ObjectiveFrom the perspective of cardiovascular-kidney-metabolic （CKM） syndrome， this study aims to construct and validate a diagnostic machine learning model integrating traditional Chinese and Western medicine for severe coronary artery stenosis in patients with CKM， thereby providing clinical decision-making support for patients with borderline lesions. MethodsBased on a retrospective study design， a total of 535 hospitalized patients from two independent campuses of Jiangsu Province Hospital of Traditional Chinese Medicine： the main campus （from January 2024 to August 2024） and Zidong branch （from September 2024 to December 2024） were screened. Data from the main campus were randomly divided into the training dataset （376 cases） and the internal validation dataset （95 cases） at a 4∶1 ratio， while data from Zidong branch served as the external validation dataset （64 cases）. Risk factors were analyzed and screened through literature review， expert interviews， and the least absolute shrinkage and selection operator （LASSO） algorithm. Nine machine learning algorithms were utilized to construct diagnostic models. Comparative analyses of common evaluation metrics， calibration curves， and decision curves were conducted to select the model through internal and external validation. The Shapley additive explanations （SHAP） method and two cases were utilized to help understand the operational logic of the best model. Finally， the best model was applied to patients with borderline lesions to calculate diagnostic efficacy. ResultsNine risk factors were screened by LASSO regression， such as phlegm， hematoma， stagnation， deficiency， hypertension duration， gender， arterial stiffness index （ASI）， uric acid to high-density lipoprotein cholesterol ratio （UHR）， and glycosylated hemoglobin （HbA1c）. After comparison from multiple dimensions， the light gradient boosting machine （LightGBM） was the best model， achieving area under the curve （AUC） of 0.918 （95% confidence interval （CI）： 0.890-0.945） in the training dataset， 0.885 （95%CI： 0.820-0.951） in the internal validation dataset， and 0.897 （95%CI： 0.818-0.975） in the external validation dataset. Calibration curves indicated good consistency in the predicted probabilities， while decision curve analysis showed clinical benefit when threshold probabilities were less than 90%. SHAP importance rankings were stagnation， deficiency， hematoma， HbA1c， gender， phlegm， hypertension duration， ASI， and UHR. When applied to the patients with borderline lesions， the diagnostic model achieved an AUC of 0.783 （95%CI： 0.637-0.930）， with 73% of patients with actual severe stenosis getting benefit. ConclusionGuided by clinical value， the diagnostic model integrating traditional Chinese and Western medicine established in this study demonstrates favorable performance， providing a basis for clinical diagnosis， treatment， and decision-making in patients with CKM.

ObjectiveFrom the perspective of cardiovascular-kidney-metabolic （CKM） syndrome， this study aims to construct and validate a diagnostic machine learning model integrating traditional Chinese and Western medicine for severe coronary artery stenosis in patients with CKM， thereby providing clinical decision-making support for patients with borderline lesions. MethodsBased on a retrospective study design， a total of 535 hospitalized patients from two independent campuses of Jiangsu Province Hospital of Traditional Chinese Medicine： the main campus （from January 2024 to August 2024） and Zidong branch （from September 2024 to December 2024） were screened. Data from the main campus were randomly divided into the training dataset （376 cases） and the internal validation dataset （95 cases） at a 4∶1 ratio， while data from Zidong branch served as the external validation dataset （64 cases）. Risk factors were analyzed and screened through literature review， expert interviews， and the least absolute shrinkage and selection operator （LASSO） algorithm. Nine machine learning algorithms were utilized to construct diagnostic models. Comparative analyses of common evaluation metrics， calibration curves， and decision curves were conducted to select the model through internal and external validation. The Shapley additive explanations （SHAP） method and two cases were utilized to help understand the operational logic of the best model. Finally， the best model was applied to patients with borderline lesions to calculate diagnostic efficacy. ResultsNine risk factors were screened by LASSO regression， such as phlegm， hematoma， stagnation， deficiency， hypertension duration， gender， arterial stiffness index （ASI）， uric acid to high-density lipoprotein cholesterol ratio （UHR）， and glycosylated hemoglobin （HbA1c）. After comparison from multiple dimensions， the light gradient boosting machine （LightGBM） was the best model， achieving area under the curve （AUC） of 0.918 （95% confidence interval （CI）： 0.890-0.945） in the training dataset， 0.885 （95%CI： 0.820-0.951） in the internal validation dataset， and 0.897 （95%CI： 0.818-0.975） in the external validation dataset. Calibration curves indicated good consistency in the predicted probabilities， while decision curve analysis showed clinical benefit when threshold probabilities were less than 90%. SHAP importance rankings were stagnation， deficiency， hematoma， HbA1c， gender， phlegm， hypertension duration， ASI， and UHR. When applied to the patients with borderline lesions， the diagnostic model achieved an AUC of 0.783 （95%CI： 0.637-0.930）， with 73% of patients with actual severe stenosis getting benefit. ConclusionGuided by clinical value， the diagnostic model integrating traditional Chinese and Western medicine established in this study demonstrates favorable performance， providing a basis for clinical diagnosis， treatment， and decision-making in patients with CKM.

ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 （STAT1）/interferon regulatory factor 3 （IRF3） signaling pathway in a pneumonia model induced by lipopolysaccharide （LPS） and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group， and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling， the rats were randomly divided into the model group， dexamethasone group （0.5 mg·kg^-1）， and Yifei Jianpi prescription high-dose （12 mg·kg^-1）， medium-dose （6 mg·kg^-1）， and low-dose （3 mg·kg^-1） groups， with 10 rats in each group. Treatment was administered once daily， and the normal control and model groups received the same volume of normal saline. After 14 days， flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of immunoglobulin G （IgG）， immunoglobulin A （IgA）， immunoglobulin M （IgM）， and the content of tumor necrosis factor-α （TNF-α）， interleukin-8 （IL-8）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in alveolar lavage fluid （BALF）. Hematoxylin-eosin （HE） staining was used to observe lung tissue pathology and score the damage. Thymus weight， spleen weight， and wet-to-dry weight ratio （W/D） were recorded. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT1， IRF3， IL-6， and interferon-alpha （IFN-α） in lung tissues， while Western blot was performed to assess the protein expression of STAT1， IRF3， IL-6， and IFN-α. ResultsCompared with the normal control group， the model group showed significantly increased proportion of B lymphocytes in peripheral blood， decreased proportions of NK cells and CD4⁺/CD8⁺ （P<0.05， P<0.01）， decreased serum levels of IgG and IgA， significantly increased IgM levels （P<0.01）， significantly elevated content of TNF-α， IL-6， and IL-8 in BALF， and significantly decreased IL-10 levels （P<0.01）. Lung tissue damage was evident， with significant increases in thymus and spleen weights and a higher W/D ratio （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly upregulated （P<0.05，P<0.01）. Compared with the model group， the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood， increased proportions of NK cells and CD4⁺/CD8⁺ ratios （P<0.05， P<0.01）， significantly increased serum levels of IgG and IgA， significantly decreased IgM levels （P<0.05， P<0.01）， significantly reduced levels of TNF-α， IL-6， and IL-8 in BALF， and significantly increased IL-10 levels （P<0.01）. Lung tissue damage was alleviated， thymus and spleen weights were significantly reduced， and the W/D ratio was markedly decreased （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly downregulated （P<0.05， P<0.01）. ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.

Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

Ribosomal protein(RP)is an important part of ribosome,which is very important for the assembly and function of ribosome.Recent studies have shown that RP is closely related to the processes of growth,senescence,apoptosis,invasion and drug resistance of tumor cells.The drug resistance of tumors is one of the main reasons for the low cure rate of tumors.RP can affect the drug resistance of tumor cells through a variety of mechanisms,such as changes in signal pathway,epithelial-mesenchymal transformation,cancer stem cells and tumor microenvironment,resulting in a poor prognosis of cancer patients.Ribosome tar-geting therapy is a promising method for the treatment of cancer patients.This review summarizes the mecha-nism of RP and many kinds of cancer drug resistance,provides new ideas for elucidating the mechanism of tumor drug resistance,and then provides new strategies for clinical prevention and reduction of tumor drug re-sistance.

Objective To analyze the epidemiology and trends of measles,tuberculosis,pertussis,scarlet fever,influenza,mumps and rubella in Beijing between 2014 and 2023 in order to provide data for prevention and control of related diseases.Methods Data on the incidences of seven respiratory infectious diseases in Beijing between 2014 and 2023 was collected.Descriptive epidemiological methods were employed to analyze their demographic,temporal and spatial distribution.Joinpoint regression analysis was used to assess temporal trends in incidence.Results A total of 1 406 777 cases of seven respiratory infectious diseases were reported in Beijing between 2014 and 2023,which corresponded to an average crude rate of 649.76/100 000 reported annually.The crude rate of incidencewas higher among females than among males,with the most vulnerable age groups being 0-4 years and 5-19 years,and was higher in the six districts than on the outskirts.Most of the respiratory infectious diseases peaked in winter and spring.The annual increase in the incidence of respiratory infectious diseases in Beijing in this period averaged 27.27％,with no statistically significant differences in trends.The incidence rates of measles,tuberculosis,scarlet fever,mumps and rubella decreased significantly while those of pertussis and influenza increased,but with no statistically significant difference.Conclusion The overall incidence of major respiratory infectious diseases in Beijing is increasing.It is recommended that more people get vaccinated,surveillance of such diseases as pertussis and influenza be enhanced,and regional health resources be allocated more effectively,all of which will be critical to subsequent prevention and control of respiratory infectious diseases in Beijing.

OBJECTIVE: To explore the genetic basis for a girl with primary microcephaly and growth retardation. METHODS: A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278). RESULTS: DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c.2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. CONCLUSION Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.
Female ; Humans ; Cell Cycle Proteins ; Heterozygote ; Microcephaly/genetics* ; Mutation ; Nerve Tissue Proteins/genetics* ; Pedigree

BACKGROUND:Internal tension-reduction technique is to reconstruct the anterior cruciate ligament through high-strength suture system combined with tendon.It can effectively reduce graft relaxation and frets by sharing the internal load of the knee joint,and has achieved good biomechanical results and clinical efficacy.However,whether it can reduce cartilage degeneration after anterior cruciate ligament reconstruction through stress sharing reduction has not been studied. OBJECTIVE:To investigate the effect of internal tension-reduction technique on articular cartilage degeneration in southern Yunnan small-ear pigs undergoing anterior cruciate ligament reconstruction. METHODS:Ten adult female Yunnan small-ear pigs were selected,and the ipsilateral knee Achilles tendon was taken from the left knee joint for anterior cruciate ligament reconstruction(normal group,n=10),and the ipsilateral knee Achilles tendon from the right knee joint combined with internal tension-reduction and augmentation system for anterior cruciate ligament reconstruction(tension-reduction group,n=10).One year after surgery,the experimental pigs were sacrificed,and the left and right knee cartilage was taken for hematoxylin-eosin staining,Safranin O-fast green staining,Osteoarthritis Research Society International scoring,and immunohistochemistry staining of type Ⅱ collagen,interleukin-1β,and tumor necrosis factor-alpha in the cartilage. RESULTS AND CONCLUSION:Hematoxylin-eosin staining showed that in the tension-reduction group,there were mild pathologic changes of osteoarthritis,with a low number of empty bone lacunae and no obvious pathological changes such as fibrosis or cell layer breakage;in the normal group,more severe cartilage damage,with an increased number of empty bone lacunae,loss of chondrocytes near the bone and even the formation of fissures.Safranin O-fast green staining indicated that the tension-reduction group had normal cartilage tissue thickness,flat cartilage surface,a neat cell arrangement in a polar pattern,and no swelling or apoptosis,while in the normal group,the thickness of cartilage tissue was obviously thinner,the cell arrangement was disordered with no polarity,the number of cells was reduced,obvious cartilage fractures and cartilage vacuoles formed,and the absence of cells near the central bone was obvious.The Osteoarthritis Research Society International score was significantly lower in the tension-reduction group than in the normal group(P＜0.05).Immunohistochemical findings showed that the protein expression of type Ⅱ collagen in cartilage tissue of the tension-reducing group was higher than that of the normal group(P＜0.05),and the protein expression of interleukin 1β and tumor necrosis factor ɑ in cartilage tissue was lower than that of normal group(P＜0.05).To conclude,internal tension-reduction technique can delay the degeneration of articular cartilage in Yunnan small-eared pigs following anterior cruciate ligament reconstruction.