisplatin were characterized using the endpoint method and time dimension, respectively. Results (X) There were significant differences in EC50 values of A549 and H1299 cells at 24 h and 48 h endpoint methods. (2) The correlation coefficient of the curve fitted with the four-parameter equation was > 0. 9, and the dynamic change of EC50 remained relatively stable (the linear fitting of EC50 at adjacent 4 points I slope 1^1) used to calculate the EC50 value within this time dimension. The EC50 of baicalin, astragaloside, hesperidin and cisplatin on A549 cells was 52. 97 ±1.75 плпо! • L~1(16~48 h) , 62.88 ± 2.91 ijunol • L"1 (32.25 -48 h) , 78.84 ±0.33 плпо1 • L"1 (21.5 -29.75 h), 13.57 ±1.54 плпо1 • L_1(27.5 -48 h), respectively; the EC50 of baicalin, astragaloside, hesperidin and cisplatin on H1299 cells was 43. 71 ± 1. 26 |лто1 • L_1 ( 19. 5 -48 h), 47.23 ±1. 19 |лто1 • L_1(14 -48 h) , 39.45 ±0.24 плпо1 • L"1 (12.75 -46.25 h), 25.97 ±4.76 плпо1 • L"1 (10. 25 -48 h) , respectively. The results showed that the time window for the anti-tumor effect of the test solution/drug was different. Conclusions Based on RTCA technology, it is more accurate and reasonable to select EC50 data that exhibit better fitting, stable changes, and time-dimensional characteristics for the evaluation of anti-tumor activity. In addition, this method of distinguishing different effective time of antitumor drugs can provide a reference for the timing of clinical combination drugs, and this approach will also provide a reference for further related studies.

This study used kidney metabolomics to investigate the underlying mechanisms of Guilingji (GLJ) on mild cognitive impairment (MCI) rats. The rats were randomly divided into 6 groups (n = 8), i.e., control group, model group, positive drug (Ginkgo biloba tablet, donepezil) group, GLJ group (low and high dose group). The MCI rat model was replicated using subcutaneous injection of D-galactose into the back of the neck along with a semi-high-fat diet for a total of 8 weeks, and drug was administered from the 5th week for 4 weeks. The kidney function and renal pathological changes of each group of rats were tested. And LC-MS based kidney metabolomics coupled with multivariate data analysis were conducted to explore the potential biomarkers, and corresponding metabolic pathways were then determined. After administration of GLJ, the level of urea nitrogen was decreased compared with those of the model group, and the abnormalities of morphology in kidney tissues were improved. The positive drugs (ginkgo biloba tablet and donepezil) had no significant modulating effect on renal function indexes. Ginkgo biloba tablet can lessen the pathological injury of kidney tissue, and donepezil had no improvement on renal histopathology. A total of 23 MCI related differential metabolites were identified in kidney, and 17 metabolites were signifcantly restored by GLJ compared with those of the model group. Additionally, we found that the cysteine and methionine metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism were significantly involved in the regulatory effect of GLJ. The results illuminate the "cong shen zhi nao" mechanism of GLJ, and also provide a research basis for the clinical use of GLJ for the treatment of MCI. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: 2020DW121).

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To observe the therapeutic effect and mechanism of Baoyuan Decoction for chronic heart failure model rat.Methods SD rats were randomly divided into blank group,model group,Baoyuan Decoction group,Captopril group,Baoyuan Decoction+CCT020312[protein kinase R-like endoplasmic reticulum kinase(PERK)activator]group,15 rats in each group.Except for the blank group,the rats in the other groups were induced by Adriamycin to construct a chronic heart failure model.After corresponding drug intervention,cardiac function indexes[left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),brain natriuretic peptide(BNP),cardiac troponin I(cTnI)],inflammation-related factors[tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)],oxidative stress factors[malondialdehyde(MDA),superoxide dismutase(SOD)]were detected in each group.Changes in apoptosis-related indicators[B-cell lymphoma 2(Bcl-2),B-cell lymphoma 2-associated X protein(Bax),Caspase-3]and PERK/transcription activator 4(ATF4)signaling pathway-related proteins glucose-regulated protein 78(GRP78),PERK,ATF4,C/EBP homologous protein(CHOP)levels.Results Compared with the blank group,LVEDD,BNP,cTnI,TNF-α,IL-1β,MDA levels,protein expression levels of Bax,Caspase-3,GRP78,PERK,ATF4,CHOP in the model group were significantly increased,LVEF,LVFS,SOD levels and Bcl-2 protein expression level were significantly decreased(all P＜0.05).Compared with the model group and Baoyuan Decoction+CCT020312 group,LVEDD,BNP,cTnI,TNF-α,IL-1β,MDA levels,protein expression levels of Bax,Caspase-3,GRP78,PERK,ATF4,CHOP in Baoyuan Decoction group and Captopril group were significantly decreased,LVEF,LVFS,SOD levels and Bcl-2 protein expression level were significantly increased(all P＜0.05).Compared with the Captopril group,there was no significant change in the above indexes(except CHOP protein expression level)in the Baoyuan Decoction group(P＞0.05).Conclusion Baoyuan Decoction can delay the progression of chronic heart failure rats,and its mechanism may be related to inhibiting the PERK/ATF4 signaling pathway to alleviate cardiomyocyte apoptosis,further reducing the degree of inflammatory response and oxidative stress,thereby promoting the repair of cardiac function and myocardial injury.

Objective To investigate the mechanism of retinal injury in rats caused by light-emitting diodes(LEDs)with different color rendering indexes(CRIs).Methods Totally 20 Sprague-Dawley rats were randomly divided into nor-mal control(NC)group(sunlight),low CRI(CRI-L)group(blue light),medium CRI(CRI-M)group(conventional LED),and high CRI(CRI-H)group(full-spectrum LED),with 5 rats in each group,exposed to light for 12 hours daily for 4 consecutive weeks.Hematoxylin & eosin staining was used to assess morphological changes in the retina.Dihydroethidi-um staining was employed to detect the levels of reactive oxygen species(ROS)in retinal tissues.The messenger ribonu-cleic acid(mRNA)expressions of NOD-like receptor family pyrin domain containing protein 3(NLRP3),Gasdermin D(GSDMD)and Caspase-1 were analyzed by real-time quantitative polymerase chain reaction(RT-qPCR),and their protein expressions were measured through immunohistochemical staining.Environmental light spectra were measured using a spectroradiometer.Results Rats in the CRI-L group showed the thinnest retina,followed by the CRI-M group and CRI-H group.The fluorescence intensity of ROS in the NC group,CRI-L group,CRI-M group and CRI-H group was 1.000±0.046,25.060±1.732,14.530±3.776 and 1.821±0.587,respectively.The ROS level in the CRI-H group was significantly lower than that in the CRI-L group and CRI-M group(both P＜0.05).RT-qPCR showed that the relative mRNA expression of NL-RP3 in the NC group,CRI-L group,CRI-M group and CRI-H group was 1.004±0.005,4.004±0.716,2.027±0.303 and 0.741±0.069,respectively;the relative mRNA expression of Caspase-1 was 1.010±0.006,4.337±0.345,2.268±0.058 and 0.713±0.021,respectively;the relative mRNA expression of GSDMD was 1.000±0.000,2.938±0.559,1.955±0.166 and 1.213±0.051,respectively.Compared with the NC group,the relative expressions of NLRP3,Caspase-1 and GSDMD in the CRI-L group and CRI-M group significantly increased(all P＜0.05).The immunohistochemical staining results showed that the fluorescence intensity of NLRP3 in the retina of rats in the NC group,CRI-L group,CRI-M group and CRI-H group was 0.379 4±0.002 2,0.400 7±0.011 4,0.379 0±0.006 9 and 0.377 0±0.007 5,respectively;the fluorescence intensity of Caspase-1 was 0.367 2±0.005 8,0.442 6±0.041 1,0.382 4±0.011 9 and 0.380 6±0.006 5,respectively;the fluorescence intensity of GSDMD was 0.159 5±0.013 4,0.167 5±0.011 9,0.397 6±0.014 3 and 0.377 2±0.022 8,respec-tively.Compared with the NC group,rats in the CRI-L group showed increased fluorescence intensity of NLRP3 and Caspase-1,and rats in the CRI-M and CRI-H showed increased fluorescence intensity of GSDMD(all P＜0.05).The spec-tral comparison revealed that the CRI-H group had a broader spectral coverage and a distribution closer to natural light spectra.Conclusion Conventional LED exposure can induce a decrease in retinal thickness,upregulate the ROS expres-sion in retinal tissues,and increase the expression levels of NLRP3,Caspase-1 and GSDMD.High CRI full-spectrum LEDs can mitigate pyroptosis through the ROS/NLRP3 pathway by optimizing their spectral distribution,offering better biosafety.

The regulatory requirements of 3D printing products were introduced.The risks during the production of 3D printed navigational template for orthopedic surgery were summarized in terms of data acquisition,medical-industrial intera-ction design,3D printing,post-processing and sterilization.Some quality control measures were proposed from the aspects of quality control of raw materials,validation of data and software,verification of printing process parameters,post-processing method and verification,sterilization verification and testing of semi-finished and final products,so as to enhance the safety and effectiveness of 3D printed navigational template for orthopedic surgery.[Chinese Medical Equipment Journal,2024,45(5):80-85]

Objective To investigate the changes in the serum levels of oxidized phospholipids(OxPLs)and endothelial nitric oxide synthase(eNOS)and their association with coronary artery disease(CAL)in children in the acute stage of Kawasaki disease(KD),as well as the clinical significance of OxPLs and eNOS.Methods A prospective study was conducted on 95 children in the acute stage of KD(KD group).According to the presence of absence of CAL,the KD group was further divided into a CAL subgroup and a non-CAL(NCAL)subgroup.Thirty children with fever due to lower respiratory tract infection were enrolled as the fever group.Thirty healthy children who underwent physical examination were enrolled as the healthy control group.The above groups were compared in terms of general information and serum levels of OxPLs,eNOS and other laboratory indexes,and the correlation between OxPLs level and eNOS level was analyzed.Results The KD group had a significantly higher level of OxPLs and a significantly lower level of eNOS compared with the fever group and the healthy control group(P<0.05).After treatment,the children with KD had a significantly decreased OxPLs level and a significantly increased eNOS level(P<0.05).Compared with the NCAL subgroup,the CAL subgroup had a significantly higher level of OxPLs and a significantly lower level of eNOS(P<0.05).Among the children of KD,the level of OxPLs was negatively correlated with that of eNOS(rs=-0.353,P<0.05).Conclusions Serum OxPLs and eNOS in the acute stage of KD may be involved in the development of CAL in children with KD,and therefore,they may be used as the biomarkers to predict CAL in these children.

Aim To study the effects of different peri-ods of hypoxia on gastrointestinal stress in mice by sim-ulating hypoxia environment at high altitude in a low-pressure oxygen chamber.Methods The normal con-trol group and the model group for 1,3 and 5 days were set up according to different periods of hypobaric hypoxia.The intestinal propulsion rate,visceral sensi-tivity and pathological damage of gastrointestinal tract were detected after hypobaric hypoxia treatment.The contents of IL-1 β,IL-6 and TNF-α in gastrointestinal tract and the contents of gastrointestinal hormone,di-amine oxidase and D-lactic acid were detected by en-zyme-linked immunosorbent assay(ELISA).The ex-pressions of tight-junction protein and tight junction in-jury pathway protein in intestinal tissues were detected by Western blot.Results Compared with the control group,the intestinal propulsion rate of the model group was accelerated,and the intestinal sensitivity in-creased.The expression of intestinal mucosal injury markers increased.Gastrointestinal motility inhibiting hormone decreased and gastrointestinal motility promo-ting hormone increased.The expression of tight junc-tion proteins ZO-1,claudin-1,occludin and VASP of tight junction injury-related pathway decreased,while the expression of NF-κB,HIF-1α and VEGF in tight junction injury-related pathway increased.The expres-sions of IL-1 β,IL-6 and TNF-α in gastrointestinal tis-sue increased.The content of pepsin in gastric tissue increased.The injury of gastrointestinal tissue was less in the 1-day group,and more serious in the 3-day and 5-day groups.Conclusions Stress injury occurs in the gastrointestinal tract of mice at different time points in hypoxia and hypoxia environment,and the gastroin-testinal function injury is more serious after three days of exposure,which may be related to the activation of NF-κB/HIF-1α/VEGF/VASP pathway.

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO₁₅) and Shen (CO₁₀), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.
Humans ; Depression/therapy* ; Magnetic Resonance Imaging/methods* ; Vagus Nerve Stimulation/methods* ; Brain/diagnostic imaging* ; Transcutaneous Electric Nerve Stimulation/methods* ; Vagus Nerve

Aim To compare the effects of different time sequence interventions on virus infected mice by using oseltamivir (Tamiflu) as a "tool drug" in view of the current situation of the too early the administration time of antiviral in vivo experiment, so as to provide a basis for selecting a reasonable model intervention time point for antiviral drug research. Methods Balb/c mice were randomly divided into six groups. The virus infection model was established by intranasal infection with influenza virus (0.25 TCID50). Tamiflu-1 group and Tamiflu-2 group were administered orally on 1st and 4th day after exposure. The body mass, survival rate, organ index, viral load and inflammatory factor content were measured. Results Compared with the blank control group, the body weight of the mice in the model group decreased and the lung index increased significantly (P < 0.05). The expression levels of 13 inflammatory factors in model 2 group were significantly different ( P < 0.05). Compared with the model-1 group ,the lung index and spleen index of the Tamiflu-1 group decreased significantly (P < 0.05). Compared with the mode-2 group,the lung index in the Tamiflu-2 group was significantly lower (P <0.05) ,and the thy-mus index was significantly higher (P<0.05). The viral load was 0. 03 times that of the model-2 group. The expression levels of 13 inflammatory factors were significantly different (P < 0. 05). Conclusions The symptoms of the mice in Scheme 2 are more obvious and stable after exposure. After administration, the lung inflammation damage is alleviated. Considering the latency, drug intervention is in line with the drug indications when the model animals show symptoms. It will be more reasonable and accurate whether in the model evaluation or drug evaluation.