ObjectiveTo investigate the correlation with cognitive function based on a new Kayser-Fleischer ring （K-F ring） grading method in Wilson’s disease （WD）. MethodsA total of 136 WD patients who were hospitalized in Encephalopathy Center， The First Affiliated Hospital of Anhui University of Chinese Medicine， from April 2022 to October 2023 were enrolled. All subjects underwent slit lamp examination， and the grade of K-F ring was determined according to the shape and extent of copper deposition in the cornea， whether it formed a ring or not， and whether there was a sunflower-like cloudy change in the lens. The patients were instructed to complete UWDRS， MoCA， and MMSE scale assessments， and these indicators were compared between patients with different K-F ring grades. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test （homogeneity of variance） or the Dunnett’s T3 test （heterogeneity of variance） was used for further multiple comparisons； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups； the chi-square test was used for comparison of categorical data between groups. The Spearman correlation analysis was used to investigate the correlation of K-F ring grade with UWDRS， MoCA， and MMSE scores. ResultsAmong the 136 patients with WD， there were 40 patients with grade 4 K-F ring， accounting for the highest proportion of 29.4%， and 14 patients with grade 0 K-F ring， accounting for the lowest proportion of 10.3%， and there were 22 patients with grade 1 K-F ring （16.2%）， 19 with grade 2 K-F ring （14%）， 25 with grade 3 K-F ring （18.4%）， and 16 with grade 5 K-F ring （11.7%）. According to the different grades of K-F ring， there was a significant increase in UWDRS score （F=22.61， P<0.001） and significant reductions in MoCA and MMSE scores （F=16.40 and 13.80， both P<0.001）. The Spearman correlation analysis showed that K-F ring grade was positively correlated with UWDRS score （r=0.67， P<0.01） and was negatively correlated with MoCA and MMSE scores in WD patients （r=-0.59 and -0.57， both P<0.01）. ConclusionThe new K-F ring grading method can determine disease severity in WD patients to a certain degree and partially reflect cognitive function and activities of daily living in such patients.

Aim To study the role of norepinephrine in regulating cancer-associated fibroblasts to promote the proliferation and migration of lung cancer cells.Meth-ods Primary cancer-associated fibroblasts and lung cancer A549 cells were cultured.RT-PCR and West-ern blotting were used to detect the expression of VEGF,IL-6 and IL-8 in cancer-associated fibroblasts after norepinephrine intervention,and the effect of nor-epinephrine on the expression of E-cadherin and vim-entin in co-cultured CAFs and lung cancer A549 cells were evaluated,and scratching experiments were used to verify that norepinephrine promoted the migration of lung cancer A549 cells.Results Norepinephrine in-duced the high expression of VEGF,IL-8 and IL-6 in CAFs cells in a concentration-dependent manner.β-adrenergic inhibitor(propranol)could inhibit the ex-pression of VEGF,IL-8 and IL-6 in CAFs cells.Norep-inephrine could inhibit the expression of E-cadherin in lung cancer A549 cells co-cultured with CAFs,promote the upregulation of vimentin,and enhance the migration ability of A549 cells.Conclusion Norepinephrine promotes the proliferation and migration of lung cancer A549 cells through CAFs.

Objective To evaluate the rabbit modle of frozen shoulder induced by persistent strain injuries and ice com-pression.Methods Twelve clean,healthy male New Zealand rabbits with a mass of(2 500±500)g were selected and randomly divided into a blank group and a control group with 6 rabbits in each group.In the control group,the rabbits were modeled with persistent strain injuries and ice compression,the general conditions of the rabbits and the active and passive activities of the shoulder joint were observed and their body weights were recorded.MRI was performed on the affected shoulder joints at 6 d and 29 d after modelling to observe the fluid and soft tissue;HE staining was used to observe the morphology of the rabbit bi-ceps longus tendon and the synovial membrane of the joint capsule;Masson staining was used to observe the fibrous deposits of the rabbit biceps longus tendon and the synovial membrane of the joint capsule,and the fibrous deposits were analysed semi-quantitatively by Image J software.Results Six days after the end of modeling,the active movement of the shoulder joints in the control group was limited,the passive movement was not significantly limited,and they walked with a limp;29 days after the end of the modeling,the active and passive movements of the shoulder joints in the model group were severely limited.Com-pared with the blank group(2.50±0.14)kg,the body weight of the model group(2.20±0.17)kg was significantly reduced(P＜0.01).MRI showed that 6 days after modelling,the muscles around the shoulder joint were not smooth in shape,the joint cap-sule structure was narrowed and a large amount of fluid was seen in the joint cavity;29 days after modelling,the muscles around the shoulder joint were rough in shape,structure of the joint capsule was unclear and the fluid in the joint cavity was reduced compared with 6 days after modelling.Pathological staining showed that the long-headed biceps tendon fibres in the control group were disorganised,curled or even broken,and the synovial tissue of the joint capsule was heavily vascularised,with col-lagen fibre deposits and severe inflammatory cell infiltration.The fiber deposition of the long head of biceps brachii in the mod-el group[(23.58±3.41)％,(27.56±3.70)％]and synovial tissue[(41.78±5.59)％,(62.19±7.54)％]were significantly higher than those in the blank group[(1.79±1.03)％,(1.29±0.63)％]at 7 and 30 days after modeling and synovial tissue fiber de-position[(8.15±3.61)％,(11.29±7.10)％],as shown by the semi-quantitative analysis of Masson staining results by Image J software.And the longer the time,the more severe the fibrosis(P＜0.01).Conclusion The behavioral,imaging and pathological findings showed that the rabbit frozen shoulder model with persistent strain injuries and ice compression is consistent with the clinical manifestations and pathogenesis of periarthritis,making it an ideal method for periarthritis research.

Objective We aimed to compare the efficacy and prognosis of percutaneous coronary intervention(PCI)in complex and high-risk patients with coronary heart disease(CHD)treated with extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)assistance,and explore the application value of combined use of mechanical circulatory support(MCS)devices in complex PCI.Methods A total of patients who met the inclusion criteria and underwent selective PCI supported by MCS at the Department of Cardiology,the First Affiliated Hospital of the Air Force Medical University from January 2018 to December 2022 were continuously enrolled.According to the mechanical circulatory support method,the patients were divided into ECMO+IABP group and IABP group.Clinical characteristics,angiographic features,in-hospital outcomes,and complications were collected.The intra-hospital outcomes and major adverse cardiovascular events(MACE)at one month and one year after the procedure were observed.The differences and independent risk factors between the two groups in the above indicators were analyzed.Results A total of 218 patients undergoing elective PCI were included,of which 66 patients were in the ECMO+IABP group and 152 patients were in the IABP group.The baseline characteristics of the two groups of patients were generally comparable,but the ECMO+IABP group had more complex lesion characteristics.The proportion of patients with atrial fibrillation(6.1％vs.0.7％,P=0.030),left main disease(43.9％vs.27.0％,P=0.018),triple vessel disease(90.9％vs.75.5％,P=0.009),and RCA chronic total occlusion disease(60.6％vs.35.5％,P＜0.001)was higher in the ECMO+IABP group compared to the IABP group.The proportion of patients with previous PCI history was higher in the IABP group(32.9％vs.16.7％,P=0.014).There was no statistically significant difference in the incidence of in-hospital complications between the two groups(P=0.176),but the incidence of hypotension after PCI was higher in the ECMO+IABP group(19.7％vs.9.2％,P=0.031).The rates of 1-month MACE(4.5％vs.2.6％,P=0.435)and 1-year MACE(7.6％vs.7.9％,P=0.936)were comparable between the two groups.Multivariate analysis showed that in-hospital cardiac arrest(OR 7.17,95％CI 1.27-40.38,P=0.025)and after procedure hypotension(OR 3.60,95％CI 1.10-11.83,P=0.035)were independent risk factors for the occurrence of 1-year MACE.Conclusions Combination use of ECMO+IABP support can provide complex and high-risk coronary heart disease patients with an opportunity to achieve coronary artery revascularization through PCI,and achieve satisfactory long-term prognosis.

Objective:To explore effect of IgG receptor FcγRⅡB on neuronal injury and imbalance of Th17/Treg in experi-mental autoimmune encephalomyelitis(EAE)model mice.Methods:C57BL/6 mice were randomly divided into control group,EAE group,FcγRⅡB group and EAE+FcγRⅡB group,with 15 mice in each group.EAE model was induced by subcutaneous injection of MOG35-55 peptide and treated with FcγRⅡB lentiviral solution.After modeling was established,body weight of mice was weighed every day,and neurological function was scored for 30 d;after 30 days,mice were sacrificed.HE staining was used to observe patho-logical changes of brain tissue,LFB staining was used to assess structural changes of spinal cord myelin,and immunofluorescence staining was used to detect spinal cord cerebral cortex neuron nuclear antigen(NeuN)and Caspase-3 expressions,TUNEL staining was used to detect apoptosis of neurons,ELISA was used to detect serum IL-6,IL-17,IL-10 and TGF-β levels,flow cytometry was used to analyze proportion of Th17 and Treg cells in spleen,Western blot was used to determine protein expressions of retinoic acid-related orphan receptor γt(RORγt)and Forkhead family transcription factor 3(Foxp3)in spinal cord tissue.Results:Compared with control group,mice in EAE group had decreased body weight,increased neurological function scores,obvious infiltration of inflamma-tory cells in brain tissue,and signs of demyelination in spinal cord,fluorescence expression intensity of NeuN was weakened and fluorescence expression intensity of Caspase-3 was enhanced,there were more TUNEL-positive stained cells,number of apoptotic cells was increased,levels of IL-6 and IL-17 in serum were increased,and levels of IL-10 and TGF-β were decreased,proportion of Th17 cells in spleen was increased,proportion of Treg was decreased,expression of RORγt protein in spinal cord tissue was up-regu-lated while relative expression of Foxp3 protein was down-regulated(P<0.05);compared with EAE group,weight of mice in EAE+FcγRⅡB group was increased,neurological function score was decreased,infiltration of inflammatory cells in brain tissue was reduced,demyelination of spinal cord was improved,fluorescence expression intensity of NeuN was enhanced,and fluorescence expression intensity of Caspase-3 was weakened,there were fewer TUNEL-positive stained cells,number of apoptotic cells was decreased,levels of IL-6 and IL-17 in serum were decreased,while levels of IL-10 and TGF-β were increased,at the same time,proportion of Th17 cells in spleen was decreased and proportion of Treg was increased,expression of RORγt protein in spinal cord tissue was down-regulated,while expression of Foxp3 protein was up-regulated(P<0.05).Conclusion:FcγRⅡB has neuroprotective effect on EAE mice,and can reduce infiltration of inflammatory cells and demyelination in brain tissue,whose mechanism may be related to regulation of cytokine levels and immune balance of Th17/Treg cells.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.

AIM To establish a UPLC-QTOF/MS method for the analyses of chemical constituents and constituents absorbed into blood from Qili Qiangxin Capsules by UPLC-QTOF/MS.METHODS The rats with heart failure after myocardial infarction were given intragastric administration of 0.5%CMC-Na suspension of Qili Qiangxin Capsules(crude drug dosage was 0.9 g/mL)for 4 weeks,after which blood collection was made.The analysis was performed on a 40℃thermostatic Acquity UPLC BEH C18 Column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile(positive ion manner)or water-acetonitrile(negative ion manner)flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning.RESULTS Total 151 constituents were identified,containing 38 flavonoids,36 terpenoids,23 alkaloids,11 saponins,11 phenylpropanol,10 phenolic acids,4 organic acids,4 cardiac glycosides and 14 others,along with 35 constituents absorbed into blood.CONCLUSION This accurate and stable method can provide data support for the rational clinical application of Qili Qiangxin Capsules,and lay foundation for the research on related effector substances of other Chinese traditional patent medicines.

AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P＜0.01);decreased retinal thickness(P＜0.01);decreased retinal blood perfusion(P＜0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P＜0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P＜0.01);increased retinal blood flow(P＜0.01);increased amplitudes of ERG a wave and b wave(P＜0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P＜0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.

Tumor-infiltrating lymphocytes (TILs), derived from the solid tumor microenvironment, have significant advantages in adoptive cell therapy for solid tumors as they are believed to have more specific antitumor activity than peripheral lymphocytes. TILs was first reported in 1986. With the development and improvement of isolation and activation techniques, TILs-based adoptive cell therapy has shown long-term clinical benefit in phase Ⅱ/Ⅲ trials for advanced melanoma in recent years, and the first TILs-based therapy has been approved for market. Gene editing technology has improved the antitumor activity of TILs and made TILs widely used in other solid tumors besides advanced melanoma, such as head and neck cancer, breast cancer, non-small cell lung cancer, and ovarian cancer. In addition, TILs-based adoptive cell therapy used in combination with other tumor therapies has shown promising therapeutic potential in a variety of solid tumors. This review summarizes the significant progress of TILs-based therapy in basic research, clinical trials, and industrial application in the past two years, and analyzes the challenges and development trends, hoping to provide reference for further development in this field.