Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

This paper explores the therapeutic approach for glaucoma based on the concept of "jueyin （厥阴） as the closing phase" from the perspectives of time and space. In traditional Chinese medicine， jueyin governs inward， converging aspect of qi， representing the crucial turning point between the end of yin and the emergence of yang， as well as the transformation between yin and yang. When the closing and descending function of jueyin operates smoothly， it promotes the inward convergence and smooth descent of qi， enabling the internal retention of blood， spirit， and emotions， which nourishes the internal organs and moistens the meridian-sinews. Conversely， dysfunction of this "closing" mechanism results in a disturbance of yin and yang， a mixture of cold and heat， and disharmony of qi and blood. It is proposed that "failure of jueyin to properly close and descend" is a core pathomechanism of glaucoma. From the perspective of spatiotemporal theory， clinical treatment should focus on "regulating the closing function of jueyin and harmonizing yin and yang". The modified Wumei Pill （乌梅丸） is recommended to adjust the ascending-descending and entering-exiting dynamics of jueyin qi transformation， thereby restoring its free flow， achieving yin and yang balance， and ensuring nourishment to the ocular system.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Retinopathy caused by myopia is the first cause of irreversible blinding eye disease in China.The TCM methods to prevent and control myopia mainly include Chinese materia medica and TCM appropriate techniques,which have the advantages of good efficacy,simple operation,and few adverse reactions.This paper believed that internal and external pathogenic factors act on the brain and eyes,breaking their homeostasis,leading to rhythmic disorders,and imbalance of essence,qi and blood is the main pathogenesis of myopia.Based on the idea of"nature and human in the same rhythm"and"the same treatment for common diseases",targeting the above pathogenesis,the method of"brain-eye synchronization"was proposed to restore the homeostasis of the brain and eyes to prevent and control myopia in children and adolescents,and the treatment rules were to regulate the rhythms of the time,harmonize the qi and blood,nourish the blood to soften the tendons,and replenish the essence and blood,so as to achieve the effect of brain-eye synchronization and the treatment of the spirit and the body together.This article summarized the theoretical basis of"brain-eye synchronization"and its clinical application in traditional Chinese and Western medicine,with a view to providing new ideas for the prevention and control of myopia in children and adolescents.

Objective The effects of carrimycin(CAM)on the biological functions of intrahepatic cholan-giocarcinoma HuCCT1 cells were examined through in vitro experiments,and a preliminary investigation was conducted into its mechanism of action.Methods The intrahepatic cholangiocarcinoma cell line HuCCT1 was selected for the study.The effect of CAM on cell viability was assessed using the CCK-8 assay,and the IC50 concen-tration was determined accordingly.The impact of CAM on cell migration was evaluated through a scratch wound healing assay.In addition,the effect of CAM on clonogenic ability was examined using a colony formation assay.Cell invasion capacity was assessed using a Transwell invasion assay.Flow cytometry was employed to analyze the effect of CAM on cell cycle progression.Furthermore,Western blotting was conducted to evaluate the expression levels of key proteins associated with epithelial-mesenchymal transition and the cell cycle.Finally,the influence of CAM on the AXL/c-Myc/c-Met signaling axis was also investigated.Results Compared with the control group,CAM significantly inhibited the proliferation of HuCCT1 cells in a concentration-dependent manner(P<0.05).Plate cloning assays demonstrated that CAM markedly suppressed the colony-forming ability of HuCCT1 cells(P<0.05).Scratch wound healing assays confirmed that CAM treatment significantly reduced the migration speed and narrowed the migration area of HuCCT1 cells(P<0.05).Flow cytometry analysis revealed that CAM treatment led to a significant increase in the proportion of cells in the G0/G1 phase and a decrease in the S phase(P<0.05).Western blot analysis further confirmed that the expression levels of key regulatory proteins CCND1 and CDK4,which are involved in the G1/S phase transition,were down-regulated,while the expression of p21 was up-regulated(P<0.05).Transwell invasion assays indicated that CAM inhibited the invasive capacity of HuCCT1 cells.Consis-tently,Western blot results showed that E-Cadherin expression was increased(P<0.05),whereas the expression levels of N-Cadherin and Vimentin were decreased(P<0.05).Moreover,Western blot analysis verified that the expression of AXL,c-Met,and c-Myc was up-regulated in HuCCT1 cells treated with AXL recombinant protein(P<0.05).However,co-treatment with CAM and AXL recombinant protein significantly attenuated the expression of these proteins(P<0.05).Conclusions CAM inhibits the proliferation,migration,and invasion of intrahe-patic cholangiocarcinoma HuCCT1 cells,thereby demonstrating antitumor effects,which may be associated with the AXL/c-Met/c-Myc signaling pathway.

Traditional Chinese medicine upholds the unity of nature and humanity as its fundamental principle,asserting that man is in harmony with heaven and earth and corresponds to the sun and moon.Human life processes align with the circadian rhythms of nature,exhibiting periodic temporal changes-concepts that Western medicine defines as biological rhythms.The"opening-closing-pivot"of the three yin and three yang meridians represents the primary mode of interaction between nature and humanity.This mechanism regulates the transformation of yin and yang to qi within the body,ensuring synchronization with the circadian rhythm.Building upon this foundation,the concept of"the harmony of rhythms and states"was proposed to explain human growth and aging."Rhythms"encompass not only circadian cycles but also the movement of qi and blood,as well as the contraction rhythm of muscle fascia,among other physiological processes."States"refer to the dynamic evolution and transformation of qi during the"opening-closing-pivot"stages in both time and space."Harmony"pertains not only to the individual physiological balance of"rhythms"or"states"but also to their coherent interaction.The fundamental cause of myopia is"the disharmony of rhythms and states",considering that rhythm disorders,qi and blood disorders,and fascia imbalances contribute to this disease.Based on this understanding,myopia prevention and treatment should center on"regulating rhythms and states",with adjusting the pivot to brighten the eyes as the core therapeutic principle throughout the entire cycle of myopia.Treatment should be tailored to different disease stages and supplemented with methods such as time-based regulation,qi and blood harmonization,tendon relaxation and collateral dredging,and essence and blood nourishment to prevent and manage myopia effectively.

To establish a TaqMan-based multiplex RT-qPCR method for the identification of Japa-nese encephalitis virus(JEV),Porcine reproductive and respiratory syndrome virus(PRRSV),and Classical swine fever virus(CSFV),this study designed and synthesized three pairs of specific primers and probes based on the conserved sequences of JEV E,PRRSV ORF6,and CSFV E2 a-vailable in the NCBI GenBank.By optimizing the reaction system and protocol,a multiplex RT-qPCR method for detecting these three viruses was developed and applied to the detection of clini-cal samples.The results showed that the established TaqMan multiplex RT-qPCR specifically am-plified the gene fragments of JEV,PRRSV,and CSFV,and did not amplify other non-target genes,indicating good specificity of the method.Intra-assay and inter-assay repeatability tests showed that the coefficient of variation(Cv)values were all below 3％,demonstrating that the method has ex-cellent repeatability.Sensitivity tests revealed that the minimum detectable amount for the recom-binant plasmids of the three viruses was 100 copies/pL.Using the established method,a total of 969 samples,including blood,aborted fetuses,semen,and deceased pigs,from 26 pig farms in Guizhou Province were tested.The detection rates were 34.3％(332/969)for JEV,28.3％(274/969)for PRRSV,and 19.8％(192/969)for CSFV.The co-infection rates were 10.1％(98/969)for JEV and PRRSV,12.1％(117/969)for JEV and CSFV,and 14.6％(141/969)for CSFV and PRRSV.Additionally,the triple co-infection rate of JEV,PRRSV,and CSFV was 7.9％(77/969).These results indicate that the TaqMan multiplex RT-qPCR method developed in this study is ef-fective for detecting these three viruses in pig farms,providing technical support for identifying vi-ral causes of reproductive disorders.

Objective The effects of carrimycin(CAM)on the biological functions of intrahepatic cholan-giocarcinoma HuCCT1 cells were examined through in vitro experiments,and a preliminary investigation was conducted into its mechanism of action.Methods The intrahepatic cholangiocarcinoma cell line HuCCT1 was selected for the study.The effect of CAM on cell viability was assessed using the CCK-8 assay,and the IC50 concen-tration was determined accordingly.The impact of CAM on cell migration was evaluated through a scratch wound healing assay.In addition,the effect of CAM on clonogenic ability was examined using a colony formation assay.Cell invasion capacity was assessed using a Transwell invasion assay.Flow cytometry was employed to analyze the effect of CAM on cell cycle progression.Furthermore,Western blotting was conducted to evaluate the expression levels of key proteins associated with epithelial-mesenchymal transition and the cell cycle.Finally,the influence of CAM on the AXL/c-Myc/c-Met signaling axis was also investigated.Results Compared with the control group,CAM significantly inhibited the proliferation of HuCCT1 cells in a concentration-dependent manner(P<0.05).Plate cloning assays demonstrated that CAM markedly suppressed the colony-forming ability of HuCCT1 cells(P<0.05).Scratch wound healing assays confirmed that CAM treatment significantly reduced the migration speed and narrowed the migration area of HuCCT1 cells(P<0.05).Flow cytometry analysis revealed that CAM treatment led to a significant increase in the proportion of cells in the G0/G1 phase and a decrease in the S phase(P<0.05).Western blot analysis further confirmed that the expression levels of key regulatory proteins CCND1 and CDK4,which are involved in the G1/S phase transition,were down-regulated,while the expression of p21 was up-regulated(P<0.05).Transwell invasion assays indicated that CAM inhibited the invasive capacity of HuCCT1 cells.Consis-tently,Western blot results showed that E-Cadherin expression was increased(P<0.05),whereas the expression levels of N-Cadherin and Vimentin were decreased(P<0.05).Moreover,Western blot analysis verified that the expression of AXL,c-Met,and c-Myc was up-regulated in HuCCT1 cells treated with AXL recombinant protein(P<0.05).However,co-treatment with CAM and AXL recombinant protein significantly attenuated the expression of these proteins(P<0.05).Conclusions CAM inhibits the proliferation,migration,and invasion of intrahe-patic cholangiocarcinoma HuCCT1 cells,thereby demonstrating antitumor effects,which may be associated with the AXL/c-Met/c-Myc signaling pathway.

The "Guidelines for prevention of respiratory syncytial virus (RSV) infection in mothers and infants (2025 Edition)" were developed by the Society of Perinatal Medicine, Chinese Medical Association. This guideline focuses on preventing RSV infections in maternal and neonatal populations, providing 15 evidence-based recommendations addressing eight clinical questions that integrate current best evidence with clinical expertise and patient preferences. The recommendations encompass non-pharmacological prevention, pharmacological prophylaxis, and vaccine strategies. This article provides a comprehensive interpretation of the guidelines, summarizes the current evidence status and practical limitations, and aims to facilitate better understanding and application of the recommendations among healthcare providers, thereby enhancing RSV infection prevention and control for maternal and neonatal populations in China.

Objective:To evaluate the short-term safety of Nirsevimab injection for preventing respiratory syncytial virus infections in infants through a physician-nurse-pharmacist collaborative model.Methods:This prospective observational study enrolled infants receiving single-dose Nirsevimab at Peking University Third Hospital from September 2024 to August 2025. A multidisciplinary team comprising pediatricians, nurses, pharmacists, and obstetricians was established to develop standardized protocols for medication management, injection procedures, follow-up processes, and safety assessment forms. Descriptive statistics analyzed on-site observations within 30 minutes post-injection and all adverse events, with causality assessment conducted.Results:Among 331 participants [171 males (51.7%), 160 females (48.3%)], 225 (68.0%) received outpatient injections and 106 (32.0%) inpatient injections. Successful administration was achieved in 330 cases (99.7%), including 207 (62.7%) receiving 50 mg/vial and 123 (37.3%) receiving 100 mg/vial formulations; one child (3 years 11 months, 19.0 kg) received two 100 mg doses. During the 30-minute observation, 11 cases (3.3%) experienced adverse events, all presenting as injection site erythema following 100 mg/vial administration, with no systemic or serious adverse events observed. All symptoms resolved spontaneously within 30 minutes. Multidisciplinary review suggested potential associations with insufficient rewarming time, larger injection volumes, or post-injection compression pressure.Conclusion:Nirsevimab demonstrated favorable short-term safety profiles in Chinese infants following single-dose administration, with feasible multidisciplinary standardized protocols, though larger sample sizes and extended follow-up are warranted for monitoring medium-to-long-term safety and special populations.