Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

Objective To systematically evaluate the risk prediction models for anastomotic leakage (AL) in patients with esophageal cancer after surgery. Methods A computer-based search of PubMed, EMbase, Web of Science, Cochrane Library, Chinese Medical Journal Full-text Database, VIP, Wanfang, SinoMed and CNKI was conducted to collect studies on postoperative AL risk prediction model for esophageal cancer from their inception to October 1st, 2023. PROBAST tool was employed to evaluate the bias risk and applicability of the model, and Stata 15 software was utilized for meta-analysis. Results A total of 19 literatures were included covering 25 AL risk prediction models and 7373 patients. The area under the receiver operating characteristic curve (AUC) was 0.670-0.960. Among them, 23 prediction models had a good prediction performance (AUC>0.7); 13 models were tested for calibration of the model; 1 model was externally validated, and 10 models were internally validated. Meta-analysis showed that hypoproteinemia (OR=9.362), postoperative pulmonary complications (OR=7.427), poor incision healing (OR=5.330), anastomosis type (OR=2.965), preoperative history of thoracoabdominal surgery (OR=3.181), preoperative diabetes mellitus (OR=2.445), preoperative cardiovascular disease (OR=3.260), preoperative neoadjuvant therapy (OR=2.977), preoperative respiratory disease (OR=4.744), surgery method (OR=4.312), American Society of Anesthesiologists score (OR=2.424) were predictors for AL after esophageal cancer surgery. Conclusion At present, the prediction model of AL risk in patients with esophageal cancer after surgery is in the development stage, and the overall research quality needs to be improved.

Abstract In April 2021, type Ⅰ vaccine-derived poliovirus (VDPV) was detected from two fecal samples of a male infant with acute flaccid paralysis (AFP) in Zhejiang Province when he was admitted to the Children's Hospital Affiliated to Fudan University in Shanghai, with 12 and 14 nucleotide mutations in the VP1 region, respectively. The case had a history of immunization with three doses of poliovirus vaccines, and grade Ⅲ proximal muscle strength and grade Ⅱ distal muscle strength of the right lower limb. After symptomatic treatment, the activity of the right lower limb and the muscle strength was significantly restored, thus he was discharged. VDPV was not detected from subsequent (the 8th to 12th) fecal samples of the case and fecal samples of close contacts. No similar cases were found in medical institutions in the county, surrounding areas, neighboring villages or towns. Since the case did not exhibit clinical symptoms of poliomyelitis caused by VDPV, poliomyelitis was excluded, and the case was diagnosed with hemophilia type A based on the epidemiological investigation, laboratory tests, and the history of poliomyelitis vaccination. This event involved cross-provincial (municipal) cooperation and was responsed promptly, preventing further spread of the virus. It suggested that the sensitivity of the AFP case surveillance system should be maintained, environmental monitoring methods should be increased, and the poliomyelitis vaccination should be promoted to prevent the spread of the virus.

ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

“Runner’s high” refers to a momentary sense of pleasure that suddenly appears during running or other exercise activities, characterized by anti-anxiety, pain relief, and other symptoms. The neurobiological mechanism of “runner’s high” is unclear. This review summarizes human and animal models for studying “runner’s high”, analyzes the neurotransmitters and neural circuits involved in runner’s high, and elucidates the evidence and shortcomings of researches related to “runner’s high”. This review also provides prospects for future research. Research has found that exercise lasting more than 30 min and with an intensity exceeding 70% of the maximum heart rate can reach a “runner’s high”. Human experiments on “runner’s high” mostly use treadmill exercise intervention, and evaluate it through questionnaire surveys, measurement of plasma AEA, miRNA and other indicators. Animal experiments often use voluntary wheel running intervention, and evaluate it through behavioral experiments such as conditional place preference, light dark box experiments (anxiety), hot plate experiments (pain sensitivity), and measurement of plasma AEA and other indicators. Dopamine, endogenous opioid peptides, endogenous cannabinoids, brain-derived neurotrophic factor, and other substances increase after exercise, which may be related to the “runner’s high”. However, attention should be paid to the functional differences of these substances in the central and peripheral regions, as well as in different brain regions. Moreover, current studies have not identified the targets of the neurotransmitters or neural factors mentioned above, and further in-depth researches are needed. The mesolimbic dopamine system, prefrontal cortex-nucleus accumbens projection, ventral hippocampus-nucleus accumbens projection, red nucleus-ventral tegmental area projection, cerebellar-ventral tegmental area projection, and brain-gut axis may be involved in the regulation of runner’s high, but there is a lack of direct evidence to prove their involvement. There are still many issues that need to be addressed in the research on the neurobiological mechanisms of “runner’s high”. (1) Most studies on “runner’s high” involve one-time exercise, and the characteristics of changes in “runner’s high” during long-term exercise still need to be explored. (2) The using of scales to evaluate subjects lead to the lacking of objective indicators. However, some potential biomarkers (such as endocannabinoids) have inconsistent characteristics of changes after one-time and long-term exercise. (3) The neurotransmitters involved in the formation of the “runner’s high” all increase in the peripheral and/or central nervous system after exercise. Attention should be paid to whether peripheral substances can enter the blood-brain barrier and the binding effects of neurotransmitters to different receptors are completely different in different brain regions. (4) Most of the current evidence show that some brain regions are activated after exercise. Is there a functional circuit mediating “runner’s high” between these brain regions? (5) Although training at a specific exercise intensity can lead to “runner’s high”, most runners have not experienced “runner’s high”. Can more scientific training methods or technological means be used to make it easier for people to experience the “runner’s high” and thus be more willing to engage in exercise? (6) The “runner’s high” and “addiction” behaviors are extremely similar, and there are evidences that exercise can reverse addictive behaviors. However, why is there still a considerable number of people in the sports population and even athletes who smoke or use addictive drugs instead of pursuing the “pleasure” brought by exercise? Solving the problems above is of great significance for enhancing the desire of exercise, improving the clinical application of neurological and psychiatric diseases through exercise, and enhancing the overall physical fitness of the population.

ObjectiveTo explore the mechanism by which Ruyan Neixiao cream （RUC） induces ferroptosis in breast precancerous lesion （BPL） cells， and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%， 2%， and 4% concentrations of Ruyanneixiao Cream transdermal solution （RUT） was assessed using cell counting kit-8 （CCK-8） and a colony formation assay. Reactive oxygen species （ROS） were measured using the DCFH-DA probe， and the levels of ferrous ions （Fe²⁺）， glutathione （GSH）， and malondialdehyde （MDA） were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY^581/591 fluorescent probe. The expression of nuclear factor E₂-related factor 2 （Nrf2）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） proteins was analyzed by Western blot. The BPL rat model was constructed using 2，2′-bis（hydroxymethyl）butyric acid （DMBA） combined with estrogen and progesterone， and the rats were treated with RUC for external application. After the 12^th cycle， the rats were euthanized， and histopathological changes in breast tissue were observed by hematoxylin-eosin （HE） staining. Fe²⁺ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2， SLC7A11， and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry （IHC） and Western blot. ResultsCompared with the matrix group， the cell viability of MCF-10AT cells in the 1%， 2%， and 4% RUT groups was significantly reduced （P<0.05） in a concentration-dependent manner， with the 24-hour half inhibitory concentration （IC₅₀） being 2.23%. Compared with the 4% RUT group， cell viability in the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the colony formation rates of MCF-10AT cells in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the cell colony formation rate of the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the levels of ROS and Fe²⁺ in the 1%， 2%， and 4% RUT groups were significantly increased （P<0.05）， while GSH levels were significantly decreased （P<0.05）， and MDA and lipid peroxidation levels were significantly increased （P<0.05）. Compared with the 4% RUT group， ROS and Fe²⁺ levels in the RUT + Fer-1 group were significantly reduced （P<0.05）， while GSH levels were significantly increased （P<0.05）， and MDA and lipid peroxidation levels were significantly reduced （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the RUT + Fer-1 group were significantly increased （P<0.05）. In the in vivo experiment， compared with the matrix group， the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved， with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group， Fe²⁺ and MDA levels in the mammary tissue of the RUC group were significantly increased （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the mammary tissue of the RUC group were significantly reduced （P<0.05）. ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway， increasing Fe²⁺ accumulation， and promoting lipid peroxidation.

ObjectiveTo explore the mechanism by which Ruyan Neixiao cream （RUC） induces ferroptosis in breast precancerous lesion （BPL） cells， and to enrich the theoretical foundation for its use in the treatment of BPL. MethodsThe inhibition of cell proliferation by 1%， 2%， and 4% concentrations of Ruyanneixiao Cream transdermal solution （RUT） was assessed using cell counting kit-8 （CCK-8） and a colony formation assay. Reactive oxygen species （ROS） were measured using the DCFH-DA probe， and the levels of ferrous ions （Fe²⁺）， glutathione （GSH）， and malondialdehyde （MDA） were determined using appropriate kits. Lipid peroxidation was detected with the C11-BODIPY^581/591 fluorescent probe. The expression of nuclear factor E₂-related factor 2 （Nrf2）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） proteins was analyzed by Western blot. The BPL rat model was constructed using 2，2′-bis（hydroxymethyl）butyric acid （DMBA） combined with estrogen and progesterone， and the rats were treated with RUC for external application. After the 12^th cycle， the rats were euthanized， and histopathological changes in breast tissue were observed by hematoxylin-eosin （HE） staining. Fe²⁺ and MDA levels in breast tissue were measured using corresponding kits. The expression of Nrf2， SLC7A11， and GPX4 proteins in BPL rat breast tissue was detected by immunohistochemistry （IHC） and Western blot. ResultsCompared with the matrix group， the cell viability of MCF-10AT cells in the 1%， 2%， and 4% RUT groups was significantly reduced （P<0.05） in a concentration-dependent manner， with the 24-hour half inhibitory concentration （IC₅₀） being 2.23%. Compared with the 4% RUT group， cell viability in the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the colony formation rates of MCF-10AT cells in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the cell colony formation rate of the RUT + Fer-1 group was significantly increased （P<0.05）. Compared with the matrix group， the levels of ROS and Fe²⁺ in the 1%， 2%， and 4% RUT groups were significantly increased （P<0.05）， while GSH levels were significantly decreased （P<0.05）， and MDA and lipid peroxidation levels were significantly increased （P<0.05）. Compared with the 4% RUT group， ROS and Fe²⁺ levels in the RUT + Fer-1 group were significantly reduced （P<0.05）， while GSH levels were significantly increased （P<0.05）， and MDA and lipid peroxidation levels were significantly reduced （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the 1%， 2%， and 4% RUT groups were significantly decreased （P<0.05）. Compared with the 4% RUT group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the RUT + Fer-1 group were significantly increased （P<0.05）. In the in vivo experiment， compared with the matrix group， the breast tissue histopathological status of the BPL rats in the RUC group was effectively improved， with less dilatation of the mammary ducts and more orderly duct arrangement. No pathological morphology indicative of invasive cancer was observed. Compared with the matrix group， Fe²⁺ and MDA levels in the mammary tissue of the RUC group were significantly increased （P<0.05）. Compared with the matrix group， the protein expression levels of Nrf2， SLC7A11， and GPX4 in the mammary tissue of the RUC group were significantly reduced （P<0.05）. ConclusionRUC may induce ferroptosis in BPL cells by inhibiting the Nrf2/SLC7A11/GPX4 signaling pathway， increasing Fe²⁺ accumulation， and promoting lipid peroxidation.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective To understand the current situation of nutrition literacy of primary and secondary school students in Shijingshan District of Beijing, and analyze its influencing factors, and to put forward targeted suggestions for improving the students’ nutrition literacy and promoting their healthy growth. Methods A multi-stage stratified cluster sampling method was used to select 2480 primary and secondary school students and their parents from 5 primary schools, 3 middle schools and 1 high school in Shijingshan District. The multivariate logistic regression model was used to analyze the factors influencing the attainment rate of nutrition literacy. Results The median score of nutrition literacy of 2480 primary and secondary school students from grades 1 to 12 was 77.86 (in hundred-mark system), the quartile range (IQR) was 16.96, and the attainment rate of nutrition literacy was 42.46%. The cognitive level (45.12%) was higher than the skill level (41.20%) among students from grades 3 to 12. In terms of skills, the attainment rate of food preparation was the lowest, at 30.38%. The scores of nutrition literacy of girls were higher than those of boys, and the scores of primary school students were higher than those of secondary school students. Students with different levels of caregiver’s education, family income, and family food environment had different scores of nutrition literacy, and the differences were statistically significant (P<0.05). Multivariate logistic regression analysis showed that the attainment rate of nutrition literacy was closely related to student’s gender and study stage, caregiver’s education level, and family food environment. Conclusion The nutrition literacy of primary and secondary school students in Shijingshan District still needs to be improved, especially in the aspect of skills. Targeted nutrition education should be carried out.