Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To apply a multidimensional neonatal nutritional risk screening scale for hospitalized premature infants to explore its predictive value for extrauterine growth restriction(EUGR)at the time of discharge.Methods A total of 104 premature infants hospitalized in the Neonatal Department of the Second Affiliated Hospital of Kunming Medical University from January 2023 to September 2023 were selected as research subjects.Nutritional risk screening was conducted within 24 hours of admission and weekly thereafter using the multidimensional neonatal nutritional risk screening scale.Scoring was based on four dimensions(birth status,weight changes,nutritional intake methods,and disease diagnosis),with a total score of ≥ 8 indicating high risk;≥4 and＜8 indicating moderate risk;and＜4 indicating low risk.EUGR at the time of discharge was the primary clinical outcome indicator.Receiver operating characteristic(ROC)curves were constructed to explore the predictive value of neonatal nutritional risk screening for EUGR in premature infants.Results At discharge,40 premature infants(38.5％)experienced EUGR.The nutritional risk screening scores of the EUGR group on day 7 of hospitalization were higher than those of the non-EUGR group(P＜0.05).The rate of high nutritional risk on day 7 of hospitalization was highest(7.9％in the non-EUGR group,22％in the EUGR group,and 13.5％overall).On both day 1 and day 7 of hospitalization,the rate of high nutritional risk in the EUGR group was higher than that in the non-EUGR group(P＜0.05).There were significant differences in the nutritional risk screening scores on day 7,birth weight Z-scores,discharge corrected gestational age weight Z-scores,and serum albumin levels between the EUGR and non-EUGR groups(P＜0.05).ROC curves were plotted,yielding AUCs of 0.625(95％CI 0.514,0.736),0.652(95％CI 0.544,0.760),0.674(95％CI 0.561,0.786),and 0.641(95％CI 0.531,0.750),indicating certain predictive value.A combined predictive ROC model yielded an AUC of 0.786(95％CI 0.692,0.880)for EUGR,which was higher than the AUCs for individual indicators(P＜0.001).Conclusion The occurrence of EUGR is relatively common among hospitalized premature infants.The nutritional risk is highest during the first week of hospitalization.The multidimensional neonatal nutritional risk screening scale can dynamically assess nutritional risk during hospitalization and may serve as one of the early warning indicators for EUGR in premature infants.The predictive efficacy for EUGR is enhanced when combined with birth weight Z-scores,discharge weight Z-scores,and serum albumin,providing a basis for individualized nutritional management of premature infants.

OBJECTIVE To investigate the current allocation status of automated equipment in pharmacy intravenous admixture services （PIVAS） of medical institutions in China， and to provide reference for understanding the current status and future direction of PIVAS automation construction. METHODS In the form of a questionnaire survey， a questionnaire was distributed to medical institutions in 30 provinces across the country through the “Wenjuanxing” platform to investigate the four aspects of PIVAS， such as the allocation of automated equipment， intelligent intravenous medication dispensing robots， design and development of workflow software and information integration methods for automated equipment， and conduct statistical analysis. RESULTS A total of 761 PIVAS participated in the survey， 373 PIVAS were equipped with automated equipment. Among 373 PIVAS with automated equipment， automatic finished infusion sorting machines and automatic labeling machines were the main equipment， and 93.56% of PIVAS were not equipped with intelligent intravenous medication dispensing robots； 511 PIVAS used workflow software designed and developed by third-party software companies. In the project of information integration for automated equipment， there was not much difference in the proportion of cases where there was no automated equipment， automated equipment directly interfaced with hospital information systems， and automated equipment interfaced with PIVAS software platform. CONCLUSIONS The automated equipment allocation rate of PIVAS in China is relatively low， and there is still a lot of room for development. We should improve the relevant guidelines for automated equipment as soon as possible， promote standardized and reasonable equipment research and development， and enable PIVAS to more efficiently complete intravenous drug dispensing， in order to provide more dengrm3@mail.sysu.edu.cn comprehensive pharmaceutical services.

Electroencephalography (EEG), as a convenient and non-invasive technique, is highly sensitive to brain function abnormalities and has been widely applied in the diagnosis and treatment of epilepsy and other neurological diseases (applied research in stroke field has a history of decades). In recent years, with the deepening of related research and rapid development of artificial intelligence technology, EEG has shown new potential in early diagnosis, disease monitoring and prognosis assessment of stroke. This review discusses the recent advance in EEG in evaluating the diagnosis, therapeutic efficacy, and prognoses of stroke in the last 5 years, so as to provide references for improving the diagnosies, treatments and prognoses of stroke patients.

Objective: To evaluate the accuracy and feasibility of coronary artery calcium score ( CACS) on virtual non-contrast scan ( VNC) images obtained from coronary artery CT angiography ( CCTA) scan with dual －layer spectral detector CT (SDCT) ． Methods : The data of 197 patients who underwent CCTA scan in hospital were analyzed retrospectively，and 88 patients with CACS ＞0 were further analyzed． Linear regression analysis of CACS and coronary artery calcium volume ( CACV) of true non-contrast (TNC) images and VNC images ( CACS-TNC， CACS-VNC，CACV-TNC，CACV-VNC) was performed to obtain linear regression equation and correction coefficients λ 1AVG and λ2AVG ．CACS-VNC and CACV-VNC were corrected by the corresponding regression equation and recorded as CCACS-VNC and CCACV-VNC，respectively．Spearman correlation coefficient was used for correlation analysis and Bland-Altman plot was used for consistency test．Mann-Whitney U test was used to compare the difference between the two groups. Results : For the total coronary artery，there was a strong correlation between CACS- TNC and CACS-VNC (rs = 0. 952，P ＜0. 001 ，λ 1AVG = 2. 19 ) ，CACV-TNC and CACV-VNC ( rs = 0. 954，P < 0. 001，λ2AVG = 1. 93) ．The results of Mann-Whitney U test showed that there was no significant difference between CACS-TNC and CCACS-VNC or between CACV-TNC and CCACV-VNC，and the Bland-Altman plot showed good consistency between CACS-TNC and CCACS-VNC ，CACV-TNC and CCACV-VNC． Conclusion VNC images based on SDCT can accurately measure CACS and be used for cardiovascular risk classification，which is expected to replace TNC scan and reduce the radiation dose of patients.

OBJECTIVE: To investigate the role of the SIRT1/NF-κB pathway in mediating the effect of puerarin against lipopolysaccharide (LPS)-induced acute kidney injury (AKI). METHODS: Fifteen BALB/C mice were randomized into control group, LPS group and puerarin treatment group, and in the latter two groups, the mice were given an intraperitoneal injection of LPS (5 mg/kg), followed by daily injection of normal saline for 3 days or injection of puerarin (25 mg/kg) given 1 h later and then on a daily basis for 3 days. On day 5 after modeling, the kidney tissues were taken for histological observation and detection of cell apoptosis. The renal function indexes including urea nitrogen (BUN), serum creatinine (Scr) and kidney injury molecule 1 (KIM-1) and the levels of tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) were measured, and the expressions of SIRT1 and NF-κB-p65(acetyl K310) in the renal tissues were detected. RESULTS: Intraperitoneal injection of LPS caused obvious glomerular capillary dilatation, hyperemia, renal interstitial edema, and renal tubular epithelial cell swelling and deformation in the mice. The mouse models of LPS-induced AKI also showed significantly increased renal tubular injury score and renal cell apoptosis (P < 0.01) with increased serum levels of BUN, Scr, KIM-1, TNF-α and IL-1β (P < 0.01), enhanced renal expressions of TNF-α, IL-1β and NF-κB p65(acetyl K310) (P < 0.01) and lowered renal expression of SIRT1 (P < 0.05). Treatment with puerarin effectively alleviated LPS-induced renal interstitial edema and renal tubular epithelial cell shedding, lowered renal tubular injury score (P < 0.01) and renal cell apoptosis rate (P < 0.01), and decreased serum levels of BUN, Scr, KIM, TNF-α and IL-1β (P < 0.01). Puerarin treatment significantly reduced TNF-α, IL-1β and NF-κB p65 (acetyl K310) expression in the renal tissue (P < 0.05) and increased SIRT1 expression by 17% (P < 0.05) in the mouse models. CONCLUSION Puerarin can effectively alleviate LPS-induced AKI in mice possibly by modulating the SIRT1/NF-κB signaling pathway.
Animals ; Mice ; Mice, Inbred BALB C ; NF-kappa B ; Lipopolysaccharides ; Sirtuin 1 ; Tumor Necrosis Factor-alpha ; Acute Kidney Injury ; Disease Models, Animal ; Edema

Humans ; Autistic Disorder ; China/epidemiology* ; Cohort Studies ; Autism Spectrum Disorder/genetics* ; Asian People

Well water could be a stable source of drinking water. Recently, the use of well water as drinking water has been encouraged in developing countries. However, many kinds of disorders caused by toxic elements in well drinking water have been reported. It is our urgent task to resolve the global issue of element-originating diseases. In this review article, our multidisciplinary approaches focusing on oncogenic toxicities and disturbances of sensory organs (skin and ear) induced by arsenic and barium are introduced. First, our environmental monitoring in developing countries in Asia showed elevated concentrations of arsenic and barium in well drinking water. Then our experimental studies in mice and our epidemiological studies in humans showed arsenic-mediated increased risks of hyperpigmented skin and hearing loss with partial elucidation of their mechanisms. Our experimental studies using cultured cells with focus on the expression and activity levels of intracellular signal transduction molecules such as c-SRC, c-RET, and oncogenic RET showed risks for malignant transformation and/or progression arose from arsenic and barium. Finally, our original hydrotalcite-like compound was proposed as a novel remediation system to effectively remove arsenic and barium from well drinking water. Hopefully, comprehensive studies consisting of (1) environmental monitoring, (2) health risk assessments, and (3) remediation will be expanded in the field of environmental health to prevent various disorders caused by environmental factors including toxic elements in drinking water.
Animals ; Arsenic ; toxicity ; Barium ; toxicity ; Drinking Water ; analysis ; Environmental Exposure ; Environmental Health ; Environmental Monitoring ; Humans ; Mice ; Water Pollutants, Chemical ; toxicity ; Water Wells

BACKGROUND: Melanin is detectable in various sense organs including the skin in animals. It has been reported that melanin adsorbs toxic elements such as mercury, cadmium, and lead. In this study, we investigated the adsorption of molybdenum, which is widely recognized as a toxic element, by melanin. METHODS: Molybdenum level of the mouse skin was measured by inductively coupled plasma mass spectrometry. The pigmentation level of murine skin was digitalized as the L* value by using a reflectance spectrophotometer. An in vitro adsorption assay was performed to confirm the interaction between molybdenum and melanin. RESULTS: Our analysis of hairless mice with different levels of skin pigmentation showed that the level of molybdenum increased with an increase in the level of skin pigmentation (L* value). Moreover, our analysis by Spearman's correlation coefficient test showed a strong correlation (r = - 0.9441, p < 0.0001) between L* value and molybdenum level. Our cell-free experiment using the Langmuir isotherm provided evidence for the adsorption of molybdenum by melanin. The maximum adsorption capacity of 1 mg of synthetic melanin for molybdenum was 131 μg in theory. CONCLUSION Our in vivo and in vitro results showed a new aspect of melanin as an adsorbent of molybdenum.
Adsorption ; Animals ; Melanins ; chemistry ; metabolism ; Mice ; Mice, Hairless ; Mice, Transgenic ; Molybdenum ; chemistry ; metabolism ; pharmacology ; Skin ; chemistry ; drug effects ; Skin Pigmentation ; drug effects ; Water Pollutants, Chemical ; chemistry ; metabolism ; pharmacology

Objective To evaluate the clinical value of 18 F-FDG PET/CT for restaging, guiding therapeutic strategy and predicting prognosis in patients with postoperative colorectal cancer (PCC). Methods Records of 91 patients (51 males, 40 females;average age (54.90±11.47) years) in whom PCC were eval-uated by 18 F-FDG PET/CT imaging from May 2010 to June 2014 were retrospectively reviewed. All patients underwent evaluation at the First Affiliated Hospital of Soochow University. 18 F-FDG PET/CT results were compared with the results from pathological examination, clinical long-term follow-up (≥6 months ) and conventional imaging. Diagnostic efficiency of 18 F-FDG PET/CT in detecting recurrence and metastases of PCC were calculated. The clinical value of 18 F-FDG PET/CT in restaging and guiding therapeutic strategy were analyzed in patients with true positive results. Kaplan-Meier survival analysis was conducted based on the results of PET/CT and the alteration of therapeutic strategy after PET/CT. Results The sensitivity, specific-ity, accuracy, positive predictive value and negative predictive value of 18 F-FDG PET/CT were 96. 36%(53/55), 83.33%(30/36), 91.21%(83/91), 89.83%(53/59) and 93.75%(30/32), respectively. The median survival time and the 5-year survival rate were 10.00 years and 84% in patients with true negative PET/CT results, and were 6. 33 years and 53% in true positive group. Patients with true negative results showed longer OS and PFS than those with true positive results (χ2=7.753, 8. 933, both P<0.01). Among the 53 patients with true positive PET/CT results, tumor restaging was up-regulated in 32 patients and down-regulated in 2 patients. Therapeutic strategies were changed in 33 patients, in whom the PFS was lon- ger than those without treatment alteration (χ2=4.905, P<0.05) . Conclusion 18 F-FDG PET/CT imaging has the high sensitivity and accuracy in detecting recurrence and metastasis of PCC, with the potential for altering clinical restaging and therapeutic strategy timely.