Taxifolin (Tax) has been proved to be a medicinal edible substance with protective effects against alcoholic liver injury, however, its poor hydrophilicity and permeability have hindered the clinical application of Tax. In this study, we prepared taxifolin-phosphatidylcholine/sodium deoxycholate/PVP-K30 micells (Tax-MLs). Box-Behnken test was used to obtain the optimal preparation process, and Tax-MLs were characterised by transmission electron microscopy and fourier transform infrared spectroscopy. Physicochemical parameters such as proximate micelle concentration, equilibrium solubility and oil-water partition coefficient were determined, and the release pattern of Tax-MLs was investigated by in vitro digestion simulation. Alcoholic liver injury model to explore the in vivo efficacy of Tax-MLs. The results showed that the average particle size, polydispersity index (PDI) and zeta potential of Tax-MLs were 36.90 ± 4.57 nm, 0.194 ± 0.01 and -32.6 ± 0.35 mV, respectively, and the uniform size and distribution of Tax-MLs were observed by transmission electron microscopy. The formation of Tax-MLs was proved by differential scanning calorimetry and fourier transform infrared spectroscopy. In terms of physicochemical properties, the solubility of Tax-MLs in water increased by 92.02 times compared with Tax, and its oil-water partition coefficient in water increased from 0.43 to 1.14, which proved that Tax-MLs could improve its solubility and permeability. The in vivo pharmacodynamic results showed that compared with the Tax group, Tax-MLs low, medium and high dose groups showed a significant reduction in liver indices and serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (P < 0.05), and enhanced the activities of superoxide dismutase (SOD) and glutathione (GSH), and lowered the levels of malondialdehyde (MDA) more significantly in the hepatic tissues. Tax-MLs effectively improved drug solubility and permeability, and enhanced the protective effect against alcoholic liver injury. Animal experiments were conducted with approval from the Animal Ethics Committee of Changchun University of Traditional Chinese Medicine (approval number: 2023601).

Objective To investigate the effects of Echinococcus multilocularis infection on levels of memory T (Tm) cells and their subsets in lymph nodes of mice at different stages of infection, so as to provide new insights into immunotherapy for alveolarechinococcosis. MethodsTwenty-four C57BL/6J mice aged 6 to 9 weeks were randomly divided into the infection group and the control group, of 12 mice in each group. Mice in the infection group were administered with 3 000 E. multilocularis protoscoleces via portal venous injection, while animals in the control group were administered with an equal volume of physiological saline. Three mice from each group were sacrificed 4, 12 weeks and 24 weeks post-infection, and lymph nodes were sampled and stained with hematoxylin and eosin (HE) to investigate the histopathological changes of mouse lymph nodes in the infection group. The expression and localization of T lymphocyte surface markers CD3, CD4, and CD8 were observed in mouse lymph nodes using immunohistochemical staining. In addition, lymphocyte suspensions were prepared from mouse lymph nodes in both groups at different time points post-infection, and the levels of Tm cell subsets and their secreted cytokines were detected using flow cytometry. Results HE staining showed diffuse structural alterations in the subcapsular cortical and paracortical regions of mouse lymph nodes in the infection group 4 weeks post-infection with E. multilocularis. Immunohistochemical staining detected CD3, CD4 and CD8 expression in mouse lymph nodes in both groups. Flow cytometry revealed higher proportions of CD4⁺ Tm cells [(55.3 ± 4.8)% vs. (38.8 ± 6.1)%; t = -4.259, P < 0.05] and CD4⁺ tissue-resident Tm (Trm) cells [(57.7 ± 3.7)% vs. (34.1 ± 11.2)%; t = -3.990, P < 0.05] in mouse lymph nodes in the infection group than in the control group 4 weeks post-infection, and higher proportions of CD4⁺ Tm cells [(34.6 ± 3.2)% vs. (23.3 ± 7.5)%; t = -2.764, P < 0.05] and CD4⁺ Trm cells [(44.0 ± 1.9)% vs. (31.2 ± 1.5)%; t = -4.039, P < 0.05] in mouse lymph nodes in the infection group than in the control group 24 weeks post-infection. The proportions of CD8⁺ Tm cells were higher in the infection group than in the control group 4 weeks [(56.8 ± 2.7)% vs. (43.9 ± 5.2)%; t = -4.416, P < 0.01] and 12 weeks post-infection [(25.4 ± 2.7)% vs. (12.0 ± 2.6)%; t = -2.552, P < 0.05], while the proportions of tumor necrosis factor (TNF)-α⁺ CD4⁺ T cells [(15.7 ± 5.0)% vs. (49.4 ± 6.4)%; t = 7.150, P < 0.01], TNF-α⁺CD8⁺ T cells [(20.7 ± 5.5)% vs. (57.5 ± 8.4)%; t = -6.694, P < 0.01], and TNF-α⁺ CD8⁺ Tm cells [7.0% (1.0%) vs. 31.0% (11.0%); Z = -2.236, P < 0.05] were lower in the infection group than in the control group 24 weeks post-infection. Conclusions Tm cells levels are consistently increased in lymph nodes of mice at different stages of E. multilocularis infection, with Trm cells as the predominantly elevated subset. The impaired capacity of CD8⁺ Tm cells to secrete the effector molecule TNF-α in mouse lymph nodes at the late-stage infection may facilitate chronic parasitism of E. multilocularis.

Humans ; Amyloidosis ; Amyloid ; Cardiomyopathies

Objective:To analyze the clinical and immunological characteristics of children with acute viral infection-related encephalopathy.Methods:Case-control study.A retrospective analysis was conducted on the clinical data of children diagnosed with acute viral infection-related encephalopathy during hospitalization at the Children′s Hospital, Capital Institute of Pediatrics from January 2020 to January 2023.According to the last follow-up modified Rankin scale (mRS) score, these children were divided into a good prognosis group (mRS score ≤2) and a poor prognosis group (mRS score >2), and the clinical and immunological characteristics of the children with different prognoses were analyzed.The binary Logistic regression was used to analyze the risk factors for poor prognosis.Results:A total of 28 children with acute viral infection-related encephalopathy aged 4 months to 11 years were included.There were 16 males (57%) and 12 females (43%). Among the preinfection viruses, there were 16 children of Corona virus disease 2019, 8 children of influenza A virus, 3 children of influenza B virus, and 1 child of norovirus.Among them, there were 21 children with acute necrotizing encephalopathy, 4 children with acute encephalopathy with biphasic seizures and late reduced diffusion, 2 children with mild encephalitis with a reversible splenial lesion, and 1 child with hemorrhagic shock and encephalopathy syndrome.Among the first symptoms, 24 children (85.7%) had consciousness disorders, 23 children (82.1%) had seizures, 17 children (60.7%) had speech disorders, 11 children (39.3%) had involuntary movements, and 10 children (35.7%) had abnormal mental behavior.For the site of lesion, the cranial nuclear magnetic resonance imaging revealed 17 in the thalamus, 10 in the brainstem, 9 in the basal ganglia, 8 in the cerebellar hemisphere, and 4 in the corpus callosum.In the last follow-up evaluation, 17 children had a mRS score of >2, and 11 children had a mRS score of ≤2.Univariate analysis showed that disturbance of consciousness, seizure cluster, brain stem lesion, absolute value of serum T lymphocytes, cerebrospinal fluid(CSF) protein, CSF cytokines [interleukin(IL)-1β, IL-6 and IL-8]were higher in the poor prognosis group than those in the good prognosis group.Multivariate Logistic regression analysis indicated that brain stem disease, CSF IL-1β and T lymphocyte absolute number were independent risk factors for poor prognosis.Conclusions:Brain stem lesions, cerebrospinal fluid IL-1β and the absolute number of T lymphocytes have predictive value for the prognosis of acute viral infection-associated encephalopathy.The more severe the conditions, the lower the T lymphocytes, and the higher the cytokines in some cerebrospinal fluid.

ObjectiveThis study aims to understand the recognition of practitioners in traditional Chinese medicine （TCM） hospitals on hospital-based health technology assessment （HB-HTA）， assessment needs， challenges， and suggestions， so as to provide references for the future work. MethodThe convenient sampling method was adopted to survey the relevant practitioners in TCM hospitals. The questionnaire included 39 questions in 4 dimensions and was distributed through the online platform Weijuanxing. ResultA total of 244 questionnaires were recovered， and the obtained data were analyzed in SPSS. The results showed that 137 practitioners were very familiar with HB-HTA and there was no significant difference in the recognition of practitioners in different occupations （F=0.251； P=0.778）. The practitioners in Hong Kong， Macao， and Taiwan had lower recognition than those in other regions. In terms of the assessment needs， 127 practitioners believed that it was very necessary to carry out HB-HTA in TCM hospitals in the future. Chinese patent medicines/Chinese herbal medicine decoction pieces （5.91） and TCM appropriate technology （5.57） had higher assessment priority scores. The assessment needs were high for the effectiveness （235 practitioners） and safety （224 practitioners） of health technology. The lack of specialized organization and standardized evaluation process system and the shortage of talents were considered to be the major challenges for the future development in this field. ConclusionThe stakeholders carrying out the health technology assessment in TCM hospitals had certain awareness of HB-HTA. Most practitioners believed that it was necessary to carry out HB-HTA in TCM hospitals in the future， while the work might face challenges such as the lack of organizations and system and the shortage of talents， which requires policy support.

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

Four pyrazines were isolated from the n-butanol fraction of Hypecoum erectum L. by using various chromatographic methods, including MCI gel, ODS, silica gel and semi-preparative HPLC. The structures of the isolated compounds were identified as hyperectpyrazin A (1), 1′S-(6-methylpyrazin-2-yl)-ethane-1′,2′-diol (2), 2-hydroxymethyl-6-methylpyrazin (3) and pyrazine-2-carboxylic acid (4) by spectroscopy methods (1D NMR, 2D NMR, UV, IR, MS, etc.). The absolute configuration of compound 2 was determined by using the Mo₂(OAc)₄ induced CD analysis for the first time. Compound 1 was a new compound, compounds 2-4 were isolated from H. erectum for the first time. Compounds 1-4 were evaluated for their inhibition against acetylcholinesterase and nitric oxide generation induced by lipopolysaccharide-RAW264.7 macrophage cells. At a concentration of 50 μmol·L^-1, compounds 2 and 4 displayed inhibitory effects on acetylcholinesterase with the inhibition rates of 44.40% and 43.99%, respectively.

Objective To investigate the risk factors of short-term adverse prognosis and the predictive value of Charlson comorbidities index(CCI)in patients with central pulmonary embolism(PE).Methods 115 cases of central PE patients were retrospectively analyzed.According to the adverse prognosis during hospitalization,the subjects were divided into adverse event group and no adverse event group.The clinical characteristics of the ad-verse event group were analyzed.Multivariate Logistic regression analysis was performed for statistically significant indicators.Results The most common clinical symptoms of central PE patients were chest distress or dyspnea(77.4％ ),followed by cough(35.7％ ),chest pain(28.7％ ),syncope(9.6％ )and hemoptysis(7.8％ ).There were no statistically significant differences in gender,smoking history,drinking history,symptoms and signs between the two groups.In univariate analysis,CCI,grouping score of thrombus location,white blood cell count,neutrophil count and urea nitrogen were associated with adverse events in central PE patients,with statistical signif-icance(P＜0.05).After Logistic regression multivariate analysis,increased neutrophil count(OR=1.494,95％ CI:1.073-2.080,P=0.017)was an independent risk factor(P＜0.05).The CCI in the group with adverse e-vents was higher than that in the group without adverse events(P=0.004).Multivariate analysis showed that in-creased CCI(Oβ=1.342,95％ CI:1.022-1.763,P=0.034)was an independent risk factor,and the risk of adverse events increased by 34.2％ for every one-point increase in CCI.The thrombus location score of the group with adverse events was significantly higher than that of the group without adverse events(OR=2.586,95％ CI:1.366-4.896,P=0.004),and the risk of adverse events increased 1.586 times with each increase of thrombus location score.Conclusion Increased neutrophil count,CCI,and thrombus location score are associated with poor short-term prognosis in central PE patients.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.