Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To investigate the relationship between appendicular skeletal muscle composition(muscle mass and muscle index)and glycosylated hemoglobin A1c(HbA1c)level in type 2 diabetes mellitus(T2DM)patients.Methods A total of 459 adult T2DM patients hospitalized in the Department of Endocrinology,Tangdu Hospital of Air Force Medical University from April 2021 to June 2022 were selected as the research objects.Bioelectrical impedance analysis was used to evaluate the body composition of the patients.The patients were divided into two groups according to HbA1c level:standard glycation group(HbA1c≤7.0%,n=145)and unqualified glycation group(HbA1c>7.0%,n=314).The two groups'general data,biochemical indexes,muscle content,fat content and other body composition were analyzed.Spearman correlation analysis and multiple logistic regression analysis were used to analyze the relationship between body composition and glycemic control in type 2 diabetic patients.Results The appendicular skeletal muscle mass and its index(ASMI)of the patients in the standard glycation group were better than those in the unqualified glycation group(P<0.05).However,there were no significant differences in gender,history of antidiabetic drugs and body fat(body fat content,limb fat content and visceral fat content)between the two groups(P>0.05).Spearman correlation analysis showed that appendicular skeletal muscle mass and its index were negatively correlated with HbA1c(r=-0.158,P=0.001;r=-0.187,P<0.001).Logistic regression analysis showed that upper limb skeletal muscle mass(OR=3.570,95%CI 2.293-5.559)and lower limb skeletal muscle mass(OR=1.297,95%CI 1.146-1.468)were independent protective factors for achieving glycation standard in HbA1c group.Conclusions The skeletal muscle mass of limbs is a protective factor for reaching the standard of HbA1c.With the increase of skeletal muscle mass of limbs,the level of HbA1c gradually decreases.Among them,the increase of upper limb muscle mass has a stronger correlation with reaching the standard of HbA1c.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

The material basis and mechanism of Chaenomelis Fructus in the treatment of rheumatoid arthritis(RA) were explored by network pharmacology, and the potential anti-RA targets of Chaenomelis Fructus were verified by molecular docking and animal experiments. The active components and targets of Chaenomelis Fructus were searched against the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. GeneCards, DisGeNET, and OMIM were used to obtain RA-related targets. The common targets shared by Chaenomelis Fructus and RA were considered as the potential targets of Chaenomelis Fructus in the treatment of RA. Cytoscape 3.9.0 was employed to establish a "traditional Chinese medicine-active component-common target-disease" network. The protein-protein interaction(PPI) network was established by STRING, and the core genes were visualized by RStudio 4.1.0. DAVID was used for Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment to predict and visualize the involved signaling pathways. Molecular docking was carried out with the active components screened out as ligands and RA core genes as the targets. Finally, the prediction results were verified by animal experiments. Four main active components of Chaenomelis Fructus were obtained, which corresponded to 137 targets. Chaenomelis Fructus and RA shared 37 common targets. GO annotation yielded 239 terms(P<0.05), and KEGG pathway enrichment analysis screened out 94 signaling pathways(P<0.05), mainly involving interleukin-17(IL-17), tumor necrosis factor, Toll-like receptor, and nuclear factor-kappa B(NF-κB) signaling pathways. Molecular docking results showed that the main active components of Chaenomelis Fructus bound well with the core targets of RA. The results of animal experiments proved that Chaenomelis Fructus can alleviate joint swelling in the mice with RA. The results of ELISA showed that Chaenomelis Fructus lowered the levels of interleukin-6(IL-6) and interleukin-1β(IL-1β). Western blot showed that Chaenomelis Fructus down-regulated the protein level of vascular endothelial growth factor A(VEGFA). Chaenomelis Fructus exerts anti-inflammatory effect and reduces pannus formation by regulating the core targets such as VEGFA, IL-1β, and IL6 in the treatment of RA. The findings of this study provide new ideas for the future treatment of RA with Chaenomelis Fructus.
Animals ; Mice ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; Molecular Docking Simulation ; Arthritis, Rheumatoid/genetics* ; Tumor Necrosis Factor-alpha ; NF-kappa B ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1β, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.
Animals ; Cattle ; Male ; Rats ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Body Weight ; Codonopsis/chemistry* ; Interleukin-6/blood* ; NF-kappa B/genetics* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Plant Extracts/therapeutic use* ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/pharmacology*

Objective To study the effect of velvet antler polypeptides (VAP) on antioxidant in Alzheimer' s disease model mice. Methods Eight months old male amyloid precursor protein (APP)/presenilin-l (PS1) double transgenic mice were selected as Alzheimer' s disease (AD) model and divided into the model group and the VAP intervention group, 12 in each group. Besides, normal mice of the same brood (with no transgene) were recruited as a control group (n= 12).After 6 months of intragastric administration, behavior, morphology and oxidative stress related indicators were detected.SH-SY5 cells were used to establish AD model of damaged by Ap2535. The expression levels of APP and p-secreatase-l(BACE1) protein in mouse hippocampus were detected by Western blotting. VAP intervention group SH-SY5Y cells was cultured with VAP (500 g/L) and amyloid P(Ap) 2535(25 ixmol/L) for 24 hours. Control group cells were normally cultured by DMEM medium. Cell apoptosis, membrane potential, reactive oxygen species (ROS) levels and oxidative stress related indexes were detected. Results In animal models, compared with the model group, the escape latency of mice in the VAP intervention group was shortened (P<0. 05). The neuronal cells in the CA1 region of the hippocampus of the model group were reduced and arranged disorderly. The arrangement of the VAP intervention group was relatively regular, and the morphology was significantly improved. Compared with the model group, senile plaques were decreased in the VAP intervention group. Compared with the model group, the malondialdehyde (MDA) content ol the VAP intervention group increased, and the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content increased, the difference was statistically significant. Compared with the control group, the APP and BACE1 content in the model group increased. Compared with the model group, the contents of APP and BACE1 in the VAP intervention group decreased, and the difference was statistically significant (P<0. 05). In the cell model, the apoptosis rates of the VAP intervention group decreased. Compared with the model group, the mitochondrial membrane potential of the VAP intervention group increased, the content ol ROS decreased, the content of MDA decreased, and the content of SOD and GSH-Px increased. The difference were statistically significant (P<0. 05). Conclusion VAP has a protective effect on oxidative stress damage caused by Alzheimer' s disease model animals and cells, which may be achieved by reducing ROS production and increasing the activity of antioxidant enzymes to reduce Ap deposition.

Objective To study the effect of velvet antler polypeptides (VAP) on Rho/ROCK pathway in APP/ PSl double transgenic mice. Methods APP/PSl double transgenic mice were randomly divided into model group and velvet antler polypeptide group, 20 mice in each group, and control group consisting of 20 mice of the same litter and the same gender negative. The mice in VAP group were given velvet antler polypeptide 100 mg/kg by intragastric administration once a day for 28 days. After treatment, the water maze experiment was detected and recorded the escape latency and the number of crossing platforms of the mice; the ultrastructures of the synapse were observed by transmission electron microscopy; the expression of Rhs homolog gene family member A(RhoA) and Rho associated coiled-coil forming protein kinase II(ROCKII) in the hippocampal CAI area were observed by immunofluorescence. The expression levels of RhoA and ROCKII protein in the hippocampus were detected by Western blotting. The contents of hippocampus amyloid (3-protein(A(3),

Objective:To investigate the clinical characteristics and electroencephalogram (EEG) of epilepsy patients with breach rhythm, improve clinical understanding of breach rhythm and avoid over-interpretation.Methods:Twelve epilepsy patients with breach rhythm who visited the Department of Neurology, Xijing Hospital, the Air Force Military Medical University from January 2016 to January 2017 were collected retrospectively. The clinical data, including etiology, clinical manifestations, EEG features and prognosis were summarized, and outpatient and telephone follow-up was performed for at least three years.Results:The clinical data of 12 patients with epilepsy with breach rhythm were collected, including eight males and four females, aged 36-78 years. After analysis, it was found that brain trauma was the most common cause of breach rhythm. Among them, two cases of skull defect were not repaired, eight cases were repaired with skull titanium mesh, one case was repaired with skull polymethylmethacrylate, and one case was repaired with skull polyetheretherketone. The distribution of the breach rhythm in 12 patients was consistent with the abnormal area of the skull. The breach rhythm can be expressed as high amplitude and fast frequency, or low amplitude and slow frequency and appear individually (similar to sharp waves, spikes). On the basis of pleomorphic slow waves, 10 patients were mixed with sharp waves and spike waves, and imaging confirmed that they had brain damage in corresponding parts. All of the 12 patients had a history of seizures, with tonic-clonic seizures and (or) focal seizures being the most common. Three patients with breach rhythm had no clinical seizures for more than five years, and had been taking antiepileptic drugs for epileptic spikes on EEG, and they were given reduction and discontinuation of the drugs and were seizure-free for three years during follow up.Conclusions:Skull repair is a common cause of breach rhythm, and repair materials with different resistances cause different waveforms and frequencies. Breach rhythm, epileptiform discharge and other pathological slow-wave activities can exist at the same time. Breach rhythm is a benign variant phenomenon which needs no special treatment.

Seizure cluster (SC) is a common clinical phenomenon in patients with epilepsy, which was reported to be associated with post-ictal psychosis, status epilepticus, and increased risk of death, with a negative impact on the quality of life of patients and caregivers, but the diagnostic criteria, management principles and pathogenesis of SC are still unclear."seizure cluster" "acute repitetive seizures" and "cluster seizures" were used to search the relevant literatures in the databases of "Pubmed" "Wanfang Medicine" and "China Knowledge Network" from 1990 to 2019. The definitions, prevalence, risk factors, consequences, possible mechanism, and current management methods of seizure clusters were summaried in this article, to help health care professionals and patients gain a clearer understanding of SC.