ObjectiveTo identify the active components in Maimendong decoction (MMDD) against pulmonary fibrosis (PF) and validate their molecular effects in vitro, while focusing on the role of methylophiopogonanone B in regulating fibrosis.MethodsData on MMDD components and targets were gathered from databases including BATMAN-TCM and PubMed, whereas the PF gene data were sourced from GeneCards, OMIM, and TTD. Shared targets were determined using the STRING database, and molecular docking was used to analyze the essential molecules associated with fibrosis. To simulate PF conditions, human embryonic lung fibroblasts (HPF) and A549 cells were exposed to transforming growth factor-β1 (TGF-β1). Various assays were used to determine the effects of MMDD and methylophiopogonanone B on signaling pathways, apoptosis, and epithelial–mesenchymal transition.ResultsWe identified 11 active components from MMDD extracts that targeted 511 shared proteins associated with PF, revealing 10 key targets in network analysis. Gene ontology analysis indicated that processes and pathways such as apoptosis regulation and PI3K/Akt signaling were involved. In vitro experiments revealed that MMDD downregulated the expression of α-smooth muscle actin (α-SMA), collagen type I (COL-I), and collagen type III and regulated Bcl-2/Bax signaling pathways to promote apoptosis. The flow cytometry apoptosis assay revealed that MMDD promoted the TGF-β1-induced apoptosis of myofibroblasts. The primary active ingredient in MMDD, methylophiopogonanone B, reduced α-SMA, COL-I, and PI3K/Akt/mTOR-related protein levels in TGF-β1-treated HPF cells, decreased Bcl-2 and cleaved caspase 3, and increased Bax. Moreover, methylophiopogonanone B increased E-cadherin levels and reduced α-SMA, fibronectin, N-cadherin, vimentin, and snail in TGF-β1-treated A549 cells.ConclusionMethylophiopogonanone B demonstrated the potential to treat PF by inducing myofibroblast apoptosis and inhibiting EMT. However, despite encouraging initial results, further clinical research is warranted to verify the safety and efficacy of methylophiopogonanone B in the management of PF

Thyroid diseases are common clinical endocrine disorders， and their pathogenesis is generally considered to be closely related to genetic predisposition factors， immune system disorders， hormone levels， etc. Xiaoyaosan is widely used in the treatment of various thyroid diseases with excellent effects. This study summarized the relevant literature on the treatment of thyroid diseases with modified Xiaoyaosan prescriptions and their active ingredients from aspects such as theoretical analysis， clinical research， and mechanism research. Theoretical analysis revealed that Xiaoyaosan could not only disperse stagnated liver qi but also replenish deficient spleen Qi， which was consistent with the etiology and pathogenesis of thyroid diseases. Clinical studies found that Xiaoyaosan and its modified prescriptions could be widely used in the treatment of multiple thyroid diseases， such as hyperthyroidism， Hashimoto's thyroiditis， and thyroid nodules. Both the use of modified Xiaoyaosan alone and in combination with medications such as methimazole， propylthiouracil， and euthyrox could effectively improve patients' clinical symptoms. In the mechanism research， this study discovered that the whole formula of Xiaoyaosan and its modified prescriptions could inhibit inflammatory reactions， regulate immune balance， and delay liver damage during the treatment of thyroid diseases. The research on Xiaoyaosan for treating thyroid diseases mainly focused on thyroid cancer， autoimmune thyroiditis， hyperthyroidism， and hypothyroidism. The mechanisms of action mainly involved promoting cell apoptosis， inhibiting cell proliferation and migration， arresting the cell cycle， and regulating thyroid hormone levels. In conclusion， this study systematically combs and summarizes the research status of Xiaoyaosan in treating thyroid diseases through literature retrieval， aiming to provide new perspectives and new ideas for the prevention and treatment of thyroid diseases with traditional Chinese medicine.

OBJECTIVE: To explore the prognostic value of C-reactive protein (CRP)/albumin (Alb) ratio combined with platelet count (PLT) and Glasgow coma score (GCS) in patients with heat stroke (HS). METHODS: A retrospective analysis was conducted on the clinical data of HS patients admitted to the department of intensive care unit (ICU) of Nanchong Central Hospital from May 1, 2020 to October 31, 2023. This included general information, admission GCS, laboratory indicators and 28-day prognosis. The differences in the above indicators were compared between two groups of patients with different prognoses. Statistically significant indicators from univariate analysis were included in multivariate Logistic regression analysis to screen for factors influencing 28-day mortality in HS patients. The predictive value of various influencing factors on the 28 days prognosis of HS patients were analyzed by receiver operator characteristic curve (ROC curve). RESULTS: A total of 73 HS patients were included, of whom 41 survived for 28-day and 32 died. There were no statistically significant differences in gender and age between the two groups of HS patients with different prognoses. The white blood cell count (WBC), neutrophil count (NEU), aspartate aminotransferase (AST), alanine aminotransferase (ALT), CRP, and CRP/Alb ratio in the death group were significantly higher than those of the survival group, and the admission GCS score, platelet count (PLT), total bilirubin (TBil) and Alb were significantly lower than the survival group [WBC (×10⁹/L): 14.80 (11.44, 17.15) vs. 11.96 (9.47, 14.82), NEU (×10⁹/L): 13.05 (8.56, 15.67) vs. 9.50 (6.68, 12.09), AST (U/L): 108.00 (52.70, 291.50) vs. 64.50 (38.25, 110.50), ALT (U/L): 62.00 (19.50, 159.00) vs. 34.50 (20.75, 70.75), CRP (mg/L): 22.49 (3.42, 58.93) vs. 3.68 (1.01, 11.46), CRP/Alb ratio: 0.53 (0.08, 1.77) vs. 0.08 (0.02, 0.44), GCS score: 7.0 (5.0, 8.0) vs. 8.5 (7.0, 11.0), PLT (×10⁹/L): 107.00 (73.50, 126.00) vs. 131.50 (107.50, 176.25), TBil (mmol/L): 15.60 (10.00, 25.30) vs. 21.40 (14.80, 30.05), Alb (g/L): 32.65 (32.53, 49.30) vs. 38.70 (36.20, 40.40), all P < 0.05]. Binary Logistic regression analysis showed that the GCS score [odds ratio (OR) = 0.686, 95% confidence interval (95%CI) was 0.491-0.959, P = 0.028], PLT (OR = 0.973, 95%CI was 0.954-0.992, P = 0.005), NEU (OR = 1.312, 95%CI was 1.072-1.606, P = 0.009) and CRP/Alb ratio (OR = 7.652, 95%CI was 1.632-35.881, P = 0.010) were independent influencing factors for 28-day mortality in HS patients. ROC curve analysis showed that the area under the curve (AUC) of GCS score, PLT, and CRP/Alb ratio for single prediction of 28-day prognosis in HS patients was 0.705, 0.752, and 0.729, and the combination of all three predicted the highest AUC of 28-day prognosis in HS patients (0.917), with a sensitivity and specificity of 86.2% and 81.2%, respectively. CONCLUSION CRP/Alb ratio, PLT, and GCS score are independent influencing factors affecting the prognosis of HS patients, and all of them have a certain predictive value for the prognosis of HS patients, in which the combination of the three has a higher predictive value for the prognosis of HS patients.
Humans ; C-Reactive Protein/analysis* ; Prognosis ; Glasgow Coma Scale ; Retrospective Studies ; Heat Stroke/diagnosis* ; Platelet Count ; Male ; Female ; Serum Albumin/analysis* ; Middle Aged ; Aged ; Adult ; ROC Curve

The plant F-box protein more axillary growth 2 (MAX2) is a key factor in the signal transduction of strigolactones (SLs) and karrinkins (KARs). As the main component of the SKP1-CUL1-FBX (SCF) complex ubiquitin ligase E3, MAX2 is responsible for specifically recognizing the target proteins, suppressor of MAX2 1/SMAX1-like proteins (SMAX1/SMXLs), which would be degraded after ubiquitination. It can thereby regulate plant morphogenesis and stress responses. There exist homologous genes of MAX2 in the important grain and oil crop soybean (Glycine max). However, its role in plant defense responses has not been investigated yet. Here, GmMAX2b, a homologous gene of MAX2, was successfully cloned from stressed soybean. Bioinformatics analysis revealed that there were two MAX2 homologous genes, GmMAX2a and GmMAX2b, with a similarity of 96.2% in soybean. Their F-box regions were highly conserved. The sequence alignment and cluster analysis of plant MAX2 homologous proteins basically reflected the evolutionary relationship of plants and also suggested that soybean MAX2 might be a multifunctional protein. Expression analysis showed that plant pathogen infection and salicylic acid treatment induced the expression of GmMAX2b in soybean, which is consistent with that of MAX2 in Arabidopsis. Ectopic expression of GmMAX2b compensated for the susceptibility of Arabidopsis max2-2 mutant to pathogen, indicating that GmMAX2b positively regulated plant disease resistance. In addition, yeast two hybrid technology was used to explore the potential target proteins of GmMAX2b. The results showed that GmMAX2b interacted with SMXL6 and weakly interacted with SMXL2. In summary, GmMAX2b is a positive regulator in plant defense responses, and its expression is induced by pathogen infection and salicylic acid treatment. GmMAX2b might exert its effect through interaction with SMXL6 and SMXL2. This study expands the theoretical exploration of soybean disease resistant F-box and provides a scientific basis for future soybean disease resistant breeding.
Glycine max/metabolism* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plant Proteins/genetics* ; Cloning, Molecular ; Gene Expression Regulation, Plant ; F-Box Proteins/genetics* ; Arabidopsis/genetics* ; Phylogeny

Objective:To discuss the clinical characteristics of the patients with hypertrophic cardiomyopathy(HCM)complicated with microcirculatory dysfunction(CMD),and to analyze the impact of concurrent CMD on the prognosis of the HCM patients.Methods:A total of 211 patients diagnosed with HCM and having complete cardiac magnetic resonance imaging(CMR)examination results from January 1,2019 to September 30,2023 were collected.They were divided into HCM complicated with CMD group(68 cases)and HCM complicated without CMD group(143 cases)based on CMR assessment.The clinical data such as age,gender,admission symptoms,and past medical history,blood test data such as troponin,electrocardiogram,echocardiography,and CMR data including abnormal Q wave,ST segment depression,inverted T wave,PR interval,QRS wavelength,corrected QT interval,ejection fraction(EF),left atrial diameter(LAD),left and right ventricular end-diastolic diameters,cardiac output,E peak,A peak,and maximum wall thickness(MWT)of the patients were compared between two groups.Logistic regression was used to analyze the clinical characteristics of the HCM patients complicated with CMD;multivariate modified Poisson regression was used to analyze the risk factors for major adverse cardiovascular events(MACE)in the HCM patients.Results:Compared with HCM complicated without CMD group,the percentage of palpitation patients in HCM complicated with CMD group was significantly increased(P<0.05),the percentage of tachycardia episode patients was significantly increased(P<0.05),the troponin level was significantly increased(P<0.05),and the percentage with a history of hypertension patients was significantly decreased(P<0.05).Compared with HCM complicated without CMD group,the percentage of abnormal Q wave on electrocardiogram in the patients in HCM complicated with CMD group were significantly increased(P<0.05),the percentage of inverted T wave and the EF of the patients was significantly decreased(P<0.05),the LAD was significantly increased(P<0.05),and the MWT was significantly increased(P<0.05).The multivariate Logistic regression analysis results showed that increased LAD(OR=1.05,95％CI:1.00-1.11,P=0.048)and increased MWT(OR=1.11,95％CI:1.03-1.19,P=0.007)were the risk factors for concurrent CMD in the HCM patients;history of hypertension(OR=0.40,95％CI:0.20-0.80,P=0.010)was a protective factor for concurrent CMD in the HCM patients.The average follow-up time in this study was 20.5 months.A total of 27 patients experienced MACE,with an overall incidence of 12.80％,including 12 patients in HCM complicated with CMD group and 15 patients in HCM complicated without CMD group.The multivariate modified Poisson regression analysis results showed that history of diabetes(RR=2.34,95％CI:1.09-5.06,P=0.030),history of arrhythmia(RR)=4.00,95％CI:1.82-8.83,P=0.001),and decreased ejection fraction(RR=0.96,95％CI:0.94-0.99,P=0.001)were risk factors for MACE in the HCM patients.Conclusion:The HCM patients complicated with CMD have unique clinical characteristics,including higher symptom burden,left atrial enlargement,myocardial hypertrophy,and increased troponin levels.Concurrent CMD does not increase the short-term risk of adverse events;diabetes,arrhythmia,and decreased EF are key risk factors for prognosis;early intervention and complication management for HCM complicated with CMD patients may improve the long-term prognosis of the HCM patients.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objective:To investigate the clinical phenotypes and genetic variant characteristics in children with epilepsy.Methods:A total of 91 children with epilepsy admitted to the Women′s and Children′s Hospital Affiliated to Ningbo University from July 2021 to October 2022 were selected as the study subjects. Peripheral blood samples were collected from the children for whole exome sequencing. Candidate genetic variants were validated by Sanger sequencing and copy number variation sequencing (CNV-seq). The clinical phenotypes and treatment outcomes of the children with epilepsy were followed up, and an analysis of the relationship between genotype and phenotype was conducted. This study was approved by the Women′s and Children′s Hospital Affiliated to Ningbo University (Ethics No.: EC2020-048).Results:Among the 91 children with epilepsy, 21 cases (23.08%, 21/91) were found to carry pathogenic or likely pathogenic variants. Of these, 18 cases had involved single base variant or insertional deletion, while 3 cases involved copy number variations. The gene with the highest detection rate was PRRT2 (38.10%, 8/21). Among the children with genetic variants, 47.62% (10/21) had onset during infancy, with 8 diagnosed with Benign familial infantile epilepsy (BFIE), 8 with Developmental epileptic encephalopathy (DEE), and 3 with Epileptic encephalopathy (EE). One case of Dravet syndrome (DS) and one case of Infantile spasms (IS) were also noted. The clinical manifestations of children were diverse and primarily included generalized tonic-clonic seizures and focal seizures. Among them, 52.38% (11/21) had exhibited cluster seizures, 23.81% (5/21) showed fever sensitivity, and 14.29% (3/21) experienced status epilepticus. After pharmacological treatment, 42.86% (9/21) of children had achieved complete seizure control, while 61.90% (13/21) had intellectual disability and 19.05% (4/21) had co-morbid autism spectrum disorder. Conclusion:Pathogenic or likely pathogenic variants were identified in 23.08% of the pediatric epilepsy cases, with the PRRT2 gene being the most frequently involved. Among children carrying genetic variants, 47.62% had seizure onset during infancy. Genetic factors are an important cause of epilepsy, and early genetic testing may facilitate precise diagnosis, treatment, and prognostic evaluation.

OBJECTIVE: To investigate the clinical phenotypes and genetic variant characteristics in children with epilepsy. METHODS: A total of 91 children with epilepsy admitted to the Women's and Children's Hospital Affiliated to Ningbo University from July 2021 to October 2022 were selected as the study subjects. Peripheral blood samples were collected from the children for whole exome sequencing. Candidate genetic variants were validated by Sanger sequencing and copy number variation sequencing (CNV-seq). The clinical phenotypes and treatment outcomes of the children with epilepsy were followed up, and an analysis of the relationship between genotype and phenotype was conducted. This study was approved by the Women's and Children's Hospital Affiliated to Ningbo University (Ethics No.: EC2020-048). RESULTS: Among the 91 children with epilepsy, 21 cases (23.08%, 21/91) were found to carry pathogenic or likely pathogenic variants. Of these, 18 cases had involved single base variant or insertional deletion, while 3 cases involved copy number variations. The gene with the highest detection rate was PRRT2 (38.10%, 8/21). Among the children with genetic variants, 47.62% (10/21) had onset during infancy, with 8 diagnosed with Benign familial infantile epilepsy (BFIE), 8 with Developmental epileptic encephalopathy (DEE), and 3 with Epileptic encephalopathy (EE). One case of Dravet syndrome (DS) and one case of Infantile spasms (IS) were also noted. The clinical manifestations of children were diverse and primarily included generalized tonic-clonic seizures and focal seizures. Among them, 52.38% (11/21) had exhibited cluster seizures, 23.81% (5/21) showed fever sensitivity, and 14.29% (3/21) experienced status epilepticus. After pharmacological treatment, 42.86% (9/21) of children had achieved complete seizure control, while 61.90% (13/21) had intellectual disability and 19.05% (4/21) had co-morbid autism spectrum disorder. CONCLUSION Pathogenic or likely pathogenic variants were identified in 23.08% of the pediatric epilepsy cases, with the PRRT2 gene being the most frequently involved. Among children carrying genetic variants, 47.62% had seizure onset during infancy. Genetic factors are an important cause of epilepsy, and early genetic testing may facilitate precise diagnosis, treatment, and prognostic evaluation.
Humans ; Female ; Male ; Epilepsy/genetics* ; Child, Preschool ; Child ; Phenotype ; Genotype ; DNA Copy Number Variations/genetics* ; Infant ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics* ; Adolescent ; Exome Sequencing

Objective Taking cerebral ischemic disease as an example,it explores the use of doctors'actual diagnosis and treatment items under DRG payment,and analyzes the matching degree between actual diagnosis and treatment items and clinical pathways.Methods Based on the actual diagnosis and treatment items for patients with cerebral ischemic diseases,it sorted out their usage and cost proportion,built a diagnosis and treatment item pool,determined the basic diagnosis and treatment items based on expert consultation,and compared and matched them with clinical pathways.Results Among all the diagnosis and treatment items of cerebral ischemic diseases,only 21.27％had a utilization rate of more than 10％,but the cost accounted for 82.96％.42 diagnosis and treatment items were screened as basic diagnosis and treatment items.The degree of matching between laboratory inspection items and clinical pathways was high,but there were certain differences in drug treatment.Conclusion There are certain differences between actual diagnosis and treatment items and clinical pathways of cerebral ischemic diseases,and there are a large number of low-utilization items,some high-utilization items are not basic diagnosis and treatment items,and most of them are concentrated in laboratory inspection items.It is recommended to enhance the attention of clinical pathway under DRG payment and update and optimize it regularly,improve doctors'awareness of diagnosis and treatment based on clinical pathways,and improve the supervision and assessment mechanism of doctors'diagnosis and treatment behaviors,regularly update and optimize clinical pathways to improve their operability.

Objective To observe the value of MR vessel wall imaging(VMI)for predicting instability status of intracranial aneurysm(IA).Methods MR angiography(MRA)and vascular wall imaging(VWI)data of 506 patients with single IA were retrospectively analyzed.Asymptomatic IA was included in stable status group(n=349),while those with enlargement during follow-up or threatened rupture symptoms were taken as instable status group(n=157).The patients were divided into training set(n=354)and validation set(n=152)at a ratio of 7:3.The least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression were performed to screen risk factors associated with IA instability based on clinical data,MRA and VWI manifestations.Then model 1 was constructed based the above indexes,while model 2 was established based only on MRA manifestations of IA.The receiver operating characteristic curve was plotted,and the area under the curve(AUC)was calculated to evaluate the efficacy of each model for predicting IA instability.Results LASSO and multivariate logistic regression showed that female patient,age＜50 years with history of cerebral infarction and IA wall enhancement on MRA were all independent predictors of IA instability status.The AUC of model 1 for predicting instability status of IA was 0.733 and 0.742 in training set and validation set,respectively,both higher than that of model 2(0.593 and 0.609,both P＜0.05).Conclusion MR VWI was helpful for predicting IA instability status.