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*

Objective To investigate the correlation between the anatomical structure of patent foramen ovale(PFO)observed by transesophageal echocardiography(TEE)and the right to left shunt(RLS)grade of contrast-enhanced transthoracic echocardiography(c-TTE).Methods Ninety cases in which the presence of PFO was suggested by TEE examination as a diagnostic criterion from November 2021 to December 2022 in the First Hospital of Nanchang were retrospectively analysed.According to the c-TTE results of patients,the RLS was divided into 4 levels,and the correlation between PFO structural characteristics and RLS grading was analyzed.Results There was a positive correlation between PFO diameter size and RLS grading in resting state(r=0.381,P<0.05);The PFO diameter of patients with hypermobile interatrial septum(HIS)was larger and the difference was statistically significant(P<0.05);The PFO diameter of patients with persistent RLS was larger than that of excited phase patients,and the difference was statistically significant(P<0.05);There was no significant difference in RLS shunt degree between patients with long tunnel and those without long tunnel;There was no significant difference in RLS grade and PFO diameter size under Valsalva state.Conclusion Research has shown that certain anatomical structures of PFO interact with RLS grading,and PFO anatomical structures can also interact with each other(the opening diameter of the foramen ovale with HIS is larger);At the same time,TEE can clearly show the morphological characteristics of PFO and predict the degree of RLS,so as to further evaluate the possibility of ischemic stroke in patients with PFO,and provide more evidence for the indications for foramen ovale closure.

Objective To explore the effects of different doses of valproate on serum thyroxine(TSH),prolactin(PRL)and dopamine(DA)in patients with bipolar disorder(BPD)level of influence.Methods A total of 90 patients with BPD who received treatment in hospital from May 2020 to May 2022 were selected as the study objects.They were randomly divided into groups A,B and C,with 30 cases in all.Groups A,B and C were orally administered 10 mg/kg,15 mg/kg and 20 mg/kg sodium valproate every day,respectively.The clinical efficacy,scores of mental diseases before and after treatment,indexes related to blood drug concentration,serum levels before and after treatment,indexes related to liver function and incidence of adverse reactions were compared among the three groups.Results There was no significant difference in the total effective rate among the three groups after treatment(P>0.05).After treatment,the scores of the three groups were significantly improved compared with before treatment(P<0.05).There was significant difference in the time to reach the stable state serum concentration(P<0.05).There were no significant differences in TSH,PRL and DA levels among the three groups after treatment compared with before treatment(P>0.05).ALT and AST levels in the three groups after treatment were increased compared with those before treatment(P<0.05),and there were statistically significant differences in ALT and AST levels among the three groups after treatment(P<0.05).There was significant difference in the incidence of adverse reactions among the three groups(P<0.05).Conclusion Sodium valproate can effectively treat BPD patients and relieve the degree of mania or depression,but has no significant effect on the level of TSH,PRL and DA.Among them,small dose of sodium valproate can guarantee the thera-peutic effect and have less impact on liver function,and less adverse reactions,high safety,worthy of clinical promotion.

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.

BACKGROUND:As a dominant breed pig in southwest China,the southern Yunnan small-ear pig has been widely used as an experimental animal in the basic research of other disciplines,but there are still no reports on its application in anterior cruciate ligament reconstruction. OBJECTIVE:To establish a large animal model of the southern Yunnan small-ear pig with anterior cruciate ligament with autologous Achilles tendon was established. METHODS:Twenty adult female Yunnan small-ear pigs were equally randomized into two groups.In the autologous Achilles tendon group,the right knee anterior cruciate ligament was reconstructed with autologous Achilles tendon as a graft,while in the sham-operated group,a similar operation was performed on the right knee without any treatment of the anterior cruciate ligament.General conditions of each pig were observed and recorded before and 12 months after surgery.Ligaments and grafts were taken for gross observation and MAS scoring.Hematoxylin-eosin staining was performed to observe morphological characteristics of ligaments.The staining and arrangement of type I and type Ⅲ collagen were evaluated by immunohistochemistry.Transmission electron microscopy was used to observe the type,size,diameter,ratio,and distribution of collagen fibers in ligaments. RESULTS AND CONCLUSION:All animals had normal diet and activity,good wound healing,no obvious inflammatory reaction,no local purulent infection,and no significant changes in mental and urinary conditions compared with those before surgery.The reconstructed cruciate ligament of the knee was intact,with no stiffness and normal range of motion.Both the anterior drawer and Lachman tests were negative.Gross observation of the graft:12 months after surgery,the grafts was in good position,with good integrity,obvious tension,ligament color close to the original anterior cruciate ligament,and complete surface synovial coverage.Most of the intraarticular ligaments in the autologous Achilles tendon group were defined as MAS I type and a few were defined as MAS Ⅱ type.In the sham-operated group,the intraarticular ligament was defined as MAS I type.Hematoxylin-eosin staining indicated that,12 months after surgery,collagen fibers in the autologous Achilles tendon group began to appear bundled,isotropic,and uniformly arranged,with more obvious isotropic corrugations,and the nuclei were mainly linear or spindle-shaped,which were similar to those in normal anterior cruciate ligament tissue of the sham-operated group.Immunohistochemistry results indicated that,12 months after surgery,there was a higher expression of type I collagen and significantly less expression of type Ⅲ collagen in the reconstructed anterior cruciate ligament in the autologous Achilles tendon group.The degree of type I and type Ⅲ staining was similar in the two groups.Under the transmission electron microscope,the diameter,arrangement and density of collagen fibers in the reconstructed anterior cruciate ligament of the autologous Achilles tendon group were similar to those of the original anterior cruciate ligament at 12 months after surgery,indicating that the ligament remodeling process had been basically completed in the autologous Achilles tendon group at 12 months after surgery.Through a comprehensive evaluation of animal general conditions,ligament general view,MAS score,hematoxylin-eosin staining,immunohistochemistry,and transmission electron microscopy observation,we successfully established a large animal model of anterior cruciate ligament reconstruction using autogenous Achilles tendon in southern Yunnan small-ear pigs,with good morphological,histological and ultrastructural results.

BACKGROUND:Warm-needling moxibustion can effectively treat knee osteoarthritis.Degeneration,injury and fracture of the anterior cruciate ligament can affect the local stability of the knee joint,and then induce the formation of knee osteoarthritis.Whether warm-needling moxibustion can repair the injured cruciate ligament and the mechanism of action are still unclear. OBJECTIVE:To observe the effects of warm-needling moxibustion on the morphology of the anterior cruciate ligament and the expression of insulin growth factor-1 and transforming growth factor-β in rabbits with knee osteoarthritis and to clarify the mechanism of anterior cruciate ligament repair by warm-needling moxibustion. METHODS:Thirty New Zealand rabbits were randomly divided into blank group,model group and warm-needling moxibustion group,with 10 rabbits in each group.Knee osteoarthritis model was established by plaster cast immobilization.The blank group was not intervened.Rabbits in the model group rabbits were fixed in a rabbit holder for 15 minutes every day.The warm-needling moxibustion group was treated with warm acupuncture,once a day,7 days as a course of treatment,a total of two courses.After treatment,the imaging changes of the anterior cruciate ligament were observed by MRI and MRI grading statistics were performed.Morphological changes of the anterior cruciate ligament were observed by transmission electron microscope and hematoxylin-eosin staining.mRNA and protein expressions of insulin growth factor-1 and transforming growth factor-β were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:MRI examination:Compared with the blank control group,the anterior cruciate ligament in the model group was thickened,edematous,and partially torn,and the difference in grading statistics was statistically significant(P＜0.05).Compared with the model group,the anterior cruciate ligament in the warm-needling moxibustion group was slightly thickened,with mild edema and no tearing,and the difference in grading statistics was statistically significant(P＜0.05).General observation:In the model group,the surface of the anterior cruciate ligament was glossy and faded,with the edge being covered with flocculent periosteum and obvious tissue necrosis;in the warm-needling moxibustion group,the surface of the ligament was glossy,and the ligament was in a normal helical shape.Hematoxylin-eosin staining:In the model group,there was obvious tissue necrosis in the anterior cruciate ligament,a large number of new capillaries,loosely arranged fibroblasts and collagen fibers.In the warm-needling moxibustion group,there was a small amount of tissue necrosis and few new vessels in the anterior cruciate ligament,and the cells and collagen fibers were loosely and irregularly arranged.Transmission electron microscopy:In the model group,the fibers in the anterior cruciate ligament were arranged in a disordered way with uneven thickness and distribution,and there are more fibroblasts that were irregular in morphology;in the warm acupuncture group,the fibers were basically arranged longitudinally,with uneven thickness and distribution,and a small number of oval-shaped fibroblasts were observed.RT-PCR and western blot assay:mRNA and protein expressions of insulin growth factor-1 and transforming growth factor-β were significantly decreased in the model group compared with the blank control group(P＜0.05),but significant increased after treatment with warm-needling moxibustion(P＜0.05).To conclude,warm-needling moxibustion can alleviate anterior cruciate ligament injury and regulate the expression of insulin growth factor-1 and transforming growth factor-β to treat knee osteoarthritis.

【Objective】 To review the scientific research advances in the field of preschool children′s nutrition from 2012 to 2022, in order to provide reference for relevant policy formulation and further scientific exploration in this area. 【Methods】 High-quality literature published both domestically and internationally between 2012 and 2022 was retrieved through Web of Science (WOS) and China National Knowledge Infrastructure (CNKI) database. Excel and CiteSpace software were applied to visualize the research hotspots and frontier trends. 【Results】 A total of 1 816 English articles and 110 Chinese articles were included in the analysis. The cooperation network density of research institutions and authors was found to be low. Excluding the search terms, the top three English keywords were vitamin A (0.74), intervention (0.67), obesity prevention (0.55); the top three Chinese keywords were "anemia" (0.41), "obesity" (0.38), and "nutritional status" (0.18). In Chinese and English clusters, "anemia" and "physical activity" ranked first, respectively. The latest burst words identified were "dietary pattern" and "diet quality". 【Conclusions】 The number of English literature published in the field of preschool children′s nutrition is increasing, but it has shown a downward trend in the past three years in China. There are few studies in this field in China. The research hotspots primarily focus on the nutritional status of preschool children, with less attention paid to intervention research and methodological exploration. Further research in the field of preschool children′s nutrition in China may need to focus on the external determinants of preschool children′s nutrition, such as parental education, diet and food supply.