A 5G-based telerobotic ultrasound system provides qualified abdominal ultrasound services for patients on a rural island: a prospective and comparative study of 401 patients.

PURPOSE: To explore the feasibility of a 5G-based telerobotic ultrasound (US) system for providing qualified abdominal US services on a rural island. METHODS: This prospective study involved two medical centers (the tele-radiologist site's hospital and the patient site's hospital) separated by 72 km. Patients underwent 5G-based telerobotic US by tele-radiologists and conventional US by on-site radiologists from September 2020 to March 2021. The clinical feasibility and diagnostic performance of the 5G-based telerobotic abdominal US examination were assessed based on safety, duration, image quality, diagnostic findings, and questionnaires. RESULTS: A total of 401 patients (217 women and 184 men; mean age, 54.96 ± 15.43 years) were enrolled. A total of 90.1% of patients indicated no discomfort with the telerobotic US examination. For the examination duration, telerobotic US took longer than conventional US (12.54 ± 3.20 min vs. 7.23 ± 2.10 min, p = 0.001). For image quality scores, the results of the two methods were similar (4.54 ± 0.63 vs. 4.57 ± 0.61, p = 0.112). No significant differences were found between the two methods in measurements for the aorta, portal vein, gallbladder, kidney (longitudinal diameter), prostate, and uterus; however, telerobotic US underestimated the transverse diameter of the kidney (p < 0.05). A total of 504 positive results, including 31 different diseases, were detected. Among them, 455 cases were identified by the two methods; 17 cases were identified by telerobotic US only; and 32 cases were identified by conventional US only. There was good consistency in the diagnosis of 29 types of disease between the two methods (κ = 0.773-1.000). Furthermore, more than 90% of patients accepted the telerobotic US examination and agreed to pay additional fees in future. CONCLUSION: The 5G-based telerobotic US system can expand access to abdominal US services for patients in rural areas, thereby reducing health care disparities.

Professional Feeding Guidance Improved Infants' Self-Feeding Proportion during Complementary Foods Introduction in Beijing, China: An Exploratory Study.

An exploratory study was undertaken to examine the prevalence of infants' feeding patterns in Beijing, China, as well as the factors linked to infants' self-feeding proportion during the introduction of complementary foods, and the impact of professional feeding guidance on this proportion. A total of 122 families with infants aged 6-11 months from Beijing were included in the study. A descriptive analysis was employed to assess the prevalence of infants' feeding patterns, while generalized linear model analysis was utilized to investigate the factors associated with these patterns. All families were provided with comprehensive and personalized professional guidance regarding the introduction of complementary foods for infants. However, 64 families were lost to follow-up, leaving 58 families who were re-evaluated and queried after one month. To exclude the influence of infants aging, both the 64 families prior to receiving feeding guidance, and the 58 families after receiving feeding guidance, were included in the analysis. The families with infants aged 6-8 months and 9-11 months were compared separately based on the presence or absence of feeding guidance. Statistical tests, including the Wilcoxon rank-sum test and χ2 test, were conducted to assess any significant differences. The study revealed that the proportion of infants engaging in self-feeding was found to be remarkably low (10% [0%, 40%]). Furthermore, a significant positive association was observed between the proportion of infants engaging in self-feeding and their age (p < 0.001). Notably, after receiving professional feeding guidance, the proportion of infants engaging in self-feeding significantly increased (from 1% [0%, 20%] to 30% [10%, 50%], p < 0.001 for infants aged 6-8 months; from 20% [10%, 50%] to 40% [30%, 50%], p < 0.001 for infants aged 9-11 months). These findings contribute valuable insights for improving postnatal care practices during the introduction of complementary foods for infants.

Glycyrrhetinic acid attenuates endoplasmic reticulum stress-induced hepatocyte apoptosis via CHOP/DR5/Caspase 8 pathway in cholestasis.

Bile acid (BA)-induced apoptosis is a common pathologic feature of cholestatic liver injury. Glycyrrhetinic acid (GA) is the hepatoprotective constituent of licorice. In the present study, the anti-apoptotic potential of GA was investigated in wild type and macrophage-depleted C57BL/6 mice challenged with alpha-naphthyl isothiocyanate (ANIT), and hepatocytes stimulated with Taurocholic acid (TCA) or Tumor necrosis factor-alpha (TNF-α). Apoptosis was determined by TUNEL positive cells and expression of executioner caspases. Firstly, we found that GA markedly alleviated liver injury, accompanied with reduced positive TUNEL-staining cells, and expression of caspases 3, 8 and 9 in mice modeled with ANIT. Secondly, GA mitigated apoptosis in macrophage-depleted mice with exacerbated liver injury and augmented cell apoptosis. In vitro study, pre-treatment with GA reduced the expression of activated caspases 3 and 8 in hepatocytes stimulated with TCA, but not TNF-α. The ability of GA to ameliorate apoptosis was abolished in the presence of Tauroursodeoxycholic Acid (TUDCA), a chemical chaperon against Endoplasmic reticulum stress (ER stress). Furthermore, GA attenuated the over-expression of Glucose regulated protein 78 (GRP78), and blocked all three branches of Unfolded protein reaction (UPR) in cholestatic livers of mice induced by ANIT. GA also downregulated C/EBP homologous protein (CHOP) expression, accompanied with reduced expression of Death receptor 5 (DR5) and activation of caspase 8 in both ANIT-modeled mice and TCA-stimulated hepatocytes. The results indicate that GA inhibits ER stress-induced hepatocyte apoptosis in cholestasis, which correlates with blocking CHOP/DR5/Caspase 8 pathway.

Reallocation of time between preschoolers' 24-h movement behaviours and executive functions: A compositional data analysis.

The objectives of the survey were to explored the associations of the 24-h movement behaviours (MB) with executive functions (EFs) and quantified the predicted changes in EFs following allocation of time among behaviours. In the cross-sectional survey, 135 preschoolers (3 ~ 5 years) were enrolled. Physical activity (PA) and sedentary (SED) time were objectively measured employing an ActiGraph GT9X. Sleep time was reported by parents. EFs were assessed using the iPad-based Early Years Toolbox which is a collection of computerized tasks consisting of brief tasks assessed from games administered and scored according to protocol. To explore the associations of the 24-h MB with EFs, compositional multiple linear regression was employed. To quantify the predicted changes in EFs following allocation of time among behaviours, compositional isotemporal substitution was used. Moderate-to-vigorous physical activity (MVPA) was positively related to cognitive flexibility. Replacing sleep or SED with MVPA was associated with positive changes in cognitive flexibility. When MVPA was replaced with sleep or SED, the predicted detriments to cognitive flexibility were larger than predicted benefits of replacing sleep or SED with MVPA. The findings highlight the key role of intensity of PA for preschoolers' EFs and the importance of meeting recommended levels of MVPA.

Yinchen decoction protects against cholic acid diet-induced cholestatic liver injury in mice through liver and ileal FXR signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestasis is a pathophysiological syndrome characterized by the accumulation of bile acids (BAs) that leads to severe liver disease. Artemisia capillaris is documented in Chinese Pharmacopoeia as the authentic resources for Yinchen. Although Yinchen (Artemisia capillaris Thunb.) decoction (YCD) has been used in China for thousands of years to treat jaundice, the underlying mechanisms to ameliorate cholestatic liver injury have not been elucidated. AIM OF THE STUDY: To investigate the molecular mechanism of how YCD protects against 1% cholic acid (CA) diet-induced intrahepatic cholestasis through FXR signaling. MATERIALS AND METHODS: Wild-type and Fxr-deficient mice were fed a diet containing 1% CA to establish the intrahepatic cholestasis model. The mice received low-, medium-, or high-dose YCD for 10 days. Plasma biochemical markers were analyzed, liver injury was identified by histopathology, and hepatic and plasma BA content was analyzed. Western blot was used to determine the expression levels of transporters and enzymes involved in BA homeostasis in the liver and intestine. RESULTS: In wild-type mice, YCD significantly improved plasma transaminase levels, multifocal hepatocellular necrosis, and hepatic and plasma BA contents, upregulated the expression of hepatic FXR and downstream target enzymes and transporters. Meanwhile, YCD significantly induced the expressions of intestinal FXR and FGF15 and hepatic FGFR4. In contrast, the hepatic protective effect of YCD on cholestasis was abolished in Fxr-deficient mice. CONCLUSION: YCD protects against cholestatic liver injury induced by a CA diet by restoring the homeostasis of BAs via activation of the liver FXR/SHP and ileal FXR/FGF15 signaling pathways. Furthermore, chlorogenic acid and caffeic acid may be the pharmacological agents in YCD responsible for protecting against cholestatic liver injury.

15,16-dihydrotanshinone I in Danshen ethanol extract aggravated cholestasis by inhibiting Cyp3a11 mediated bile acids hydroxylation.

Our previous study found that high-dose Tanshinones Capsule (TC) aggravated cholestasis in mice. To explore its underlying mechanism, main tanshinones components (15,16-dihydrotanshinone I (DTI), cryptotanshinone (CTS) and tanshinone IIA (TSA)) form TC were studied separately. Bile acids (BAs) that were primarily metabolized by hydroxylation were identified, and then the inhibitory effect of each tanshinones on their hydroxylation were evaluated. The anti-cholestasis effect of each tanshinones were studied in mice, the hepatic concentrations of BAs and tanshinones were measured and analyzed as well. The effect of tanshinones on Cyp3a11 protein expression was investigated. DTI exhibited inhibitory effect on the hydroxylation of lithocholic acid (LCA), taurolithocholic acid (TLCA) and taurochenodeoxycholic acid (TCDCA), their IC50 values were 0.81, 0.36 and 1.29 µM, respectively. The hydroxylation of LCA, TLCA and TCDCA were mediated by Cyp3a11. Low-dose DTI, CTS and TSA ameliorated cholestatic liver injury in mice, while high-dose DTI didn't exhibit anti-cholestatic effect. The hepatic BAs profiles indicated that hydroxylation of BAs was inhibited in high-dose DTI group. DTI and TSA up-regulated the protein expression of Cyp3a11. As the hepatic concentration of DTI increased, the inhibitory effect at enzymatic activity level overwhelmed its up-regulation effect at protein level, thus resulted in worsening of cholestasis.

The choleretic role of tauroursodeoxycholic acid exacerbates alpha-naphthylisothiocyanate induced cholestatic liver injury through the FXR/BSEP pathway.

The aim of this study was to determine the effect of tauroursodeoxycholic acid (TUDCA) on the alpha-naphthylisothiocyanate (ANIT)-induced model of cholestasis in mice. Wild-type and farnesoid X receptor (FXR)-deficient (Fxr-/- ) mice were used to generate cholestasis models by gavage with ANIT. Obeticholic acid (OCA) was used as a positive control. In wild-type mice, treatment with TUDCA for 7 days resulted in a dramatic increase in serum levels of alanine aminotransferase (ALT), with aggravation of bile infarcts and hepatocyte necrosis with ANIT-induction. TUDCA activated FXR to upregulate the expression of bile salt export pump (BSEP), increasing bile acids (BAs)-dependent bile flow, but aggravating cholestatic liver injury when bile ducts were obstructed resulting from ANIT. In contrast, TUDCA improved the liver pathology and decreased serum ALT and alkaline phosphatase (ALP) levels in ANIT-induced Fxr-/- mice. Furthermore, TUDCA inhibited the expression of cleaved caspase-3 and reduced the area of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining in the model mice. TUDCA also upregulated anion exchanger 2 (AE2) protein expression, protecting cholangiocytes against excessive toxic BAs. Our results showed that TUDCA aggravated cholestatic liver injury via the FXR/BSEP pathway when bile ducts were obstructed, although TUDCA inhibited apoptotic activity and protected cholangiocytes against excessive toxic BAs.

Potential therapeutic action of tauroursodeoxycholic acid against cholestatic liver injury via hepatic Fxr/Nrf2 and CHOP-DR5-caspase-8 pathway.

Cholestasis is a pathophysiologic syndrome with limited therapeutic options. Tauroursodeoxycholic acid (TUDCA) has been employed to treat hepatobiliary disorders and is as effective as UDCA in alleviating cholestatic liver disease in clinical trials. Until now, TUDCA's mechanism of action toward cholestasis remains unclear. In the present study, cholestasis was induced with a cholic acid (CA)-supplemented diet or α-naphthyl isothiocyanate (ANIT) gavage in wild-type and Farnesoid X Receptor (FXR) deficient mice, using obeticholic acid (OCA) as control. The effects of TUDCA on liver histological changes, transaminase level, bile acid composition, hepatocyte death, expression of Fxr and nuclear factor erythroid 2-related factor 2 (Nrf2) and target genes, as well as apoptotic signaling pathways, were investigated. Treating CA-fed mice with TUDCA markedly alleviated liver injury, attenuated bile acids retention in liver and plasma, increased Fxr and Nrf2 nuclear levels and modulated the expression of targets regulating synthesis and transportation of bile acids, including BSEP, MRP2, NTCP and CYP7A1. TUDCA, but not OCA, activated Nrf2 signaling and exerted protective effects against cholestatic liver injury in Fxr-/- mice fed with CA. Furthermore, in both mice with CA- and ANIT-induced cholestasis, TUDCA decreased expression of GRP78 and CCAAT/enhancer-binding protein homologous protein (CHOP), reduced death receptor 5 (DR5) transcription, caspase-8 activation, and BID cleavage, and subsequently inhibited activation of executioner caspases and apoptosis in liver. We confirmed that TUDCA protected against cholestatic liver injury by alleviating BAs burden of dually activating hepatic Fxr and Nrf2. Moreover, inhibiting CHOP-DR5-caspase-8 pathway contributed to the anti-apoptotic effect of TUDCA in cholestasis.

Hepatoprotective Effects of Glycyrrhetinic Acid on Lithocholic Acid-Induced Cholestatic Liver Injury Through Choleretic and Anti-Inflammatory Mechanisms.

Cholestasis is a clinical syndrome triggered by the accumulation and aggregation of bile acids by subsequent inflammatory responses. The present study investigated the protective effect of glycyrrhetinic acid (GA) on the cholestatic liver injury induced by lithocholic acid (LCA) from both anti-inflammatory and choleretic mechanistic standpoints. Male C57BL/6 mice were treated with LCA twice daily for 4 days to induce intrahepatic cholestasis. GA (50 mg/kg) and pregnenolone 16α-carbonitrile (PCN, 45 mg/kg) were intraperitoneally injected 3 days before and throughout the administration of LCA, respectively. Plasma biochemical indexes were determined by assay kits, and hepatic bile acids were quantified by LC-MS/MS. Hematoxylin and eosin staining of liver sections was performed for pathological examination. Protein expression of the TLRs/NF-κB pathway and the mRNA levels of inflammatory cytokines and chemokines were examined by Western blotting and PCR, respectively. Finally, the hepatic expression of pregnane X receptor (PXR) and farnesoid X receptor (FXR) and their target genes encoding metabolic enzymes and transporters was evaluated. GA significantly reversed liver necrosis and decreased plasma ALT and ALP activity. Plasma total bile acids, total bilirubin, and hepatic bile acids were also remarkably preserved. More importantly, the recruitment of inflammatory cells to hepatic sinusoids was alleviated. Additionally, the protein expression of TLR2, TLR4, and p-NF-κBp65 and the mRNA expression of CCL2, CXCL2, IL-1ß, IL-6, and TNF-α were significantly decreased. Moreover, GA significantly increased the expression of hepatic FXR and its target genes, including BSEP, MRP3, and MRP4. In conclusion, GA protects against LCA-induced cholestatic liver injury by inhibiting the TLR2/NF-κB pathway and upregulating hepatic FXR expression.

Clarify the potential cholestatic hepatotoxicity components from Chinese Herb Medicine and metabolism's role via hBSEP vesicles and S9/hBSEP vesicles.

In this study, the inhibitory effect of components from Chinese Herb Medicine (CHMs) with potential hepatotoxicity was assessed by human bile salt export pump (hBSEP) vesicles with and without S9 metabolism. Sixty-three compounds from 22 hepatoxicity CHMs were selected as the test articles. In hBSEP vesicles, eighteen of them were found to have moderate or strong inhibitory effect towards BSEP. Further studies were performed to determine the IC50 values of strong inhibitors. For the compounds belong to CHMs reported to cause cholestasis and strong inhibitors defined in hBSEP vesicles, their relative transport activities of Taurocholic acid (TCA) were evaluated in hBSEP vesicles as well as hBSEP vesicles with S9 system (S9/hBSEP vesicles). The differences of their relative transport activities of TCA between the above two system were compared to reveal the net effect of metabolism on BSEP's activity. It was found that the inhibitory effect of Saikogenin A (SGA), Saikogenin D (SGD), Diosbulbin B (DB) and rhein were significantly increased; while the inhibitory effect of isobavachalcone, saikosaponin d and saikosaponin b2 were significantly decreased after S9 metabolizing. Identification of metabolic pathways suggested that CYP3A4 was responsible for aggravating inhibitory effect of SGA and SGD against BSEP.

Effect of Different Ratios of Yinchen and Gancao Decoction on ANIT-Treated Cholestatic Liver Injury in Mice and Its Potential Underlying Mechanism.

Cholestasis is a pathological state that leads to serious liver disease; however, therapeutic options remain limited. Yinchen and Gancao are often used in combination at different ratios in traditional Chinese formulae for the treatment of jaundice and cholestasis. In the present study, we investigated the effect of decoctions containing different ratios of Yinchen and Gancao (YGD) on alpha-naphthyl isothiocyanate (ANIT)-treated intrahepatic cholestasis (IC) in mice, and further explored the underlying mechanism. Treatment with 0:4 and 1:4 YGD significantly reduced plasma total bile acid (TBA), total bilirubin (TBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities; decreased unconjugated and conjugated bile acid levels; and improved hepatocyte necrosis and inflammatory cells recruitment to hepatic sinusoids. Moreover, the expression levels of Toll-like receptor 4 (TLR4), interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor alpha (TNF-α), C-C ligand 2 (CCL2), and C-X-C ligand 2 (CXCL2) in the liver were significantly reduced. However, treatment with 4:1 and 4:0 YGD increased plasma TBA, TBIL, AST, ALT, and ALP activities and aggravated liver cell injury and inflammation. Moreover, the mRNA expression of the bile salt export pump (BSEP) in the liver was significantly increased in mice treated with 4:0 YGD. The present study demonstrates that YGD containing a high proportion of Gancao, which inhibits the TLR4/NF-κB pathway and reduces the inflammatory response, had protective effects against ANIT-treated IC in mice. However, YGD containing a high proportion of Yinchen aggravated the ANIT-treated IC in mice, which may be related to upregulation of BSEP and boosting bile acid regurgitation from damage cholangiocytes to liver in ANIT-treated IC mice.

[Association between serum allergens and asthma in children].

OBJECTIVE: To study the association between serum-specific immunoglobulin E (sIgE) allergens and asthma in children. METHODS: The serum sIgE allergens were determined using Western blot in 2239 children aged 1-14 years, consisting of 1415 children with asthma alone and 824 children with non-allergic diseases between December 2004 and April 2013. The case-control models of asthma alone and non-allergic diseases were established. The association between allergens and asthma was investigated using multivariate logistic regression analysis. RESULTS: In the 2239 children, 1028 children (45.91%) were serum sIgE-positive, and the allergen with the highest positive rate was house-dust mite (15.68%), followed by house dust (14.29%) and moulds (13.40%). The results of the case-control analysis showed that house-dust mite, moulds, house dust, and cashew nut/peanut/soybean were significantly associated with the development of asthma. House dust was associated with the development of asthma in the 1-2 years old group (P<0.05). House dust and house-dust mite as allergens were identified as the risk factors for the development of asthma in the 3-14 years old group (P<0.05). In the 6-14 years old group, moulds as allergens were identified as the risk factors for the development of asthma (P<0.05). House dust and house-dust mite as allergens increased the risk of asthma in boys and girls, while moulds and cashew nuts/peanuts/soybeans as allergens increased the risk of asthma in boys. CONCLUSIONS: House-dust mite, house dust, and moulds are the most common allergens in children with asthma, and they are closely associated with the development of asthma.