OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

Background and aims:Primary sclerosing cholangitis(PSC)is an autoimmune liver disease characterized by complex pathogenesis and limited available therapeutic options.The mechanisms underlying the development and progression of PSCs remain unclear.Liver X receptor beta(LXR-β)is recognized to modulate lipid metabolism and immune response,but its specific involvement in the PSC has not been elucidated.Here,we explored the role and mechanism of LXR-β in PSC induced by 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine(DDC).Methods:CRISPR-Cas9 technology was applied to generate Abcb4(coding MDR2,next named as Mdr2),Nr1h2(coding LXR-β,next named as Lxrβ),and Rag2(coding RAG2)knockout mice.DDC was used to induce PSC.Hematoxylin and eosin and Sirius red staining were used to assess the extent of hepatic injury and fibrosis.Flow cytometry was used to observe immune cell subsets.Results:We observed a declining trend in hepatic Lxrβ in the PSC model.Unexpectedly,Lxrβ knockout failed to modulate DDC-induced PSC pathogenesis.Concomitantly,assessment of the influence of Rag2 deficiency on PSC progression revealed the absence of aggravated or alleviated hepatic injury or fibrosis in the Rag2-/-DDC mice.However,Lxrβ depletion intensified DDC-induced PSC in the Rag2-/-mice,with more abundant infiltrative inflammatory cells and more severe liver fibrosis.Compared with Rag2-/-DDC mice,Lxrβ-/-Rag2-/-DDC mice had higher serum ALT and AST levels and mRNA expression of proinflammatory and profibrotic genes.Flow cytometry showed that LXR-β deficiency resulted in a diminished population of hepatic innate immune cells.Conclusion:This study indicated innate immune cell LXR-β deficiency can exacerbate hepatic injury and fibrosis in murine models of PSC suggesting that LXR-β may regulate the function of innate immunity in the fibrotic advancement of PSC.

AIM: To evaluate the refractive status through computer refractometer and OPD-Scan III auto refractometer in cataract patients after extended depth of focus(EDOF)intraocular lens implantation.METHODS: Retrospective observational study. A total of 61 cases(76 eyes)that received phacomulsification and implanted with TECNIS® Symfony ZXR00 intraocular lens in Shanghai Eye Diseases Prevention & Treatment Center from May 2022 to May 2023 were collected. Measurements from the computer refractometer, OPD-Scan III auto refractometer, and subjective refraction, were taken from all patients on the same day postoperatively.RESULTS: There were statistical significant difference in sphere(S)and spherical equivalent(SE)readings from the computer refractometer and subjective refraction(all P<0.01), with mean differences of -0.67±0.37 D and -0.75±0.35 D, respectively, and the S and SE obtained from computer refractometer more incline to myopia than those from subjective refraction; there were statistical significant difference in computer refractometer and subjective refraction(P<0.01), with a relative small absolute difference(0.21±0.24 D). The S, cylinder(C)and SE of computer refractometer(S, C, SE)were positively correlated with subjective refraction(r=0.7994, 0.7929, and 0.8118, respectively, all P<0.01). Additionally, there were statistical significant differences in S, C and SE of OPD-Scan Ⅲ and subjective refraction(P<0.01), and the absolute differences of S(0.63±0.36 D), C(0.35±0.26 D)and SE(0.53±0.36 D)were small. Furthermore, the S, C and SE of OPD-Scan Ⅲ were positively correlated with subjective refraction(r=0.4410, 0.4982, 0.5224, all P<0.01).CONCLUSION: In patients who received implantation of EDOF lenses, the consistency of computer refractometer, OPD-Scan III auto refractometer and subjective refraction was good. The average difference of the S and SE obtained via computer refractometer was large, but both exhibited a myopic shift relative to those derived from subjective refraction, and the C values demonstrated minimal discrepancy. Furthermore, the differences between OPD-Scan III auto refractometer and subjective refraction were small, but the direction of the difference is unstable, sometimes it is myopic deviation, while sometimes it is hyperopic deviation.

Objective To design a medical order pre-evaluation tool for perioperative prophylactic application of antibiotics,and to improve the efficiency of antibiotics management in hospitals during the perioperative period.Methods Using the open-source software R as the platform,a web application was built with tidy verse and shiny package based on related documents and guidelines.The discharge records of Affiliated Hospital of North Sichuan Medical College from April 1,2021,to December 31,2022,were retrospectively reviewed using the constructed pre-evaluation tool and compared with previous manual evaluation results using McNemar's Chi-squared test.Results This medical order pre-evaluation tool can quickly complete perioperative antibiotics order sampling,batch pre-evaluation,result statistics,visualization,and result output,and flexibly adjust the evaluation rules according to actual needs.The pre-evaluation tool is more efficient,with a review speed of 13.46 ms per medical record.Among the 2 642 discharge medical records of manual review,there was no significant difference between systematic pre-evaluation and manual evaluation results(ratio of prophylactic use:76.85%vs.78.21%)in terms of the type of use(preventive or curative)(P= 0.078).Among the 1 857 discharge records judged to be prophylactic for both manual and systematic reviews,the difference in unreasonable detection rate(39.90%vs.30.32%)was statistically significant(P＜0.001).Among the 63 typical ludicrous medical records confirmed by the review of clinical pharmacists with senior professional titles,60 were judged and limited by the pre-evaluation tool,and the detection rate of typical unreasonable was 95.24%.Conclusions The pre-evaluation tool based on R in this study can improve the efficiency of perioperative antibacterial drug evaluation.The evaluation conclusions and statistical results are reliable and are worthy of further development and application.

Objective To observe the value of MRI texture features combined with apparent diffusion coefficient(ADC)for differentiating uterine sarcoma(US)and cellular uterine leiomyoma(CUL).Methods Pelvic MRI data of 27 US patients(US group)and 34 CUL patients(CUL group)were retrospectively analyzed.The texture features of lesions were extracted from T2WI and diffusion weighted imaging(DWI),the ADC value were measured,and the average ADC value(ADCmean),the minimum ADC value(ADCmin)and standard ADC value(ADCst)were recorded.Then logistic regression(LR)models were constructed based on ADC value,optimal texture features alone and their combination,respectively,including LRADC,LRtexture and LRADC+texture models.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for differentiating US and CUL.Results The ADCmean,ADCmin and ADCst in US group were all lower than those in CUL group(all P＜0.05).A total of 3 750 texture features were extracted from pelvic T2WI and DWI,5 optimal features were finally obtained,and the constructed LRADC+texture model and LRtexture model had similar efficacy of differentiating US and CUL(AUC=0.921,0.887;P＞0.05),which were both higher than that of LRADC model(AUC=0.696;both P＜0.05).The calibration curve of LRADC+texture model was basically consistent with the ideal curve,which had better clinical benefits than LRADC and LRtexture models.Conclusion MRI texture features combined with ADC value could improve efficacy for differentiating US and CUL.

Based on the International Federation of Nursing Anesthetists (IFNA) education and training base, our hospital has built a training base for anesthesia specialized nurses in Nanjing from the following aspects: the application for training base of anesthesia specialized nurses, the qualification and examination of students' and teachers' qualification, the settings of training curriculum, the examination contents and methods, and the evaluation of post-training effect. This article summarizes the construction experience of this base, therefore, providing support and standard for the training of anesthesia specialized nurses.

Objective:To study the ability of the Retinal Health Assessment (RHA) system to obtain fundus images in patients with different types and degrees of cataracts.Methods:A cross-sectional study was performed.Forty-five eyes of 41 patients with cataract were enrolled in First People's Hospital, Shanghai Jiaotong University from December 2016 to January 2017.Lens opacity grading and RHA fundus imaging were performed after pupil dilation.Forty-five eyes were divided into 4 groups according to the degree of lens opacity: cortical cataract group 18 eyes, nucleus cataract group 21 eyes, posterior subcapsular cataract group 2 eyes, hybrid cataract group 4 eyes.Fundus images were obtained by FullSpectrum mode of RHA2020, and the clearness of fundus images was evaluated.Scores of fundus images clarity were compared between the cortical cataract group and nucleus cataract group.This study was approved by the Ethics Committee of First People's Hospital, Shanghai Jiaotong University.Written informed consent was obtained from each patient prior to any medical examination.Results:In all 45 eyes, the phacoscotasmus classification ranged from mildest (C0N2P0, 1 eye) to very serious (C2N5P2 and C4N2P4, 2 eyes). The grade Ⅳ nuclear opacity, grade Ⅲ cortical opacity, and grade Ⅲ posterior subcapsular opacity reduced the quality of RHA images significantly, especially for images with red and green light.In cortical cataract group, images showed peripapillary vessels and retinal vessels at 580 nm and 590 nm, while retinal and choroidal vessels, as well as choroidal pigmentation, were visible at 810 nm.The clarity scores at 580, 590 and 810 nm were 2.0 (1.0, 3.0), 2.0 (2.0, 3.0) and 2.0 (2.0, 3.0), which were lower than that with red and green light (620 nm + 550 nm) (3.0[2.0, 3.0]), with statistically significant differences (all at P<0.05). In nucleus cataract group, the quality of fundus images from the eyes with grade Ⅲ nucleus cataracts was good, the image quality decreased when the nucleus opacity was grade Ⅳ, retinal vessels were occasionally observed at 580 nm and 590 nm.Additionally, retinal and choroidal vessels and choroidal pigment were visible at 810 nm and 850 nm.The clarity scores at 580, 590, 810 and 850 nm were 1.0 (1.0, 3.0), 2.0 (1.0, 3.0) and 2.0 (1.0, 3.0), which were lower than that with red and green light (620 nm + 550 nm) (3.0[1.5, 3.0]), with statistically significant differences (all at P<0.05). In posterior subcapsular cataract group, the retinal vessels were visible at 580 nm, meanwhile retinal and choroidal vessels and choroidal pigment could be observed at 810 nm and 850 nm.In hybrid cataract group, running lines of retinal vessels could be seen at 850 nm, while the central reflection was absent.Focal choroidal vessels were observed. Conclusions:Except for severe cases, RHA system can produce good quality fundus images in cataract eyes at 580, 590, 810 and 850 nm, facilitating the evaluation of fundus disease before surgery and prediction of visual outcomes after surgery.

Objective To explore the classic MRI appearance of secondary hemochromatosis (SHC)related liver iron overload, and the feasibility of quantitative evaluation of liver iron overload by iterative decomposition of water and fat with echo asymmetry and leastGsquares estimationGiron quantification (IDEALGIQ).Methods 20 patients with SHCGrelated liver iron overload (experimental group)and 20 healthy adults (control group)underwent routine liver MRI and IDEALGIQ.The MRI images were comparatively analyzed to assess the hallmark of liver iron overload.In both two groups,the R2 ? values were measured on R2 ? maps,which were generated by IDEALGIQ,then the differences in age,gender and R2 ? value between two groups were comparatively analyzed.In experimental group,the serum ferritin (SF)was detected,and a correlation analysis was tested with R2 ? value.Results For all of the 20 patients, there was signal drop of liver parenchyma on T1 and T2 Gweighted images,signal loss with susceptibility artifact on DWI images,and signal dropped on inGphase images relative to outGofGphase images.Among the 20 patients,18 cases appeared "a dark liver parenchyma"on T2 G weighted images,and the spleen signal in 3 cases was similar to liver parenchyma’s hallmark.The R2 ? values in experimental group and control group were 395.58±255.75 Hz and 41.18±7.86 Hz (t＝－6.12,P＝0.00),respectively.No significant differences between two groups were found in gender and age (χ2＝0.10,P＝0.10 and t＝0.09,P＝0.93).The liver iron overload R2? value was not correlated with SF (r＝0.1 5 3 , P＝0.15).Conclusion On MRI,the typical appearance of liver iron overload is hypointense on T1 and T2Gweighted images,especially"a dark liver parenchyma"on T2 WI,signal drops on inGphase images relative to outGofGphase images,and signal loss with susceptibility artifact on DWI images.R2 ? value of IDEALGIQ can quantitatively evaluate the liver iron overload,without a correlation with SF.

Cystic echinococcosis (CE), a zoonotic disease caused by Echinococcus granulosus at the larval stage, predominantly develops in the liver and lungs of intermediate hosts and eventually results in organ malfunction or even death. The interaction between E. granulosus and human body is incompletely understood. Exosomes are nanosized particles ubiquitously present in human body fluids. Exosomes carry biomolecules that facilitate communication between cells. To the best of our knowledge, the role of exosomes in patients with CE is not reported. Here, we isolated exosomes from the sera of patients with CE (CE-exo) and healthy donors and subjected them to liquid chromatography-tandem mass spectrometry analysis. Proteomic analysis identified 49 proteins specifically expressed in CE-exo, including 4 proteins of parasitic origin. The most valuable parasitic proteins included tubulin alpha-1C chain and histone H4. And 8 proteins were differentially regulated in CE-exo (fold change>1.5), as analyzed with bioinformatic methods such as annotation and functional enrichment analyses. These findings may improve our understanding about the interaction between E. granulosus and human body, and may contribute to the diagnosis and prevention of CE.
Computational Biology ; Diagnosis ; Echinococcosis ; Echinococcus granulosus ; Echinococcus ; Exosomes ; Gene Ontology ; Histones ; Human Body ; Humans ; Liver ; Lung ; Mass Spectrometry ; Tissue Donors ; Tubulin ; Zoonoses

Objective To explore the effect of apolipoprotein E (ApoE) on secretions of matrix metalloproteinase-9 (MMP-9),matrix metalloproteinase tissue inhibitor-1 (TIMP-1) and inflammatory factors in spleen macrophages at early stage of experimental autoimmune encephalomyelitis (EAE).Methods In accordance with random number table,20 ApoE knockout (ApoE-/-) C57BL/6J mice were divided into ApoE-/-EAE group and ApoE-/-control group (n=10);and 20 wild type (WT) C57BL/6J mice were divided into WT EAE group and WT control group (n=10).Myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) was used as antigen to induce EAE models in the ApoE-/-EAE group and WT EAE group,and MOG35-55 was replaced by normal saline in ApoE-/-control group and WT control group.The spleen macrophages were isolated from mice after 7th d of modeling and cultured in vitro;the rnacrophages of the ApoE-/-EAE group and WT EAE group were stimulated by MOG35-55,while the macrophages of the ApoE-/-control group and WT control group were treated with equivalent normal saline.Forty-eight hafter that,the contents of MMP-9,TIMP-1,interferon gamma-γ(IFN-γ),tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the culture medium were determined by ELISA.Results The contents of MMP-9,TFN-γ TNF-α and IL-6 in the WT EAE group were significantly higher than those in the WT control group (P＜0.05);the contents of MMP-9,IFN-γ 、TNF-α and IL-6 in the ApoE-/-EAE group were significantly higher than those in the ApoE-/-control group (P＜0.05);the content ofMMP-9,IFN-γ,TNF-cα and IL-6 in ApoE-/-EAE group were significantly higher than those in the WT EAE group (P＜0.05).The TIMP-1 secretion ofmacrophages in WT EAE group was significantly higher than that in WT control group (P＜0.05).Conclusions At early stage of EAE,macrophages secrete high levels of MMP-9 and inflammatory factors,and the deficiency of ApoE further contributes to the secretions of MMP-9 and inflammatory factors by macrophages.ApoE may play a role in protecting the integrity of blood-brain barrier and alleviating the inflammatory response of the central nervous system through the effects on macrophages.