Objective To study the spatial arrangement of mouse connecting tubules（CNT）and their transition to collecting duct system.Methods The renal tissues of three C57/BL/6J mice were fixed by perfusion and embedded in Epon 812.Totally 2 000 consecutive sections with the thickness of 2.5 μm were obtained from the renal surface to the papilla.The serial images under microscope were digitalized and aligned.Thirty eight CNT were traced with a series of computer programs.Results The CNT from long loop nephron ascended towards renal capsule and merged with 5 to 6 CNT from short loop nephrons to form the so-called arcade,while the latter or some of the CNT from the superficial cortex directly drained into the collecting duct in the superficial cortex.The lengths of CNT and the arcade ranged from 150 μm to 500 μm and 600 μm to 900 μm respectively.Conclusion The arcade or CNT drains into collecting duct only at superficial cortical level,which suggests that the reabsorption of the glomerular ultra-filtration in collecting ducts keeps unaffected when collecting duct runs through middle to deeper cortex.

Objective To investigate the effect and mechanisms of β hydroxybutyrate (βOHB) regulation on p75NTR expression in Alzheimer's disease (AD) model cells.Methods First,cultured SH-SY5Y cells were exposed to Aβ (final concentrations:10,20,40,80 μmol/L) with or without 5 mmol/L βOHB pretreatment,and sham-treated cells were used as the control.At 24 h after treatment,the viability of cells was determined by the MTT assay.Secondly,cultured cells were divided into four groups.Cells in the Aβ group were exposed to Aβ (final concentration:20 μ mol/L)with or without 5 mmol/L βOHB pretreatment.Cells in the βOHB group were treated only with 5 mmol/L βOHB,and sham treated cells were used as the control.At 6 h and 24 h after treatment,the expression of p75NTR,HDAC1/2 mRNA and its protein expression,and p65 protein expression were measured by qRT-PCR or Western blot.Finally,the expression of p75NTR mRNA and protein was analyzed in cultured cells after silencing HDAC1 / 2 with siRNA.Results The viability of cells with 40 μmol/L or 80 μmol/L treatment was lower than that in the control group (P＜0.01),and there was a significant increase (P＜0.01) in cell viability of the βOHB intervention group,compared with the Aβ group.At 6 h or 24 h after treatment,the expression of p75NTR mRNA,its protein expression,and p65 protein expression were clearly increased in the βOHB group (P＜0.05) and markedly decreased (P＜0.01) in the Aβ group,compared with the control.Additionally,the expression of HDAC1 / 2 mRNA and protein was higher (P＜0.01) in the Aβ group at 6h or 24h after treatment and lower(P＜0.05 or P＜0.01)in the βOHB group at 6 h after treatment than in the control group.Compared with the Aβ group,there were significant increases (P＜0.01) observed in p75NTR mRNA,its protein expression,and p65 protein expression,and a notable decrease (P＜0.05) in HDAC1 / 2 mRNA and protein expression in cells of the βOHB intervention group at 6 h and 24 h after treatment.The expression of p75NTR mRNA and protein increased in HDAC1 knock-down cells compared with the control (P＜0.05).However,no difference was found in p75NTR expression in HDAC2 knock-down cells (P＞0.05).Conclusions βOHB up-regulates p75NTR expression by inhibiting HDAC1 of βOHB.It also activates p65 and prevents the decrease of cell viability.

Objective:To further understand the real experience of the nurse in the rotation of NICU in neurosurgery.Methods:Qualitative research method was used to analyze the reflective diary of 26 nurses and the semi-structured interview data of 8 nurses.Results:Three primary themes and 11 secondary themes were extracted from the real experience of rotation of nurses in the neurointensive care unit: department integration and mental process, role competency and influencing factors, career expectations and coping strategies.Conclusions:At present, the integration process of the nurses in the neurointensive care unit is slow. Influenced by many factors, it is difficult to change their roles. It is the direction that nursing managers should pay attention to establish a diversified discipline training system and create a better organizational commitment

Objective: This study used cardiac magnetic resonance imaging (MRI) to compare the characteristics of left ventricular remodeling in patients with primary aldosteronism (PA) with those of patients with essential hypertension (EH) and healthy controls (HCs). Materials and Methods: This prospective study enrolled 35 patients with PA, in addition to 35 age- and sex-matched patients with EH, and 35 age- and sex-matched HCs, all of whom underwent comprehensive clinical and cardiac MRI examinations. The analysis of variance was used to detect the differences in the characteristics of left ventricular remodeling among the three groups. Univariable and multivariable linear regression analyses were used to determine the relationships between left ventricular remodeling and the physiological variables. Results: The left ventricular end-diastolic volume index (EDVi) (mean ± standard deviation [SD]: 85.1 ± 13.0 mL/m2 for PA, 75.9 ± 14.3 mL/m2 for EH, and 77.3 ± 12.8 mL/m2 for HC; p = 0.010), left ventricular end-systolic volume index (ESVi) (mean ± SD: 35.2 ± 9.8 mL/m2 for PA, 30.7 ± 8.1 mL/m2 for EH, and 29.5 ± 7.0 mL/m2 for HC; p = 0.013), left ventricular mass index (mean ± SD: 65.8 ± 16.5 g/m2 for PA, 56.9 ± 12.1 g/m2 for EH, and 44.1 ± 8.9 g/m2 for HC; p < 0.001), and native T1 (mean ± SD: 1224 ± 39 ms for PA, 1201 ± 47 ms for EH, and 1200 ± 44 ms for HC; p = 0.041) values were higher in the PA group compared to the EH and HC groups. Multivariable linear regression demonstrated that log (plasma aldosteroneto-renin ratio) was independently correlated with EDVi and ESVi. Plasma aldosterone was independently correlated with native T1. Conclusion Patients with PA showed a greater degree of ventricular hypertrophy and enlargement, as well as myocardial fibrosis, compared to those with EH. Cardiac MRI T1 mapping can detect left ventricular myocardial fibrosis in patients with PA.

Objective: This study used cardiac magnetic resonance imaging (MRI) to compare the characteristics of left ventricular remodeling in patients with primary aldosteronism (PA) with those of patients with essential hypertension (EH) and healthy controls (HCs). Materials and Methods: This prospective study enrolled 35 patients with PA, in addition to 35 age- and sex-matched patients with EH, and 35 age- and sex-matched HCs, all of whom underwent comprehensive clinical and cardiac MRI examinations. The analysis of variance was used to detect the differences in the characteristics of left ventricular remodeling among the three groups. Univariable and multivariable linear regression analyses were used to determine the relationships between left ventricular remodeling and the physiological variables. Results: The left ventricular end-diastolic volume index (EDVi) (mean ± standard deviation [SD]: 85.1 ± 13.0 mL/m2 for PA, 75.9 ± 14.3 mL/m2 for EH, and 77.3 ± 12.8 mL/m2 for HC; p = 0.010), left ventricular end-systolic volume index (ESVi) (mean ± SD: 35.2 ± 9.8 mL/m2 for PA, 30.7 ± 8.1 mL/m2 for EH, and 29.5 ± 7.0 mL/m2 for HC; p = 0.013), left ventricular mass index (mean ± SD: 65.8 ± 16.5 g/m2 for PA, 56.9 ± 12.1 g/m2 for EH, and 44.1 ± 8.9 g/m2 for HC; p < 0.001), and native T1 (mean ± SD: 1224 ± 39 ms for PA, 1201 ± 47 ms for EH, and 1200 ± 44 ms for HC; p = 0.041) values were higher in the PA group compared to the EH and HC groups. Multivariable linear regression demonstrated that log (plasma aldosteroneto-renin ratio) was independently correlated with EDVi and ESVi. Plasma aldosterone was independently correlated with native T1. Conclusion Patients with PA showed a greater degree of ventricular hypertrophy and enlargement, as well as myocardial fibrosis, compared to those with EH. Cardiac MRI T1 mapping can detect left ventricular myocardial fibrosis in patients with PA.

OBJECTIVE To provide reference for the application of patient preference information in China by studying the application of patient preference information in the premarketing decision-making of medical products in the United States. METHODS The literature research method was used to explore the general situation， legal basis， and participants of the collection and application of patient preference information in the United States， analyze the application of patient preference information in premarketing decision-making of medical products in detail， and analyze the application status and challenges of patient preference information in China， so as to put forward suggestions. RESULTS & CONCLUSIONS United States has promoted the collection and application of patient preference information through several patient participation projects and legislation. The patient preference information is used to support premarketing decision-making of medical products： providing information for medical product development and design， and assisting clinical trial design in the research and development process； helping to support FDA’s marketing approval decisions， identifying patient groups whose benefits outweigh risks， and included in medical product descriptions in the marketing approval process. The application of patient preference information in China lacks the guidance of higher-level legal documents， and there are no targeted guidance documents. It is suggested that China should learn from the experience of the United States and clearly encourage the research and application of patient preference in higher-level legal documents； develop specific guidance documents for the collection and application of patient preference information； determine the weight and form of patient preference information to be considered in regulatory decision-making according to national conditions.

Oral health is an integral component of overall well-being, with the oral cavity serving as a channel for external communication and expression of emotions such as stress and pessimism. Oral diseases can intensify feelings of depression, whereas depression can worsen oral health conditions. As a crucial part of the human microbiome, an imbalance in oral microbiota can release oral pathogenic microbes, which, through pathways including the circulation, nervous, and immune systems, can reach the brain and significantly affect the central nervous system. This can lead to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, further intensifying the development of depression. Similarly, an imbalance in oral microbiota in individuals with depression can intensify the occurrence of oral diseases. The relationship between depression and oral diseases is not isolated but rather a complex interplay in which they mutually influence and act as causative factors. To elucidate the causal relationship between oral diseases and depression and devise strategies for the prevention and treatment of both conditions, we explore the interaction mechanisms between oral diseases and depression from the perspective of oral microbiota. The occurrence of dental caries, periapical periodontitis, and periodontal diseases is closely associated with the excessive proliferation of specific bacteria in the oral cavity, such as Streptococcus mutans, Porphyromonas gingivalis, and Fusobacterium nucleatum. These bacteria can directly invade the brain through the compromised blood-brain barrier, activating pro-inflammatory cytokines and worsening depressive symptoms. Inflammatory conditions and ulcers in the oral mucosa are caused by various factors, including infection and immune abnormalities. Because of compromised immune function in individuals with depression, these inflammatory responses are often more severe and difficult to control. Malocclusion, trigeminal neuralgia, and temporomandibular joint disorders increase the risk of depression because of psychological stress and changes in the immune system. We also outline the diagnostic and therapeutic considerations for oral diseases in patients with depression, emphasizing the importance of early intervention for disease management. Future research will explore the therapeutic potential of oral microbiota in individuals with depression, with the aim to improve symptoms and treatment outcomes by adjusting oral microbiota, thus providing novel avenues for the prevention and treatment of depression.

The human oral microbiome harbors one of the most diverse microbial communities in the human body, playing critical roles in oral and systemic health. Recent technological innovations are propelling the characterization and manipulation of oral microbiota. High-throughput sequencing enables comprehensive taxonomic and functional profiling of oral microbiomes. New long-read platforms improve genome assembly from complex samples. Single-cell genomics provides insights into uncultured taxa. Advanced imaging modalities including fluorescence, mass spectrometry, and Raman spectroscopy have enabled the visualization of the spatial organization and interactions of oral microbes with increasing resolution. Fluorescence techniques link phylogenetic identity with localization. Mass spectrometry imaging reveals metabolic niches and activities while Raman spectroscopy generates rapid biomolecular fingerprints for classification. Culturomics facilitates the isolation and cultivation of novel fastidious oral taxa using high-throughput approaches. Ongoing integration of these technologies holds the promise of transforming our understanding of oral microbiome assembly, gene expression, metabolites, microenvironments, virulence mechanisms, and microbe-host interfaces in the context of health and disease. However, significant knowledge gaps persist regarding community origins, developmental trajectories, homeostasis versus dysbiosis triggers, functional biomarkers, and strategies to deliberately reshape the oral microbiome for therapeutic benefit. The convergence of sequencing, imaging, cultureomics, synthetic systems, and biomimetic models will provide unprecedented insights into the oral microbiome and offer opportunities to predict, prevent, diagnose, and treat associated oral diseases.
Humans ; Phylogeny ; Biomimetics ; Dysbiosis ; Homeostasis ; Mass Spectrometry

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.
Animals ; Mice ; Candida albicans ; Candidiasis, Oral/drug therapy* ; Antifungal Agents/pharmacology* ; Hyphae ; Artemisinins/pharmacology*