Objective To investigate the effect and mechanism of baicalin on blood lipid metabolism and immune function in rats with gestational diabetes mellitus (GDM). Methods Female rats fed with high-fat and high-sugar diet and male rats fed with ordinary diet were caged together to prepare pregnant rats, and the GDM rat model was established by intraperitoneal injection of streptozotocin (35 mg/kg). GDM rats were randomly divided into a model group, a fasudil (FA) (RhoA/RocK inhibitor) group (10 mg/kg), low-dose (100 mg/kg) and high-dose (200 mg/kg) baicalin groups, and a high-dose baicalin combined with LPA (RhoA/RocK activator) group (200 mg/kg baicalin+1 mg/kg LPA ), with 12 rats in each group. Another 12 pregnant rats fed with high-fat and high-sugar diet were selected as the control group. After 2 weeks of corresponding drug intervention in each group, the level of fasting blood glucose (FBG) was detected by blood glucose meter. The level of fasting insulin (FINS) in serum was detected by ELISA, and the insulin resistance index (HOMA-IR) was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) in serum, and the levels of immunomodulator tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-10 in peripheral blood were detected by the kit. The histopathological changes of liver were observed by HE staining. The proportion of T lymphocyte subsets in peripheral blood was detected by flow cytometry. The mRNA and protein expressions of Ras homolog gene family member A (RhoA), Rho associated coiled-coil forming protein kinase 1 (ROCK1), and ROCK2 in liver tissue were detected by real-time quantitative PCR and Western blot. Results Compared with the control group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the model group were higher; the level of HDL-C in serum, the percentage of IL-10 levels, CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were lower. Compared with the model group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the the FA group and low-dose and high-dose baicalin groups were lower; the level of HDL-C in serum, IL-10 level, the percentage of CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were higher. LPA could obviously weaken the improvement effects of baicalin on blood lipid metabolism and immune function in GDM rats. Conclusion Baicalin may improve blood lipid metabolism and immune function in GDM rats by inhibiting the RhoA/ROCK pathway.
Animals ; Female ; Diabetes, Gestational/metabolism* ; Pregnancy ; rho-Associated Kinases/genetics* ; Flavonoids/pharmacology* ; Rats ; rhoA GTP-Binding Protein/genetics* ; Lipid Metabolism/drug effects* ; Male ; Signal Transduction/drug effects* ; Rats, Sprague-Dawley ; Blood Glucose/metabolism* ; Lipids/blood* ; Tumor Necrosis Factor-alpha/blood* ; rho GTP-Binding Proteins

OBJECTIVE To estimate the cost-utility of sacituzumab govitecan （SG） versus single-agent chemotherapy in the treatment of hormone receptor-positive （HR+）/human epidermal growth factor receptor 2-negative （HER2－） advanced metastatic breast cancer. METHODS From the perspective of the Chinese medical system， a three-state partitioned survival model was constructed to examine the cost-utility of SG versus single-agent chemotherapy based on TROPiCS-02 trial. The cycle length was set to 1 month， and the time horizon was 10 years. The annual discount was 5%. The model output included total costs and quality adjusted life month （QALM）， and incremental cost-effectiveness ratio （ICER） was calculated for cost-utility analysis， by setting willingness-to-pay （WTP） threshold at 3 times gross domestic product （GDP） per capita of China in 2023 （22 340 yuan/QALM）. Univariate sensitivity analyses， probability sensitivity analyses， and scenario analyses were performed to evaluate the robustness of the results and calculate the price threshold when SG had economic advantages. RESULTS SG group gained incremental 4.25 QALM and 561 570 yuan compared with single-agent chemotherapy， which resulted in an ICER of 132 102/QALM that was higher than WTP. The results of the univariate sensitivity analysis showed that the monthly average cost of SG had the greatest impact on the results； the results of probability sensitivity analysis showed that the probability of SG scheme being cost-effective at the WTP threshold was 0. The results of scenario analysis showed that the conclusions of this study were robust under different time horizons （5， 10， 15 years）. The price threshold for SG being cost-effective was 1 344 yuan per 180 mg. CONCLUSIONS Based on the perspective of Chinese medical system， SG appears to be not cost-effective compared with single-agent chemotherapy for HR+/ HER2－ advanced metastatic breast cancer at the price of 8 400 yuan per 180 mg. A substantial price cut should be taken to be cost- effective.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the correlation between the degree of hepatic fibrosis and early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke (AIS) and its predictive value.Methods:Patients with AIS received intravenous thrombolysis at Nanjing Jiangbei Hospital from January 2018 to March 2023 were retrospectively included. Hepatic fibrosis-4 index (FIB-4) was used to evaluate the degree of hepatic fibrosis in patients. FIB-4 ≥ 2.67 was defined as severe hepatic fibrosis. END was defined as an increase of ≥4 from baseline on the National Institutes of Health Stroke Scale (NIHSS) score within 24 h after intravenous thrombolysis. The relevant factors of END were analyzed through univariate analysis and multivariate logistic regression model. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of FIB-4 for END. Results:A total of 313 patients were included, of which 184 (58.8%) were male, aged 64.8±11.8 years old. The median baseline NIHSS score was 6 (interquartile range, 4-9), and the median FIB-4 was 1.76 (interquartile range, 1.28-2.56). Forty-five patients (14.4%) experienced END. Multivariate logistic regression analysis showed that after adjusting for other confounding factors, higher FIB-4 was significantly independently correlated with END (odds ratio 2.121, 95% confidence interval 1.422-3.162; P=0.001). ROC curve analysis shows that FIB-4 has a good predictive value for END (the area under the curve 0.689, 95% confidence interval 0.595-0.784; P=0.001). The optimal cutoff value of FIB-4 was 1.82, and its sensitivity and specificity in predicting END were 71.1% and 54.9%, respectively. Conclusion:FIB-4 has good predictive value for END in patients with AIS after intravenous thrombolysis.

Objective:To explore the mediating roles of family resilience and perceived social support between fear of progression and quality of life in patients with adult pulmonary hypertension, so as to provide guidance for grassroots medical staff to deeply understand and improve the long-term quality of life of adult pulmonary hypertension patients.Methods:Using a convenience sampling method, 219 adult pulmonary hypertension patients who attended Qilu Hospital, Shandong University from July 2021 to February 2022 were selected for a cross-sectional study using the World Health Organization Quality of Life Questionnaire Abbreviated Version (WHOQOL-BREF), Perceived Social Support Scale (PSSS), Shortened Chinese version of the Family Resilience Assessment Scale (FRAS-C) and Chinese version of Fear of Progression Questionnaire-Short Form (FoP-Q-SF) for investigation. A structural equation model was established to evaluate the mediating effect of family resilience and perceived social support on fear of progression and quality of life.Results:The scores of WHOQOL-BREF, PSSS, FRAS-C, and FoP-Q-SF were (45.85 ± 10.22), 66(56, 75), 94(89, 97) and 39(32, 46) points in adult pulmonary hypertension patients. The total scores of WHOQOL-BREF were negatively correlated with FoP-Q-SF ( r = -0.63, P<0.01), and positively correlated with FRAS-C and PSSS ( r=0.54, 0.46, both P<0.01). Family resilience played a partial mediating role between fear of progression and quality of life, accounting for 13.43% of the total effect. Family resilience and perceived social support played a chain mediating role between fear of progression and quality of life, accounting for 2.71% of the total effect. Conclusions:Family resilience-perceived social support play mediating roles between fear of progression and quality of life, healthcare workers can alleviate fear of progression and improve quality of life by promoting the levels of family resilience and perceived social support of adult pulmonary hypertension parents.

Objective To investigate the effects of a multi-component exercise nursing intervention on frailty,activities of daily living and quality of life in elderly patients with chronic heart failure.Methods Through literature analysis and expert meeting,the multi-component exercise nursing intervention program was formed.A total of 71 elderly patients with chronic heart failure who admitted from January 2022 to September 2022 in a tertiary A hospital in Shandong Province were randomly divided into an intervention group(35 cases)and a control group(36 cases).The control group received usual care,while the intervention group received an additional multi-component exercise nursing training.2 groups were evaluated by Tilburg frailty indicator scale,modified Barthel index scale and 12-item short form health survey scale before the intervention,4 weeks and 12 weeks after the intervention.Results A total of 62 patients(31 in the experimental group and 31 in the control group)completed the study.Generalized estimation equation results showed that the inter-group effect,time effect and interaction effect of frailty,activities of daily living and quality of life in the 2 groups were statistically significant(P＜0.05).At 4 weeks and 12 weeks after the intervention,the Tilburg Frailty Indicator scale scores in the intervention group were lower than that in the control group(P＜0.05),and the scores of the modified Barthel index scale and 12-item short form health survey scale were significantly higher than those in the control group(P＜0.05).Conclusion The multi-component exercise nursing intervention can effectively improve frailty,activities of daily living and quality of life in elderly patients with chronic heart failure.

Objective:To investigate the correlation between malnutrition and early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke.Methods:Patients with ischemic stroke received intravenous thrombolysis in the Department of Neurology, Nanjing Jiangbei People's Hospital from January 2018 to December 2021 were retrospectively enrolled. Nutritional status was assessed by geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI). END was defined as an increase of ≥4 in the National Institutes of Health Stroke Scale score within 24 h after intravenous thrombolysis compared with the baseline value. The demographic and baseline clinical data of the patients in the END group and the non-END group were compared. Multivariate logistic regression analysis was used to determine the independent correlation between malnutrition and END. Results:A total of 256 patients were enrolled, including 156 males (60.9%), aged 65.6±12.0 years. According to GNRI and PNI, there were 122 (46.7%) and 62 (24.2%) patients with malnutrition respectively. END occurred in 37 patients (14.5%) during hospitalization. Multivariate logistic regression analysis showed that after adjusting for other confounding factors, there was a significant independent correlation between malnutrition and END after intravenous thrombolysis in patients with acute ischemic stroke (severe malnutrition as assessed by GNRI compared to normal nutritional status: odds ratio 5.736, 95% confidence interval 1.033-31.866, P=0.046; severe malnutrition as assessed by PNI compared to normal nutritional status: odds ratio 4.928, 95% confidence interval 1.589-15.282, P=0.006). Conclusion:Malnutrition is very common in patients with acute ischemic stroke and has a significant correlation with END after intravenous thrombolysis.

Objective:To investigate the relationship between plasma Dickkopf-1 and early neurological deterioration (END) and outcome in patients with acute ischemic stroke.Methods:From January 2020 to December 2020, consecutive patients with first-ever ischemic stroke form the Department of Neurology, Nanjing Jiangbei Hospital were included. All patients were hospitalized within 24 h after onset. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 d after admission increased by ≥2 or motor function score increased by ≥1 compared with the baseline. Poor outcome was defined as the modified Rankin Scale score >2 at 90 d after onset. Multivariate logistic regression analysis was used to determine the independent correlation between plasma Dickkopf-1 and END and outcome. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of plasma Dickkopf-1 for END and poor outcome. Results:A total of 176 patients were enrolled, including 92 males (52.3%), aged 66.7±9.6 years. The median Dickkopf-1 was 4.30 μg/L, 52 patients (29.5%) developed END, and 81 (46.0%) had poor outcome. Multivariate logistic regression analysis showed that the higher Dickkopf-1 was an independent predictor of END (odds ratio [ OR] 1.696, 95% confidence interval [ CI] 1.223-2.351; P=0.002) and poor outcome ( OR 1.566, 95% CI 1.156-2.121; P=0.004). ROC curve analysis showed that plasma Dickkopf-1 had good predictive value for END, and its area under the curve was 0.717 (95% CI 0.634-0.801); the optimal cut-off value was 4.40 μg/L, and the corresponding predictive sensitivity and specificity were 71.2% and 60.5%, respectively. Dickkopf-1 also had good predictive value for poor outcome, and its area under the curve was 0.701 (95% CI 0.624-0.778); the optimal cut-off value was 4.25 μg/L, and the corresponding predictive sensitivity and specificity were 65.4% and 61.1%, respectively. Conclusion:Plasma Dickkopf-1 has good predictive value for END and poor outcome in patients with acute ischemic stroke.

Objective:This study mainly discussed the clinical characteristics, autoimmune status and lymphocyte subsets of patients with Takayasu arteritis (TA) without hormone and immunosuppressive therapy, in order to provide guidance for immunotherapy.Methods:Using cross-sectional study, twenty-nine patients with TA admitted to the Department of Rheumatology and the Department of Vasculitis of Beijing Anzhen Hospital from January 2018 to November 2019 were selected, including 28 females and 1 male, with the middle age of 39 year. These patients met the diagnostic criteria of American Society of Rheumatology for TA, and were not treated with hormone and immunosuppressant. Clinical data of these patients were collected, and the immunological indexes and lymphocyte subsets of peripheral blood were detected simultaneously. At the same time, the immunological indexes and peripheral blood lymphocyte subsets of 21 healthy normal people were detected as control. Chi square test, independent sample t test and nonparametric test were used for analysis. Results:Among the 29 patients with TA, 28 were female, 26 were in the active stage of disease; the main manifestations of systemic symptoms were malaise (62.07%) and headache (41.38%), the main manifestations of vascular symptoms were bruits and pulse weakening (68.97%), and the most of Numano type was V type (79.31%). The absolute value of total T (CD3) lymphocytes [(1 337.14±312.46)μl vs (1 139.95±340.96)μl, t=2.120, P=0.039], the percentage [46.29%±6.55% vs 36.55%±7.42%, t=4.903, P<0.000 1] and the absolute value [(815.52±194.11)μl vs (571.44±187.55)μl, t=4.450, P<0.000 1] of helper T (CD4) lymphocytes, the ratio of CD4/CD8 [1.83 (1.41-2.30) vs 1.32 (1.03-1.39), Z=3.401, P=0.001] were higher compared with those of healthy controls, while the percentage of natural killer (NK) cells (CD56) [10.71%(6.45%-14.30%) vs 14.57%(10.87%-18.47%), Z=2.408, P=0.016] decreased. The complement C3 [1.16 (1.02-1.31) g/L vs 1.05 (0.93-1.15) g/L, Z=2.383, P=0.021] in patients with TA was higher than those in healthy controls and immunoglobulin (Ig) G [11.97 (8.74-14.43) g/L vs 14.37 (13.11-15.47) g/L, Z=3.017, P=0.003] in patients with TA was lower than those in healthy controls. Compared with the control group, the ESR [19.31 (9.50-28.50) mm/h vs 3.71 (2.00-5.00) mm/h, Z=5.338, P<0.000 1], hs-CRP [6.52 (0.32-8.62) mg/L vs 0.73 (0.35-1.07) mg/L, Z=2.983, P=0.003] and Q-CRP [8.73 (1.03-7.72) mg/L vs 0.57 (0.08-0.98) mg/L, Z=4.263, P<0.000 1] of patients with TA were all increased. Conclusions:The autoimmunity of patients with TA without hormone or immunosuppressant treatment is in active state, and the total T-lymphocytes and helper T-lymphocytes in peripheral blood are significantly increased in order to cope with the inflammatory response of the systemic artery vessels.

Objective:To investigate the relationship between neutrophil/lymphocyte (NLR), red blood cell distribution width (RDW), platelet/lymphocyte (PLR), platelet mean volume (MPV), platelet hematocrit (PCT) and platelet distribution width (PDW) and the disease activity of Takayasu arteritis (TA).Methods:A retrospective analysis was conducted on 86 TA patients (TA group) in Anzhen hospital from January 2017 to June 2019. Meanwhile, 85 healthy controls (control group) whose age and gender matched with TA were selected from the health examination center of Beijing Anzhen hospital. The blood samples were collected to measure the neutrophil/lymphocyte (NLR), red blood cell distribution width (RDW), platelet/lymphocyte (PLR), platelet mean volume (MPV), platelet hematocrit (PCT) and platelet distribution width (PDW) by resistance method. TA activity was determined according to the national institutes of health (NIH) score and India TA clinical activity score (ITAS2010). Spearman correlation analysis was used to evaluate the relationship between whole blood cell count indicators and ESR and hs-CRP. ROC curve was used to determine the threshold of TA disease activity.Results:The NLR, RDW and PDW in the TA group were higher than those in the control group [3.00 (1.78-3.48) vs. 1.76 (1.34-2.01), 14.10 (13.00-14.83) vs. 13.08 (12.50-13.35) and 13.65 (11.20-16.00) vs. 12.24 (11.20-13.20), P<0.000 1]. MPV and PCT in the TA group were lower than those in the control group [10.06±1.11 vs. 10.44±0.83 and 0.25 (0.20-0.28) vs. 0.27 (0.23-0.31), P = 0.011 and 0.014, respectively]. RDW and PCT in the active group of TA patients were both higher than those in the inactive group [14.61 (13.38-15.48) vs. 13.81 (12.88-14.33) and 0.27±0.07 vs. 0.23±0.06], with P values of 0.007 and 0.008, respectively. PCT in the active group of TA patients was positively correlated with ESR ( r=0.33, P=0.002). The optimal RDW threshold for determining the activity of TA disease was 14.150 (sensitivity was 55.0%, specificity was 100.0%, area under ROC curve was 0.802). The optimal threshold for judging the activity of TA disease by PCT was 0.245 (sensitivity was 66.7%, specificity was 92.3%, area under ROC curve was 0.84). The optimal threshold for PLR to determine the activity of TA disease was 131.257 (sensitivity was 71.7%, specificity was 76.9%, area under ROC curve was 0.714). Conclusion:RDW and PCT may be helpful to judge the activity of TA, however, the other indexes of whole blood cell count were not closely related to the activity of TA.