Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

ObjectiveMyelodysplastic syndromes （MDS） is a group of clonal hematopoietic stem cell disorders，and this study aims to investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS，the therapeutic efficacy of arsenic-containing Chineseherbal compound，and the survival prognosis. MethodAccording to the inclusion and exclusion criteria，27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology，Xiyuan Hospital，China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included，and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction （PCR） to analyze its correlation with clinical features，and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia（r=0.384，P<0.05） and bone marrow granulocytic system%（G%）（r=0.560，P<0.01）. Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment（P<0.05）and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients ［odds ratio（OR）=398.968，95% confidence interval（CI）（1.281，116 858.743），P<0.05］. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%，and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.

ObjectiveTo investigate the immunological characteristics of the patients with aplastic anemia （AA） and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters， thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen. MethodA retrospective study was conducted， involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital， China Academy of Chinese Medical Sciences from September 2018 to March 2021. The patients were assigned into two groups according to the elevations in hemogram parameters ［including hemoglobin （HGB）， white blood cell count （WBC）， platelet （PLT）， and absolute neutrophil count （ANC）］ after 6 months of treatment. One group had the elevation <50%， and the other group had the elevation ≥50% compared with the baseline. The clinical and immunological characteristics were compared between the two groups. Result① Compared with the group with HGB elevation<50%， the group with HGB elevation≥50% showed elevated level of CD3⁺ human leukocyte antigen-DR （HLA-DR）⁺ and increased proportion of patients with T-helper cell type 2 （Th2）<5%， CD8⁺≥50%， and CD3⁺HLA-DR⁺≥9% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD8⁺≥50% before treatment was the independent influencing factor for HGB elevation ≥50% ［odds ratio （OR）=12.000， 95% confidence interval （CI） 2.218， 64.928， P<0.01］. ② Compared with the group with WBC elevation<50%， the group with WBC elevation≥50% showed increased proportion of patients with CD3⁺HLA-DR⁺<6% and T-box transcription factor （T-bet）≥200% before treatment （P<0.05）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<6% （OR=2.998， 95%CI 1.036， 8.680， P<0.05） and T-bet≥200% （OR=3.634， 95%CI 1.076， 12.273， P<0.05） before treatment were independent influencing factors for WBC elevation≥50%. ③ Compared with the group with PLT elevation<50%， the group with PLT elevation≥50% presented lowered Th1 and CD3⁺HLA-DR⁺ levels and increased proportion of patients with Th1<12%， CD4⁺≥6%， and CD3⁺HLA-DR⁺<5% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<5% before treatment was the independent influencing factor for PLT elevation≥50% （OR=16.190， 95%CI of 3.430 to 76.434， P<0.01）. ④ Compared with the group with ANC elevation<50%， the group with ANC elevation≥50% showed no significant changes in the hemogram parameters before treatment. ConclusionAs for the AA patients with rapid elevation in HGB， Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5% and CD3⁺HLA-DR⁺≥9%， especially those with CD8⁺≥50%. As for the AA patients with rapid elevation in WBC， the therapy was particularly effective in the patients with CD3⁺HLA-DR⁺<6% and T-bet≥200%. As for the AA patients with rapid growth in PLT， the therapy was particularly effective in the patients with Th1<12% and CD4⁺≥6%， especially those with CD3⁺HLA-DR⁺<5%.

In the context of high-quality development in medical institutions, the supply-processing-distribution(SPD) management mode has gradually been widely applied. The authors described in detail the procurement, supply, inventory, distribution, and settlement management of medical consumables and in vitro diagnostic reagents in a certain hospital under the SPD mode. It was found that SPD was conducive to strengthening the supervision of medical consumables and in vitro diagnostic reagents in the hospital, ensuring quality and safety of use, reducing hospital operating costs, and improving hospital′s competitiveness. However, attention should be paid to preventing data security risks, strengthening operational management, and improving the cost-benefit analysis of in vitro diagnostic reagents.

Acute kidney injury （AKI） is a clinical syndrome characterized by a rapid decline in renal function over a short period due to various etiologic factors. If left untreated， AKI can progress to chronic kidney disease （CKD） or even end-stage renal disease （ESRD）. Although continuous renal replacement therapy （CRRT） can manage severe AKI， effective pharmacological treatments for AKI remain largely unavailable. Chinese medicine， with its multi-target and multi-pathway approaches， has accumulated substantial theoretical and practical knowledge in treating AKI and related complications. Rehmanniae Radix is a commonly used Chinese medicinal， known for its functions in clearing heat， cooling blood， nourishing yin， and promoting fluid production. The primary active ingredients of Rehmanniae Radix include catalpol， acteoside， and aucubin. In this study， we summarized recent research on the effect of the active ingredients of Rehmanniae Radix in preventing and treating AKI. We found that the key mechanisms underlying its anti-AKI effects include amelioration of inflammation， alleviation of oxidative stress， and inhibition of apoptosis. Additionally， the antifibrotic properties of the active ingredients of Rehmanniae Radix suggest its potential in slowing CKD progression. We reviewed the mechanisms of Rehmanniae Radix in treating AKI and its antifibrotic effects to provide a scientific basis for developing new AKI drugs， promoting the utilization of Rehmanniae Radix resources， and reducing the transition from AKI to CKD.

【Objective】 To explore the relationship between the methylation level of CNR1 and autism spectrum disorder (ASD), in order to provide a theoretical basis for the etiology of ASD. 【Methods】 A case-control study was conducted, recruiting 30 children with ASD from the Child Development and Behavior Research Center of Harbin Medical University and a rehabilitation facility, and 30 matched typically developed children from June 2017 to December 2018. The methylation levels of CNR1 in peripheral blood were measured by the Agena MassArray^® Mass Spectrometry System. A univariate conditional Logistic regression model was used to analyze the potential association between the methylation level of CNR1 and the risk of ASD with adjustment for age, BMI, body fat percentage and body fat. The correlations between the methylation level of CNR1 and the score of Social Responsiveness Scale (SRS) were evaluated by Pearson/Spearman correlation analysis. 【Results】 The methylation levels of the average methylation (t=2.224), CpG_3.4 (Z=2.187), CpG_9.10.11 (t=2.308), and CpG_28.29 (t=2.943) of the CNR1 promoter region in ASD children were significantly higher than controls (P<0.05). The methylation levels of the average methylation (OR=1.117, 95%CI: 1.003 - 1.245), CpG_9.10.11 (OR= 1.072, 95%CI:1.006 - 1.142), and CpG_28.29 (OR=1.078, 95%CI: 1.018 - 1.141) of the CNR1 promoter region were positively correlated with the risk of ASD (P<0.05). The methylation level of CpG_28.29 in ASD children was positively correlated with the scores of social motivation in SRS (r=0.421, P<0.05). 【Conclusions】 The methylation levels of CNR1 in peripheral blood are abnormal in ASD children and might be correlated with the risk of ASD and social function. The underlying mechanism needs to be further explored.

Autoimmune hemolytic anemia (AIHA) is characterized by the accelerated destruction of erythrocytes due to the presence of antibodies and/or complement that bind to antigens on erythrocytes. It can be subdivided into warm, cold or mixed AIHA based on the type of autoantibody and the optimal temperature of antigen-antibody reaction. Glucocorticoid with or without rituximab is the first-line treatment of warm AIHA (wAIHA), and splenectomy was once the preferred second-line treatment for relapsed or refractory wAIHA. However, due to the various complications of splenectomy, rituximab has gradually become the preferred treatment for patients who have failed glucocorticoid therapy. Other available treatments including immunosuppressants and plasma exchange can be chosen. Rituximab with or without bendamustine is generally taken as the first-line regimen for cold autoimmune hemolytic anemia (cAIHA), while glucocorticoid and splenectomy are ineffective. Sutimlimab, a kind of complement inhibitor, has been approved for the treatment of cold agglutinin disease (CAD). In recent years, many new drugs have emerged as treatment options for AIHA. Emerging therapies, including B-cell-directed therapies, plasma cell-directed therapies, complement inhibitors, and phagocytosis inhibition, provide a new perspective for AIHA therapy, showing great potential for clinical applications

ObjectiveTo build an evaluation index system for traditional Chinese medicine （TCM） medicated diet， promoting the scientific and standardized development of medicated diet in TCM. MethodsThe framework of the evaluation index system was constructed through literature review and Delphi expert consultation method. The analytic hierarchy process was used to construct a hierarchical structure model. Pairwise comparisons between the indicators were conducted using the Saaty 1-9 scale method， and the weight of each indicator was calculated using Yaahp 10.3. ResultsThe response rates for the two rounds of expert consultation were 93.33% and 100%， respectively. The Kendall's W coefficients for the first-level and second-level indicators in the second round were 0.270 and 0.281， respectively （both P＜0.001）. Finally， an evaluation index system for TCM medicated diet therapy was constructed， consisting of 6 primary indicators and 27 secondary indicators. The weightings of the primary indicators were as follows： sensory appearance （0.1843）， health value （0.3569）， ingredient compatibility （0.1271）， packaging （0.0370）， production and preparation （0.1005）， and reliability （0.1940）. ConclusionA comprehensive and universally applicable evaluation index system for TCM medicated diet has been developed， taking into conside-rations of color， taste， appearance， efficacy， preparation， quality and others. This system can provide valuable reference for the evaluation of the value of medicated diet as well as its development.

Objective:To analyze the medication and compatibility law of TCM compound patents in the treatment of diabetic nephropathy (DN) based on data mining method; To provide basis for research and development of new drug in clinic.Methods:TCM compound patents for DN treatment were retrieved from national patent platform. Excel 2019 was used to conduct statistical analysis on drug frequency, property and taste and meridian. SPSS Modeler 18.0 and SPSS Statistic 26.0 were used for drug association rules and clustering analysis. The complex network of co-occurrence of core drugs was constructed with Cytoscape 3.9.0, and the potential of the correlation between new prescriptions and drugs was demonstrated.Results:A total of 261 TCM compound patents were included, including 438 kinds of Chinese materia medica. High-frequency drugs included Astragali Radix, Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma, Lycii Fructus, etc. Drug categories were mainly deficiency tonic drugs. The properties and tastes were mainly cold and sweet, and the meridians were mainly liver and kidney meridians. The commonly used medicinal pair was Ganoderma-Rehmannine Radix. The commonly used triple medicinal combination was Notoginseng Radix et Rhizoma-Angelicae Sinensis Radix-Ganoderma. There were 7 groups of clustering medicines, including Notoginseng Radix et Rhizoma, Ganoderma, Angelicae Sinensis Radix, Euryales Semen, Rehmanniae Radix and Lycii Fructus. There were 5 groups of potential medicines, including Campsis Flos-Caulis Tinosporae Sinensis-Kalopanacis Radix-Fimbristylis Rigiduta Nees-Padicularisdis Dissectae Radix -Korshinsk Peashrub-Alismatis Fructus-Cynanchi Wallichii Radix. The core new prescriptions for treating DN were obtained through topological attribute analysis and screening.Conclusions:The national TCM compounds patents treatment for DN is based on the pathogenesis of this disease, which is characterized by deficiency in nature and excess in superficiality. It often uses methods such as tonifying qi and spleen, nourishing yin and tonifying kidney, promoting blood circulation and resolving blood stasis to improve clinical efficacy, providing ideas for the development of new drugs.

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins