In recent years， hyperuricemia （HUA） has shown a rapidly increasing incidence and tends to occur in increasingly young people， with a wide range of cardiac， renal， joint， and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage， medication restriction， and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid （UA）， and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology， which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine （TCM） can treat HUA via multiple targets and multiple pathways from a holistic view， with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However， its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA， this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora， intestinal metabolites， intestinal UA transporters， and intestinal barriers. Furthermore， we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology， with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.

ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.

Objective:To explore the mediating effect of professional self-efficacy between professional values and willingness to work on gerontological care of nursing students in higher vocational colleges.Methods:A total of 391 nursing students from Chengdu area full-time university were investigated by general information questionnaire, gerontological nursing career motivation questionnaire, professional values scale, and professional self-efficacy scale. Pearson correlation analysis and descriptive statistical analysis were performed by SPSS 21.0. Amos 26.0 was used to establish mediating effect model and verify the mediating effect.Results:The total score of 391 nursing students' willingness to work on gerontological care was (47.05±6.93), the willingness to work on gerontological care was positively correlated with professional self-efficacy and professional values ( r = 0.826, 0.775, respectively, all P<0.01), and professional self-efficacy played a partial mediating role between professional values and willingness to work on gerontological care, accounting for 64.82% of the total effect. Conclusions:The willingness to work on gerontological care of nursing students in higher vocational colleges is at a middle level. Professional values not only directly affect the willingness to work on gerontological care, but also indirectly take function through the professional self-efficacy. Professional self-efficacy plays a mediating role in professional values and willingness to work on gerontological care of nursing students in higher vocational colleges.

To determine the main components of the fishy smell of the Eupolyphaga Steleophaga, and to provide a theoretical basis for deodorizing the Eupolyphaga Steleophaga. METHODS Head space-solid phase microextraction-gas chromatography-mass spectrometry was used to identify the components of 10 batches of Eupolyphaga Steleophaga, and area normalization method and chemometrics method were used to analyze the smelly gas of different batches. Odor activity value(OAV) was used to evaluate the contribution of odor components and identify key odor components. RESULTS A total of 87 volatile odor components were identified, the key fishy smell compounds(OAV≥1) were m-methylphenol, dimethyltrisulfide, 4-methylphenol, 2-methyliso-borneol, 2-etzol, 4-methylvaleric acid, iso-valeric acid, etc. Modified fishy gas composition(0.1

Objective: To explore the neuroprotective effects of the Shaoyao Gancao decoction (SGD) against excitatory damage in PC12 cells and the role of the Src-NR2-nNOS pathway mediation by SGD in regulating γ-aminobutyric acid (GABA)-glutamate (Glu) homeostasis. Methods: N-Methyl-d-aspartic acid (NMDA) was used to establish a PC12 cell excitability injury model. To investigate the neuroprotective effect of SGD, a cell counting kit-8 (CCK-8) assay was used to determine PC12 cell viability, Annexin V/Propidium Iodide (Annexin V/PI) double staining was used to determine PC12 cell apoptosis, and Ca2+ concentration was observed using laser confocal microscopy. GABA receptor agonists and antagonists were used to analyze the neuroprotective interactions between γ-aminobutyric acid (GABA) and NMDA receptors. Additionally, molecular biology techniques were used to determine mRNA and protein expression in the Src-NR2-nNOS pathway. We analyzed the correlations between the regulatory sites of GABA and NMDA interactions, excitatory neurotoxicity, and brain damage at the molecular level. Results: NMDA excitotoxic injury manifested as a significant decrease in cell activity, increased apoptosis and caspase-3 protein expression, and a significant increase in intracellular Ca2+ concentration. Administration of SGD, a GABAA receptor agonist (muscimol), or a GABAB receptor agonist (baclofen) decreased intracellular Ca2+ concentrations, attenuated apoptosis, and reversed NMDA-induced upregulation of caspase-3, Src, NMDAR2A, NMDAR2B, and nNOS. Unexpectedly, a GABAA receptor antagonist (bicuculline) and a GABAB receptor antagonist (saclofen) failed to significantly increase excitatory neurotoxicity. Conclusions Taken together, these results not only provide an experimental basis for SGD administration in the clinical treatment of central nervous system injury diseases, but also suggest that the Src-NR2A-nNOS pathway may be a valuable target in excitotoxicity treatment.

Objective To investigate the pathogenic bacteria distribution,clinical features and risk factors of urinary tract infection in patients with ischemic stroke. Methods A retrospective study was conducted on 634 patients with ischemic stroke in Beijing Bo'ai Hospital from Janu-ary,2020 to December,2023.They were divided into control group(n=551,without urinary tract infection)and observation group(n=83,with urinary tract infection)according to whether they developed urinary tract infec-tion.The incidence of urinary tract infection,the distribution of pathogenic bacteria and the resistance of main pathogenic bacteria to different antibacterial drugs were analyzed.The clinical characteristics of the two groups were compared and analyzed.The independent risk factors of urinary tract infection in patients with ischemic stroke were analyzed with multivariate Logistic regression. Results A total of 83 cases of 634 patients with ischemic stroke developed urinary tract infection,and incidence was 13.09%.A total of 127 strains of pathogenic bacteria were isolated from the urine samples of the observation group,of which Gram-negative bacteria accounted for 62.99%(80/127),Gram-positive bacteria accounted for 20.47%(26/127)and strains of fungi accounted for 16.54%(21/127).The main Gram-negative pathogens were Escherichia coli and Klebsiella pneumoniae,which were high resistant to second-generation and third-generation cephalosporins,co-trimoxazole,and levofloxacin;moderately resistant to carbapenems,β-lactamase inhibitor compound preparation and aminoglycosides,etc.;and highly sensitive to tigecycline and polymyxin,etc.The main Gram-positive pathogens were Enterococcus faecalis and Enterococcus faecalis,which were a high resistant to erythromycin and gentamicin,and highly sensitive to linezolid,daptomycin,teicoplanin and vancomycin.The pathogenic fungi detected were not obviously resistant to common antifungal drugs.The proportion of female,di-abetes,indwelling catheter and neurogenic bladder were significantly higher in the observation group than in the control group(χ2>5.043,P<0.05).The female,diabetes,indwelling catheter and neurogenic bladder were inde-pendent risk factors for urinary tract infection in patients with ischemic stroke(P<0.05). Conclusion The pathogenic bacteria of patients with ischemic stroke with urinary tract infection are mainly Gram-nega-tive bacteria,followed by Gram-positive bacteria and fungi.The Gram-negative bacteria showed multiple drug re-sistance.Meanwhile,female,diabetes,indentured catheter and neurogenic bladder are the independent risk fac-tors for urinary tract infection.

Objective This study aimed to observe the outcomes of iRoot BP Plus full pulpotomy in primary molars with partial irreversible pulpitis retrospectively.Methods Collect 102 cases of primary molars with partial irreversible pulpitis undergoing iRoot BP Plus full pulpotomy from January 2019 to August 2023,with a follow-up period of 24-47 months.Based on the presence of irreversible pulpitis symptoms before surgery,the included cases will be divided into asymptomatic group(n=53)and symptomatic group(n=49).Observe the clinical and imaging success rates of both groups.Results Clinical success rates were 96.2%and 97.9%in asymptomatic and symptomatic groups,and ra-diographic success rates were 96.2%and 93.9%respec-tively.Conclusion iRoot BP Plus full pulpotomy can be used for the treatment of primary molars with partial irreversible pulpitis under an enhanced pulpotomy protocol.

Objective:To explore the characteristics of anorectal motility and sensation in patients with functional anorectal pain (FAP) by high-resolution anorectal manometry (HR-ARM) .Methods:The clinical data of 81 FAP patients (FAP group) who underwent HR-ARM in Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from January 1, 2020 to January 31, 2022 were retrospectively collected, and 80 healthy volunteers were recruited as healthy control group during the same period. The HR-ARM characteristics were compared between FAP group and the healthy control group, between the patients with different genders in the FAP group, the patients with different subtypes (proctalgia fugax, levator syndrome, and non-specific FAP) in the FAP group, which included anal resting pressure, anal squeeze pressure, rectal pressure during simulated defecation, anal residual pressure during simulated defecation, paradoxical contractions, initial sensation threshold, defecation threshold, defecation urgency threshold, and tolerance threshold. Visual analogue scale (VAS) was used to assess the pain level of the patients in the FAP group, and Spearman correlation analysis was used to analyze the correlation between VAS and HR-ARM characteristics. Independent sample t-test, least significant difference test, Tamhane′s T2 test, and Mann-Whitney U test were used for statistical analysis. Results:The anal resting pressure, anal squeeze pressure, anal residual pressure during simulated defecation, defecation urgency threshold, and tolerance threshold of the FAP group were all lower than those of the healthy control group ((59.56±24.71) mmHg (1 mmHg=0.133 kPa) vs. (81.94±15.87) mmHg, (119.04±46.94) mmHg vs.(154.62±37.95) mmHg, 59.00(40.75, 80.95) mmHg vs. 83.10(61.78, 94.30) mmHg, 70.00(55.00, 90.00) mL vs. 85.00(60.00, 110.00) mL, 105.00(87.50, 150.00) mL vs. 140.00(100.00, 180.00) mL), and the differences were all statistically significant ( t=-6.83 and -5.29, Z=-4.12, -3.12 and -2.82; all P<0.01).The rectal pressure during simulated defecation of male patients in the FAP group was higher than that of males in the healthy control group, and the defecation urgency threshold was lower than that of males in the healthy control group (42.40(29.60, 57.95) mmHg vs. 31.10(25.85, 36.80) mmHg, 80.00(62.50, 107.50) mL vs. 92.00(81.00, 140.00) mL), and the differences were statistically significant ( Z=-1.99 and -2.53, both P<0.05). The anal resting pressure, anal squeeze pressure, anal residual pressure during simulated defecation, defecation urgency threshold, and tolerance threshold of female patients in FAP group were all lower than those of female in the healthy control group ((55.67±21.61) mmHg vs. (87.04±15.54) mmHg, (102.70±37.09) mmHg vs. (155.98±31.44) mmHg, 52.55(40.53, 67.48) mmHg vs. 83.10(61.10, 94.50) mmHg, 60.00(52.50, 81.50) mL vs. 80.00(60.00, 100.00) mL, 101.00(80.00, 128.75) mL vs. 120.00(94.00, 155.00) mL), and the differences were statistically significant ( t=-8.77 and -8.16, Z=-4.57, -2.24 and -2.14; all P<0.05). The anal resting pressure, anal squeeze pressure, anal residual pressure during simulated defecation, incidence rate of paradoxical contractions, defecation urgency threshold, and tolerance threshold of female patients in FAP group were all lower than those of male patients in FAP group ((55.67±21.61) mmHg vs. (68.28±29.16) mmHg, (102.70±37.09) mmHg vs. (155.62±46.66) mmHg, 52.55(40.53, 67.48) mmHg vs. 79.00(59.55, 99.25) mmHg, 28.6%(16/56) vs. 68.0%(17/25), 44.00(35.00, 60.00) mL vs. 60.00(45.00, 70.00) mL, 60.00(52.50, 81.50) mL vs. 80.00(62.50, 107.50) mL), and the differences were statistically significant( t=2.17 and 5.47, Z=-2.96, χ2=11.10, Z=-2.93 and -2.34; all P<0.05). The anal squeeze pressure of patients with proctalgia fugax subtype was higher than that of patients with levator syndrome subtype ((140.19±56.51) mmHg vs. (80.56±30.79) mmHg), and the tolerance threshold was lower than that of patients with non-specific FAP subtype ((87.86±17.80) mL vs. (125.14±48.31) mL), and the differences were statistically significant ( t=2.35 and 2.02, both P<0.05). The results of Spearman correlation analysis showed that VAS was negatively correlated with anal resting pressure, anal squeeze pressure, and defecation urgency threshold in the patients of the FAP group ( r= -0.28, -0.23, and -0.24; all P< 0.05). Conclusion:The presence of anorectal dismotility and sensory dysfunction in FAP may be related to pelvic floor muscle abnormalities, muscle coordination disorders during defecation, and rectal hypersensitivity.