OBJECTIVE: To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer. METHODS: Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve. RESULTS: A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration. CONCLUSION It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.
Humans ; Female ; Adult ; Middle Aged ; Adolescent ; Breast Neoplasms/epidemiology* ; Cardiovascular Diseases/etiology* ; Proportional Hazards Models ; Logistic Models ; China/epidemiology*

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.
Animals ; Disease Models, Animal ; Dopamine ; Melatonin ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Myopia ; Retina ; Sensory Deprivation

Aim To establish an in vitro fluorescence spectrophotometry based on the end-product malondialdehyde(MDA)for evaluating hydroxyl radical-scavenging ability, and compare the advantages and disadvantages of fluorescence and visible methods.Methods The reaction time, temperature, and the concentration of key reactant deoxyribose were investigated and optimized respectively.Under different solvent conditions, sensitivity and the measurement window of two methods were compared.The hydroxyl radical scavenging ability of tanshinone I was determined by these two methods.Results The optimal temperature and time was 37 °C and 60 min, and the concentration of deoxyribose was 2.8 mmol·L-1.The limit of detection for the fluorescence method(4.49 nmol·L-1)was much lower than that of the visible spectrophotometry(39.15 nmol·L-1).The ratio of model/control(the measurement window)of the fluorescence method was much larger than that of visible spectrophotometry in both the aqueous system and the organic system(containing DMSO).Within the concentrations of 62.5 mg·L-1-1 000 mg·L-1, tanshinone I showed scavenging ability on hydroxyl radicals in a concentration-dependent manner using the fluorescence method, but the visible method could not.Conclusions In contrast to visible method, fluorescence method has the advantages of higher sensitivity and stronger anti-interference ability to the color of test substance and the specificity of solvents.By virtue of large measurement window, it can be applied to evaluating the effect of fat-soluble test substances.

As the pipelines of nutrient and oxygen in the brain, cerebral vessels play an important role in the development and normal function of the brain. The development of the cerebrovascular system is divided into two processes, primitive vasculogenesis and angiogenesis. In this review, we summarize the roles, regulation mechanisms, as well as the interactions of the essential signaling molecules, such as the family members of vascular endothelial growth factor（VEGF）, neuropillin, Wnt, Notch, Hedgehog, in the vessel development, aiming to provide a reference for the basic and clinical investigation and the prevention and treatment of vascular diseases. Reset.

Activation and inflammation of microglial correlate with progressive neuronal apoptosis in neurodegenerative disorders such as Parkinson’ s disease (PD). γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, has recently been shown to play an inhibitory role in the immune system, but the mechanism is unclear. In this study, the results showed that LPS promoted the release of inflammatory factors in a dose-dependent manner compared with the control group (P<0. 01). Meanwhile, cell viability and cytotoxicity assays showed that the released inflammatory factors could induce the decline of SH-SY5Y cell viability. BV2 microglia cells were pretreated with GABA and Muscimol, a GABA

Objective:To compare the contents of adenosine， gastrodin， p-hydroxybenzyl alcohol， p-hydroxybenzaldehyde， parisinin B and parisinin A in Chijian （the aerial part of Gastrodia elata） and Gastrodiae Rhizoma， and compare their effects on immune function and intestinal microflora， evaluating whether it is necessary to study and develop Chijian. Method:The contents of these six constituents were determined by ultra performance liquid chromatography （UPLC）， the mobile phase was 0.1% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-4 min， 0.5%B； 4-5 min， 0.5%-2%B； 5-10 min， 2%-15%B； 10-12 min， 15%-20%B； 12-15 min， 20%-95%B； 15-17 min， 95%B； 17-17.5 min， 95%-0.5%B； 17.5-20 min， 0.5%B）， the flow rate was 0.5 mL·min^-1， the detection wavelength was 270 nm. The difference of pharmacological activity of water extracts of Chijian and Gastrodiae Rhizoma was compared， the clearance index， corrected clearance index and peripheral blood were measured in mice model with low immune function induced by cyclophosphamide， B lymphocyte proliferation was determined by lymphocyte transformation test in vitro， intestinal microflora was analyzed by 16S rDNA technology and bioinformatics was conducted. Result:The total contents of these six components in powder and ethanol extract of Chijian were higher than that of Gastrodiae Rhizoma， but the total contents of these six components in their water extract were similar， and the total contents of gastrodin and p-hydroxybenzyl alcohol met the requirements of the 2020 edition of Chinese Pharmacopoeia. Compared with the blank group， the clearance index of immunocompromised mice was significantly increased in the middle-dose （10 g·kg^-1） group of Chijian water extract， middle- and low-dose （10， 5 g·kg^-1） groups of Gastrodiae Rhizoma water extract （P<0.05）， the levels of erythrocyte and hematocrit in peripheral blood were significantly increased in the high-dose （20 g·kg^-1） groups of water extracts of Chijian and Gastrodiae Rhizoma （P<0.05， P<0.01）， water extract of Gastrodiae Rhizoma with concentration of 400 g·L^-1 and the water extract of Chijian with the concentration of 100 g·L^-1 could promote the proliferation of B lymphocytes induced by lipopolysaccharide. Studies on intestinal microflora showed that compared with the blank group， at the phylum level， the water extracts of Chijian and Gastrodiae Rhizoma increased the relative abundance of Bacteroidetes and decreased the relative abundance of Firmicutes， at the genus level， they increased the relative abundance of Prevotellaceae_UCG-001 and Ruminococcaceae_UCG-005， and decreased the relative abundance of Anaerotruncus， unclassified_f_Erysipelotrichaceae and Candidatus_Stoquefichus. These intestinal bacteria were related to the immune system， cell proliferation， and metabolism regulation. Conclusion:The total contents of 6 components in the powder， the ethanol and the water extracts of Chijian are higher than or close to those of the corresponding samples of Gastrodiae Rhizoma， the pharmacological activity of Chijian water extract is similar to that of Gastrodiae Rhizoma water extract， indicating that Chijian is worthy of further research and development.

Objectives: To investigate the prevalence and associated risk factors of tinnitus in Sichuan and Chongqing. Methods: We designed a tinnitus epidemiological questionnaire. The multi-stage stratified cluster random sampling methods was applied to obtain study subjects in six areas (Nanchong, Jiangjin, Fengdu, Yunyang, Suining and Ya'an), which were selected for epidemiological investigation. Home visit completion of epidemiological questionnaires was conducted. The trained investigators guided the respondents to fill in the tinnitus epidemiological questionnaires, and the epidemiological status of six areas on prevalence and risk factor was investigated. SPSS 22.0 software was used for statistical analysis. Results: Sampling population were 10 289, in which 9 273 were valid questionnaires. There were 4 281 males and 4 992 females, with an average age of 47.3 years, among which 34.83% (3 230/9 273) had tinnitus. 3.99% (370/9 273) were diagnosed with bothersome tinnitus. In a multivariable logistic regression mod, the following factors were associated with onsetting of tinnitus: sleep disorder [Odds Ratio(OR)=3.74] and noise exposure(OR=1.99). The risk of disease was lowest in the age of 30-40 years old, while the risk of disease was higher for people under 30 and over 40. In another multivariable logistic regression mode, the following factors were associated with having bothersome tinnitus: older people were more likely to suffer from tinnitus, sleep disorders (OR=4.68) and noise exposure (OR=1.56). Conclusions: The prevalence of tinnitus in Sichuan and Chongqing is about 34.83%, but most of the tinnitus is short-lived and has low loudness, which will not affect the patients. Only a small number of patients with tinnitus (3.99%) persist and affect their health and need treatment. The occurrence and exacerbation of tinnitus may be related to sleep, age, and noise exposure.
Adult ; Aged ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; Tinnitus/epidemiology*

Coronary artery disease (CAD)is a major cause of death and disability worldwide, and consumes a considerable amount of medical resources every year.Clopidogrel is a first-line antiplate-let therapy for CHD, butit is associated with substantial variability in PK and pharmacodynamics re-sponse. To date, gene variants explain only a smallproportion of the variability.The study aimed to identify new genetic loci-modifying antiplatelet response to clopidogrel in Chinese patients with CAD by a systematic analysis combining antiplatelet effects and PK, and further to investigate the PON1 gene promoter DNA methylation and genetic variations possibly influencing clinical outcomes in pa-tients undergoing PCI. We identified novel variants in two transporter genes (SLC14A2rs12456693, ATP-binding cassette [ABC]A1 rs2487032) and in N6AMT1 (rs2254638) associated with P2Y12 reac-tion unit (PRU) and plasma active metabolite (H4) concentration. These new variants dramatically im-proved the predictability of PRU variability to 37.7％. The associations between these loci and PK pa-rameters of clopidogrel and H4 were observed in additional patients, and its function on the activation of clopidogrel was validated in liver S9 fractions (P<0.05). Rs2254638 was further identified to exert a marginal risk effect formajor adverse cardiac events in an independent cohort.Multivariate logistic regression analysis indicated that PON1methylation level at CpG site-161 (OR=0.95; 95％ CI=0.92–0.98;P<0.01)and the use of angiotensin converting enzyme inhibitors(OR=0.48;95％ CI=0.26–0.89;P<0.01) were associated with decreased risk of bleeding events. In conclusion, new genetic variants were systematically identified as risk factors for the reduced efficacy of clopidogrel treatment.The ab-normal expression of DNA methylation-regulating key genes in the pharmacokinetic and pharmacody-namics pathways of clopidogrel and aspirin may modify clinical outcomes in dual antiplatelet-treated pa-tients undergoing PCI.

This prospective study was conducted to compare risk factors and pregnancy outcomes between women with complete placenta previa and those with incomplete placenta previa diagnosed in mid-pregnancy.The study was carried out from April 2014 to December 2015,during which 70 patients with complete previa and 113 with incomplete previa between 20+0 weeks and 25+6 weeks of gestation were included.Maternal demographics and pregnancy outcomes were compared between the two groups.Comparisons between categorical variables were tested by chi-squared test and those between continuous variables by Student t test.Resolution ofprevia occurred in 87.43％ of the studied women.The mean gestational age at resolution was 32.1±4.4 weeks.Incidence of maternal age ≥35 years and incidence of prior uterine operation ＞3 were high in women with complete previa (28.6％vs.8.8％,P=0.003;28.6％ vs.8.8％,P=0.003).Resolution of previa occurred less often in complete previa group (74.3％ vs.95.6％,P=0.001).Women with complete previa admitted earlier (37.3±2.0 weeks vs.38.1±1.4 weeks,P=0.011) and delivered earlier (37.7±1.2weeks vs.38.3±1.4 weeks,P=0.025).Maternal age ≥35 years and prior uterine operation ＞3 increase the risk of complete previa in mid-pregnancy.Placenta previa is more likely to persist in women with complete previa than those with incomplete previa diagnosed in midpregnancy.What is more,women with complete previa in mid-pregnancy deliversearlier.