OBJECTIVE To investigate the mechanisms of rutin in alleviating depressive symptoms associated with premenstrual dysphoric disorder （PMDD） characterized by liver qi stagnation syndrome. METHODS Network pharmacology was employed to identify the intersecting targets of action between PMDD and rutin. A protein-protein interaction network was constructed to screen core targets， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Molecular docking simulations validated rutin’s binding affinity to core targets. The bilateral ovaries of female Wistar rats were removed， followed by artificial hormone induction. The rats were then randomly divided into normal group （10 rats） and modeling group （50 rats）. PMDD rat model with liver qi stagnation syndrome was established via restraint stress. The successfully modeled rats were further divided into model group， fluoxetine group （positive control） and rutin group， with 12 rats in each group. The corresponding drug solutions or water were administered by gavage at 9：00 a.m. every day， continuing for two estrous cycles. The open-field test， forced swimming test and Y-maze test were utilized to evaluate the effects of rutin on the behavioral indexes of model rats. Additionally， the density of neuronal dendritic spines in the hippocampal tissues of the rats was observed. Serum brain-derived neurotrophic factor （BDNF） levels and the expressions of BDNF， tyrosine kinase receptor type B （TrkB）， synuclein （Syn）， and postsynaptic density protein 95 （PSD95） in hippocampal tissues were quantified， respectively. RESULTS Network pharmacology and molecular docking revealed the core targets through which rutin ameliorated PMDD characterized by liver qi stagnation syndrome included BDNF， TrkB， PSD65， Syn， etc. The results of experimental validation demonstrated that rutin significantly increased the spontaneous alternation behavior scores of PMDD model rats with liver qi stagnation syndrome during the non-receptive phase， shortened their immobility time during the forced swimming test， and enhanced the density of neuronal dendritic spines in the hippocampal tissues. Additionally， rutin upregulated the levels of serum BDNF and the protein expressions of BDNF， TrkB and Syn in the hippocampal tissues （P＜0.05）. However， it had no significant effect on the above indexes in model rats during the receptive phase （P＞0.05）. CONCLUSIONS Rutin ameliorates depressive symptoms， enhances spatial memory capabilities， and reduces neuronal damage in PMDD model rats with liver qi stagnation syndrome. These effects may be associated with the activation of BDNF/TrkB signaling pathway and upregulation of Syn protein expression.

ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

Objective:To investigate the factors influencing the short-term prognosis of patients with acute diquat poisoning (ADQP).Methods:Patients with ADQP admitted to the Affiliated Hospital of Xuzhou Medical University and Xuzhou Occupational Disease Prevention Hospital from August 2015 to July 2022 were retrospectively selected. Patients were divided into survival group and death group according to 30-day survival status after poisoning. The general data and the results of the first laboratory examination after admission were compared between the two groups. Logistic regression analysis was used to analyze the independent risk factors associated with prognosis. And the receiver operating characteristic (ROC) curve was drawn to evaluate the prognostic value of risk factors in patients with ADQP.Results:A total of 79 ADQP patients were included in this study, including 40 patients in the survival group and 39 patients in the death group. There were statistically significant differences in the age, poisoning dose, white blood cell, alanine aminotransferase, aspartate aminotransferase, serum creatinine, blood urea, neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, and systemic immune inflammation index (SII) between survival and death groups (all P<0.05). Multivariate logistic regression analysis showed that the poisoning dose ( OR=1.018, 95% CI: 1.001-1.035, P=0.033), serum creatinine ( OR=1.049, 95% CI: 1.005-1.095, P=0.028), and SII ( OR=1.001, 95% CI: 1.000-1.002, P=0.029) were independent risk factors for the prognosis of patients with diquat poisoning. The areas under the curves of the combined detection of poisoning dose, serum creatinine and SII was 0.968, the sensitivity was 0.949, and the specificity was 0.900, which were higher than those of the single index. Conclusions:The poisoning dose, serum creatinine and SII are independent prognostic predictors of patients with ADQP. The combination of three independent factors has higher sensitivity and specificity in evaluating the prognosis of ADQP, which could be used as a reliable indicator to predict the prognosis of patients with ADQP.

Objective:To investigate the therapeutic effect of exosomes derived from remote ischemic conditioning on neurological dysfunction after cardiopulmonary resuscitation in a rat model of cardiac arrest and the relationship with glycocalyx protection.Methods:Exosomes were isolated from the blood of healthy adult male Sprague-Dawley rats using ultracentrifugation after undergoing remote ischemic conditioning for use as intervention drugs. Nanoparticle tracking analysis technology was used for exosome detection. Thirty-six adult male Sprague-Dawley rats were randomly assigned to 3 groups ( n=12 each) :Sham group, Control group and Exosome group. Cardiac arrest was induced by asphyxia for 7 min in the Control and Exosome groups. Placebo or exosomes (1×10 10 Particles) were infused intravenously at 5 min after the rats had returned of spontaneous circulation. Neuropsychological deficit score (NDS), open field test, Y maze and Morris water maze were used to assess neurological outcomes. The levels of plasma Hyaluronic acid (HA) and syndecan-1 (Sdc-1) were detected by Elisa. The expression levels of matrix metalloproteinase-2/9 (MMP-2/9) in hippocampal CA1 region were detected by Western blot. Results:After undergoing remote ischemic conditioning, the plasma levels of exosomes were elevated in rats compared to normal rats. Compared with the control group, the behavioral experiment of rats in the exosomes group were significantly improved, as evidenced by an increase in horizontal locomotor distance (5.86±2.89 vs. 17.53±5.51, P< 0.05), an increase in the correct rate of spontaneous alternation (13.29±15.07 vs. 42.63±10.25, P< 0.05), and a shortening of avoidance latency (25.83±8.54 vs. 13.49±4.55, P< 0.05). Plasma HA and Sdc-1 levels were significantly lower 24 h after resuscitation (HA: 26.34±9.83 vs. 14.84±6.26, P< 0.05; Sdc-1: 0.05±0.03 vs. 0.02±0.02, P<0.05), along with significantly lower MMP-2/9 levels in hippocampal tissue. Conclusions:Exosomes extracted from the plasma of rats undergoing remote ischemic conditioning can improve neurological dysfunction after cardiac arrest in rats, and the mechanism may be related to the inhibition of metalloproteinases and the reduction of endothelial glycocalyx degradation.

Standardized cardiopulmonary resuscitation (CPR) of patients prior to the arrival of emergency medical services can significantly improve survival rate after out-of-hospital cardiac arrest (OHCA). According to statistics, about 40% to 85% of CPR led to chest fractures, making bystanders alarm, and reducing the willingness of rescuing by CPR. Therefore, there is an urgent need to develop a CPR protection device that is convenient for placing in public places outside the hospital and conforms to the operation habit of freehand CPR. In view of the above problems, medical students majored in emergency and rescue medicine and anesthesiology in Xuzhou Medical University, together with students majored in product design in Southeast University, designed a portable CPR protection device under the guidance of doctors working in department of emergency medicine of the Affiliated Hospital of Xuzhou Medical University, and obtained the national invention patent authorization of China (patent number: ZL 2021 1 0309001.4) and the national utility model patent authorization of China (patent number: ZL 2021 2 0591084.6). The device is composed of a foldable frame, support components, guide slide rails and compression body, which provides guidance and guarantee for the implementation of CPR, thus users can accurately grasp the implementation process, compression amplitude, strength and frequency, and effectively prevent accidental injuries such as rib fractures caused by CPR compression. The device is small, easy to store and move, with low manufacturing cost, making it suitable for social popularization.

Objective To investigate the role of tolerogenic dendritic cell (tolDC) in inducing immune tolerance in liver transplantation. Methods Liver transplantation rat models of spontaneous tolerance [Brown Norway (BN)→Lewis, tolerance group, n=6] and acute rejection (AR) (Lewis→BN) were established. In AR rat models, tolDC transfusion was performed in the study group (tolDC group, n=6) and no intervention was given in the control group (AR group, n=6). The survival time of rats in each group was observed. The transplant liver tissues of rats were prepared for pathological examination in each group. The expression of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) in rat peripheral blood, transplant liver, spleen and lymph nodes in each group was detected by flow cytometry. The expression levels of serum interleukin (IL)-10 and interferon (IFN)-γ in each group were measured by enzyme-linked immune absorbent assay. Results Pathological manifestations of rats in the AR group mainly included inflammatory cell infiltration and tissue structural disorder in transplant liver, and the survival time was 7-14 d. In the tolDC and tolerance groups, the transplant liver tissues were almost normal, and the longest survival time exceeded 100 d. Compared with the AR group, the expression levels of CD11⁺mDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05), and those of CD86 and major histocompatibility complex (MHC)Ⅱon the surface of CD11⁺mDC were also significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of pDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly up-regulated in the tolerance and tolDC groups (all P < 0.05), whereas those of MHCⅡon the surface of pDC were all significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of serum IL-10 were significantly up-regulated, and IFN-γ were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05). Conclusions As tolDC subsets, mDC and pDC play a positive role in regulating the incidence of graft immune tolerance in rats after liver transplantation.

Objective To investigate the role of CD4⁺CD45RC^low regulatory T cell (Treg) in the immune tolerance induction of rats undergoing liver transplantation. Methods Liver transplantation rat models of acute rejection (AR) [Lewis→Brown Norway (BN), AR group] and spontaneous tolerance (BN→Lewis, tolerance group) were established, with 6 rats in each group. Moreover, 3 Lewis rats and 3 BN rats were assigned into the sham operation group (control group). The liver tissues of rats in each group were subject to pathological staining. The expression of T cell subsets and plasmacytoid dendritic cells (pDC) in the peripheral blood, liver graft and spleen of rats was detected in each group. The correlation between pDC and CD4⁺CD45RC^lowTreg was analyzed. The expression levels of CD4, CD45RC and CD103 in the liver graft and spleen of rats were quantitatively measured in each group. Results In the AR group, pathological manifestations mainly consisted of inflammatory cell infiltration and structure disorders of transplant liver. Compared with the AR group, the expression levels of CD4⁺CD25⁺Treg and CD8⁺Treg in the peripheral blood were significantly up-regulated in the tolerance group (all P < 0.05). In the peripheral blood, the expression level of CD4⁺CD25⁺Treg was positively correlated with that of CD8⁺Treg (r=0.742, P=0.022). In the AR group, the expression level of CD4⁺CD45RC^highT cell in the peripheral blood was significantly higher than those in the tolerance and control groups (both P < 0.05). Compared with the AR group, the expression level of CD4⁺CD45RC^lowTreg in the spleen, and the expression levels of CD8⁺CD45RC^lowTreg in the peripheral blood, transplant liver and spleen were significantly up-regulated in the tolerance group (all ^P < 0.05). Compared with the control and AR groups, the ratio of CD8⁺CD45RC^lowTreg/CD8⁺T in the peripheral blood and the expression levels of pDC in the peripheral blood, transplant liver and spleen were all significantly up-regulated in the tolerance group (all P < 0.05). The expression level of CD4⁺CD45RC^lowTreg was positively correlated with the changes of pDC (r=0.506, P=0.016). The expression levels of CD4, CD45RC and CD103 in the transplant liver and spleen of rats were up-regulated in the tolerance group. In the AR group, the expression levels of CD4 and CD45RC were up-regulated, whereas that of CD103 was down-regulated. Conclusions CD4⁺CD45RC^lowTreg is a cell subgroup with negative immune regulation, which may construct a regulatory cell network of immune tolerance induction along with CD8⁺CD45RC^lowTreg and pDC.

Objective:To investigate the predicting value of high sensitivity C-reactive protein (hs-CRP) and albumin (Alb) ratio on prognosis of patients with in-hospital cardiac arrest (IHCA).Methods:A total of 107 patients with IHCA and spontaneous circulation recovery (ROSC) after cardiopulmonary resuscitation (CPR) in the Affiliated Hospital of Xuzhou Medical University during January 1, 2017 and September 30, 2020 were selected as the subjects and divided into the survival group and death group according to the survival condition on day 14 after IHCA. The correlation between ratio of high sensitivity C-reactive protein/albumin (hs-CRP/Alb) and the prognosis of patients was analyzed.Results:No statistical significant differences were found between the survival and death groups in sex, age, medical history, ECG monitoring, recovery ventilation mode, percentage of first monitoring of heart rate and pre-resuscitation Alb (all P > 0.05). However, there were significant differences in the percentage of non-cardiogenic CA and adrenaline dose > 5 mg, time of CPR, concentrations of blood lactic acid, Alb, hs-CRP, and ratio of hs-CRP/Alb (all P < 0.05). Logistic regression analysis showed that percentage of adrenaline dose > 5 mg, concentration of blood lactic acid, time of CPR, and ratio of hs-CRP/Alb were independent risk factors for predicting death. ROC curve analysis showed that hs-CRP/Alb ratio, and concentration of hs-CRP and Alb had predictive value on the death of patients with IHCA; the areas under the curves of hs-CRP/Alb ratio, hs-CRP and Alb concentration were 0.876, 0.864 and 0.745, respectively. The predictive efficiency of hs-CRP/Alb ratio was better than that of hs-CRP concentration or Alb concentration. Conclusions:hs-CRP/Alb ratio has predictive value for the prognosis of patients with IHCA and the predictive value is superior to that of hs-CRP and Alb concentration.

Objective:To explore the clinical utility of liquid chromatography tandem mass spectrometry forprimary aldosteronism screening.Methods:From January to October 2019, 413 inpatients diagnosed hypertension from Fuwai Hospital of Chinese Academy of Medical Sciences were enrolled, including 60 Primary aldosteronism(PA)patients and 353 primary hypertension patients. The plasma aldosterone concentration (PAC) and renin concentration (DRC) were measured after 2 h of standing. The 24 h urine samples were collected for measurement of aldosterone using LC-MS/MS. The performance of urine aldosterone and urine aldosterone/renin ratio (UADRR) in PA screening was evaluated by ROC, and compared with PAC/DRC ratio (ADRR). Meanwhile, the efficiency of urine aldosterone in elderly patients or patients with low blood potassium or 24 h urine sodium over 200 mmol was investigated.Results:Area under the curve (AUC)of urine aldosterone was 0.725 (95 %CI 0.679-0.767), and the best cut-off was 7.13 μg/24 h, which was lower than AUC of ADRR (0.958, 95 %CI 0.934-0.975). The AUC of UADRR was 0.947 (95 %CI 0.920-0.966), the best cut-off was 1.11 (μg/24 h)/(μIU/ml), the sensitivity and specificity were 91.7% and 89.0%, respectively. There is no significant differences found with ADRR. In patients with 24 h urine sodium over 200 mmol, AUC of aldosterone was 0.834 (95 %CI 0.730-0.910) and the best cut-off was 9.31 μg/24 h. The sensitivity and specificity were 90.9% and 68.7%, respectively. For the elderly patients over 60 years old, the AUC of urinary aldosterone was 0.860 (95 %CI 0.770-0.925), and the best cut-off was 6.91 μg/24 h. The sensitivity and specificity were 84.6% and 81.3%, respectively. When admission blood potassium was less than 3.50 mmol/L, AUC of urinary aldosterone was 0.822 (95 %CI 0.684-0.917), and the best cut-off was 10.63 μg/24 h. The sensitivity and specificity were 85.7% and 66.7%, respectively. Conclusion:The detection of aldosterone in urine by LC-MS/MS can provide clinical information for PA screening, and the screening performance is better in patients with 24-hour urine sodium over 200 mmol, elderly patients or patients with low blood potassium. If combined with renin, screening efficiency was the same as that in ADRR.

Objective: To assess the value of multi-parametric MRI in mammographically detected breast imaging reporting and data systems (BI-RADS) 3 to 4 exclusive microcalcifications. Methods: A retrospective analysis was performed in 152 patients with mammographically detected BI-RADS 3 to 4 exclusive microcalcifications from January 2013 to December 2017. All patients underwent bilateral breast multi-parametric MRI before surgical biopsy. Microcalcifications were classified according to BI-RADS by two radiologists with more than 10 years′ experience in breast imaging. The area under the curve (AUC), sensitivity and specificity of BI-RADS 3 to 4 exclusive microcalcifications diagnosis by mammography and mammography plus MRI were calculated and compared using pathology as the gold standard. Results: A total of 152 lesions (93 benign lesionsand 59 malignant lesions) were assessed in this study. The positive predictive value (PPV) of mammography for BI-RADS 3, 4A, 4B and 4C microcalcifications diagnosis were 22.2%(16/72), 5.0%(1/20), 48.5%(17/35) and 100.0%(25/25) respectively. The PPV of MRI for BI-RADS 2, 3, 4, 5 microcalcifications diagnosis were 1.6%(1/62), 7.1%(2/28), 72.2%(13/18) and 97.7%(43/44).The area under curve, sensitivity and specificity of mammography for BI-RADS 3 to 4 microcalcifications diagnosis were 0.676,72.9% and 60.2%. The area under curve, sensitivity and specificity of mammography plus MRI for BI-RADS 3 to 4 microcalcifications diagnosis were 0.982, 94.9% and 93.6%. Conclusions Multi-parametric MRI can improve the diagnostic accuracy in mammographically detected BI-RADS 3 to 4 exclusive microcalcifications, which is helpful to differentiate benign and malignant breast lesions with microcalcifications and avoid unnecessary biopsies.