Aim To investigate the effects of 2-dode-cyl-6-methoxycyclohexa-2 , 5-diene-l, 4-dione ( DM-DD) on resisting hepatic fibrosis induced by carbon tetrachloride ( CC14 ) in rats and the underlying mechanisms , with a specific focus on the TGF-pi/Smads signaling pathway. Methods The hepatic fibrosis model was replicated using 50% CC14. Various parameters, including levels of aspartate transferase ( AST) , ala-nine transferase ( ALT ) , albumin/globulin ( A/G ) , total protein (TP) , total bilirubin (T-BIL) , hyaluron-ic acid ( HA ) , laminin ( LN ) , collagen type Ж ( Col Ж) , and collagen type IV(ColIV) in the blood, were measured. Liver tissue lesions and fiber formation were observed using HE and Masson staining. The expression levels of a smooth muscle actin (a-SMA) , collagen type I ( Col I ) , transformed growth factor (TGF-pi), Smad2, and Smad7 proteins were assessed using immunohistochemistry. a-SMA, Coll, TGF-pi, and Smad7 mRNA levels in liver tissue were measured by RT-PCR. Additionally, the expression levels of TGF-pi, Smad4, and Smad7 proteins in liver tissue were determined by Western blot. Results In comparison to the normal control group, the model group exhibited significantly elevated levels of AST, ALT, TP, T-BIL, HA, LN, Col Ш and Col IV in serum. But A/G level notably decreased. Successful modeling was confirmed by the presence of extensive fiber formations observed through HE and Massonstaining in liver tissue. The DMDD administration group demonstrated a notable decrease levels of AST, ALT, TP, T-BIL, HA, LN, Col III, and CollV, but A/G was significantly elevated when compared to the model group. Furthermore, a-SMA, Coll, TGF-f31, Smad2 and Smad4 mRNA and protein levels in the DMDD administration group were significantly reduced, while Smad7 significantly declined. HE and Masson staining results reflected a marked reduction in fibrous hyper-plasia. Conclusion DMDD exhibits a protective effect against CCl4-induced hepatic fibrosis, and its mechanism appears to be associated with the TGF-fJl/ Smads signaling pathway.

Humans ; Clinical Relevance ; Leukemia, Myeloid, Acute ; Transcription Factors ; Neoplasm Proteins ; Antigens, CD ; GPI-Linked Proteins

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.
Child ; Female ; Male ; Humans ; Retrospective Studies ; Cytokine Release Syndrome ; COVID-19/complications* ; SARS-CoV-2 ; Brain Diseases/etiology* ; Prognosis ; Seizures ; Cytokines

OBJECTIVE: To detect the gene mutations in patients with myeloid malignancies by high-throughput sequencing and explore the correlation between gene mutations and prognosis. METHODS: A retrospective analysis was performed on 56 patients with myeloid malignancies who were hospitalized in the department of hematology, Peking University International Hospital from January 2020 to May 2021. The genetic mutations of the patients were detected by next-generation sequencing technology, and the correlation between the genetic mutations and prognosis of myeloid malignancies was analyzed. RESULTS: In 56 patients, the number of mutated genes detected in a single patient is 0-9, with a median of 3. Sequencing results showed that the most common mutated genes were RUNX1(21.4%), TET2(17.9%), DNMT3A(17.9%), TP53(14.3%) and ASXL1(14.3%), among which the most common mutations occurred in the signaling pathway-related genes (23.3%) and the transcription factor genes (18.3%). 84% of the patients carried multiple mutated genes (≥2), and correlation analysis showed there were obvious co-occurring mutations between WT1 and FLT3, NPM1 and FLT3-ITD, and MYC and FLT3. TP53 mutation was more common in MDS patients.The overall survival time of patients with NRAS mutation was significantly shortened (P =0.049). The prognosis of patients with TP53 mutation was poor compared with those without TP53 mutation, but the difference wasn't statistically significant (P =0.08). CONCLUSION The application of next-generation sequencing technology is of great significance in myeloid malignancies, which is helpful to better understand the pathogenesis of the disease, to judge the prognosis and to find possible therapeutic targets.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Prognosis ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Myeloproliferative Disorders ; Mutation

The current research status of human-computer interaction(HCI)devices applied in disease warning,disease surveillance and medication monitoring for the elderly was introduced,the problems of HCI devices during the application were analyzed in high cost,portability,privacy and high technical requirements,and its future development directions were pointed out.

Abstract: Objective　To understand the distribution and drug resistance of bacteria in clinical blood culture specimens in Ningxia in recent years, and to provide a basis for the prevention and treatment of bloodstream infection diseases. 　　　Methods　The blood culture isolation bacteria and drug resistance of Ningxia bacterial resistance monitoring network hospitals from 2018 to 2020 were statistically analyzed by WHONET5.6 software. Results　In the past three years, a total of 6 757 strains of bacteria were isolated from blood samples, including 3 697 strains (54.7%) of gram-negative bacteria and 3 060 (45.3%) of gram-positive bacteria. Among the gram-negative bacteria, Escherichia coli (2 074 strains,30.7%), Klebsiella pneumoniae (696 strains), Pseudomonas aeruginosa (139 strains), and Acinetobacter baumannii (121 strains). Among the gram-positive bacteria, coagulase-negative Staphylococcus (1 691 strains,25.0%), Staphylococcus aureus (442 strains), Streptococcus spp. (431 strains), Enterococcus spp. (379 strains). Resistance to Escherichia coli and Klebsiella pneumoniae was 56.6% and 22.6% against third-generation cephalosporins, and resistance to carbapenems was 1.0% and 3.7%, respectively. Pseudomonas aeruginosa and Acinetobacter baumannii were resistant to carbapenems at 9.0%（12/139） and 80.7%（71/121）. Methicillin-resistant Staphylococcus aureus (MRSA) was detected at 26.8%, methicillin-resistant coagulase-negative Staphylococcus was detected at 70%, and no Staphylococcus bacteria resistant to vancomycin and linezolid were found. For three years, only 1 strain of vancomycin-resistant Enterococcus faecalis was detected, and no linezolid-resistant Staphylococcus and Enterococcus were detected. Conclusions　Ningxia clinical blood specimen isolates of Escherichia coli, coagulase-negative Staphylococcus, and Klebsiella pneumoniae are more common. Among them, the resistance rate of Escherichia coli and Klebsiella pneumoniae to the third generation of cephalosporins is relatively stable, and the resistance rate to carbapenems is low. Acinetobacter baumannii is highly resistant to carbapenems, and methicillin-resistant Staphylococcus aureus detection rates are on the rise and should be closely monitored.

ObjectiveTo observe the effect of Jiangzhi Tongluo soft capsule on the protein levels of silent mating-type information regulation 2 homolog 1 （SIRT1） and forkhead transcription factor FoxO3 and podocyte apoptosis in the renal tissue of rats with membranous nephropathy and to reveal the underlying molecular mechanisms for the treatment of MN. MethodSixty male SD rats were randomly assigned into 6 groups with 10 rats each. The six groups included a normal group， a model group， benazepril hydrochloride group， and Jiangzhi Tongluo soft capsule groups of low， medium and high doses （25， 50， 100 mg·kg^-1， respectively）. The model rats were established by injection with cationized bovine serum albumin into the tail vein. After modeling， the rats were administrated with corresponding agents by gavage for 4 weeks. At the end of the 4^th week， an electron microscope was used to observe the pathological changes in the kidney. Western blot was employed to detect the protein levels of SIRT1 and FoxO3 protein in rat kidney， and immunohistochemistry to detect the expression of B lymphocytoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， Bcl-2-associated death promoter （Bad）， and podocyte split diaphragm proteins nephrin and podocin. ResultCompared with normal group， the expression of pro-apoptotic factors Bax， Bad， and FoxO3 in the kidney was up-regulated （P<0.05）， while that of anti-apoptotic factors Bcl-2， SIRT1， nephrin， and podocin was down-regulated （P<0.05） after modeling. Compared with the model group， the treatments down-regulated the expression of Bax， Bad， and FoxO3 （P<0.05） and up-regulated that of Bcl-2， SIRT1， nephrin， and podocin （P<0.05）. ConclusionJiangzhi Tongluo soft capsule may regulate the SIRT1/FoxO3 pathway to reduce podocyte apoptosis and maintain podocyte structure stability， thereby exerting the renal protection effect.

Exosomes are lipid bilayer membranous vesicles actively secreted by various cells in the organism， which are like nanoparticles and have messenger targeting. Combining with the theory of supramolecular "Qi chromatography" of traditional Chinese medicine （TCM）， research ideas and strategies of modernization of TCM can be constructed. Exosomes are secreted by cells， and the membrane contains nucleic acids， proteins， lipids and small molecular metabolites and others， which can accurately coordinate the functions of each cell， concentrate and transmit the functional information of the parent cell， and is the concise form of reflecting cell functions. At the same time， it is loaded with the "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM. If the "imprinted templates" carrying rules among the gene-protein-lipid-small molecules wrapped in it is studied， the modern experimental research ideas and strategies of TCM theory can be established for revealing the functions of the body's meridians and viscera. Firstly， the present situation of exosomes， including discovery， secretion， characteristics， functions， attribution， uptake， research methods and application status， were reviewed in this paper. And the natural properties of its precise messenger targeted delivery vehicle were elaborated， reflecting the operation law of microscopic substances in meridians and viscera. Secondly， to explore it as an important carrier of the concentrated "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM， and integrating the research methods of exosomes and supramolecular chemistry of TCM， this paper proposes experimental research ideas and strategies on the microscopic material basis of meridians and viscera， compatibility of TCM compound， and targeting of TCM targeted preparations.

Objective: A multicenter Chinese mainland survey was conducted to investigate the sensitization distribution characteristics of cat, dog and horse dander in patients with allergic diseases, so as to provide clinicians with epidemiological data of common animal allergens and useful information for the prevention and treatment of allergies in cats, dogs and horses. Methods: The epidemiological investigation and design was adopted. This study is based on the national epidemiological survey of allergic diseases led by the first affiliated Hospital of Guangzhou Medical University. From January to December in 2021, a total of 2 122 patients diagnosed with allergic diseases were included in the outpatient department of respiratory department/pediatrics/allergy department of 14 units such as the First Affiliated Hospital of Guangzhou Medical University, and 222 healthy subjects were included as controls from the physical examination center of the above units in the same period. All the subjects filled out the allergic disease questionnaire under the guidance of doctors, and the allergen-specific immunoglobulin E (sIgE) of cats, dogs and horses of all subjects were detected by magnetic particle chemiluminescence system. The epidemiological characteristics of three animal allergens in different diseases, ages and regions were analyzed. Chi square test was used to analyze the frequency difference between groups, t test or Mann Whitney U test was used to test the distribution difference between two groups, and one-way ANOVA or Kruskal Wallis H test was used to compare the distribution difference between multiple groups. Bar chart, Venn-plot and radar chart were drawn to show the sensitization distribution characteristics. A small number of missing values caused by subjects' omission have been excluded during the analysis. Results: The 2 122 patients with allergic diseases were 57.35% male (1 217/2 122) and 40.95% female (869/2 122), and 1.70% (36/2 122) patients had loss of gender information. The age of patients with allergic diseases was 9.0 (6.0, 28.0) years, while that of healthy controls was 29.0 (13.0, 39.0) years old, and there were 1.7% (36/2 122) and 0.9% (2/222) subjects with missing age information, respectively. The proportion of caesarean section in allergic patients was significantly higher than that in healthy controls (31.4% vs. 17.6%,χ²=16.582,P<0.001) [2.5% (54/2 122) of the patient group and 5.4% (12/222) of the control group had missing birth mode information], and the proportion of patients with allergic diseases who reported that both parents had allergic diseases was significantly higher than that of the control group (35.7% vs. 9.5%, χ²=65.171,P<0.001). Patients with allergic diseases are mainly school-age (6-12 years old) and adolescents (12-18 years old). 16.4% of patients with allergic diseases were sensitized to cat dander, 10% and 6% to dog and horse dander. The sensitization rate of cat dander in patients with rhinitis, asthma, conjunctivitis, food allergy and atopic dermatitis was the highest (16.4%-21.6%), followed by dog dander (10.2%-15.2%). The prevalence of allergic rhinitis was the highest among different animal sensitized populations. The proportion of cat, dog and horse allergens sensitized at the same time is between 10%-15%, and the proportion of any two or more animal dander sensitized at the same time is about 45%. Animal allergens are associated with respiratory allergic diseases, especially allergic rhinitis with allergic conjunctivitis. There were significant differences in the distribution of positive rates of three animal allergens in different regions, and the highest positive rate of cat dander was found in all provinces of the country. Conclusion: The sensitization rate of animal dander allergens increased significantly, and the highest was in children and adolescents. Cat dander is the most common animal allergen, followed by dog. Different animals show obvious cross or common sensitization due to their high homology.
Allergens ; Animals ; Cats ; Cesarean Section ; Dander ; Dogs ; Female ; Horses ; Immunoglobulin E ; Male ; Pregnancy ; Rhinitis, Allergic

Objective: To analyze the epidemiology and spatial-temporal distribution characteristics of hand, foot and mouth disease (HFMD) in Shanxi province. Methods: The data of HFMD in Shanxi province from 2009 to 2020 were collected from notifiable disease management information system of Chinese information system for disease control and prevention and analyzed by descriptive epidemiology, Joinpoint regression, spatial autocorrelation analysis and spatio- temporal scanning analysis. Results: A total of 293 477 HFMD cases were reported in Shanxi province from 2009 to 2020, with an average annual incidence of 67.64/100 000 (293 477/433 867 454), severe disease rate of 5.36/100 000 (2 326/433 867 454), severe disease ratio of 0.79%(2 326/293 477), mortality of 0.015/100 000 (66/433 867 454), and fatality rate of 22.49/100 000 (66/293 477). The reported incidence rate, severe disease rate, mortality rate and fatality rate of HFMD showed decreasing trends. The main high-risk groups were scattered children and kindergarten children aged 0-5. The incidence of HFMD had obvious seasonal variation, with two peaks every year: the main peak was during June-July, the secondary peak was during September-October and the peak period is from April to November. A total of 13 942 laboratory cases were confirmed, with a diagnosis rate of 4.75% (13 942/293 477), including 4 438 (35.11%, 4 438/293 477) Enterovirus A71 (EV-A71) positive cases, 4 609 (33.06%, 4 609/293 477) Coxsackievirus A16 (CV-A16) positive cases, and 4 895 (31.83%, 4 895/293 477) other enterovirus positive cases. There was a spatial positive correlation (Moran's I ranged from 0.12 to 0.58, all P<0.05) and the spatial clustering was obvious. High-risk regions were mainly distributed in Taiyuan in central Shanxi province, Linfen and Yuncheng in southern Shanxi province, and Changzhi in southeastern Shanxi province. Spatial-temporal scanning analysis revealed 1 the most likely cluster and 8 secondary likely clusters, of which the most likely cluster (RR=2.65, LLR=22 387.42, P<0.001) located in Taiyuan and Jinzhong city, Shanxi province, including 12 counties (districts), and accumulated from April 1, 2009 to November 30, 2018. Conclusions: There was obvious spatial-temporal clustering of HFMD in Shanxi province, and the epidemic situation was in decline. The key areas were the districts in urban areas and the counties adjacent to it. Meanwhile, the monitoring and classification of other enterovirus types of HFMD should be strengthened.
Child ; Humans ; Hand, Foot and Mouth Disease/epidemiology* ; Spatial Analysis ; Enterovirus Infections ; Spatio-Temporal Analysis ; Cluster Analysis