OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland （HMG）. METHODS Female SD rats were divided into control group and HMG group according to body weight， with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling， two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid （calculated by crude drug） intragastrically， once a day， for 7 consecutive days. Blood samples were collected before the first administration （0 h）， and at 5， 15， 30 minutes and 1， 2， 4， 8， 12， 24 hours after the last administration， respectively. Using chlorzoxazone as the internal standard， the plasma concentrations of ferulic acid， paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve （AUC0－24 h， AUC0－∞）， mean residence time （MRT0－∞）， half-life （t1/2）， peak time （tmax）， peak concentration （cmax）] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group， the AUC0－24 h， AUC0－∞ and cmax of ferulic acid in the HMG group were significantly increased （P＜0.05）； the AUC0－24 h， AUC0－∞ ， MRT0－∞ ， t1/2 and cmax of paeoniflorin increased， but there was no significant difference between 2 groups （P＞0.05）； the AUC0－24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged （P＜0.05）. C ONCLUSIONS In HMG model rats， the exposure of ferulic acid， paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase， and the retention time of rosmarinic acid is significantly prolonged.

OBJECTIVE To investigate the effects of metformin （Met） on liver injury in non-alcoholic steatohepatitis （NASH） rats by regulating the PI3K/AKT/PDGF signaling pathway. METHODS NASH model was constructed by feeding rats with a high- glucose and high-fat diet， and assigned into Model group， Met low-dose group （Met-L group， 100 mg/kg）， Met medium-dose group （Met-M group， 200 mg/kg）， Met high-dose group （Met-H group， 400 mg/kg）， and high dose of Met+PI3K activator group （Met-H+740 Y-P group， 400 mg/kg Met+50 mg/kg 740 Y-P）， with 12 rats in each group. Another 12 rats were regarded as the Control group. Each group of rats was orally administered/injected with the corresponding medication once a day for 6 consecutive weeks. The changes in body weight and liver index of rats were recorded and analyzed. The pathological damage [evaluation of non-alcoholic fatty liver disease activity score （NAS）]， lipid deposition （calculation of the proportion of oil red O-positive staining area）， and fibrosis （calculation of collagen deposition score） were observed in liver tissue of rats. The levels of inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] in serum and liver tissue， the levels of serum lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）] and liver function indicators [aspartate aminotransferase （AST） and alanine Δ 基金项目 武汉市知识创新专项项目（No.2022020801010588）； aminotransferase （ALT）] were measured. The expression levels of PI3K/AKT/PDGF signaling pathway-related proteins and Caspase-3 in liver tissue of rats were determined. RESULTS Compared with the Control group， body weight， liver index， the levels of serum lipid metabolism indicators and liver function indicators， the levels of IL-6 and TNF-α in serum and liver tissue， the NAS， the proportion of oil red O-positive staining area， the collagen deposition fraction， and the levels of phosphorylated PI3K and AKT proteins， as well as the expression levels of PDGF and Caspase-3 proteins in liver tissue， were all significantly increased （P＜0.05）. The liver tissue showed severe pathological damage， characterized by an abundance of lipid droplets and pronounced collagen deposition. After the intervention with Met， the aforementioned quantitative indicators and pathological changes in rats were significantly improved in a dose- dependent manner （P＜0.05）. 740 Y-P could reverse the improvement effects of high dose of Met on the above indexes of rats （P＜ 0.05）. CONCLUSIONS Met can improve liver damage， and alleviate inflammatory reactions and liver fibrosis of NASH rats， the mechanism of which may be associated with inhibiting PI3K/AKT/PDGF signaling pathway.

OBJECTIVE To investigate the effect and mechanism of Jingangteng capsules in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Thirty-two SD rats were randomly divided into normal group and modeling group. The modeling group was fed a high-fat diet to establish a NAFLD model. The successfully modeled rats were then randomly divided into model group， atorvastatin group[positive control， 2 mg/（kg·d）]， and Jingangteng capsules low- and high-dose groups [0.63 and 2.52 mg/（kg·d）]， with 6 rats in each group. The pathological changes of the liver were observed by hematoxylin-eosin staining and oil red O staining. Enzyme-linked immunosorbent assay was performed to determine the serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， alanine transaminase （ALT）， aspartate transaminase （AST）， tumour necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， IL-6， IL-18. 16S rDNA amplicon sequencing and metabolomics techniques were applied to explore the effects of Jingangteng capsules on gut microbiota and metabolisms in NAFLD rats. Based on the E-mail：591146765@qq.com metabolomics results， Western blot analysis was performed to detect proteins related to the nuclear factor kappa-B （NF-κB）/NOD-like receptor family protein 3 （NLRP3） signaling pathway in the livers of NAFLD rats. RESULTS The experimental results showed that Jingangteng capsules could significantly reduce the serum levels of TG， TC， LDL-C， AST， ALT， TNF-α， IL-1β， IL-6， IL-18， while increased the level of HDL-C， and alleviated the hepatic cellular steatosis and inflammatory infiltration in NAFLD rats. They could regulate the gut microbiota disorders in NAFLD rats， significantly increased the relative abundance of Romboutsia and Oscillospira， and significantly decreased the relative abundance of Blautia （P＜0.05）. They also regulated metabolic disorders primarily by affecting secondary bile acid biosynthesis， fatty acid degradation， O-antigen nucleotide sugar biosynthesis， etc. Results of Western blot assay showed that they significantly reduced the phosphorylation levels of NF-κB p65 and NF-κB inhibitor α， and the protein expression levels of NLRP3， caspase-1 and ASC （P＜0.05 or P＜0.01）. CONCLUSIONS Jingangteng capsules could improve inflammation， lipid accumulation and liver injury in NAFLD rats， regulate the disorders of gut microbiota and metabolisms， and inhibit NF-κB/NLRP3 signaling pathway. Their therapeutic effects against NAFLD are mediated through the inhibition of the NF-κB/NLRP3 signaling pathway.

[摘 要] 目的：探讨lncRNA SOX2-OT是否通过调控miR-215-5p/NIN1/RPN12结合蛋白1同源物（NOB1）信号通路抑制结直肠癌（CRC）HCT-116细胞增殖和迁移。方法：收集2022年6月至2024年5月期间武汉市金银潭医院收治的29例CRC患者的癌及癌旁组织标本，以及CRC细胞SW480、HCT-116、HP116和LoVo及人结肠上皮细胞HCoEpiC。qPCR法检测CRC组织和细胞中SOX2-OT、miR-215-5p和NOB1 mRNA的表达水平。利用RNA干扰技术分别将敲低或过表达SOX2-OT质粒及阴性对照质粒转染至HCT-116细胞，实验分为对照组、si-NC组、si-SOX2-OT组、si-SOX2-OT + inhibitor（Inh）NC组、si-SOX2-OT + miR-215-5p Inh组、si-SOX2-OT + oe-NC组、si-SOX2-OT + oe-NOB1组。qPCR法检测各组细胞中SOX2-OT、miR-215-5p和NOB1 mRNA表达水平，通过MTT、划痕愈合实验、Transwell实验和流式细胞术分别检测各组细胞的增殖、迁移、侵袭及凋亡水平，WB法检测各组细胞中E-cadherin、N-cadherin、vimentin、Bcl-2、BAX、PCNA、MMP-9和NOB1蛋白表达水平。通过双萤光素酶报告基因实验验证miR-215-5p与SOX2-OT和NOB1之间的靶向关系。结果：CRC组织和细胞中SOX2-OT和NOB1 mRNA均呈高表达、miR-215-5p低表达（均P < 0.05）。敲低SOX2-OT表达的HCT-116细胞中SOX2-OT和NOB1 mRNA表达水平、增殖、划痕愈合率和侵袭细胞数量，以及细胞中N-cadherin、vimentin、Bcl-2、NOB1、PCNA和MMP-9蛋白表达均显著降低（均P < 0.05），miR-215-5p、细胞凋亡率、E-cadherin和BAX蛋白表达均显著升高（均P < 0.05）。敲低miR-215-5p表达或上调NOB1表达均可减弱敲低SOX2-OT表达对细胞的抑制作用（均P < 0.05）。miR-215-5p与SOX2-OT和NOB之间存在靶向关系。结论：敲低SOX2-OT表达可促进miR-215-5p表达，抑制NOB1表达进而抑制HCT-116细胞的增殖、迁移、侵袭并促进细胞凋亡。

eToyBox is a learning management system for preschool teachers to improve their health literacy, which ultimately aims to improve children’s obesity-related behaviour. As part of the development process of eToyBox, assessment on digital literacy, acceptance of digitization of education materials, and perceived barriers in adopting online learning is needed. Fifty-four preschool teachers under the Community Development Department (KEMAS) in Kuala Lumpur, Selangor, and Sarawak, who participated in ToyBox Study Malaysia intervention in 2018, took part in this cross-sectional study. An online self-administered questionnaire was used to assess sociodemographic background, use of communication tools and media, and teacher’s views on adapting the ToyBox modules to digital education materials. Respondents were contacted, and questionnaire link was shared through WhatsApp messages. Most participants (74.0%) were Malay females aged 31 to 40 years old. Most participants had internet access (94.4%) and owned at least a smart phone, laptop or tablet (94.4%). Participants perceived their computer skills to be average (75.0%). Majority of respondents (65.0%) reported advanced and higher abilities in word processing and email, but only 22.0% in spreadsheet skills. The main barrier to accessing online material was unstable internet connection (74.1%). Most respondents (90.0%) agree that adapting effective modules to online learning will be beneficial for professional development and teaching practices. In conclusion, most participants supported digitizing Toybox Study Malaysia educational content and were comfortable 72 with its implementation via an online learning platform. The findings from this study can advise future development of online learning materials for preschool teachers in Malaysia.

AIM: To explore the mechanism of osthole on elderly spontaneously hypertensive rats. METHODS: 20-month-old spontaneously hypertensive rats (SHRs) and healthy Wistar-Kyoto (WKY) rats were purchased. SHRs were treated with osthole (i.g.) for 8 weeks. The systolic blood pressure and diastolic blood pressure of rats were monitored. Hematoxylin-eosin staining (H&E), periodic acid-schiff staining (PAS) and Masson staining were used to observe the pathological changes of rat kidney tissues. The activity of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in rat kidney was detected by ELISA kit. PI3K/Akt/mTOR signaling pathway related proteins were detected by western blot. RESULTS: Osthole reduced the systolic and diastolic blood pressure of SHRs, improved the histopathological changes of SHRs kidney, reduced the activity of MDA in SHRs kidney, and increased the activity of SOD and GSH. Osthole reduced the levels of p-PI3K, p-Akt and p-mTOR. CONCLUSION: Osthole reduces the activity of PI3K/Akt/mTOR signaling pathway and exerts a protective effect on renal oxidative stress injury in aged spontaneously hypertensive rats.

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

Objective·To evaluate the changes in cognitive function in overweight and obese adolescents,and explore the association between cognitive function and fibroblast growth factor 21(FGF21).Methods·A total of 175 adolescents from a senior high school in Shanghai were divided into normal weight group(n=50),overweight group(n=50)and obese group(n=75)based on their body mass index(BMI).General information,anthropometric data and laboratory testing indicators of the adolescents were collected and compared.The cognitive function of the three groups of adolescents was assessed by using the accuracy(ACC)and reaction time of Flanker task and n-back task.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum FGF21 level of the three groups of adolescents.Partial correlation analysis and multiple linear regression model were used to evaluate the correlation between cognitive task performance and anthropometric data and laboratory testing indicators.Results·Compared with the normal weight group,systolic blood pressure,diastolic blood pressure,and the levels of fasting plasma glucose,glycosylated hemoglobin and triacylglycerol in the obese group were higher(all P<0.05).Under congruent or incongruent stimulus conditions in the Flanker task,there was no significant difference in ACC between any two groups;compared with the normal weight and overweight groups,the reaction time of the adolescents in the obese group was prolonged(all P<0.05).In the n-back task,there were no significant differences in ACC between any two groups,while the obese group had longer reaction time in the 1-back and 2-back tasks compared to the normal weight and overweight groups(all P<0.05).Compared with the normal weight group,serum FGF21 levels of the adolescents in the obese group were higher(P=0.000).Partial correlation analysis showed that the reaction time of the adolescents in Flanker and n-back tasks was correlated with their BMI,body fat mass,waist circumference,waist-to-hip ratio and FGF21 level(all P<0.05).Multiple linear regression analysis further confirmed that BMI was associated with prolonged reaction time in cognitive-related behavioral tasks in the adolescents(all P<0.05),and FGF21 level was associated with ACC in the 2-back task(P=0.000)and reaction time in the incongruent stimulus condition(P=0.048).Conclusion·Overweight and obese adolescents have cognitive impairments,and BMI and serum FGF21 levels are associated with changes in their cognitive function.

The current situation of the construction and application of orthopaedic subspecialty nursing quality standards at home and abroad is reviewed, and the overview of orthopaedic subspecialty nursing quality standards, theoretical foundations, the content of the standard construction, the form and results of the application, and the shortcomings and outlooks are elaborated and illustrated, with a view to providing theoretical references for the further improvement and application of China′s orthopaedic subspecialty nursing quality standard system, and providing scientific suggestions and reflections for the promotion of the high-quality development of orthopaedic subspecialty nursing.

Objective:To evaluate the efficacy of oral midazolam solution for preoperative sedation in the pediatric outpatients undergoing root canal treatment under general anesthesia.Methods:One hundred and forty-seven pediatric patients of either sex, aged 2-7 yr, weighing 10-30 kg, of American Society of Anesthesiologists Physical Status classificationⅠ or Ⅱ, were divided into 3 groups ( n=49 each) using a random number table method: oral midazolam solution group (OM group), midazolam injection group (M group), and dexmedetomidine group (D group). In OM group, patients received oral midazolam solution at a dose of 0.5 mg/kg along with a placebo (an equivalent amount of normal saline based on body weight) administered via nasal drops. In M group, patients were given oral midazolam injection at a dose of 0.5 mg/kg along with a placebo via nasal drops. In D group, patients were administered a placebo orally along with dexmedetomidine at a dose of 2 μg/kg via nasal drops. The Induction Compliance Checklist (ICC) scores upon entering the operating room, sedation success rates (ICC score ≤ 3), drug acceptance scores, mask acceptance scores, and separation anxiety scores were recorded. The emergence time, time of stay in postanesthesia care unit (PACU), and occurrence of adverse events such as bradycardia, hypotension, hypoxemia, and laryngospasm during surgery and in PACU were recorded. Results:A total of 143 pediatric patients were finally included in the study, with 48 cases in OM group, 48 cases in M group and 47 cases in D group. Compared with M and D groups, the ICC scores upon entry to the operating room were significantly decreased, the sedation success rates were increased, drug acceptance scores were increased, separation anxiety scores were decreased, and mask acceptance scores were decreased in OM group ( P<0.05). Compared with D group, the ICC scores upon entry to the operating room were significantly decreased, the sedation success rates were increased, and mask acceptance scores were decreased in M group ( P<0.05). There were no statistically significant differences in the emergence time, time of stay in PACU, and incidence of adverse events during surgery and in PACU among the three groups ( P>0.05). Conclusions:Oral midazolam solution provides good effect with less adverse reactions when used for preoperative sedation in the pediatric outpatients undergoing root canal treatment under general anesthesia.