AIM To investigate the effect of Fuzheng Hefu Zhiyang Formula(FZHFZY)on psoriasis-like skin lesions and immune regulation in mice.METHODS In the in vivo experiment,30 BALB/c mice were randomly divided into the blank group,the model group,the dexamethasone group(1.5 g/kg of compound dexamethasone acetate cream),and the low-dose(2.5 g/kg)and high-dose(5 g/kg)FZHFZY groups,with six mice in each group.The experiment groups were treated with respective FZHFZY and dexamethasone,and the other groups were given normal saline for 10 consecutive days,during which psoriatic skin lesions were induced with imiquimod cream for 7 consecutive days.The mice had their area and severity of psoriasis assessed by PASI score;their histological changes of skin lesions.observed with Hematoxylin-eosin(HE)staining;their F4/80 ratio of skin lesions observed with immunohistochemical(IHC)staining;their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected by Western blot;and their mRNA expressions of tumor necrosis factor-α(TNF-α),IL-17,IL-23 and IL-1β detected by RT-qPCR.In the in vitro research,the cultured RAW264.7 cells were divided into the blank group,the LPS group,and the FZHFZY groups(1 200,600,300,150 μg/mL).The cells had their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected with Western blot;and their mRNA expressions of IL-6,TNF-α,IL-23 and IL-8 detected by RT-qPCR.RESULTS The in vivo experiment showed that compared to the model group,the FZHFZY groups demonstrated decreased PASI score(P＜0.01);improved epidermal thickening and parakeratosis of skin lesions as revealed by HE staining result and increased expression of F4/80 in IHC staining sections;decreased protein expression ratios of p-P38/P38,p-ERK/Erk and p-P65/P65 in skin(P＜0.05,P＜0.01);and reduced mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β in the skin(P＜0.01).FZHFZY(0～2 400 μg/mL)showed no significant cytotoxicity towards RAW264.7 cells in vitro(P＞0.05).Compared to those of the LPS group,the cells exposed to FZHFZ at concentrations of 1 200 and 600 μg/mL demonstrated decreased protein expression ratios of p-P38/P38,p-ERK/Erk,and p-P65/P65(P＜0.05,P＜0.01);and significantly decreased mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β(P＜0.01).CONCLUSION FZHFZY alleviates imiquimod-induced psoriatic lesions in mice and suppresses inflammatory response in LPS-stimulated RAW264.7 cells by inhibiting P38/Erk/NF-κB signaling pathway.

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

AIM To investigate the effect of Fuzheng Hefu Zhiyang Formula(FZHFZY)on psoriasis-like skin lesions and immune regulation in mice.METHODS In the in vivo experiment,30 BALB/c mice were randomly divided into the blank group,the model group,the dexamethasone group(1.5 g/kg of compound dexamethasone acetate cream),and the low-dose(2.5 g/kg)and high-dose(5 g/kg)FZHFZY groups,with six mice in each group.The experiment groups were treated with respective FZHFZY and dexamethasone,and the other groups were given normal saline for 10 consecutive days,during which psoriatic skin lesions were induced with imiquimod cream for 7 consecutive days.The mice had their area and severity of psoriasis assessed by PASI score;their histological changes of skin lesions.observed with Hematoxylin-eosin(HE)staining;their F4/80 ratio of skin lesions observed with immunohistochemical(IHC)staining;their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected by Western blot;and their mRNA expressions of tumor necrosis factor-α(TNF-α),IL-17,IL-23 and IL-1β detected by RT-qPCR.In the in vitro research,the cultured RAW264.7 cells were divided into the blank group,the LPS group,and the FZHFZY groups(1 200,600,300,150 μg/mL).The cells had their protein expressions of P38,p-P38,Erk,p-Erk,P65 and p-P65 detected with Western blot;and their mRNA expressions of IL-6,TNF-α,IL-23 and IL-8 detected by RT-qPCR.RESULTS The in vivo experiment showed that compared to the model group,the FZHFZY groups demonstrated decreased PASI score(P＜0.01);improved epidermal thickening and parakeratosis of skin lesions as revealed by HE staining result and increased expression of F4/80 in IHC staining sections;decreased protein expression ratios of p-P38/P38,p-ERK/Erk and p-P65/P65 in skin(P＜0.05,P＜0.01);and reduced mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β in the skin(P＜0.01).FZHFZY(0～2 400 μg/mL)showed no significant cytotoxicity towards RAW264.7 cells in vitro(P＞0.05).Compared to those of the LPS group,the cells exposed to FZHFZ at concentrations of 1 200 and 600 μg/mL demonstrated decreased protein expression ratios of p-P38/P38,p-ERK/Erk,and p-P65/P65(P＜0.05,P＜0.01);and significantly decreased mRNA expressions of TNF-α,IL-17,IL-23 and IL-1β(P＜0.01).CONCLUSION FZHFZY alleviates imiquimod-induced psoriatic lesions in mice and suppresses inflammatory response in LPS-stimulated RAW264.7 cells by inhibiting P38/Erk/NF-κB signaling pathway.

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
Humans ; Mice ; Animals ; Transcranial Magnetic Stimulation ; Alzheimer Disease/therapy* ; Cognitive Dysfunction/therapy* ; Cognition ; Sulfur ; Iron ; Iron-Sulfur Proteins ; Mitochondrial Proteins

Objective:This article took the investment project of using T Group′s drug patents to value invest in Ruijin Hospital as an example, exploring the significance of the integration of production and medicine innovation base in the implementation of valuation investment pilot in public hospitals and the role of medical institutions in promoting the transformation of scientific and technological achievements and the continuous high-speed development of the biopharmaceutical industry.Methods:By sorting the policies and regulations issued by national and local departments in recent years, and reviewing literature and real cases related to the transformation of scientific and technological achievements in medical institutions in the past five years, an analysis was conducted.Results:Based on an exploratory case study of the National Major Science and Technology Infrastructure for Translational Medicine (Shanghai), strategies and suggestions were proposed to promote the transformation of scientific and technological achievements in new research and development institutions.Conclusions:Through the establishment of a professional transfer office team in a scientific research and development and verification platform mainly based on large scientific facilities, and the construction and governance of a scientific and technological achievements transformation system in a hospital park close transformation mode, it is more conducive to the transformation of high-value scientific and technological achievements, the promotion of the two-way integration and development of the biopharmaceutical industry and medical institutions, and the facilitation of the rapid marketization of medical scientific and technological achievements.

Objective:Based on an exploratory case study of the National Major Science and Technology Infrastructure for Translational Medicine (Shanghai), this study aims to investigate the current development status of the construction and governance of the achievement transformation system in China′s new research and development institutions, explore the tools and means to improve the efficiency of scientific and technological achievement transformation in the biopharmaceutical field, and explore effective ways for medical institutions to promote scientific and technological achievement transformation in the biopharmaceutical achievement transformation chain.Methods:By reviewing the policies and regulations issued by national and local departments in recent years, and reviewing literature and real cases related to the transformation of scientific and technological achievements in medical institutions in the past five years, an analysis was conducted.Results:Based on an exploratory case study of the National Major Science and Technology Infrastructure for Translational Medicine (Shanghai), strategies and suggestions were proposed to promote the transformation of scientific and technological achievements in new research and development institutions.Conclusions:A scientific research and development and verification platform mainly based on large scientific facilities, through the establishment of a professional transfer office team, is more conducive to the construction and governance of a hospital park close transformation model of scientific and technological achievements, promoting the two-way integration and development of the biopharmaceutical industry and medical institutions, and promoting the rapid marketization of medical scientific and technological achievements.

Objective:Based on an exploratory case study of the National Major Science and Technology Infrastructure for Translational Medicine (Shanghai), this study aims to investigate the current development status of the construction and governance of the achievement transformation system in China′s new research and development institutions, explore the tools and means to improve the efficiency of scientific and technological achievement transformation in the biopharmaceutical field, and explore effective ways for medical institutions to promote scientific and technological achievement transformation in the biopharmaceutical achievement transformation chain.Methods:By reviewing the policies and regulations issued by national and local departments in recent years, and reviewing literature and real cases related to the transformation of scientific and technological achievements in medical institutions in the past five years, an analysis was conducted.Results:Based on an exploratory case study of the National Major Science and Technology Infrastructure for Translational Medicine (Shanghai), strategies and suggestions were proposed to promote the transformation of scientific and technological achievements in new research and development institutions.Conclusions:A scientific research and development and verification platform mainly based on large scientific facilities, through the establishment of a professional transfer office team, is more conducive to the construction and governance of a hospital park close transformation model of scientific and technological achievements, promoting the two-way integration and development of the biopharmaceutical industry and medical institutions, and promoting the rapid marketization of medical scientific and technological achievements.

AIM: Lipopolysaccharide (LPS) on the cell membrane of gram negative bacteria is closely related to the occurrence and development of severe acute pancreatitis (SAP). Local and systemic monocyte / macrophages play an important role in the inflammatory process of SAP. Artesunate (AS) was reported to protect rats with severe acute pancreatitis by reducing the release of proinflammatory cytokines. This study further explored the molecular mechanism of anti-inflammatory effect of AS. METHODS: The release of proinflammatory cytokines in the supernatant were studied by enzyme-linked immunosorbent assay. Then, the mRNA expressions of PI3K-III and its key molecules in signaling pathway were detected by real-time quantitative PCR. Finally, the phosphorylation levels of PI3KIII were detected by Western blot. RESULTS: AS could significantly inhibit the release of proinflammatory cytokines from mouse macrophage induced by LPS. Autophagy inhibitor 3-methyladenine (3-MA) could significantly inhibit the release of TNF-α from mouse macrophages induced by LPS; LPS significantly increased the mRNA expression of PI3KIII and its key molecules in mouse peritoneal macrophages (PMs). Finally, AS could significantly inhibit the increase of PI3K-III phosphorylation induced by LPS in PMs. CONCLUSION: The anti-inflammatory mechanism of AS is closely related to the inhibition of PI3K-III phosphorylation.

UNC-51-like kinase 1 (ULK1), as a serine/threonine kinase, is an autophagic initiator in mammals and a homologous protein of autophagy related protein (Atg) 1 in yeast and of UNC-51 in Caenorhabditis elegans. ULK1 is well-known for autophagy activation, which is evolutionarily conserved in protein transport and indispensable to maintain cell homeostasis. As the direct target of energy and nutrition-sensing kinase, ULK1 may contribute to the distribution and utilization of cellular resources in response to metabolism and is closely associated with multiple pathophysiological processes. Moreover, ULK1 has been widely reported to play a crucial role in human diseases, including cancer, neurodegenerative diseases, cardiovascular disease, and infections, and subsequently targeted small-molecule inhibitors or activators are also demonstrated. Interestingly, the non-autophagy function of ULK1 has been emerging, indicating that non-autophagy-relevant ULK1 signaling network is also linked with diseases under some specific contexts. Therefore, in this review, we summarized the structure and functions of ULK1 as an autophagic initiator, with a focus on some new approaches, and further elucidated the key roles of ULK1 in autophagy and non-autophagy. Additionally, we also discussed the relationships between ULK1 and human diseases, as well as illustrated a rapid progress for better understanding of the discovery of more candidate small-molecule drugs targeting ULK1, which will provide a clue on novel ULK1-targeted therapeutics in the future.

Objective: To investigate the relationship between nutritional risk status and clinical outcome in children with tuberculous meningitis (TBM). Methods: The clinical data (basic information, clinical symptoms and laboratory test results) of 112 patients with TBM, who were admitted to Department of Pediatric Infectious Diseases of West China Second Hospital of Sichuan University,from January 2013 to December 2020 were retrospectively analyzed. The patients were divided into the nutritional risk group and the non-nutritional risk group according to the assessment of the nutritional risk by the STRONGkids Scale. The variables of basic information, clinical symptoms and laboratory test measurements etc. were compared between the two groups by using Student t test, Rank sum test or Chi-square test. Multivariate Logistic regression analysis were used to analyze nutritional risk factors. Results: Among 112 patient with TBM, 55 were males and 57 females. There were 62 cases in the nutritional risk group and 50 cases in the non-nutritional risk group. The proportion of cases with nutritional risk was 55.4% (62/112). Patients in the nutritional risk who lived in rural areas, had symptoms of brain nerve damage, convulsions, emaciation and anorexia, with a diagnosis time of ≥21 days, and the level of cerebrospinal fluid (CSF) protein were all higher than those in the non-nutritional risk group ((50 cases (80.6%) vs. 32 cases (64.0%), 20 cases (32.3%) vs.8 cases (16.0%), 33 cases (53.2%) vs. 15 cases (30.0%), 30 cases (48.4%) vs. 2 cases (4.0%), 59 cases (95.2%) vs. 1 case (2.0%),41 cases (66.1%) vs.18 cases (36.0%), 1 406 (1 079, 2 068) vs. 929 (683, 1 208) mg/L, χ²=3.91, 3.90, 6.10, 26.72, 98.58, 10.08, Z=4.35, all P<0.05). The levels of serum albumin,hemoglobin,lymphocyte count, white blood cell count, and CSF glucose were significantly lower in patients with nutritional risk ((36±5) vs. (41±4) g/L, (110±17) vs. (122±14) g/L, 1.4 (1.0, 2.0)vs. 2.3 (1.6, 3.8)×10⁹/L, 7.8 (6.3, 10.0)×10⁹ vs. 10.0 (8.3, 12.8)×10⁹/L, 1.0 (0.8, 1.6) vs. 2.1 (1.3, 2.5) mmol/L, t=-6.15, -4.22, Z=-4.86, -3.92, -4.16, all P<0.05).Increased levels of serum albumin (OR=0.812, 95%CI:0.705-0.935, P=0.004) and lymphocyte count (OR=0.609, 95%CI:0.383-0.970, P=0.037) may reduce the nutritional risk of children with TBM; while convulsions (OR=3.853, 95%CI:1.116-13.308, P=0.033) and increased level of CSF protein (OR=1.001,95%CI:1.000-1.002, P=0.015) may increase the nutritional risk of children with TBM. Similarly, the rate of complications and drug-induced liver injury was higher in the nutritional risk group (47 cases (75.8%) vs. 15 cases(30.0%), 31 cases (50.0%) vs.8 cases (16.0%), χ²=23.50, 14.10, all P<0.05). Moreover, the length of hospital stay was also longer in the nutritional risk group ((27±13) vs. (18±7) d, t=4.38, P<0.05). Conclusions: Children with TBM have a high incidence of nutritional risk. Convulsive, the level of serum albumin, the level of lymphocyte count and CSF protein may affect the nutritional risk of children with TBM. The nutritional risk group has a high incidence of complications and heavy economic burden.It is necessary to carry out nutritional screening and nutritional support for children with TBM as early as possible.
Female ; Humans ; Leukocyte Count ; Male ; Nutrition Assessment ; Nutritional Status ; Retrospective Studies ; Tuberculosis, Meningeal/diagnosis*