Circular RNA(circRNA)is a novel class of endogenous non-coding RNA with complex biological func-tions,participating in various physiological and pathological processes.Due to their relatively stable stucture and tissue-specific and temporal expression patterns,circRNA have become a recent focus of biomedical research.Heart failure(HF)is characterized by impaired ventricular filling and/or ejection function caused by primary myocardial injury and car-diac overload,leading to the inability of the heart to meet the metabolic demands of the body's tissues.It is the end stage of numerous cardiac diseases.Studies have found that circRNA may play a crucial regulatory role in the progression of HF,particularly in cardiomyocyte hypertrophy,cardiomyocyte apoptosis,autophagy and myocardial fibrosis.This review summarizes the formation,classification,functional forms,and roles in HF of circRNA,aiming to provide new insights for the prevention and treatment of HF.

Objective To explore the protective mechanism of icariin on neuronal oxidative damage,providing a basic pharmacological basis for the treatment of cognitive impairment.Methods Glutamate was used to induce oxidative stress injury in HT22 cells.HT22 cells were divided into control group(normal cultured cells),model group(glutamate injury model)and experimental-L,-M,-H groups(5,10 and 20 μmol·L-1 icariin pretreatment for modeling,respectively).Cell proliferation was detected by cell counting kit-8(CCK-8)method;cytotoxicity was detected by lactate dehydrogenase(LDH)method;reactive oxygen species(ROS)levels were detected by flow cytometry;superoxide dismutase(SOD)levels were detected by biochemical kits;the expression levels of Kelch-like epichlorohydrin-related protein-1(Keap1),nuclear factor E2-related factor 2(Nrf2)were detected by Western blotting;the corresponding mRNA expression was detected by real-time fluorescence quantification polymerose chain reaction.Results The cell viability of control group,model group and experimental-L,-M,-H groups were(100.00±1.31)％,(66.38±2.44)％,(72.07±4.95)％,(82.41±3.57)％and(87.97±4.98)％;LDH release were(0.48±0.52)％,(18.82±2.09)％,(15.32±1.17)％,(10.37±1.39)％and(6.51±0.87)％;ROS level were(14.23±1.13)％,(41.74±1.60)％,(35.69±1.08)％,(33.28±1.69)％and(30.32±2.03)％;SOD levels were(54.84±1.17),(37.95±1.13),(48.02±1.28),(50.56±1.34)and(52.55±1.04)U·mg-1;Keap1 protein levels were 0.36±0.01,0.52±0.03,0.46±0.04,0.39±0.09 and 0.35±0.12;Nrf2 protein levels were 0.29±0.02,0.13±0.08,0.18±0.03,0.21±0.11 and 0.26±0.04;catalase(CAT)mRNA levels were 1.01±0.08,0.81±0.06,0.90±0.04,1.05±0.15 and 1.33±0.26;SOD mRNA levels were 1.09±0.12,0.83±0.03,0.86±0.08,0.94±0.08 and 1.09±0.16.Among the above indicators,the differences between the model group and the control group were statistically significant(all P＜0.01);the differences between the experimental-M,-H groups and the model group were statistically significant(P＜0.01,P＜0.05).Conclusion Icariin may activate the Keap1/Nrf2/antioxidant response element(ARE)signaling pathway,regulate the expression of related proteins,and reduce the level of ROS to effectively alleviate oxidative stress injury in neuronal cells.

The aim of this study was to investigate the effect of baicalein on a Drosophila model of hereditary Parkinson's disease caused by gene mutations and to preliminarily elucidate the mechanism of baicalein in delaying hereditary Parkinson's disease. In this paper, PTEN-induced putative kinase 1 (PINK1)-RNAi Parkinson's Drosophila were used as the model group and wild-type Drosophila w¹¹¹⁸ were used as the control group. Different doses of baicalein and Madopa were administered to the model group to observe their effects on the life span, motor ability, the abnormal rate of wings, dopamine content and dopaminergic neurons of PINK1-RNAi Parkinson's Drosophila and their effects on mitochondrial dysfunction including adenosine triphosphate (ATP), mitochondrial DNA (mtDNA) and reactive oxygen species (ROS) content. The results showed that the effective administration doses of baicalein were 0.8 mg·mL^-1 for low concentration, 1.6 mg·mL^-1 for medium concentration and 3.2 mg·mL^-1 for high concentration, and the optimal administration dose of the positive drug Madopa was 0.1 μg·mL^-1. Baicalein and Madopa could significantly improve the life span, exercise ability and reduce the abnormal rate of wings of PINK1-RNAi male Drosophila (P < 0.05), and low dose baicalein showed the best effect; baicalein could improve the loss of dopaminergic neurons, and the effects of low dose and high dose were the best, but Madopa showed no significant effect; baicalein and Madopa had no significant effect on dopamine content (P > 0.05). Baicalein and Madopa could increase the ATP content of PINK1-RNAi male Drosophila (P < 0.05), and low dose baicalein showed the best effect; middle dose baicalein could significantly increase the mtDNA content of PINK1-RNAi male Drosophila (P < 0.05), but Madopa had no significant effect; baicalein and Madopa had no significant effect on ROS content (P > 0.05).

A UPLC-Q-Orbitrap-MS based metabolomic approach combined with biochemical assay and histopathological inspection were employed to study the intervention effects of Suanzaoren Decoction (SZRD) on chronic unpredictable mild stress (CUMS) depression rats, and to clarify the metabolic regulation pathway of SZRD. The rats were randomly divided into normal control group, CUMS model group, positive drug venlafaxine group, SZRD high (24 g·kg^-1) and low (12 g·kg^-1) dose groups, respectively. The CUMS model was replicated by subjecting to a variety of stimulus, such as thermal stimulation, ice water swimming, ultrasonic stimulation, tail clamping, day and night reversal, plantar electric shock and so on for rats. After oral administration of drugs for 28 days, the behavioral indexes of rats in each group were observed and the hippocampus and serum samples of rats were collected for biochemical assay and histopathological inspection. Compared with the CUMS model group, low dose and high dose SZRD groups can significantly reduce the immobility time of forced swimming (P < 0.001, P < 0.001), increase the sucrose preference rate (P < 0.01, P < 0.05), the number of crossings (P < 0.05, P < 0.01) and the number of uprights (P < 0.05, P < 0.01) in the open field test, suggesting that SZRD can significantly improve the depression-like behavior of CUMS model rats. In addition, SZRD could significantly reduce the levels of serum IL-6, IL-1β and TNF-α of CUMS model rats. A total of 21 differential metabolites in serum were identified by comparison with the data from the literature and databases. In addition, low-dose SZRD and high-dose SZRD improved the 8 and 11 perturbed potential serum biomarkers that were induced by CUMS, respectively, which related to alanine, aspartic acid and glutamic acid, tryptophan and arachidonic acid metabolism. This study provides a scientific basis for expanding the clinical indications of SZRD. This experiment was approved by the Animal Ethics Committee of Shanxi University (Approval No. SXULL2020028).

Humans ; Gemcitabine ; Neoplasms

Ethnic medicine has a rich history of application. Because of the large number of ethnic groups, wide geographical distribution, and unique medical systems in China, the research on the human use experience(HUE) of ethnic medicine should combine the characteristics of ethnic medicine, be based on practical experience, and respect folk practice and tradition. The clinical positioning of ethnic medicine should consider three factors, i.e., population region, dominant diseases, and clinical demand. We should consider the development of traditional preparations that meet the needs of ethnic regions and encourage the development of new drugs that can be popularized and used nationwide for the dominant diseases of ethnic medicines. Attention should be paid to the problems such as a large number of customary articles or substitutes of ethnic medicinal materials, the phenomena of foreign bodies with the same name and different names for the same substance, the different standards of medicinal materials, and the poor processing standards. The name, processing method, source, medicinal parts, and dosage of ethnic medicinal materials or decoction pieces should be determined, and resources should be carefully evaluated to ensure the safety of medicinal resources and ecology. The preparation of ethnic medicine is mostly in the form of pills, powder, ointment, etc., with simple processing technology. The problems of low-quality stan-dards of some preparations, different prescriptions with the same name, and inconsistent processing technology should be overcome, and the process route and main process parameters should be clarified to lay the foundation for the subsequent empirical research on HUE. In the collection and analysis of the HUE data of ethnic medicine, the core guiding ideology of "patient-centered" should be established, and the experience data of patients should be collected. The problems of weak links existing in the inheritance of ethnic medicine should be solved, and flexible and diverse methods should be adopted. Meanwhile, on the premise of complying with the requirements of the principles of medical ethics, we should respect the religion, culture, and customs of ethnic areas to obtain the key HUE information of ethnic medicine. On the basis of the patient preference information and differences in regional disease epidemiology, population characteristics, and medical practice, whether the HUE conclusions of ethnic medicine can be extrapolated to patients outside the region is evaluated from the aspects of clinical benefits, risk tolerance, risk acceptance, etc. The HUE research on ethnic medicine is carried out in a clear way to guide the research and development of new ethnic medicines.
Humans ; Medicine, Chinese Traditional ; China ; Reference Standards ; Technology ; Drugs, Chinese Herbal/therapeutic use*

Objective:To explore the prognostic prediction value of quantitative digital subtraction angiography (DSA) parameters in patients with acute anterior circulation ischemic stroke undergoing mechanical thrombectomy, and whether the clinical values vary by stroke etiology.Methods:This study was a post hoc analysis of the Multicenter Prospective Captor Trial. Patients with acute anterior circulation large-vessel occlusion and successful recanalization from April 2018 to July 2019 were screened. Post-processing analysis was performed on the DSA imaging sequence after recanalization, and 4 regions of interest (ROI) were selected in the target vessel: ROI1 (the proximal of the internal carotid artery-C2 segment), ROI2 (the starting point of the internal carotid artery-C7 segment), ROI3 (the end of the middle cerebral artery-M1 segment), and ROI4 (the end of the middle cerebral artery-M2 segment). Time to peak (TTP) was defined as the time at contrast concentration of selected ROI reached its maximum. Relative TTP (rTTP) was calculated by subtracting the TTP of ROI1 from the TTP of distalis ROIs. Successful recanalization was defined as modified Thrombolysis In Cerebral Infarction (mTICI) grade≥2b. Favorable outcomes at 3 months were defined as the modified Rankin Scale score≤2. According to the modified Rankin Scale score, the patients were divided into good prognosis group and poor prognosis group. The differences in clinical characteristics, postoperative hemodynamic parameters, and other data were compared between patients with good and poor prognoses. Univariate and multivariate Logistic regression was used to analyze factors related to a good prognosis. Finally, the prognostic prediction value of hemodynamic parameters was analyzed in patients with different Trial of Org10172 in Acute Stroke Treatment etiological classifications.Results:A total of 245 patients were collected, of which 161 patients [age 69 (60, 76) years, 92 (57.1%) male] were finally included in the analysis, including 36 cases of large artery atherosclerosis (LAA) stroke, 76 cases of cardiogenic embolism (CE), and 49 cases of other causes of stroke. Seventy-one (44.1%) patients had favorable outcomes at 3 months. The post-operative hemodynamic analysis indicated that patients with favorable outcomes ( n=71) had a higher proportion of mTICI grade 3 [54/71 (76.1%) vs 41/90 (45.6%),χ 2=15.26, P<0.001] and lower rTTP 31 [means TTP ROI3-TTP ROI1;0.33 (0.23, 0.54) s vs 0.47 (0.31, 0.65) s, Z=-2.71, P=0.007] than patients with unfavorable outcomes ( n=90). The mTICI score and rTTP 31 were respectively included in multivariate Logistic regression models. It was shown that mTICI grade 3 (adjusted OR=5.97, 95% CI 2.49-14.27, P<0.001) and rTTP 31 (adjusted OR=0.24, 95% CI 0.06-0.99, P=0.048) were significantly associated with favorable outcomes, and the area under the receiver operating characteristic curve of the models had no statistically significant difference ( P=0.170). Subgroup analysis showed that rTTP 31 was significantly associated with the prognosis of patients with LAA stroke ( OR=0, 95% CI 0-0.25, P=0.014), while mTICI grade was associated with the prognosis of patients with CE ( OR=3.91, 95% CI 1.40-10.91, P=0.009) and other etiologies ( OR=7.35, 95% CI 1.92-28.14, P=0.004). Conclusions:In patients with acute anterior circulation ischemic stroke and successful recanalization, both mTICI score and rTTP 31 had significant predictive value for favorable outcomes at 3 months. Moreover, rTTP 31 was significantly associated with the prognosis of patients with LAA stroke, while mTICI score was significantly related to the prognosis of patients with CE and other causes of stroke.

OBJECTIVE: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options. METHODS: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed. RESULTS: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ²= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS. CONCLUSION POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.
Child ; Electrolytes ; Female ; Humans ; Male ; Metoprolol ; Midodrine ; Orthostatic Intolerance/therapy* ; Postural Orthostatic Tachycardia Syndrome/diagnosis* ; Retrospective Studies ; Salts ; Sitting Position ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Adolescent ; Body Mass Index ; Child ; Child, Preschool ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity/epidemiology* ; Overweight/epidemiology* ; Puberty ; Puberty, Precocious ; Sexual Development

Objective To understand the growth and dietary diversity status of children in multi-ethnic areas of Sichuan province,and to explore the associations of dietary diversity with growth and development indicators. Methods Children of 18-36 months old and their primary caregivers were selected with multi-stage cluster random sampling method from rural areas of Han,Tibetan,and Yi ethnic groups in Sichuan province. The sociodemographic information of children and their caregivers was collected using self-designed questionnaire.The dietary diversity score(DDS)was calculated according to the criteria in the Guidelines for Measuring Household and Individual Dietary Diversity released by the Food and Agriculture Organization of the United Nations.The body height(length)and body weight of each child were measured by standard equipment for anthropological measurement,and the height for age Z score(HAZ),weight for age Z score(WAZ),and weight for height Z score(WHZ) were calculated.Multivariate linear regression was performed to analyze the relationship between dietary diversity and growth indicators of children. Results A total of 1092 children were enrolled in this study,and the prevalence of stunting(HAZ<-2),underweight(WAZ<-2),and wasting(WHZ<-2)was 21.1%,4.9%,and 2.5%,respectively.The children had the mean DDS of 4.8±1.7,and 45.3% of children had poor dietary diversity(DDS≤4).The children of Han ethnic group(5.8±1.4)had higher DDS than those of Tibetan ethnic group(4.9±1.6)and Yi ethnic group(3.9±1.6)(P<0.001).The results of multivariate linear regression indicated that DDS was positively correlated with HAZ(β=0.206,95%CI=0.158-0.254,P<0.001)after adjustment of sex,age,birth weight,preterm birth,and parental body height.After further adjustment of family fixed assets,ethnic group,caregiver's type,and caregiver's education background,the correlation between DDS and HAZ remained significant(β=0.077,95%CI=0.026-0.128, P=0.003). Conclusions The children in the multi-ethnic rural areas of Sichuan province showed troublesome growth and development status and low dietary diversity,which were conspicuously different between ethnic groups,especially in the rural areas of Yi ethnic group.The dietary diversity was positively associated with HAZ.It is recommended to carry out nutrition and health education according to the local dietary characteristics and thus improve the growth and development of children in multi-ethnic rural areas in Sichuan.
Child ; Child, Preschool ; China/epidemiology* ; Ethnicity ; Female ; Growth and Development ; Humans ; Infant ; Infant, Newborn ; Nutritional Status ; Pregnancy ; Premature Birth ; Rural Population