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1.
Sensors (Basel) ; 24(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38894333

ABSTRACT

In recent years, hypertension has become one of the leading causes of illness and death worldwide. Changes in lifestyle among the population have led to an increasing prevalence of hypertension. This study proposes a non-contact blood pressure estimation method that allows patients to conveniently monitor their blood pressure values. By utilizing a webcam to track facial features and the region of interest (ROI) for obtaining forehead images, independent component analysis (ICA) is employed to eliminate artifact signals. Subsequently, physiological parameters are calculated using the principle of optical wave reflection. The Nelder-Mead (NM) simplex method is combined with the particle swarm optimization (PSO) algorithm to optimize the empirical parameters, thus enhancing computational efficiency and accurately determining the optimal solution for blood pressure estimation. The influences of light intensity and camera distance on the experimental results are also discussed. Furthermore, the measurement time is only 10 s. The superior accuracy and efficiency of the proposed methodology are demonstrated by comparing them with those in other published literature.


Subject(s)
Algorithms , Blood Pressure Determination , Blood Pressure , Humans , Blood Pressure/physiology , Blood Pressure Determination/methods , Hypertension/physiopathology , Hypertension/diagnosis , Signal Processing, Computer-Assisted
2.
EClinicalMedicine ; 73: 102656, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38828130

ABSTRACT

Background: Gastrointestinal stromal tumors (GISTs) represent the most prevalent type of subepithelial lesions (SELs) with malignant potential. Current imaging tools struggle to differentiate GISTs from leiomyomas. This study aimed to create and assess a real-time artificial intelligence (AI) system using endoscopic ultrasonography (EUS) images to differentiate between GISTs and leiomyomas. Methods: The AI system underwent development and evaluation using EUS images from 5 endoscopic centers in China between January 2020 and August 2023. EUS images of 1101 participants with SELs were retrospectively collected for AI system development. A cohort of 241 participants with SELs was recruited for external AI system evaluation. Another cohort of 59 participants with SELs was prospectively enrolled to assess the real-time clinical application of the AI system. The AI system's performance was compared to that of endoscopists. This study is registered with Chictr.org.cn, Number ChiCT2000035787. Findings: The AI system displayed an area under the curve (AUC) of 0.948 (95% CI: 0.921-0.969) for discriminating GISTs and leiomyomas. The AI system's accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) reached 91.7% (95% CI 87.5%-94.6%), 90.3% (95% CI 83.4%-94.5%), 93.0% (95% CI 87.2%-96.3%), 91.9% (95% CI 85.3%-95.7%), and 91.5% (95% CI 85.5%-95.2%), respectively. Moreover, the AI system exhibited excellent performance in diagnosing ≤20 mm SELs (ACC 93.5%, 95% CI 0.900-0.969). In a prospective real-time clinical application trial, the AI system achieved an AUC of 0.865 (95% CI 0.764-0.966) and 0.864 (95% CI 0.762-0.966) for GISTs and leiomyomas diagnosis, respectively, markedly surpassing endoscopists [AUC 0.698 (95% CI 0.562-0.834) for GISTs and AUC 0.695 (95% CI 0.546-0.825) for leiomyomas]. Interpretation: We successfully developed a real-time AI-assisted EUS diagnostic system. The incorporation of the real-time AI system during EUS examinations can assist endoscopists in rapidly and accurately differentiating various types of SELs in clinical practice, facilitating improved diagnostic and therapeutic decision-making. Funding: Science and Technology Commission Foundation of Shanghai Municipality, Science and Technology Commission Foundation of the Xuhui District, the Interdisciplinary Program of Shanghai Jiao Tong University and the Research Funds of Shanghai Sixth people's Hospital.

4.
Arch Dermatol Res ; 316(6): 235, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38795154

ABSTRACT

The aim of this study is to delineate the expression patterns of prolyl cis-trans isomerase NIMA-interacting protein 1 (Pin1), Glial cell-derived neurotrophic factor (GDNF), and Angiotensin II (ANG II) during the process of wound repair, and to ascertain the effects of Pin1, GDNF, and ANG II on the healing of wounds in a rat model. A total of 18 rats were allocated into three groups-sham (control), DMSO (vehicle control), and Pin1 inhibitor (treatment with juglone)-with six animals in each group. An animal model of wound healing was established, followed by the intraperitoneal administration of juglone. Tissue samples from the wounds were subsequently collected for histopathological evaluation. Expression levels of Pin1, GDNF, and Ang II were quantified. In addition, an in vitro model of wound healing was created using human umbilical vein endothelial cells (HUVEC), to assess cell proliferation, migration, and tube formation under conditions of juglone pre-treatment. The expression levels of Pin1, GDNF, and ANG II were notably elevated on 7-, and 10- days post-wound compared to those measured on 3-day. Contrastingly, pre-treatment with juglone significantly inhibited the expression of these molecules. Histological analyses, including HE (Hematoxylin and Eosin), Masson's trichrome, and EVG (Elastic van Gieson) staining, demonstrated that vascular angiogenesis, as well as collagen and elastin deposition, were substantially reduced in the juglone pre-treated group when compared to the normal group. Further, immunohistochemical analysis revealed a considerable decrease in CD31 expression in the juglone pre-treatment group relative to the normal control group. Pin1 serves as a pivotal facilitator of wound repair. The findings indicate that the modulation of Pin1, GDNF, and ANG II expression impacts the wound healing process in rats, suggesting potential targets for therapeutic intervention in human wound repair.


Subject(s)
Angiotensin II , Cell Proliferation , Glial Cell Line-Derived Neurotrophic Factor , Human Umbilical Vein Endothelial Cells , NIMA-Interacting Peptidylprolyl Isomerase , Naphthoquinones , Wound Healing , Animals , Wound Healing/drug effects , NIMA-Interacting Peptidylprolyl Isomerase/metabolism , NIMA-Interacting Peptidylprolyl Isomerase/genetics , Humans , Rats , Naphthoquinones/pharmacology , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Glial Cell Line-Derived Neurotrophic Factor/genetics , Male , Cell Proliferation/drug effects , Angiotensin II/metabolism , Cell Movement/drug effects , Disease Models, Animal , Rats, Sprague-Dawley , Skin/pathology , Skin/metabolism , Skin/injuries , Skin/drug effects , Adaptor Proteins, Signal Transducing
5.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2210-2221, 2024 Apr.
Article in Chinese | MEDLINE | ID: mdl-38812236

ABSTRACT

In this study, J774A.1 macrophages stimulated by lipopolysaccharide(LPS) and adenosine triphosphate(ATP) were used to establish an in vitro model of pyroptosis, and the intervention mechanism of free total rhubarb anthraquinones(FTRAs) on pyroptosis was investigated. J774A.1 macrophages were cultured in vitro, and the experiment was assigned to the control group and groups with different concentrations of LPS(0.25, 0.5, and 1 µg·mL~(-1)) and ATP(1.25, 2.5, and 5 mmol·L~(-1)). An in vitro model of macrophage pyroptosis was established by detecting cell viability through CCK-8, propidium iodide(PI) apoptotic cell staining, lactate dehydrogenase(LDH), interleukin(IL)-18, and tumor necrosis factor(TNF)-α release. Then, J774A.1 macrophages were randomly divided into six groups: blank control group, LPS+ATP group, high-dose FTRA group, and low, medium, and high-dose FTRA pre-protection group. The phenotypic characteristics and key indicators of pyroptosis were detected as the basis for evaluating the effect of FTRAs on pyroptosis induced by LPS and ATP. Western blot and RT-PCR were used to detect the expression levels of protein and mRNA related to the pyroptosis pathway in caspase-1/11 and elucidate the molecular mechanism of the anti-pyroptosis effect. The results showed that the stimulation condition of 0.50 µg·mL~(-1) LPS+5.00 mmol·L~(-1) ATP was the most effective in the in vitro model of macrophage pyroptosis. FTRAs pre-protected cells for 24 h and then can increase cell viability under pyroptosis conditions, alleviate cell damage, lower the positive rate of PI staining, and reduce the release of LDH, IL-18, and TNF-α. FTRAs were able to significantly inhibit the activation of GSDMD proteins and significantly down-regulate the protein expression of the pyroptosis pathway signature molecules, TLR4, NLRP3, cleaved-caspase-1, and cleaved-caspase-11, but they had no significant effect on ASC proteins. FTRAs were also able to significantly inhibit the mRNA expression of caspase-1, caspase-11, and GSDMD. These results indicate that FTRAs have an inhibitory effect on the pyroptosis model induced by LPS and ATP and play an anti-pyroptosis effect by regulating classical and non-classical pyroptosis signaling pathways and reducing the production of inflammatory cytokines.


Subject(s)
Anthraquinones , Macrophages , Pyroptosis , Rheum , Pyroptosis/drug effects , Rheum/chemistry , Animals , Mice , Macrophages/drug effects , Macrophages/metabolism , Macrophages/cytology , Anthraquinones/pharmacology , Anthraquinones/chemistry , Cell Line , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Adenosine Triphosphate/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Lipopolysaccharides/pharmacology , Cell Survival/drug effects , Interleukin-18/genetics , Interleukin-18/metabolism
6.
Mucosal Immunol ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38555025

ABSTRACT

E26 transformation-specific translocation variant 5 (ETV5) has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). However, the exact roles of ETV5 in regulating CD4+ T cell-mediated intestinal inflammation and fibrosis formation remain unclear. Here, we reveal that ETV5 overexpression induced interleukin (IL)-9 and its transcription factor IRF4 expression in IBD CD4+ T cells under T helper type 9 (Th9) cells-polarizing conditions. The silencing of IRF4 inhibited ETV5-induced IL-9 expression. CD4+ T cell-specific ETV5 deletion ameliorated intestinal inflammation and fibrosis in trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis and CD4+ T cell-transferred recombination-activating gene-1 knockout (Rag1-/-) colitis mice, characterized by less CD4+ T cell infiltration and lower fibroblast activation and collagen deposition in the colonic tissues. Furthermore, IL-9 treatment aggressive TNBS-induced intestinal fibrosis in CD4+ T cell-specific ETV5 deletion and wild-type control mice. In vitro, human intestinal fibroblasts cocultured with ETV5 overexpressed-Th9 cells expressed higher levels of collagen I and III, whereas an inclusion of anti-IL-9 antibody could reverse this effect. Ribonucleic acid sequencing analysis demonstrated that IL-9 upregulated TAF1 expression in human intestinal fibroblasts. Clinical data showed that number of α-smooth muscle actin+TAF1+ fibroblasts are higher in inflamed mucosa of patients with IBD. Importantly, TAF1 small interfering ribonucleic acid treatment suppressed IL-9-mediated profibrotic effect in vitro. These findings reveal that CD4+ T cell-derived ETV5 promotes intestinal inflammation and fibrosis through upregulating IL-9-mediated intestinal inflammatory and fibrotic response in IBD. Thus, the ETV5/IL-9 signal pathway in T cells might represent a novel therapeutic target for intestinal inflammation and fibrosis in IBD.

7.
Cell Mol Life Sci ; 81(1): 135, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38478096

ABSTRACT

Parkinson's disease (PD) is a motor disorder resulting from dopaminergic neuron degeneration in the substantia nigra caused by age, genetics, and environment. The disease severely impacts a patient's quality of life and can even be life-threatening. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a member of the HCN1-4 gene family and is widely expressed in basal ganglia nuclei. The hyperpolarization-activated current mediated by the HCN channel has a distinct impact on neuronal excitability and rhythmic activity associated with PD pathogenesis, as it affects the firing activity, including both firing rate and firing pattern, of neurons in the basal ganglia nuclei. This review aims to comprehensively understand the characteristics of HCN channels by summarizing their regulatory role in neuronal firing activity of the basal ganglia nuclei. Furthermore, the distribution and characteristics of HCN channels in each nucleus of the basal ganglia group and their effect on PD symptoms through modulating neuronal electrical activity are discussed. Since the roles of the substantia nigra pars compacta and reticulata, as well as globus pallidus externus and internus, are distinct in the basal ganglia circuit, they are individually described. Lastly, this investigation briefly highlights that the HCN channel expressed on microglia plays a role in the pathological process of PD by affecting the neuroinflammatory response.


Subject(s)
Parkinson Disease , Humans , Parkinson Disease/genetics , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/genetics , Quality of Life , Basal Ganglia/physiology , Substantia Nigra
8.
Front Nutr ; 11: 1344699, 2024.
Article in English | MEDLINE | ID: mdl-38549748

ABSTRACT

Background and aim: Gallstone disease (GSD) is a major public health problem worldwide. The dietary inflammatory index (DII) and the energy-adjusted DII (E-DII) have been used to describe dietary inflammatory potential. The current study sought to investigate the pro-inflammatory role of diet on GSD among outpatients in the United States. Methods: Cross-sectional data from 7,334 individuals older than 20 years who participated in the National Health and Nutrition Examination Survey (NHANES) from January 2017 to March 2020 were obtained. The relationship between GSD and DII was assessed using self-reported data. An association between DII and the risk of GSD was determined using sample-weighted logistic regression and restricted cubic splines (RCS). Subgroup analyzes were conducted to assess the interaction between DII and related factors. Sensitivity analysis was further used to confirm the stability of the relationship. To control for the effect of total energy intake, E-DII was calculated and analyzed. Results: A total of 10.5% of the study participants had GSD. The DII ranged from -5.52 to 5.51, and the median DII was significantly higher for participants with GSD than those without (1.68 vs. 1.23, p < 0.001). There was a significant and stable positive relationship between DII and GSD in adjusted models (OR 1.10, 95% CI 1.00-1.20). In the fully adjusted model, subjects with DII scores in the highest tertile were more likely to have GSD than those in the lowest tertile (OR 1.52, 95% CI 1.19-1.93). An apparent dose-response association between DII and GSD was detected. The association between E-DII and GSD remained stable. Conclusion: Higher DII/E-DII scores linked to the intake of a pro-inflammatory diet were positively associated with a higher risk of GSD. These findings suggest that pro-inflammatory dietary patterns can promote the formation of gallstones.

9.
Inorg Chem ; 63(9): 4393-4403, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38375640

ABSTRACT

The immobilization of tiny active species within inert mesoporous silica imparts a range of functions, enhancing their applicability. A significant obstacle is the spontaneous migration and aggregation of these species within the mesopores, which threaten their uniform distribution. To address this, we propose a postmodification method that involves grafting transition metal oxide nanoclusters into silica mesopores via interfacial condensation, catalyzed by acetate ions. Specifically, CuO nanoclusters, in the form of oligomeric [O1-x-Cu2-(OH) 2x]n2+, have a strong interaction with the silica framework. This interaction inhibits their growth and prevents mesopore blockage. Theoretical calculation results reveal that the acetate ion promotes proton transfer among various hydroxy species, lowering the free energy and thereby facilitating the formation of Cu-O-Si bonds. This technique has also been successfully applied to the encapsulation of four other types of transition metal oxide nanoclusters. Our encapsulation strategy effectively addresses the challenge of dispersing transition metal oxides in mesoporous silica, offering a straightforward and widely applicable method for enhancing the functionality of mesoporous materials.

10.
Front Public Health ; 12: 1325298, 2024.
Article in English | MEDLINE | ID: mdl-38344238

ABSTRACT

Objective: The government has recently implemented reforms aimed at delegating power, streamlining administration, and optimizing government services. This reform has eliminated barriers that impede the growth of various industries, thereby unleashing innovative potential. Additionally, there have been several medical policies, including changes to medical insurance and centralized volume-based procurement. China's pharmaceutical market has undergone significant changes, leading to increased demands for innovation technology efficiency in pharmaceutical manufacturing. Methods: The three-stage BCC theory was employed to assess the effectiveness of technology innovation in the industry under this reform. Calculate precise comprehensive technical efficiency values, pure technical efficiency values, and scale efficiency values for technological innovation in the pharmaceutical industry across 30 provinces from 2018 to 2020, after removing environmental factors. Results: In 2020, Jiangsu and Shandong and nine other provinces reached the comprehensive technical efficiency frontier surface, joining Tianjin, Zhejiang, and Guangdong provinces. However, Gansu, Qinghai, Ningxia, and Xinjiang still need to catch up due to their smaller industrial scale and lack of technology. Discussion: To ensure the effectiveness of reforms, it is crucial to fully consider provincial differences. Articulating national and provincial policies is necessary to allow efficient provinces to continue and allocate resources toward less efficient provinces to improve overall efficiency.


Subject(s)
Inventions , Manufacturing Industry , Pharmaceutical Preparations , Drug Industry , Technology , Government , China
11.
J Ethnopharmacol ; 326: 117873, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38346523

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Rhubarb is the peeled and dried roots of Rheum palmatum L. and Rheum tanguticum Maxim. ex Balf. or Rheum officinale Baill. Free total rhubarb anthraquinones (FTRAs) were isolated and extracted from rhubarb. Previous studies have revealed that the early administration of FTRAs protects the intestinal mucosal barrier in rats with severe acute pancreatitis (SAP), the mechanism of which is not yet clear. However, we observed an enhanced expression of intestinal pyroptotic factors in rats treated with SAP, which may be related to the mechanism of intestinal barrier protection by FTRAs. AIM OF THE STUDY: The main objective of this study was to investigate the mechanism by which FTRAs protect the intestinal mucosal barrier in SAP rats, focusing on the classical pyroptosis pathway. MATERIALS AND METHODS: SAP was induced in rats through retrograde injection of sodium taurocholate via the pancreaticobiliary duct. Subsequently, FTRAs (22.5, 45, and 90 mg/kg), rhubarb (900 mg/kg, positive control), and saline (control) were administered at 0 h (immediately), 12 h, and 24 h post-surgery. Pancreatic and intestinal tissue injury, positive PI staining rate, and expression levels of various factors in intestinal tissues were compared across different groups. These factors include diamine oxidase (DAO), lactate dehydrogenase (LDH), high mobility group box chromosomal protein 1(HMGB1) and pro-inflammatory factors in intestinal and serum, pyroptosis-associated factors, toll-like receptor 4 (TLR-4), nuclear factor kappa-B (NF-kB), apoptosis-associated speck-like protein (ASC), NOD-like receptor protein 3 (NLRP3), cysteine protease-1 (caspase-1) and Gasdermin (GSDMD). RESULTS: The findings indicated that FTRAs protected the damaged intestine and pancreas and restored the expression of intestinal epithelial junction proteins in SAP rats. Additionally, it reduced intestinal and serum levels of DAO, interleukin 1, interleukin 18, HMGB1, and LDH, attenuated intestinal Positive PI staining rate, and significantly decreased the expressions of TLR-4, NF-kB, ASC, NLRP3, caspase-1 and GSDMD in SAP rats. CONCLUSIONS: The results suggest that FTRAs inhibited pyroptosis through down-regulation of the NLRP3-Caspase-1-GSDMD and TLR-4- NF-kB signaling pathways of intestinal tissues., thereby protecting the intestinal barrier of SAP rats.


Subject(s)
HMGB1 Protein , Pancreatitis , Rheum , Rats , Animals , Pancreatitis/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Toll-Like Receptor 4/metabolism , NF-kappa B/metabolism , Caspase 1 , Rats, Sprague-Dawley , Acute Disease , NLR Proteins , Anthraquinones/pharmacology , Anthraquinones/therapeutic use
12.
Front Microbiol ; 15: 1319895, 2024.
Article in English | MEDLINE | ID: mdl-38343715

ABSTRACT

In recent years, the problems associated with continuous cropping (CC) that cause soil degradation have become increasingly serious. As a key soil quality property, dissolved organic matter (DOM) affects the circulation of carbon and nutrients and the composition of bacterial communities in soil. However, research on the changes in the molecular composition of DOM after CC is limited. In this study, the soil chemical properties, DOM chemical diversity, bacterial community structure, and their interactions are explored in the soil samples from different CC years (CC1Y, CC3Y, CC5Y, and CC7Y) of tobacco. With increasing CC year of tobacco, most of the soil chemical properties, such as total carbon, total nitrogen and organic matter, decreased significantly, while dissolved organic carbon first decreased and then increased. Likewise, the trends of DOM composition differed with changing duration of CC, such as the tannin compounds decreased from 18.13 to 13.95%, aliphatic/proteins increased from 2.73 to 8.85%. After 7 years of CC, the soil preferentially produced compounds with either high H/C ratios (H/C > 1.5), including carbohydrates, lipids, and aliphatic/proteins, or low O/C ratios (O/C < 0.1), such as unsaturated hydrocarbons. Furthermore, core microorganisms, including Nocardioides, wb1-P19, Aquabacterium, Methylobacter, and Thiobacillus, were identified. Network analysis further indicated that in response to CC, Methylobacter and Thiobacillus were correlated with the microbial degradation and transformation of DOM. These findings will improve our understanding of the interactions between microbial community and DOM in continuous cropping soil.

13.
Chin Med ; 19(1): 16, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38268006

ABSTRACT

BACKGROUND: Cholesterol gallstone (CG) disease is a worldwide common disease characterized by cholesterol supersaturation in gallbladder bile. Ganoderma lucidum polysaccharide (GLP) has been shown to possess various beneficial effects against metabolic disorders. However, the role and underlying mechanism of GLP in CG formation are still unknown. This study aimed to determine the role of GLP in ameliorating lithogenic diet (LD)-induced CG formation. METHODS: Mice were fed either a normal chow diet, a LD, or LD supplemented with GLP. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of genes involved in cholesterol and bile acid (BA) metabolism. The BA concentrations in the ileum were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The microbiota in cecal contents were characterized using 16S ribosomal RNA (16S rRNA) gene sequencing. RESULTS: GLP effectively alleviated CG formation induced by LD. Specifically, GLP reduced the total cholesterol (TC) levels, increased the total BA levels, and decreased the cholesterol saturation index (CSI) in gallbladder bile. The protective effect of GLP was attributed to the inhibition of farnesoid X receptor (FXR) signaling, increased hepatic BA synthesis and decreased hepatic cholesterol synthesis and secretion. GLP also altered the BA composition in the ileum, reducing FXR-agonistic BAs and increasing FXR-antagonistic BAs, which may contribute to the inhibition of intestinal FXR signaling. Additionally, GLP improved dysbiosis of the intestinal flora and reduced the serum levels of hydrogen sulfide (H2S), a bacterial metabolite that can induce hepatic FXR, thereby inhibiting hepatic FXR signaling. Moreover, the protective effect of GLP against CG formation could be reversed by both the global and gut-restricted FXR agonists. CONCLUSIONS: Taken together, GLP ameliorates CG formation by regulating cholesterol and BA metabolism in an FXR-dependent manner. Our study demonstrates that GLP may be a potential strategy for the prevention against CG disease.

14.
Commun Biol ; 7(1): 109, 2024 01 19.
Article in English | MEDLINE | ID: mdl-38242969

ABSTRACT

Outcomes of past decisions profoundly shape our behavior. However, choice-outcome associations can become volatile and adaption to such changes is of importance. The present study combines pharmaco-electroencephalography with computational modeling to examine whether intranasal oxytocin can modulate reinforcement learning under a volatile vs. a stable association. Results show that oxytocin increases choice accuracy independent of learning context, which is paralleled by a larger N2pc and a smaller P300. Model-based analyses reveal that while oxytocin promotes learning by accelerating value update of outcomes in the volatile context, in the stable context it does so by improving choice consistency. These findings suggest that oxytocin's facilitatory effects on learning may be exerted via improving early attentional selection and late neural processing efficiency, although at the computational level oxytocin's actions are highly adaptive between learning contexts. Our findings provide proof of concept for oxytocin's therapeutic potential in mental disorders with adaptive learning dysfunction.


Subject(s)
Learning , Oxytocin , Humans , Attention , Learning/physiology , Mental Disorders , Oxytocin/pharmacology , Social Behavior
15.
J Clin Invest ; 133(24)2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38099500

ABSTRACT

Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA utilization in the prostate gland correlated with tumor aggressiveness at early disease stages, and 3ßHSD1 inhibitors were promising for early intervention. [3H]-labeled DHEA consumption was traced in fresh prostatic biopsies ex vivo. Active DHEA utilization was more frequently found in patients with metastatic disease or therapy-resistant disease. Genetic and transcriptomic features associated with the potency of prostatic DHEA utilization were analyzed to generate clinically accessible approaches for patient stratification. UBE3D, by regulating 3ßHSD1 homeostasis, was discovered to be a regulator of patient metabolic heterogeneity. Equilin suppressed DHEA utilization and inhibited tumor growth as a potent 3ßHSD1 antagonist, providing a promising strategy for the early treatment of aggressive prostate cancer. Overall, our findings indicate that patients with active prostatic DHEA utilization might benefit from 3ßHSD1 inhibitors as early intervention.


Subject(s)
Prostate , Prostatic Neoplasms , Male , Humans , Prostate/metabolism , Prostate/pathology , Dehydroepiandrosterone , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism
16.
J Dig Dis ; 24(11): 611-618, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37915286

ABSTRACT

OBJECTIVES: Anti-reflux mucosectomy (ARMS) is an emerging and promising endoscopic treatment for gastroesophageal reflux disease (GERD). In the current study we aimed to evaluate the safety and efficacy of ARMS in treating Chinese GERD patients. METHODS: This was a single-center prospective cohort study. ARMS was performed in GERD patients by an experienced endoscopist. The patients were required to undergo symptom assessment as well as endoscopic examination, high-resolution manometry (HRM), and impedance-pH monitoring before and after ARMS. RESULTS: Twelve patients were enrolled. Follow-up was completed by all patients at 3 and 6 months, 11 patients at 1 year, and 8 patients at 2 years after ARMS, respectively. Symptom improvement was achieved in 66.7%, 75.0%, 72.7%, and 50.0% of the patients at 3 months, 6 months, 1 year, and 2 years after ARMS, respectively. Postoperative dysphagia was reported by 25.0%, 25.0%, 27.3%, and 25.0% of patients at 3 months, 6 months, 1 year, and 2 years after surgery, none of whom required additional invasive treatment. All patients with preoperative esophagitis healed after ARMS. For impedance-pH monitoring parameters, number of acidic reflux episodes and the proportion of patients with acid exposure time (AET) >4.0% decreased significantly after ARMS. CONCLUSIONS: ARMS was safe and effective in Chinese GERD patients. The efficacy of ARMS was not short-term and remained evident throughout the 2-year follow-up. Further multicenter studies with larger sample sizes are needed to verify our findings.


Subject(s)
Esophagitis, Peptic , Gastroesophageal Reflux , Humans , Prospective Studies , Esophageal pH Monitoring , Gastroesophageal Reflux/surgery , Gastroesophageal Reflux/diagnosis , Manometry , China , Treatment Outcome
17.
Methods Enzymol ; 689: 237-261, 2023.
Article in English | MEDLINE | ID: mdl-37802572

ABSTRACT

Steroid 5α-reductases (SRD5As), also known as 3-oxo-5α-steroid 4-dehydrogenases, are essential membrane-bound enzymes involved in steroid metabolism. Belonging to the NADPH-dependent oxidoreductase family, 5α-reductases catalyze steroids with 3-oxo-Δ4 structure, such as testosterone or progesterone, to produce their corresponding 3-oxo-5α steroids, which are necessary for a variety of physiological and pathological activities. Despite their significance, SRD5A structures are still in short supply to date. Here we describe a protocol for expression, purification, crystallization, structural determination, and functional analysis of PbSRD5A, the 5α-reductase from Proteobacteria bacterium sharing high sequence identity with human SRD5A1 and SRD5A2 isozymes, which we have recently structurally characterized using a lipidic cubic phase approach. Application of similar methods to other 5α-reductase isozymes will lead to breakthroughs in the understanding of the structure, function, and mechanism of oxidoreductases implicated in steroid metabolism.


Subject(s)
Isoenzymes , Oxidoreductases , Humans , Oxidoreductases/genetics , Steroids , Progesterone/metabolism , Membrane Proteins , 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics
18.
Front Pharmacol ; 14: 1178026, 2023.
Article in English | MEDLINE | ID: mdl-37886133

ABSTRACT

Objective: To explore the changes in social welfare before and after the implementation of the national volume-based procurement (NVBP). Explore whether the NVBP promotes the healthy development of manufacturers under the premise of benefiting patients. Then put forward relevant suggestions on how to effectively intervene the government in the pharmaceutical market. Methods: Starting with consumer surplus and producer surplus, social welfare was studied from the three perspectives of price, supply, and demand. Results: Consumer surplus was significantly increased, and the drug welfare of patients was significantly improved. The profits of the whole pharmaceutical industry have decreased but will increase in the future. The welfare of individual pharmaceutical enterprises varies. Overall social welfare has been significantly improved. Conclusion: The core purpose of the NVBP is to improve the medication welfare of patients, and through the increase of consumer surplus, it can affect the increase of producer surplus. Under such a linkage mechanism, the diversified linkage system of "price, demand, and supply" will achieve the effect of "1 + 1+1 > 3".

19.
J Dig Dis ; 24(10): 522-529, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37681236

ABSTRACT

OBJECTIVE: In this study we aimed to compare the need for further examination with conventional gastroscopy within 1 year after magnetically assisted capsule endoscopy (MCCE) examination between patients with gastrointestinal (GI) symptoms and asymptomatic individuals. METHODS: After propensity score matching analysis, 372 patients with GI symptoms and 372 asymptomatic individuals who had undergone MCCE at the First Affiliated Hospital of Sun Yat-sen University from January 1, 2019 to December 30, 2020 were retrospectively enrolled. Demographic and clinical characteristics of the participants and their MCCE and gastroscopic findings (performed within 1 year after MCCE) were analyzed. RESULTS: Fifty-one (6.85%) patients underwent further examination with conventional gastroscopy within 1 year after MCCE. Those with GI symptoms were more likely to undergo conventional gastroscopy than those without (9.95% vs 3.76%, P < 0.001). Polyps were the most common finding of MCCE. The rate of conventional gastroscopy in patients with focal lesions was significantly higher than that in those without focal lesions (P < 0.05). However, such rate did not differ in the different age groups (P = 0.106). CONCLUSIONS: MCCE is an optimal alternative for gastric examination, especially for large-scale screening of asymptomatic individuals. Patients with GI symptoms or focal lesions detected by MCCE are more likely to seek further examination with conventional gastroscopy for biopsy or endoscopic treatment than those without.


Subject(s)
Capsule Endoscopy , Gastroscopy , Humans , Retrospective Studies , Magnetics , Prospective Studies
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