Objective To investigate the effect of spleen on hepatic macrophages mediated activation of hepatic stellate cells(HSCs)in mice with liver fibrosis.Methods Eighteen male C57BL/6 mice were randomly divided into three groups.Mice in Group A and Group B were injected intraperitoneally with CCl4 to establish liver fibrosis mouse model,while those in Group C were injected with corn oil as normal control.Four weeks later,mice with liver fibrosis received splenectomy(Spx)or sham operation(Sham),respectively.After continuous injection for 2 weeks,liver homogenates(L-Homo)were prepared and liver cells were isolated from the three groups.Expressions of IL-1β,IL-13,TGF-β,TNF-α,PDGF-β and VEGF in the liver homogenates of the three groups were detected by Luminex multifactor analysis.The expressions of these cytokines in liver macrophages(L-Mψ)and other non-parenchymal cells of Sham and Spx mice were analyzed by Real-time quantitative PCR(RT-qPCR)and flow cytometry.Macrophage cell line RAW264.7 or bone marrow-derived macrophages(BMDMs)were treated with liver homogenates from the Sham and Spx groups.Then the differently treated RAW264.7 cells were analyzed for mRNA expressions of cytokines and glutamine metabolism-related molecules by RT-qPCR,or transwell co-cultured with hepatic stellate cell line JS1.After co-culture,the survival and extracellular matrix expression of JS1 cells were analyzed.For comparison,Student's t test(between two groups)or one-way analysis of variance(among multiple groups)were used.Results Compared with normal control group,the concentrations of IL-1β,IL-13,TGF-β and TNF-α in the L-Homo of model group were significantly increased and showed higher levels in Sham group than in Spx group.Moreover,the hepatic macrophages were indicated as the major source of these cytokines.Consistently,macrophages treated with liver homogenate of Sham mice had increased expressions of IL-1β,TGF-β and TNF-α and glutaminase(GLS).After co-culture with macrophages treated with liver homogenate of Sham group rather than Spx group,JS1 expressed higher expressions of α-SMA and collagens.Conclusion The spleen is involved in regulating the secretion of cytokines by hepatic macrophages and enhancing their ability to activate hepatic stellate cells.

[Objective]Embedding data information literacy in postgraduate education of traditional Chinese medicine,to provide an innovative approach to improve the quality of graduate theses.[Methods]By collecting blind review data of 891 doctoral dissertations submitted from 2016 to 2021 in Zhejiang Chinese Medical University,the quality of graduate theses based on factors such as postgraduate training category,subject,submission year,affiliated unit,thesis review indicators,proposes current problems and relevant countermeasures and suggestions was statistically analyzed.[Results]The proportion of articles in grades A,B and C was 85.07%,12.01%and 2.92%,respectively,with statistically significant differences among grades(P<0.001).According to the classification of first level disciplines,the results show that the overall quality of doctoral dissertations in traditional Chinese medicine is superior to other disciplines;according to the classification of training categories,the results show that the overall quality of non-directed doctoral dissertations is better than that of directed categories;classified by the year of submission for review,the results show that with the increasing of doctoral blind review papers in recent years,the overall quality of doctoral theses has gradually been improved;according to the classification of affiliations,the results show that the overall quality of doctoral dissertations from the second school of clinical medicine,school of pharmacy,and school of basic medicine is better than other colleges.A comprehensive explanation of factors such as the training category,discipline and major,year of submission for review affiliation and evaluation indicators for the doctoral thesis effectively provides feedback on the overall quality of the thesis.[Conclusion]Embedding data information literacy in postgraduate education is of great significance for improving the quality of postgraduate education,especially the quality of graduate theses.

In response to the challenges of small scale and huge labor cost in biomedical feature modeling in current skin disease assisted diagnosis,as well as the inability to accurately describe the time series of patient disease features,a fusion text classification algorithm is used to integrate commonly used text classification models(TextLSTM,TextCNN,and RCNN)to obtain a model based on transfer learning and neural networks(TLNN model).By extracting the medical features of image sensors and quantizing them,the pretreatment reduces the number of foci and eliminates the feature information with large deviations,thus improving the accuracy of decision data.TLNN model achieves an accuracy of 72.36%on ISIC2018 and PH2 datasets,which is higher than those of the other 3 text classification models.The diagnostic accuracy of TLNN model is close to doctor's diagnosis(92%vs 94%),but the effective diagnostic efficiency is significantly higher than doctor's diagnosis(1.17 min/case vs 4.57 min/case),and the overall efficiency is improved by 290%.The results demonstrate that the fusion text classification algorithm model can obtain accurate diagnosis in less time than the traditional manual diagnosis.TLNN model can be applied to disease diagnosis,and assist doctors in medical decision-making,thereby providing patients with high-quality and convenient intelligent diagnosis and treatment services.

Objective:To explore surgical strategies for acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries.Methods:From January 2019 to March 2023, a total of 29 patients with acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries were included in the study. All patients underwent emergency surgery, with simultaneous intraoperative neck incision and replacement of the unilateral or bilateral carotid arteries. Among them, there were 19 males with a mean age of(49.57±2.14)years old. Preoperative brain CT indicated abnormalities in 15 cases, transient neurological dysfunction occurred in 5 cases, and syncope in 1 case.Results:Procedures included ascending aorta replacement in 10 cases, Bentall procedure in 18 cases, and Wheat procedure in 1 case. Arch operations involved partial arch replacement in 3 cases and Sun’s procedure in 26 cases. Simple left carotid artery replacement was performed in 6 cases, simple right carotid artery replacement in 19 cases, and bilateral carotid artery replacement in 4 cases. Cerebral protection measures during circulatory arrest included unilateral cerebral perfusion in 24 cases and bilateral cerebral perfusion in 5 cases. The mean operation time was(7. 6±0. 3) h, with a mean cardiopulmonary bypass time of(196. 3±8. 7) min, aortic cross-clamp time of(113.2±6.4) min, ischemic time 12(5-16.5) min, and lowest temperature of(26.3±0.4)°C. One patient experienced in-hospital mortality. Postoperatively, new neurological dysfunction occurred in 2 cases, including 1 case with coma and permanent neurological deficit.Conclusion:In patients with acute type A aortic dissection involving severe stenosis or occlusion of the carotid arteries, simultaneous carotid artery replacement via neck incision during aortic surgery is a safe and reliable surgical approach.

Diabetes mellitus (DM) is a major metabolic disease endangering global health, with diabetic nephropathy (DN) as a primary complication lacking curative therapy. Sporoderm-broken spores of Ganoderma lucidum (GLP), an herbal medicine, has been used for the treatment of metabolic disorders. In this study, DN was induced in Sprague-Dawley rats using streptozotocin (STZ) and a high-fat diet (HFD), and the protective mechanisms of GLP were investigated through transcriptomic, metabolomic, and network pharmacology (NP) analyses. Our results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats. Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes. GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression (Igfbp1 and Angptl4) and enhanced metabolic biomarkers of 4-Aminocatechol. In addition, NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways. In conclusion, this study provides supportive evidence of the anti-inflammatory effects of GLP supplements, highlighting their potential for promising clinical applications in treating DN.

Urate oxidase (Uox) plays a pivotal role in uric acid (UA) degradation, and it has been applied in controlling serum UA level in clinical treatment of hyperuricemia (HUA). However, because Uox is a heterogenous protein to the human body, the immune rejections typically occur after intravenous administration, which greatly hampers the application of Uox-based agents. In this study, we used Lactococcus lactis NZ9000, a food-grade bacterium, as a host to express exogenous Uox genes, to generate the Uox-expressing engineered strains to treat HUA. Aspergillus flavus-derived Uox (aUox) and the "resurrected" human-derived Uox (hUox) were cloned into vector and expressed in NZ9000, to generate engineered strains, respectively. The engineered NZ9000 strains were confirmed to express Uox and showed UA-lowering activity in a time-dependent manner in vitro. Next, in an HUA mice model established by oral gavage of yeast paste, the UA levels were increased by 85.4% and 106.2% at day 7 and day 14. By contrast, in mice fed with NZ9000-aUox, the UA levels were increased by 39.5% and 48.3% while in mice fed with NZ9000-hUox were increased by 57.0% and 82.9%, suggesting a UA-lowering activity of both engineered strains. Furthermore, compared with allopurinol, the first-line agent for HUA treatment, mice fed with NZ9000-aUox exhibited comparable liver safety but better kidney safety than allopurinol, indicating that the use of engineered NZ9000 strains not only alleviated kidney injury caused by HUA, but could also avoided the risk of kidney injury elicited by using allopurinol. Collectively, our study offers an effective and safe therapeutic approach for HUA long-term treatment and controlling.
Animals ; Lactococcus lactis/metabolism* ; Urate Oxidase/genetics* ; Mice ; Uric Acid/blood* ; Hyperuricemia ; Humans ; Administration, Oral ; Aspergillus flavus/genetics* ; Male

OBJECTIVE To optimize the pr eparation technology of the baicalin lipid nano foam aerosol （BC-LN-FA）. METHODS Baicalin lipid nanoparticle （BC-LN）and BC-LN-FA were prepared by the thin film dispersion method and homogeneous emulsification method ，respectively，using baicalin （BC） as the model drug. The preparation technology was optimized by Box-Behnken design-response surface methodology using particle size and encapsulation efficiency （EE）as indexes ，with dosage ， emulsifier dosage ，co-emulsifier dosage and homogenization time as factors. The morphology ，particle size ，polymerdispersity index（PDI），EE，the viscosity ，the foam dissolution rate and in vitro transdermal release of BC-LN-FA were characterized. RESULTS The optimal technology included 25 mg BC ，40 mg emulsifier （mass ratio of stearic acid-soybean lecithin-glycerol was 1∶1∶1），30 mg co-emulsifier （mass ratio of octadecanol-lactic acid was 1∶1），homogenization time of 20 min. Results of 3 times of validation tests showed that particle size of prepared BC-LN-FA was （151.70±2.40）nm，EE was （68.62±1.16）％；the deviation of them from the predicted value （particle size of 150.80 nm，EE of 67.02％）were 0.60％ and 2.39％ respectively. The BC-LN-FA prepared by the optimal process was light yellow opalescence ，uniform in particle size and round-like in shape. The viscosity，the foam dissolution rate ，the content of BC and PDI were （122.92±5.09）mPa·s，（65.32±3.22）％，（7.01±0.12）％ and（0.199±0.006），respectively. At 48 h，the cumulative release rates of BC-LN-FA in phosphate buffer saline （PBS）at pH 7.4， 6.8，5.0 were（54.12±2.69）％，（57.85±4.25）％ and（59.47±1.83）％，respectively；those of free BC in PBS at pH 7.4 was only （15.04±1.43）％. CONCLUSIONS The optimized technology is stable and feasible. Prepared BC-LN-FA has a uniform particle size，high digestion rate and certain viscosity.

Objective:To investigate the effects of hyperuricemia on the prognosis of IgA nephropathy (IgAN) using propensity score matching (PSM) method.Methods:IgAN patients proven by biopsy were included. PSM was used to match patients. Kaplan-Meier method was used for survival analysis, and Cox regression analysis was used to analyze the effects of hyperuricemia on IgAN prognosis. Primary outcome events were defined as death, or end-stage renal disease (dialysis, transplantation), or a decrease in estimated glomerular filtration rate (eGFR) greater than 40%. Renal outcome was defined as end-stage renal disease (dialysis, transplantation), or a decrease in eGFR greater than 40%.Results:A total of 1 454 IgAN patients were included in this study, including 850 females and 604 males. Uric acid level was (368.26±92.87) μmol/L in the males, and (277.23±92.71) μmol/L in the females. The median follow-up time was 85.00(56.10, 106.33) months. During the follow-up period, a total of 134 patients reached the primary outcome events, including 5 deaths, 24 dialysis patients, 5 kidney transplant patients, and 100 patients with eGFR decreased by more than 40%. After 1∶1 matching, 131 males and 159 females in the hyperuricemia group were successfully matched with 131 males and 159 females in the normal uric acid group, and there was no significant statistical difference in each parameter in baseline between the hyperuricemia group and normal uric acid group after matching. Kaplan-Meier survival analysis showed that either before or after matching, the incidence of primary outcome events in male or female patients with hyperuricemia was higher than those with normal uric acid, but there was no statistically significant difference in incidence of primary outcome events between female hyperuricemia group and female normal uric acid group after matching (Log-rank test, χ2=3.586, P=0.058). Cox proportional hazard regression model showed that, in the pre-match fully adjusted model, the hazard ratio ( HR) of entering primary outcome events was 2.29-fold (95% CI 1.27-4.11, P=0.006) for men with hyperuricemia and 1.85-fold (95% CI 1.01-3.37, P=0.045) for women with hyperuricemia compared with those with normal uric acid. In the post-match fully adjusted model, the HR of entering primary outcome events was 2.41-fold (95% CI 1.18-4.93, P=0.016) for men with hyperuricemia and 1.83-fold (95% CI 0.91-3.67, P=0.091) for women with hyperuricemia compared with those with normal uric acid. In the pre-match fully adjusted model, the HR of entering renal outcome events was 2.68-fold (95% CI 1.47-4.88, P=0.001) for men with hyperuricemia and 1.81-fold (95% CI 0.99-3.33, P=0.056) for women with hyperuricemia compared with those with normal uric acid. In the post-match fully adjusted model, the HR of entering renal outcome events was 2.89-fold (95% CI 1.36-6.15, P=0.006) for men with hyperuricemia and 1.81-fold (95% CI 0.88-3.72, P=0.106) for women with hyperuricemia compared with those with normal uric acid. Conclusion:Hyperuricemia may be associated with IgAN progression, and it has a more significant effect on male IgAN patients.

HuR (human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization (FP) based high-throughput screening (HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay (EMSA), simulation docking and surface plasmon resonance (SPR). Further, we showed that eltrombopag inhibited cell proliferation of multiple cancer cell lines and macrophages, and the anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells (HUVECs) mediated by macrophages with cell scratch assay and Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.

In this study,the intestinal microbial flora diversity of adult and young African lions in the same breeding environment was detected by PCR-DGGE technique.Total bacterial DNA was extracted and 16S rDNA V3 region was amplified,then conducting PCR-DGGE.Subsequently,the specific bands of DGGE were cloned and sequenced.The bacterial species were identified by comparing the sequence through BLAST.The results indicated that the intestinal microbial flora of adult African lions includes Clostridium,Lachnospiraceae bacterium,Anaerovorax,Lactococcus,Peptostreptococcus and Blautia.While the intestinal microbial flora of young African lions is lesser,most bacteria are common to adult and young lions,such as Bacteroidetes bacterium and rumen bacterium.The UPGMA clustering analysis of the DGGE fingerprint showed the similarities of the bacteria structures between adult and young African lions were only 34％.These results revealed that the intestinal microbial flora has significant difference in different stages of African lions.This study lays a foundation for the development of microecological agents in different growth stages of wild animals.