Hypoxic-ischemic brain damage (HIBD) is one of the main causes of disability in middle-aged and elderly people, as well as high mortality rates and long-term physical impairments in newborns. The pathological manifestations of HIBD include neuronal damage and loss of myelin sheaths. Tau protein is an important microtubule-associated protein in brain, exists in neurons and oligodendrocytes, and regulates various cellular activities such as cell differentiation and maturation, axonal transport, and maintenance of cellular cytoskeleton structure. Phosphorylation is a common chemical modification of Tau. In physiological condition, it maintains normal cell cytoskeleton and biological functions by regulating Tau structure and function. In pathological conditions, it leads to abnormal Tau phosphorylation and influences its structure and functions, resulting in Tauopathies. Studies have shown that brain hypoxia-ischemia could cause abnormal alteration in Tau phosphorylation, then participating in the pathological process of HIBD. Meanwhile, brain hypoxia-ischemia can induce oxidative stress and inflammation, and multiple Tau protein kinases are activated and involved in Tau abnormal phosphorylation. Therefore, exploring specific molecular mechanisms by which HIBD activates Tau protein kinases, and elucidating their relationship with abnormal Tau phosphorylation are crucial for future researches on HIBD related treatments. This review aims to focus on the mechanisms of the role of Tau phosphorylation in HIBD, and the potential relationships between Tau protein kinases and Tau phosphorylation, providing a basis for intervention and treatment of HIBD.
Humans ; tau Proteins/physiology* ; Phosphorylation ; Hypoxia-Ischemia, Brain/physiopathology* ; Animals ; Oxidative Stress

OBJECTIVE: To investigate the effect of non-chemotherapy strategy of retinoic acid (ATRA) combined with arsenic trioxide (ATO) on the survival of patients with acute promyelocytic leukemia (APL). METHODS: The data of APL patients with complete information diagnosed in the hematology department of our hospital from June 2009 to November 2024 were retrospective analyzed. All patients in the non-CHT group received ATRA-ATO induction, consolidation and maintenance therapy. Patients in the CHT group received ATRA-ATO+chemotherapy induction therapy, followed by 3 cycles of ATRA-ATO+CHT consolidation therapy and 6-10 cycles of ATRA-ATO maintenance therapy. The primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival (OS), remission rate, differentiation syndrome (DS) and safety. RESULTS: There were 182 patients with APL and 15 patients with early death (ED), accounting for 8.24%, which was related to age and risk stratification. There was no significant difference in remission rate between the non-CHT group and the CHT group (P =0.486). As of February 2025, the median follow-up time of patients was 39.5 months. The EFS of the non-CHT group was significantly better than that of the CHT group (P =0.038). There was no significant difference in OS between the two groups (P =0.442). Subgroup analysis showed that EFS in the non-CHT was longer in standard-risk patients (P =0.012). There was no significant difference in EFS (P =0.585) and OS (P =0.473) between the CHT and non-CHT groups in high-risk patients. The incidence of mild DS was 23.6% in the non-CHT group and 23.1% in the CHT group, respectively, with no statistically significant difference(P =0.937). Compared with CHT group, the incidence of serious adverse events was lower in the non-CHT group. CONCLUSION The non-chemotherapy regimen of ATRA combined with ATO is a feasible method to cure APL patients.
Humans ; Leukemia, Promyelocytic, Acute/drug therapy* ; Arsenic Trioxide/therapeutic use* ; Tretinoin/administration & dosage* ; Retrospective Studies ; Female ; Treatment Outcome ; Male ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Middle Aged ; Remission Induction

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

The interaction between Mycobacterium tuberculosis and host, as well as the regulation of some signaling pathways in the host, were involved in pathogen latency in macrophages. microRNAs (miRNAs) regulate the gene expression and biological functions, indicating that miRNAs played a regulatory role in bacterial infections. However, whether the host's miRNAs were also involved in the process of Mycobacterium tuberculosis infection had not been thoroughly studied. This study infected macrophages with pathogenic Mycobacterium tuberculosis strain H37Rv and low virulence strain H37Ra to explore the functional miRNAs. By identifying the expression profile of miRNAs in host cells after infection, the expression of 17 miRNAs significantly changed (P < 0.05) in the human macrophage THP-1 infected with highly pathogenic H37Rv strain (Rv), H37Rv inactivated strain (Rv-), and non-pathogenic H37Ra (Ra) strains respectively, indicating that host miRNAs may be involved in the interaction of Mycobacterium tuberculosis and host. Meanwhile, 10 types of miRNAs showed significant differences in cells infected with pathogenic and non-pathogenic Mycobacterium tuberculosis, suggesting that host miRNAs may play an important role in the pathogenicity and intracellular survival of Mycobacterium tuberculosis. Further study had found that miR-449a, miR-502-5p, and miR-708 were downregulated in cells infected with Mycobacterium marinum. Overexpression of these three miRNAs displayed the significant inhibitory effect on the growth of Mycobacterium marinum, indicating that miRNAs played a pivotal role in the interaction between the host and Mycobacterium marinum. This study provided the new insights into the pathogenesis of Mycobacterium tuberculosis and the treatment of tuberculosis.

Objective To analyze the incidence of venous thromboembolism(VTE)in pulmonary patients and explore the assessment and prevention of the risk of pneumonia accompanied VTE.Methods The patients with pneumonia were divided into control group(simple pneumonia)and treatment group(with VTE)according to the condition of VTE.Demographic data,blood routine,coagulation index,liver and kidney function index and blood gas index were collected.Statistical methods like chi square test,t-test and nonparametric rank sum test were applied to compare the differences between the two groups.Finally,the nomogram was established according to the logistic regression results and the receiver operating characteristic(ROC)curve was calculated.Results 106 cases in control group and 29 cases in treatment group.Univariate analysis showed that age,D-dimer,fibrinogen degradation products,white blood cell count,neutrophil count,albumin-globulin ratio were statistically significant(P＜0.05).Multivariate logistic regression analysis suggests that age[odds ratio(OR)=1.052],D-dimer(OR=2.339),and albumin/globulin(OR=0.042)are independent affecting factors for VTE in pneumonia patients.A nomogram was developed and ROC was calculated,the area under curve(AUC)was 0.754.Conclusion High age,elevated D-dimer and decreased albumin/globulin are independent risk factors for VTE in pneumonia patients.More over,the established prediction model has good accuracy.

ObjectiveTo compare the effects and differences of Yiqi Liangxue Shengji Formula （益气凉血生肌方） and atorvastatin on the repair of vascular injury in rats from the perspective of metabolomics. MethodsTwenty-four male SD rats were randomly divided into sham-surgery， model， traditional Chinese medicine （TCM）， and ator-vastatin groups， with 6 rats in each group. The rat model was established by balloon-induced abdominal aorta injury. Gavage was started on the day after surgery in all groups of rats. The sham and model groups were given with deio-nized water， TCM group received Yiqi Liangxue Shengji Formula 6 g/（kg·d）， and the atorvastatin group treated with atorvastatin suspension 2 mg/（kg·d） for 4 weeks. HE staining was used to observe the pathological morphology of the injured segment of the abdominal aorta； ELISA detection was used to test serum nitric oxide （NO） and C-reactive protein （CRP） levels； UPLC MS/MS technology was used for widely targeted metabolomics detection in serum， and multivariate statistical analysis was used to screen metabolic markers and pathways of two drugs； finally， compare serum levels of key metabolic markers of the above two medications in rats of each group. ResultsCompared with the sham-surgery group， the neointima significantly thickened， the level of NO decreased significantly and the level of CRP increased in serum of the model group （P＜0.01）； compared with the model group， the degree of arterial intimal hyperplasia in TCM group and atorvastatin group reduced， with an increase in NO levels and a decrease in CRP levels （P＜ 0.05 or P＜0.01）. The results of serum metabolomics showed that TCM group obtained 49 metabolic markers and 6 metabolic pathways， while atorvastatin group obtained 41 metabolic markers and 4 metabolic pathways. The two medications jointly regulated 38 metabolites. Glycerophospholipid metabolism and arginine-related metabolism were common metabolic pathways for both medications. Lysophosphatidylcholine （16∶1/0∶0） ［LPC （16∶1/ 0∶0）］， phosphatidylcholine （15∶0/15∶0） ［PC （15∶0/15∶0）］ were the key metabolites of glycerophospholipid metabolic pathway； ornithine， spermidine were the key metabolites of arginine-related metabolic pathway. The tricarboxylic acid cycle and glutathione metabolism were the unique metabolic pathways of Yiqi Liangxue Shengji Formula. Compared with the sham-surgery group， LPC （16∶1/0∶0）， ornithine， and spermidine levels elevated and PC （15∶0/15∶0） levels decreased in the model group （P＜0.05 or P＜0.01）. Compared with the model group， LPC （16∶1/0∶0）， ornithine， and spermidine levels decreased， and PC （15∶0/15∶0） levels increased in both TCM group and atorvastatin group （P＜0.05 or P＜0.01）. The degree of LPC reduction （16∶1/0∶0） was more significant in atorvastatin group compared with that in the TCM group （P＜0.01）. ConclusionsBoth sham-surgery and atorvastatin could regulate lipid metabolism and arginine-related metabolism， exert the characteristics of lipid-lowering， anti-inflammatory， improve arginine/NO bioavailability， and improve endothelial dysfunction. Atorvastatin showed more advantages in lipid-lowering and anti-inflammatory， while Yiqi Liangxue Shengji Formula has unique characteristics in regulating energy metabolism and improving oxidative stress.

Parkinson's disease (PD) is a chronic neurodegenerative disease. At present, levodopa and other drugs are mainly used for dopamine supplementation therapy. However, the absorption of levodopa in the gastrointestinal tract is unstable and its half-life is short, and long-term use of levodopa will lead to the end-of-dose deterioration, dyskinesia, the "ON-OFF" phenomenon and other symptoms. Therefore, new preparations need to be developed to improve drug efficacy, reduce side effects or improve compliance of patients. Based on the above clinical needs, this review briefly introduced the preparation modification strategies for the treatment of PD through case analysis, in order to provide references for the research and development of related preparations.

Objective To explore the core drugs and antidepressant molecular mechanisms of Chinese herbal compound in the clinical treatment of depression.Methods Relevant literature was searched through CNKI,Wanfang and VIP to screen and sort out the Chinese Herbal compounds used in clinical practice.By analyzing the frequency of medication and the association rules of Chinese medicines,Bupleuri Radix,Paeoniae Radix Alba,Curcumae Radix were determined as the core Chinese medicinals for the treatment of depression.The active components and target proteins of these drugs were screened by TCMSP database,and depression-related targets were obtained from TTD,OMIM,DrugBank and GeneCards.Protein-protein interaction(PPI)network and'core drug-active ingredient-intersection target'network were constructed by STRING and Cytoscape.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by Metascape.Molecular docking analysis used RCSB database,AutoDockTools and PyMOL to verify the binding activity of key active components with core targets.Results The drugs for the treatment of depression in clinical Chinese herbal compound prescriptions were mainly cold,sweet,bitter and pungent,and the liver meridian was the first.Bupleuri Radix,Paeoniae Radix Alba,Curcumae Radix had the highest frequency of medication,and the combination of"Paeoniae Radix Alba-Bupleuri Radix"and"Curcumae Radix-Paeoniae Radix Alba-Bupleuri Radix"had the highest support.In the PPI network,SLC6A4,AKT1 and CHRNA4 were the key targets.GO enrichment analysis results showed that core drugs play a role in synaptic membranes and other parts through biological processes such as chemical synaptic transmission,as well as molecular functions such as G protein-coupled receptor activity.KEGG pathway enrichment analysis results showed that core drugs may treat depression through neuroactive ligand-receptor interaction,calcium signaling pathway and other pathways.Molecular docking confirmed that there was a strong binding activity between the key active ingredients and the core target.Conclusion Bupleuri Radix,Paeoniae Radix Alba,Curcumae Radix are the core drugs for clinical treatment of depression,which can treat depression through multi-component,multi-target and multi-pathway.

Objective As primary Sj?gren's syndrome(pSS)primarily affects the salivary glands,saliva can serve as an indicator of the glands'pathophysiology and the disease's status.This study aims to illustrate the salivary proteomic profiles of pSS patients and identify potential candidate biomarkers for diagnosis. Methods The discovery set contained 49 samples(24 from pSS and 25 from age-and gender-matched healthy controls[HCs])and the validation set included 25 samples(12 from pSS and 13 from HCs).Totally 36 pSS patients and 38 HCs were centrally randomized into the discovery set or to the validation set at a 2:1 ratio.Unstimulated whole saliva samples from pSS patients and HCs were analyzed using a data-independent acquisition(DIA)strategy on a 2D LC-HRMS/MS platform to reveal differential proteins.The crucial proteins were verified using DIA analysis and annotated using gene ontology(GO)and International Pharmaceutical Abstracts(IPA)analysis.A prediction model for SS was established using random forests. Results A total of 1,963 proteins were discovered,and 136 proteins exhibited differential representation in pSS patients.The bioinformatic research indicated that these proteins were primarily linked to immunological functions,metabolism,and inflammation.A panel of 19 protein biomarkers was identified by ranking order based on P-value and random forest algorichm,and was validated as the predictive biomarkers exhibiting good performance with area under the curve(AUC)of 0.817 for discovery set and 0.882 for validation set. Conclusions The candidate protein panel discovered may aid in pSS diagnosis.Salivary proteomic analysis is a promising non-invasive method for prognostic evaluation and early and precise treatments for pSS patients.DIA offers the best time efficiency and data dependability and may be a suitable option for future research on the salivary proteome.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.