ObjectiveTo explore the potential mechanism of Changji'an Formula （肠激安方） on intestinal permeability for rats with diarrhea-predominant irritable bowel syndrome （IBS-D） of liver depression and spleen deficiency syndrome by the microRNA-29b-3p （miR-29b-3p）/tumor necrosis factor receptor-associated factor 3 （TRAF3）/nuclear factor-κB （NF-κB）/myosin light chain kinase （MLCK） axis. MethodsTwenty-four 1-day-old male Sprague-Dawley （SD） suckling rats were selected， and the IBS-D rat model of liver depression and spleen deficiency syndrome was established via a three-factor method，i.e. maternal separation plus acetic acid stimulation and restraint stress， for 6 consecutive weeks. After successful modeling， the rats were randomly divided into a model group， pinaverium bromide group， low-dose and high-dose Changji'an Formula groups， with 6 rats in each group. Another 6 age-matched non-modeled SD rats were included as the control group. The low-dose and high-dose Changji'an Formula groups were given intragastric administration of Changji'an Formula solution at doses of 16.74 g/（kg·d） and 33.48 g/（kg·d）， respectively； the pinaverium bromide group received intragastric administration of pinaverium bromide tablets at 0.018 g/（kg·d）； and the control group was given distilled water at 10 ml/（kg·d） via intragastric gavage. The intervention was conducted once daily for 14 consecutive days. After the gavage treatment， the fecal water content of rats in each group was measured. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum levels of intestinal permeability indicators， including D-lactic acid （D-LA）， diamine oxidase （DAO）， and lipopolysaccharide （LPS）. Quantitative real-time polymerase chain reaction （qRT-PCR） was conducted to determine the mRNA expression levels of miR-29b-3p， TRAF3， tumor necrosis factor-α （TNF-α）， p65， p50， and MLCK in colonic tissues. Western Blot analysis was employed to detect the protein expression levels of TRAF3， TNF-α， p65， phosphorylated p65 （p-p65）， MLCK， myosin light chain （MLC）， phosphorylated MLC （p-MLC）， and tight junction proteins including junctional adhesion molecule-A （JAM-A）， Occludin， and Claudin-1 in colonic tissues. ResultsCompared with the control group， the model group exhibited significantly increased fecal water content and serum levels of D-LA， DAO， and LPS， along with decreased protein expression levels of JAM-A， Occludin， and Claudin-1 in colonic tissues （P＜0.05 or P＜0.01）. Additionally， in the model group， the mRNA expression levels of miR-29b-3p， TNF-α， p65， p50， and MLCK in colonic tissues were up-regulated， while the mRNA and protein expression levels of TRAF3 were down-regulated； the protein levels of TNF-α and MLCK， as well as the ratios of p-p65/p65 and p-MLC/MLC， significantly elevated （P＜0.01）. Compared with the model group， all treatment groups showed reduced fecal water content and serum levels of D-LA， DAO， and LPS， along with down-regulated mRNA expression levels of miR-29b-3p， TNF-α， p65， p50， and MLCK， and up-regulated TRAF3 mRNA expression in colonic tissues. Moreover， the pinaverium bromide group and high-dose Changji'an Formula group presented increased protein levels of Occludin， Claudin-1， and TRAF3， as well as decreased protein levels of TNF-α and MLCK， and reduced ratios of p-p65/p65 and p-MLC/MLC in colonic tissues （P＜0.05 or P＜0.01）. Compared with the low-dose Changji'an Formula group， the high-dose group had lower fecal water content and serum levels of DAO and LPS （P＜0.01）. In comparison with the pinaverium bromide group， the high-dose Changji'an Formula group showed a significant decrease in serum DAO level （P＜0.01）. ConclusionsChangji'an Formula can reduce intestinal permeability and restore intestinal barrier function in IBS-D rats of liver depression and spleen deficiency syndrome by regulating the miR-29b-3p/TRAF3/NF-κB/MLCK axis.

ObjectiveTo observe the effects of Dihuang Yinzi （DY） on motor dysfunction in rats with advanced Parkinson's disease （PD） and to investigate the mechanisms by which DY improves advanced PD symptoms through the "gut microbiota-short-chain fatty acids （SCFAs）-inflammation-neuroprotection pathway". MethodsAn advanced PD rat model was induced by rotenone. Rats were divided into a normal group， model group， positive drug group （levodopa， 50 mg·kg^-1）， and DY low-， medium-， and high-dose groups （5.2， 10.4， 20.8 g·kg^-1）. After 7 days of administration， motor function was evaluated using the open-field， pole-climbing， and inclined plate tests. Hematoxylin-eosin （HE） staining was used to observe pathological changes in the substantia nigra and colon， and immunohistochemistry was performed to detect α-Synuclein （α-Syn） and tyrosine hydroxylase （TH） expression in the substantia nigra. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of dopamine （DA）， 5-hydroxytryptamine （5-HT）， 3，4-dihydroxyphenylacetic acid （DOPAC）， Levodopa， homovanillic acid （HVA）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β）. Western blot analysis was used to detect the expression of zonula occludens-1 （ZO-1） and occludin. Gut microbiota diversity was analyzed by 16S rRNA sequencing， and gas chromatography （GC） was used to determine the content of SCFAs in colonic contents. ResultsCompared with the normal group， the model group showed significantly decreased movement speed and distance in the open-field test， prolonged pole-climbing time， and reduced retention angle on the inclined plate （P<0.01）， accompanied by increased α-Syn expression （P<0.01） and decreased TH expression （P<0.01） in the brain. Compared with the model group， all DY dose groups improved motor dysfunction in advanced PD rats to varying degrees （P<0.05， P<0.01） and alleviated pathological damage in the brain and colon. High-dose DY significantly reduced α-Syn aggregation in the substantia nigra （P<0.01） and increased TH expression （P<0.01）. ELISA and Western blot results showed that， compared with the normal group， the model group exhibited decreased levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum （P<0.01）， increased levels of TNF-α， IL-6， and IL-1β in the colon and striatum （P<0.01）， and significantly reduced expression of ZO-1 （P<0.05） and occludin in the colon （P<0.01）. Compared with the model group， all DY dose groups increased the levels of DA， 5-HT， DOPAC， Levodopa， and HVA in the striatum to varying degrees （P<0.05， P<0.01）. In the high-dose DY group， the levels of TNF-α， IL-6， and IL-1β in the colon and striatum were reduced （P<0.01）， while the expression of ZO-1 （P<0.05） and occludin in the intestine was increased. The 16S rRNA sequencing results indicated that the relative abundances of Actinobacteriota， Enterobacteriaceae， and Erysipelotrichaceae were increased in the model group， whereas the relative abundances of Bacteroidota， class Clostridia， Lachnospiraceae， and Akkermansia muciniphila were decreased. These changes were effectively reversed after high-dose DY intervention. GC analysis showed that the content of SCFAs in the colonic contents of rats in the model group was decreased （P<0.05， P<0.01）， while after high-dose DY intervention， the levels of acetate， propionate， isobutyrate， and butyrate were significantly increased （P<0.05， P<0.01）. ConclusionDY may exert therapeutic effects in advanced PD by regulating the gut microbiota-SCFAs-inflammation pathway.

Recently, there has been an increasing risk of importation of tropical diseases into China and the resultant re-transmission in the country with the in-depth implementation of the “Belt and Road” Initiative, which poses a serious threat to the national public health security. To effectively respond to the cross-border transmission risk of tropical diseases and facilitate the process towards tropical disease control and elimination in China and the countries along the “Belt and Road” Initiative, this article analyzes the current status and governance risks of major imported tropical diseases, cross-border joint prevention and control polices implemented for tropical diseases and challenges in the establishment of the joint prevention and control system for tropical diseases in China, and discusses the establishment and implementation path of the joint prevention and control system for tropical diseases in countries along the “Belt and Road” Initiative. This path covers the establishment of cross-border cooperation mechanisms, research and development and pilot production of Chinese public health products, and implementation of key cross-border tropical disease prevention and control projects. The establishment of this system will further improve Chinese prevention and control capabilities for key cross-border tropical diseases, build a demonstrative prevention and control model for tropical diseases, and promote international technical exchanges and cooperation of tropical diseases.

OBJECTIVE To systematically evaluate medication risk prediction models for hospitalized adult patients and provide references for their development and clinical application. METHODS Databases including PubMed， Embase， Web of Science， CNKI， Wanfang data， VIP and CBM were searched for studies on medication risk prediction models from their inception to May 2024. After screening the literature， extracting data， and evaluating the quality of the literature， descriptive analysis was performed on the results of the included studies. RESULTS A total of 13 studies were included， involving 12 models. Nine studies used Logistic regression algorithm for modeling， and the number of included predictive factors ranged from 3 to 11； the area under the receiver operating characteristic curve ranged from 0.65 to 0.865. The literature quality evaluation results showed that 10 studies had high risk of bias； 10 studies had high applicability risk. A total of 31 predictive factors were extracted， including 15 items of basic patient information， 3 test indicators， and 5 items of medication information， and 8 others. CONCLUSIONS The existing medication risk prediction models for hospitalized adult inpatients are mainly Logistic regression algorithm， with predictive factors mainly focusing on basic indicators such as demographics. The overall prediction performance of the models needs to be improved， and the overall risk of bias is relatively high.

BackgroundMigraine is a common chronic neurological disease， and patent foramen ovale （PFO） has been closely associated with migraine. Current research primarily focuses on the pathological mechanism and the therapeutic effects of interventional closure， with limited attention paid to the impact of PFO on sleep quality in migraine patients. ObjectiveTo compare the difference in sleep quality between PFO-positive and PFO-negative migraine patients， and to analyzes influencing factors of sleep quality in PFO-positive migraine patients， so as to provide references for clinical interventions to improve sleep quality in PFO-positive migraine patients. MethodsA total of 673 migraine patients who met the diagnostic criteria of migraine in the International Classification of Headache Disorders， third edition （ICHD-3）， and all patients underwent contrast-enhanced transcranial Doppler （c-TCD） and transthoracic echocardiographic right heart contrast echocardiography （cTTE） in the Third Hospital of Mianyang from January 2020 to October 2024. Basic demographic data were collected using a self-designed questionnaire， headache severity was assessed with the Visual Analogue Scale （VAS）， and sleep quality was invaluated using the Pittsburgh Sleep Quality Index （PSQI）. PFO patients was diagnosed through c-TCD combined with c-TTE. Binary logistic regression analysis was employed to examine the influencing factors of sleep quality in PFO-positive migraine patients. ResultsA total of 673 （100.00%） migraine patients were enrolled， including 223 PFO-positive cases （33.14%） and 450 PFO-negative cases（66.86%）. The PFO-positive group showed significantly more severe headache severity （χ²=15.799， P<0.01） and poorer sleep quality （χ²=14.377， P<0.01） compared with PFO-negative group. PFO-positive patients demonstrated significantly higher barrier factor scores of sleep quality， sleep latency， sleep efficiency， sleep disturbance， hypnotic medication use， and daytime dysfunction compared with PFO-negative counterparts （t=3.634， 3.269， 2.785， 3.428， 2.907， 3.637， Bonferroni adjust P<0.05/7=0.007）.By contrast， no significant difference was noted in sleep duration scores between the two groups（t=2.349， Bonferroni adjust P>0.05/7=0.007）.The Binary Logistic regression analysis revealed that age （OR=1.021， 95% CI： 1.001~1.041）， headache severity （OR=6.030， 95% CI： 4.085~8.901）， and PFO grade （OR=1.893，95% CI： 1.288~2.784）were significant influencing factors for sleep quality in migraine patients with PFO. ConclusionMigraine patients with PFO-positive exhibited poorer sleep quality compared wtih PFO-negative patients. Older age， higher headache servity， and more severe PFO grade are identified as risk factors for impaired sleep quality in PFO-positive migraine patients.

Cerebral small vessel disease （CSVD） is a spectrum of pathological conditions affecting intracranial small blood vessels and is associated with a variety of clinical manifestations， including cognitive impairment， gait abnormalities， and sleep disorders. In recent years， the association between CSVD and sleep disorders has attracted increasing attention. This article reviews the association of CSVD with various sleep disorders such as obstructive/central sleep apnea hypoventilation syndrome， restless legs syndrome， and insomnia， analyzes the mechanisms by which sleep disorders cause CSVD， and proposes potential directions for future research.

Objective To evaluate the protective effect of radiation protection safety education (RPSE) on patients with differentiated thyroid carcinoma (DTC) undergoing iodine-131 (¹³¹I) treatment. Methods The DTC patients who undergo ¹³¹I treatment were divided into the control group and the RPSE group using the convenience sampling method, with 142 patients in each group. Patients in the control group received routine health education, while the RPSE group received routine health education combined with RPSE. Dose equivalent rate (DER) on pillows, bed sheets, quilt covers, and household waste of patients were compared between the two groups upon discharge. Results The median (M) DERs of patients' pillows, bed sheets, quilt covers and household waste were 3.86, 3.63, 3.91 and 56.59 times higher in the control group compared with the environmental background level, respectively. The M DERs of patients' pillows, bed sheets, quilt covers were 2.23, 2.18, and 2.55 times higher in the RPSE group compared with the environmental background level, while the M DER of household waste was equivalent to the environmental background level. The DERs of patients' pillows, bed sheets, quilt covers, and household waste in the RPSE group were significantly lower than those in the control group (all P<0.001). The DERs of the above four items were lower in both male and female patients in RPSE group compared with same-gender patients in the control group (all P<0.001). The patients' DERs of the above indicators had no significant difference among different gender in both control group and RPSE group (all P>0.05), except for higher DER of household waste in female patients than that of male patients in the control group (P<0.05). There were no significant differences in the DERs of pillows, bed sheets, quilt covers, and household waste across subgroups, where patients received different treatment doses, of both the control group and the RPSE group (all P>0.05). Conclusion RPSE for DTC patients treated with ¹³¹I, reduces the DERs of pillows, bed sheets, quilt covers, and particularly household waste.

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

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide, with above 80% of cases be non-small cell lung cancer (NSCLC), among which lung squamous cell carcinoma (LUSC) occupies a significant proportion. Although comprehensive cancer therapies have considerably improved the overall survival of patients, patients with advanced LUSC have a poorer prognosis. Therefore, there is a need for a biomarker to predict the progress of advanced LUSC in order to improve prognosis through early diagnosis. Previous studies have shown that miRNAs are differentially expressed in lung cancer tissues and play roles as potential oncogenes or tumor suppressors. The aim of this study is to identify differentially expressed miRNAs between early-stage and advanced-stage LUSC, and to establish a set of miRNAs that can predict the progress of advanced LUSC. METHODS: Clinical data and miRNA-related data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatic methods were applied to analyze the data. Receiver operating characteristic (ROC) curves were plotted, and various online tools were used to predict target genes, with subsequent analysis of the potential biological mechanisms of these genes. RESULTS: A total of 58 differentially expressed miRNAs were identified between the experiment group and the control group. Seven miRNAs were selected for potential construction of a miRNA biomarker through LASSO regression, and based on the area under the curve (AUC) values of each miRNA, four of these miRNAs (miR-377-3p, miR-4779, miR-6803-5p, miR-3960) were ultimately chosen as biomarkers for predicting advanced LUSC. The AUC under the ROC curve for the combined four miRNAs was 0.865. Enrichment analysis showed that these target genes were involved in several pathways, including cancer-related pathways, mitogen-activated protein kinase (MAPK) signaling pathway, serine/threonine kinase, and tyrosine kinase signaling pathways. CONCLUSIONS The combined use of miR-377-3p, miR-4779, miR-6803-5p and miR-3960 provides a good predictive ability for the progress of advanced LUSC patients, with an AUC of 0.865.
Humans ; MicroRNAs/metabolism* ; Lung Neoplasms/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Prognosis ; ROC Curve ; Middle Aged

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.