OBJECTIVE To investigate the effects of total flavonoids from Carthamus tinctorius L. （TFCTL） on hepatic stellate cell （HSC） activation based on the microRNA （miRNA）-204/NUAK family SNF1-like kinase 1 （NUAK1）/Hippo signaling axis， thereby elucidating the potential mechanism underlying their antifibrotic effects. METHODS The HSC-T6 cells were divided into control group， model group， TFCTL low-concentration group （20 μg/mL）， TFCTL medium-concentration group （40 μg/mL）， and TFCTL high-concentration group （60 μg/mL）. Except for control group， the remaining groups were treated with 5 ng/mL of transforming growth factor-β to induce the activation of hepatic stellate cells， followed by the addition of corresponding drug solutions/culture medium and incubation for 24 hours. Cell apoptosis was assessed， the expression levels of α-smooth muscle actin （α-SMA）， type Ⅰ collagen （Collagen Ⅰ） and proteins associated with the Hippo/Yes-associated protein （YAP） pathway [YAP， large tumor suppressor kinase 1 （LATS1）， and mammalian STE20-like kinase 1 （MST1）] were detected. Additionally， cell transfection was used to investigate the activity of the miRNA-204/NUAK1/Hippo signaling axis at both the genetic and protein levels. RESULTS After intervention with TFCTL， the apoptosis rate of HSC-T6 cells and the protein expressions of MST1 （except for the TFCTL high-concentration group） and LATS1 were significantly increased （P＜0.05）， while the protein expressions of α-SMA， CollagenⅠ， and YAP （except for the TFCTL medium-concentration group） were significantly decreased （P＜0.05）. Further results from cell transfection experiments revealed that after transfection with miRNA-204 mimics， the mRNA it’s protein expressions of α-SMA， CollagenⅠ， NUAK1， and YAP in HSC-T6 cells were significantly decreased （P＜0.05）， while the mRNA and protein expressions of LATS1 and the mRNA expression of MST1 were significantly increased （P＜0.05）. Conversely， the results were opposite following transfection with miRNA-204 inhibitors. CONCLUSIONS TFCTL can exert anti-hepatic fibrosis effects by up-regulating the expression of miRNA-204， thereby down- regulating the expressions of NUAK1， inactivating the Hippo/YAP pathway， which in turn suppresses the activation of HSC and promotes their apoptosis.

OBJECTIVE: To evaluate the differential expression of RNA in blood monocytes in patients with Juvenile idiopathic arthritis (JIA) treated with TNF antagonists (TNFi), and to explore the effect and mechanism of gene expression on the efficacy of JIA. METHODS: A total of 29 children with JIA treated with methotrexate (MTX) and TNFi in Guangzhou Women and Children's Medical Center of Guangzhou Medical University from April 2021 to November 2023 were enrolled. After 6 months, the children were divided into two groups according to the treatment effect, i.e., 13 cases in the ineffective group and 16 cases in the effective group, the peripheral blood of the children was collected, the blood mononuclear cells were isolated for transcriptome sequencing, the differentially expressed genes between the groups were analyzed, the signaling pathways and metabolic pathways related to the efficacy of TNFi were analyzed by GO and KEGG enrichment, and the mechanism related to the efficacy of TNFi was explored. This study was approved by Medical Ethics Committee of the Guangzhou Women and Children's Medical Center of Guangzhou Medical University (Ethics No.: 2023-330B00). RESULTS: There was a statistically significant difference in the gender and age distribution between the two groups of children (P < 0.05), while no statistically significant differences were observed in disease duration, rheumatoid antibody levels, or JIA subtypes (P > 0.05). After sequencing data quality control and comparison of reference genomes, a total of 18 523 protein-coding genes were identified in all children's samples. A total of 705 differentially expressed genes (DEGs) were identified between the effective group and the invalid group through differential analysis, of which 579 were up-regulated in the effective group and 126 in the inactive group. GO function and KEGG pathway enrichment analysis showed that DEG was significantly enriched in 55 GO entries and 32 KEGG metabolic pathways, which were mainly related to IL-1β production and regulation, cytokine production and regulation, cytokine-cytokine receptor interaction, immune response regulation, and Toll-like receptor signaling pathway. CONCLUSION DEG between the effective and ineffective groups of TNFi treatment may be involved in the biological processes such as cytokine production and regulation, cytokine-receptor interaction, and immune response regulation, which will be helpful to predict the efficacy and prognosis of TNFi treatment for JIA.
Humans ; Arthritis, Juvenile/blood* ; Female ; Male ; Child ; Methotrexate/therapeutic use* ; Child, Preschool ; Tumor Necrosis Factor-alpha/antagonists & inhibitors* ; Transcriptome ; Adolescent ; RNA/genetics* ; Signal Transduction ; Gene Expression Profiling

OBJECTIVE To explore the effect and mechanism of the alcoholic extract from Scabiosa comosa against hepatic fibrosis （HF）. METHODS Intragastrical administration of carbon tetrachloride was given to induce HF model. By observing the pathological changes in liver tissue， mRNA and protein expressions of HF indexes [α-smooth muscle actin （α-SMA）， collagen type Ⅰ] and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） pathway-related factors were detected， and the improvement effects and possible mechanism of low-dose， medium-dose and high-dose （50， 100， 200 mg/kg） of alcoholic extract from S. comosa on HF model rats were investigated. Drug-containing serum was prepared by intragastrical administration of alcoholic extract from S. comosa at a concentration of 1 800 mg/（kg·d） （calculated by the amount of raw material）. The effects of drug- containing serum of alcoholic extract from S. comosa on the expression of miRNA-21 were observed through the intervention of HSC-T6 cells with low， medium and high concentrations of drug-containing serum of alcoholic extract from S. comosa （diluted to 10%， 15%， 20%）. miRNA-21 mimics or inhibitors were used to transfect HSC-T6 cells， and the mRNA and protein expressions of factors related to the PI3K/Akt signaling pathway were detected. RESULTS The results of in vivo experiments showed that low， medium and high doses of alcoholic extract from S. comosa significantly ameliorated the histopathological changes in liver tissue of HF rats， and the percentage of collagen was significantly reduced （P＜0.01）； mRNA and protein expressions of the indicators related to HF as well as PI3K and Akt were significantly reduced （P＜0.01）， and mRNA and protein expressions of phosphatase and tensin homolog deleted on chromosome ten （PTEN） were increased in liver tissue of rats （P＜0.01）. The results of in vitro experiments showed that drug-containing serum of alcoholic extract from S. comosa significantly inhibited the expression of miRNA-21 at low， medium and high concentrations （P＜0.01）； whereas after transfection with miRNA-21 mimics， it was found that miRNA-21 mimics significantly increased mRNA and protein expressions of PI3K and Akt （P＜0.01）， while significantly decreased mRNA and protein expressions of PTEN （P＜0.01）； after transfection with miRNA-21 inhibitor， the changes of above indexes were opposite to the above results （P＜0.01）. CONCLUSIONS Alcoholic extracts of S. comosa may inhibit the PI3K/Akt signaling pathway by affecting the expression of miRNA-21， so as to achieve the effect of anti-hepatic fibrosis.

Objective: To investigate the epidemiological characteristics of hemorrhagic fever with renal syndrome (HFRS) in Shaoxing City from 2006 to 2022, so as provide insights into improvements of the HFRS control strategy. Methods: Data pertaining to HFRS cases in Shaoxing City from 2006 to 2022 were captured from the Surveillance System of China Information System for Disease Control and Prevention. The temporal, population and regional distributions of HFRS were analyzed using the descriptive epidemiological method, and the trends in incidence of HFRS were evaluated using annual percent change (APC). Results: Totally 1 022 HFRS cases were reported in Shaoxing City from 2006 to 2022, with annual average incidence of 1.22/105 and three deaths. The incidence of HFRS appeared a tendency towards a decline in Shaoxing City from 2006 to 2022 (APC=-11.101%, t=-9.930, P<0.001), and the incidence of HFRS peaked from May to June and from November to January of the next year. A higher incidence of HFRS was seen in men than in women (1.76/105 vs. 0.68/105; χ2=201.361, P<0.001). There were 714 HFRS cases at ages of 30 to 59 years (69.86%), and farmers were the predominant occupation (78.18%). The three counties with the largest number of HFRS cases included Zhuji (366 cases), Xinchang (263 cases) and Shengzhou (134 cases). The incidence of HFRS was lower in urban districts (Yuecheng, Keqiao and Shangyu) than in counties (Zhuji, Shengzhou and Xinchang) (0.58/105 vs. 1.96/105; χ2=326.880, P<0.001). Conclusion The incidence of HFRS appeared a tendency towards a decline in Shaoxing City from 2006 to 2022, and the incidence was high in late spring, early summer and winter. The HFRS cases were mainly males, young and middle-aged people, and farmers, and predominantly distributed in counties. Targeted control measures are needed.

Objective:To explore more clinical characteristics and outcomes of children with severe pneumonia induced by adenovirus type 7(Adv-7).Methods:Seventy children with severe pneumonia induced by Adv-7 admitted to the pediatric intensive care unit of Guangzhou Women and Children′s Medical Center from January 2016 to October 2019 were enrolled.The clinical features, treatments and outcomes of these children were recorded.Results:(1)There were 43 males(61.4%)and 27 females(38.6%). Thirty(42.9%)patients were 0-12 months old, 28(40.0%)patients were 13-36 months old, and 12(17.1%)patients were over 36 months old.(2)The average onset time of severe pneumonia induced by Adv-7 was(11.87±7.10)days before being admitted to PICU.The average sequential organ failure assessment score was 6.80±3.13.The average Murray lung injury score was 2.49±1.15.The average P/F value was(150.57±86.25)mmHg(1 mmHg=0.133 kPa). Sixty-four cases(91.4%)were involved in two or more area of lung on X-rays.All cases were diagnosed with sepsis.(3)Laboratory examination: white blood cell count was(7.6±5.5) ×10 9/L, platelet count was(238.8±164.2)×10 9/L, and C-reactive protein was(39.4±37.2)mg/L.(4)Treatments: intravenous gamma globulin was used in 65 cases(92.9%). Intravenous glucocorticoid was used in 45 cases(64.3%). Fiberoptic bronchoscopy was performed in 43 cases(61.4%). Blood purification treatment was performed in 21 cases(30%). Sixty-three patients(90.0%)were treated with non-invasive or invasive ventilator, high frequency ventilator-assisted ventilation was used in 20 cases(28.6%). Surfactant was used in six cases(8.6%). Extracorporeal membrane oxygenation was used in 19 cases(27.1%). (5)The average treatment time for ventilation was(13.10±11.58)days.The average time for temperature recover was(4.69±4.01)days in PICU.The average PICU stay time was(15.76±12.20)days.The average length of stay was(27.04±13.10)days.There were 16 patients died and the mortality was 22.9%. Conclusion:The children with severe pneumonia induced by Adv-7 were critical and had significant lung injuries.Suffering from active clinical treatment such as extracorporeal membrane oxygenation, some of these patients still had poor prognosis.

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.

Disclosure ; Genetic Counseling ; Genetic Testing ; United States

Objective To implement pediatric nurses' ability level system based on the construction of pediatric nurses' ability level model and competency index databases and set up nurses' core competency requirements and advanced conditions so as to provide evidences for pediatric nurses′ ability level management. Methods Nurses' core competency requirements and advanced conditions were set up. N1 and N2 certificated of nurses' ability level were implemented in the whole hospital. Satisfaction of nurses and family members of children before and after the implementation were compared.Results A total of 354 nurses applied for N1 and N2 ability level in the whole hospital. A number of 289 out of 354 applications passed the audit and 237 out of 289 applications have been certificated. For N1 level,148 out of 180 (82.22%) applications were certificated. For N2 level, 90 out of 174 applications (51.72%) were certificated. Satisfaction rates of nurses increased from (83.88±11.886) to (89.84±10.740) after the implementation, with a statistically significant difference (t=-5.180,P＜0.01). Satisfaction rates of family members developed from 84.27% to 93.01% after the implementation. The difference was statistically significant (χ2=9.766,P＜0.05).Conclusions The implementation of nurses' ability level system improves nurses' work enthusiasm and increases nurses' work satisfaction and family members' satisfaction.

Objective To observe the influence of Qingwen Baidu decoction (QBD) on serum procalcitonin (PCT) and C-reactive protein (CRP) levels in septic rats and study the mechanism of heat-clearing and detoxifying method for treatment of sepsis. Methods Fifty male Sprague-Dawley (SD) rats were randomly divided into control group (n=5), model group (n=25), and heat-clearing and detoxifying experimental group (experimental group, n=20). The septic model was reproduced by intra-peritoneal injection of lipopolysaccharide (LPS, 5 mg/kg). In control group, an equal volume of normal saline was given. After modeling for 2 hours, the heat-clearing and detoxifying experimental group received QBD the first time (composition of the decoction: Gypsum Fibrosum Recens 30 g, Rehmanniae Radix 10 g, Bubali Cornu 15 g, Coptidis Rhizoma 4 g, Gardeniae Fructus 5 g, Platycodonis Radix 5 g, Scutellariae Radix 5 g, Anemarrhenae Rhizoma 5 g, Paeoniae Radix Rubra 5 g, Scrophulariae Radix 5 g, Forsythiae Fructus 5 g, Glycyrrhizae Radix 5 g, Moutan Cortex 5 g, Lophatheri Herba 5 g) by gavage (0.01 mL/g); the rest administration time was 08:00 to 09:00, once a day. The rats in model group were given an equal volume of warm water by gavage. At different time points after modeling, the blood of 5 rats in control group, model group, and experimental group was collected from the abdominal aorta. The serum PCT and CRP levels were tested by the enzyme linked immunosorbent assay (ELISA), and the pathological changes in lung and intestinal tissue were observed under a light microscope. Results Compared with the control group, the PCT level of the model group after modeling for 2 hours was significantly increased (ng/L:332.32±22.85 vs. 70.46±3.18, P<0.01), this situation continued until 72 hours after modeling. CRP level in the comparison between the control and model groups did not have statistical significant difference at 2, 8, and 48 hours after modeling (all P > 0.05). The level of CRP in model group was lower than that of control group at 24 hours and 72 hours after modeling (μg/L:281.34±32.81, 237.84±41.42 vs. 350.09±56.67, P<0.05 and P<0.01). There were no statistically significant differences in PCT levels between model group and experimental group after modeling for 8 hours and 24 hours (both P > 0.05). The PCT level of experimental group was significantly lower than that of model group beginning from 48 hours after modeling (ng/L: 321.57±28.00 vs. 358.12±10.14, P < 0.05), and this situation continued until 72 hours after modeling (ng/L: 269.50±49.10 vs. 347.69±26.90, P <0.05). The CRP level of experimental group was significantly lower than that of model group beginning from 8 hours after modeling (μg/L:232.73±13.29 vs. 335.35±53.78, P<0.05), this statistical significant difference between the two groups persisted until 72 hours after modeling (μg/L:177.31±6.70 vs. 237.84±41.42, P<0.05). Compared to those in the model group, the lung tissue inflammatory cell infiltration, the intestinal mucosal inflammation and interstitial edema were milder in the experimental group. Conclusion Heat-clearing and detoxifying therapy can effectively reduce the serum PCT and CRP levels of septic rats induced by LPS, and it can alleviate the infiltration of inflammatory cells in lung tissues so as to play a role in protection of tissue organ.