OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.

Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals ; Deep Brain Stimulation/methods* ; Nucleus Accumbens/physiology* ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

The liver's remarkable regenerative capacity is crucial to restore its function, which can be compromised in cases of severe or chronic liver injury. Thus, the search of new methods to promote liver regeneration is of great clinical importance. In recent years, the gut microbiota is an emerging field of research that attracts the scientific community. The gut microbiota not only affects the integrity of digestive system but also exerts a significant impact on liver function via the so-called " gut-liver axis". Increasing evidence suggests that an imbalance in gut microbiota is associated with the development of various liver diseases, and modulation of gut microbiota might be a potential cure for liver diseases. Research into the role of gut microbiota in liver regeneration not only help us understand the pathogenesis of liver diseases but also facilitate the development of new therapeutic strategies.

AIM:To investigate the role of ClC-3 chloride channel in the promotion of radio sensitization of na-sopharyngeal carcinoma CNE-2Z cells by dihydroartemisinin(DHA).METHODS:MTT was used to detect the inhibito-ry effect of DHA on the viability of CNE-2Z cells and normal nasopharyngeal epithelial NP69-SV40T cells,the radio sensi-tization effect of DHA on CNE-2Z cells was detected by cloning assay,the expression of ClC-3 protein was detected by Western blot,the expression of ClC-3 protein was down-regulated by siRNA technology,and the chlorine current of cells was recorded by whole cell patch-clamp technology.RESULTS:(1)Compared with NP69-SV40T cells,DHA selective-ly inhibited the proliferation of CNE-2Z cells,with IC10 values of(13.020±4.831)μmol/L and(5.244±1.050)μmol/L,respectively(P＜0.01).(2)The results of clonal formation experiments showed that DHA had a radio sensitizing effect on CNE-2Z cells,with a radio sensitization ratio of 1.9.(3)DHA could activate the chlorine channel of CNE-2Z cells and produce an outward chlorine current,but had no effect on the chlorine channel of NP69-SV40T cells.(4)DHA promoted the expression of ClC-3 chloric channel protein in CNE-2Z cells(P＜0.01).(5)Chlorine channel blocker NPPB could in-hibit the radio sensitizing effect of DHA on CNE-2Z cells by 1.84 times,and also inhibited the chlorine current activated by DHA.(6)the down-regulation of CNE-2Z ClC-3 protein could inhibit the radio sensitization effect of DHA on CNE-2Z cells by 4.19 times,and the activation of chlorine current by DHA on CNE-2Z cells was no longer produced.CONCLU-SION:DHA has a radio sensitizing effect on nasopharyngeal carcinoma CNE-2Z cells,which is likely to be related to the activation of ClC-3 chloride channel.

Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1)in ath-erosclerosis induced by chronic intermittent hypoxia(CIH).Methods ApoE-/-mice were randomly divided into blank group,model group and experimental group.The mice in the model group and the experimental group were kept in a hypoxic environment and fed with a high-fat diet.After 4 weeks of high-fat feeding,mice in the experi-mental group were intraperitoneally injected with TREM-1 inhibitor LR12(5 mg/kg)for 8 weeks.After 12 weeks of feeding,the level of serum total cholesterol(TC),low density lipoprotein(LDL),triglyceride(TG),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)were detected.Histological analysis of aortic TREM-1 expression,plaque area and macrophage level were examined.Results Compared with blank group,the expression of TREM-1 in the aorta of the model group significantly increased(P＜0.05).Com-pared with model group,the aortic plaque,the level of lipids in serum(TC,LDL,TG)and inflammatory factors(TNF-α,IL-1β,IL-10),aortic plaque,the expression of TREM-1 and infiltrating macrophages in aortic plaque of the experimental group were all significantly reduced(P＜0.05).Conclusions TREM-1 is involved in the develop-ment of CIH-induced AS.Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.

【Objective:】 To analyze and explore the key points of the ethical review of real-world research in pediatric population, and to provide reference for ethical review of real-world research in pediatric population. 【Methods:】 According to the characteristics of real-world research and pediatric clinical trials, the review points of real-world research in pediatric population were analyzed and discussed in comparison with the principles and focus of ethical review in general clinical research. 【Results:】 The ethics committee should pay particular attention to the review of informed consent, privacy protection, risk benefit assessment, cost and compensation, and should also take into account the research design, data governance, research conflicts of interest, research registration and publication, etc., and conduct scientific and reasonable ethical review of real-world research in pediatric population. 【Conclusion:】 Clinical trials in pediatric population should have stricter and scientific ethical review, which can not only protect the interests of vulnerable groups of minors, but also standardize real-world research in pediatric population and promote the healthy development of pediatric clinical research, so as to better protect children and promote their health.

By collecting 475 protocol violation reports of pediatric clinical trials accepted by the ethics committee of a grade A tertiary hospital from January 2016 to December 2022, and conducting classification statistics of the responsible body, types of violation, and natures of violation, this paper analyzed and discussed the specific reasons and response measures for protocol violation. The results showed that the most common types of protocol violation included missed medication and incorrect medication dosage for pediatric research participants, missed laboratory inspection, over-windowed follow-up, and non-compliance with inclusion/exclusion criteria. And the responsibility bodies were pediatric research participants and/or their guardians, followed by the researchers. Besides, the sponsor, clinical trial coordinator, and other factors also contributed to protocol violation. Establishing awareness of responsible body, emphasizing subject management, building sound quality control system, and strengthening ethical supervision are the main countermeasures to prevent and reduce protocol violation in pediatric clinical trials, which helps to protect the safety and rights of pediatric research participants and promote standardized research in pediatric clinical trials.

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.

Objective:To comprehensively evaluate the tricuspid valve, right heart anatomical characteristics and related dynamic parameters in patients with different degrees of functional tricuspid regurgitation (FTR) using four-dimensional auto tricuspid valve quantitative(4D Auto TVQ), four-dimensional auto right ventricle quantitative(4D Auto RVQ), and four-dimensional auto left atrium quantitative(4D Auto LAQ), and to investigate the structural and functional changes of the tricuspid valve and right heart in them.Methods:Sixty-three patients with FTR diagnosed by echocardiography at the First Affiliated Hospital of Guangxi Medical University from February to July 2022 were prospectively selected as the case group, including 30 patients with mild FTR and 33 patients with moderate or above FTR, and 30 healthy subjects were selected as the control group. Transthoracic echocardiography was used for two-dimensional and three-dimensional image acquisition of the heart. The tricuspid regurgitation volume, left ventricular ejection fraction (LVEF), right ventricular global strain (RVGS) were measured by 2D images, and pulmonary artery systolic pressure (PASP) were measured from the tricuspid regurgitation pressure difference. The 3D images were imported into EchoPAC 204 to obtain the tricuspid valve, right heart structure and related dynamic parameters. The annulus area (AA), annulus perimeter(AP), spherical index (SI), annulus area change fraction (AC), coaptation point height (CPH), and tenting volume (TV) were measured by 4D Auto TVQ. The right atrial maximum volume (RAVmax) and right atrial minimum volume (RAVmin) were measured by 4D Auto LAQ. Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), right ventricular fractional area change (RVFAC) and tricuspid annular plane systolic excursion (TAPSE) were measured by 4D Auto RVQ. After standardizing the dimension parameters with body surface area (BSA), the differences in the above parameters were compared between the three groups, the correlation between regurgitant volume and each parameter was compared by correlation analysis, and the independent factors of increased tricuspid regurgitant volume were investigated by univariate and multivariate linear regression analysis.Results:There were statistically significant differences in PASP, AA/BSA, AP/BSA, AC, TV, RAVmax/BSA, RAVmin/BSA, RVFAC, RVGS, and TAPSE between the three groups (all P<0.05). There were statistically significant differences in LVEF, CPH, RVEDV/BSA, and RVESV/BSA in the moderate and above FTR group compared with the control and mild FTR groups (all P<0.05). Correlation analysis showed that RAVmin was the most highly correlated with tricuspid regurgitant volume ( r=0.875, P<0.001) and TV and end-systolic annulus area(ESAA) were highly correlated with tricuspid regurgitant volume ( r=0.747, 0.683; both P<0.001) in patients with FTR. Multifactorial linear regression showed that RAVmin, TV and regurgitant volume were independently positively correlated (β=0.721, 0.205; both P<0.05). Conclusions:The four quantification technique can provide valid structural and functional information by quantifying the tricuspid valve as well as the right heart in patients with FTR, and RAVmin and TV are independent correlates of increased tricuspid regurgitant volume.