Objective To establish a reversed-phase HPLC method for determining three stereoisomers in baloxavir marboxil and provide a basis for the quality specification of baloxavir marboxil.Methods The chromatographic column was CHIRALPAK IC-3(4.6 mm × 150 mm,3 μm),The mobile phase was acetonitrile-0.1％formic acid aqueous solution-isopropanol(35:50:15).The column temperature was 40 ℃.The flow rate was 0.5 mL·min-1.The injection volume was 10 μL.The detection wavelength was 259 nm.Result The isomer peaks were completely separated from the principal component peak.The detection limits for stereoisomers 1,2 and 3 were 0.024 7,0.038 7,0.038 1 μg·mL-1 respectively.The quantitation limits for stereoisomers 1,2 and 3 were 0.049 4,0.077 3,0.076 1 μg·mL-1 respectively.There were good linear relationships between the concentrations and peak area within the ranges of the study,and the linearity concentration ranges of stereoisomers 1,2 and 3 were 0.049 5-0.989 0 μg·mL-1,0.051 6-1.031 0 μg·mL-1,0.050 8-1.015 0 μg·mL-1 respectively.The linear correlation coefficients were 0.999 4.The recovery was 92.28％-103.90％.The sample solution was stable in 48 h at room temperature.Conclusion The method is accurate and reliable for determining stereoisomers in baloxavir marboxil,and provide a guideline of quality standards of baloxavir marboxil and safety evalution.

Objective To establish a reversed-phase HPLC method for determining three stereoisomers in baloxavir marboxil and provide a basis for the quality specification of baloxavir marboxil.Methods The chromatographic column was CHIRALPAK IC-3(4.6 mm × 150 mm,3 μm),The mobile phase was acetonitrile-0.1％formic acid aqueous solution-isopropanol(35:50:15).The column temperature was 40 ℃.The flow rate was 0.5 mL·min-1.The injection volume was 10 μL.The detection wavelength was 259 nm.Result The isomer peaks were completely separated from the principal component peak.The detection limits for stereoisomers 1,2 and 3 were 0.024 7,0.038 7,0.038 1 μg·mL-1 respectively.The quantitation limits for stereoisomers 1,2 and 3 were 0.049 4,0.077 3,0.076 1 μg·mL-1 respectively.There were good linear relationships between the concentrations and peak area within the ranges of the study,and the linearity concentration ranges of stereoisomers 1,2 and 3 were 0.049 5-0.989 0 μg·mL-1,0.051 6-1.031 0 μg·mL-1,0.050 8-1.015 0 μg·mL-1 respectively.The linear correlation coefficients were 0.999 4.The recovery was 92.28％-103.90％.The sample solution was stable in 48 h at room temperature.Conclusion The method is accurate and reliable for determining stereoisomers in baloxavir marboxil,and provide a guideline of quality standards of baloxavir marboxil and safety evalution.

Objective This study utilized regadenoson stress D-SPECT to evaluate the impact of remote ischemic precondi-tioning combined with adenosine injection in patients undergoing percutaneous coronary intervention(PCI)using D-SPECT imaging.Methods Three hundred patients requiring coronary angiography and stent implantation were randomly assigned into two groups utilizing the random number table method.The conventional treatment group(150 patients)and the experimental group(150 patients)received standard treatment for coronary heart disease PCI.The experimental group underwent two sessions of remote ischemic precon-ditioning on the day of PCI,wherein the left and right upper arms were inflated to 200 mmHg with continuous pressure for 5 minutes using a blood pressure cuff.Additionally,during the PCI procedure,adenosine was administered to the experimental group at a rate of 50 μg/(kg·min)until the end of the procedure,with other treatments aligning with the conventional treatment group.Each patient received a coronary SYNTAXⅡscore.Resting D-SPECT and regadenoson stress D-SPECT were employed to evaluate total myocardial perfusion score,total myocardial ischemia segments,and left ventricular ejection fraction across 17 segment distributions before and 7 days after PCI.Results Before PCI,the differences in the number of myocardial ischemic segments,total myocardial perfusion score,and left ven-tricular ejection fraction between the two patient groups were not statistically significant(P>0.05).However,7 days post-PCI,compared with the conventional treatment group,the experimental group exhibited significantly improved numbers of myocardial ischemic segments,total myocardial perfusion score,and left ventricular ejection fraction(P<0.05).Furthermore,the differences in adverse drug reactions between the two patient groups were not statistically significant(P>0.05).Conclusion The combined application of remote ischemic preconditioning and adenosine injection in patients undergoing PCI is deemed safe and effective.

Objective To analyze the effect of Hedysari Radix Chinese herbal pieces treatment in acute inferior myocardial infarction patients undergoing percutaneous coronary intervention(PCI).Methods A total of 200 patients with acute inferior myocardial infarction undergoing emergency PCI admitted to department of cardiology of Shijiazhuang People's Hospital from March 31,2020 to March 31,2023 were selected as the study objects.The patients were randomly divided into a control group and a treatment group according to a digital random table method.The control group received routine treatment after PCI,and the patients drank 500 mL of warm water in the morning and afternoon every day,continuing this regimen for up to 30 days post-surgery.The treatment group took 10 g of Hedysari Radix Chinese Herbal pieces in 500 mL of boiling water in the morning and afternoon,soaking it and drinking it coolly and temperately,continuing to take it until 30 days after surgery.Blood pressure,Dopamine dosage,and duration were observed in all patients on 1-5 days after surgery.Major adverse cardiovascular event(MACE),such as cardiac death,myocardial infarction,heart failure,and re-admission were tracked in all patients within 30 days,and adverse reactions and clinical symptom improvement were followed up,using the somatic self-rating scale(SSS).Results The total Dopamine dose in the treatment group was significantly lower than that in the control group(mg:960.4±287.9 vs.1 160.4±610.5,P<0.05),and the duration of use was significantly shorter than that in the control group(hours:60.7±16.9 vs.71.6±20.4,P<0.05).The systolic blood pressure in the treatment group was significantly higher than that in the control group at 1 day after PCI[mmHg(1 mmHg≈0.133 kPa):96.8±19.5 vs.90.2±11.1,P<0.05],until 5 days after PCI(mmHg:106.3±14.4 vs.99.7±13.9,P<0.05),while the changes in diastolic blood pressure were not significant in both groups.The incidence of MACE in the treatment group was significantly lower than that in the control group within 30 days after PCI[4.0%(4/100)vs.13.0%(13/100),P<0.05],and the SSS score was also significantly lower than that in the control group(31.56±11.58 vs.40.72±18.67,P<0.05).Conclusion The effect of Hedysari Radix Chinese herbal pieces treatment can significantly improve clinical efficacy without significant adverse reactions.

Objective To investigate the curative effect of interventional therapy on postoperative multiple metastases of breast cancer.Methods A total of 15 patients with multiple metastases after breast cancer surgery were treated with interventional therapy.After comprehensive evaluation,all patients were treated with chemoembolization.The therapeutic regimen was docetaxel loaded on drug-eluting bead(DEB)combined with carboplatin,once in 1 d for 21 d,2 times in total,and then the regimen was changed to docetaxel and carboplatin combined with ordinary embolization microspheres,once in 1 d for 21 d,4 times in total.CT/MRI was performed on every 2 cycles and 1,3,and 6 months after interventional therapy to evaluate its efficacy and record adverse reactions.Results The overall remission rate(ORR)at 3 months after treatment was 75％,and the disease control rate(DCR)was 91.7％.The ORR and DCR at 6 months after treatment were 50％and 83.3％,respectively.Most of the common adverse reactions were below grade Ⅲ.Conclusion Interventional therapy for multiple metastases of breast cancer after operation has a definite short-term effect,with little adverse reactions.It is worthy of further promotion in the comprehensive treatment of postoperative metastases of breast cancer.

Objective To evaluate the role of quantitative flow ratio(QFR)in percutaneous coronary intervention(PCI)by using regadenoson stress dynamic single-photon emission computed tomography(D-SPECT).Methods We selected 200 patients with unstable angina admitted to Department of Cardiology,Hebei Medical University First Hospital,from June 31,2021 to June 31,2023 for elective PCI.The patients were aged 57.56±8.23 years and were randomly divided into a conventional group(n=100)and a QFR group(n=100)according to a random number table.The trial was conducted using a double-blind method.The conventional group received PCI treatment based on the experience of the physician,while the QFR group received PCI treatment based on the QFR measurement results.All enrolled patients underwent pre-operative and 7-day post-operative D-SPECT stress imaging using regadenoson stress D-SPECT,and their images were acquired from short axis,vertical long axis,and horizontal long axis to calculate the total myocardial perfusion score and the total myocardial ischemia segment number under the distribution of 17 myocardial segments.Results There was no significant difference in the number of myocardial ischemia segments(7.59±3.14 vs.7.48±3.36,P=0.811)or the total myocardial perfusion score(15.87±7.61 vs.15.63±5.97,P=0.860)between the two groups before PCI.The number of myocardial ischemia segments(5.58±3.36 vs.6.51±2.14,P=0.020)and the total myocardial perfusion score(10.55±4.41 vs.12.96±6.50,P=0.002)in the QFR group were significantly better than those in the conventional group 7 days after PCI(P＜0.05).Conclusion Applying QFR guidance for PCI can better improve the degree of myocardial ischemia in patients.

Objective:To explore the effect of serum lactic acid (Lac) level on acute kidney injury (AKI) in patients with sepsis and whether Lac level affects the in-hospital mortality of patients with sepsis-associated AKI.Methods:A retrospective cohort study was conducted. Clinical data of patients with sepsis admitted to the internal intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2019 and the ICU of the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2020 were collected. According to the first quartile of Lac within 24 hours of admission to ICU, the patients were divided into Lac ≤ 1.4 mmol/L group (group Q1), Lac 1.5-2.4 mmol/L group (group Q2), Lac 2.5-4.0 mmol/L group (group Q3), and Lac ≥ 4.1 mmol/L group (group Q4). The incidence of sepsis-associated AKI after admission to ICU and hospital mortality were compared among four groups. The effect of elevated Lac on the incidence and mortality of sepsis-associated AKI was investigated by binary Logistic regression analysis. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of Lac on the incidence and mortality of sepsis-associated AKI, and the cut-off value was obtained to analyze the incidence and death risk of sepsis-associated AKI at different Lac levels. Results:A total of 655 sepsis patients were enrolled, of which 330 patients (50.4%) developed AKI and 325 patients (49.6%) did not. Among 330 patients with sepsis-associated AKI, 134 (40.6%) died and 196 (59.4%) survived. With the increase of Lac level, the incidence of sepsis-associated AKI increased gradually (34.5%, 41.0%, 58.4%, 66.3%, respectively, in group Q1- Q4), meanwhile, the in-hospital mortality also increased gradually (23.4%, 29.2%, 33.1%, 43.4%, respectively, in group Q1- Q4), the differences were statistically significant (both P < 0.01). Compared with the non-AKI group, the Lac level in the AKI group was significantly increased [mmol/L: 3.08 (1.84, 5.70) vs. 1.91 (1.20, 3.10), P < 0.01]. After adjustment for factors such as gender (male), site of infection (abdominal cavity), vasoactive drugs, basal mechanical ventilation, mean arterial pressure (MAP), basal renal insufficiency, uric acid, procalcitonin (PCT), platelet count (PLT), basal serum creatinine (SCr) and basal estimated glomerular filtration rate (eGFR), and other influencing factors, multivariate Logistic regression analysis showed that elevated Lac was an independent risk factor for sepsis-associated AKI [odds ratio ( OR) = 1.096, 95% confidence interval (95% CI) was 1.022-1.175, P = 0.010]. Compared with the survival group, the Lac level in the death group was significantly increased [mmol/L: 3.55 (2.00, 6.76) vs. 3.00 (1.70, 4.50), P < 0.01]. After adjusting for age, diabetes, vasoactive drugs, basal eGFR, and other factors, multivariate Logistic regression analysis suggested that increased Lac was an independent risk factor for in-hospital mortality in sepsis-associated AKI patients ( OR = 1.074, 95% CI was 1.004-1.149, P = 0.037). ROC curve analysis showed that the area under the ROC curve (AUC) of Lac for predicting the incidence and mortality of sepsis-associated AKI was 0.653 (95% CI was 0.611-0.694) and 0.593 (95% CI was 0.530-0.656, both P < 0.01), respectively, and the cut-off values were 2.75 mmol/L (sensitivity was 57.8%, specificity was 69.2%) and 5.95 mmol/L (sensitivity was 56.7%, specificity was 83.7%). When the Lac ≥ 2.75 mmol/L, the risk of sepsis-associated AKI was 2.772 times higher than that of < 2.75 mmol/L ( OR = 2.772, 95% CI was 1.754-4.380, P < 0.001). When the Lac ≥ 5.95 mmol/L, the patients with sepsis-associated AKI had a 2.511 times higher risk of in-hospital death than those with Lac < 5.95 mmol/L ( OR = 2.511, 95% CI was 1.378-4.574, P = 0.003). Conclusions:Elevated Lac level is an independent risk factor for the incidence and mortality of sepsis-associated AKI. When Lac ≥ 2.75 mmol/L, the risk of AKI in patients with sepsis increased by 1.772 times; when Lac ≥ 5.95 mmol/L, the risk of in-hospital death in patients with sepsis related AKI increased by 1.511 times.

Objective:To investigate the effect of hyperuricemia on acute kidney injury in sepsis patients.Methods:It is a retrospective cohort study of 459 adult sepsis patients who were admitted to the Department of Intensive Care Unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2019, and the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2019. The patients were divided into the hyperuricemia group and the non-hyperuricemia group according to the first serum uric acid level within 24 h after ICU admission, and the incidence of AKI within 7 days after ICU admission was compared between the two groups. The effect of hyperuricemia on sepsis-associated AKI was analyzed by univariate analysis and binary logistic regression analysis.Results:Among the 459 sepsis patients, 81 patients (17.6%) had hyperuricemia, and 127 patients (27.7%) had AKI. The incidence of AKI in the hyperuricemia group and the non-hyperuricemia group were 60.5% (49/81) and 20.6% (78/378), respectively, which showed significantly statistical difference ( χ2=52.954, P<0.01). After adjusting for gender, associated diseases (diabetes, coronary heart disease), sequential organ failure score (SOFA) on the day of ICU admission, the use of diuretics within one week before and after ICU admission, invasive mechanical ventilation, basal renal function, lactic acid, and procalcitonin, binary logistic regression analysis showed that hyperuricemia was an independent risk factor for AKI in sepsis patients ( OR=5.091, 95% CI: 2.768-9.362, P<0.01); For every 1 mg/dL increase in serum uric acid in sepsis patients, the risk of developing AKI increased by 28.4% ( OR=1.284, 95% CI: 1.165-1.414, P<0.01). Conclusions:AKI is a common complication in sepsis patients admitted to ICU, and hyperuricemia is an independent risk factor for AKI in sepsis patients.

Objective:To investigate the effect of postoperative hypoalbuminemia on acute kidney injury (AKI) after cardiac surgery under cardiopulmonary bypass (CPB).Methods:The clinical data of adult patients undergoing cardiac surgery under CPB were retrospectively analyzed. The difference between preoperative and postoperative serum albumin level was compared. The patients were divided into hypoalbuminemia group (≤35 g/L) and non-hypoalbuminemia group (>35 g/L) according to the lowest serum albumin concentration within 48 hours after surgery. The incidence and severity of postoperative AKI were compared between the two groups. Univariate analysis and binary logistic regression analysis were used to evaluate the effect of postoperative hypoalbuminemia on the incidence of postoperative AKI.Results:Among the 749 patients, the serum albumin level after cardiac surgery was significantly lower than that before surgery ( Z=-15.739, P<0.001), and the proportion of patients with hypoalbuminemia increased from 9.6% to 27.6% ( χ2=83.516, P<0.001). Postoperative AKI occurred in 273 patients, including 109 cases (52.7%) in hypoalbuminemia group and 164 cases (30.3%) in non-hypoalbuminemia group. The incidence of AKI in hypoalbuminemia group was significantly higher than that in non-hypoalbuminemia group ( χ2=32.443, P<0.001), and the severity of AKI in hypoalbuminemia group increased than that in non-hypoalbuminemia group ( Z=-2.098, P=0.036), and the time of hospital stay extended ( Z=-2.442, P=0.015). After adjusted by gender, age, preoperative hypoalbuminemia, comorbidities (hypertension, hyperuricemia, diabetes mellitus, cerebrovascular disease), renal insufficiency, preoperative heart function, coronary angiography, CPB time, aorta blocking time, type of heart surgery and postoperative hypotension, binary logistic regression analysis revealed that postoperative hypoalbuminemia was an independent risk factor for CPB-associated AKI ( OR=2.319, 95% CI 1.586-3.392, P<0.001). Conclusions:AKI is a common complication following cardiac surgery under CPB. Serum albumin after CBP is significantly lower than that before CBP, and postoperative hypoalbuminemia within 48 hours after surgery is an independent risk factor for AKI.

Objective To investigate the effects and the mechanism of thrombospondin 4 (Thbs4) gene-edited bone marrow mesenchymal stem cells (BMSCs) transplantation on vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) in diabetic rats with hind limb ischemia. Methods Thirty Sprague-Dawley rats were randomly divided into the model group, BMSCs treatment group and Thbs4-BMSCs treatment group on average. After constructing the typeⅡdiabetic rat model with hind limb ischemia, 100μl normal saline, BMSCs suspension and Thbs4-BMSCs suspension (cell number: 2×106) were locally injected into the ischemic injury area of rats for the model group, BMSCs group and Thbs4-BMSCs group, respectively. The rats were sacrificed on the 14th day after stem cell transplantation, and the muscle tissues near the ischemic area were collected. The relative expression of VEGF and p-Smad2/3 protein was detected by Western Blot. The Ang-1 protein expression was detected by immunofluorescence staining. The levels of related genes were detected by qRT-PCR, and the von Willebrand Factor (vWF) protein expression was detected by immunohistochemistry staining. Results The relative expression levels of VEGF, Ang-1 and vWF protein in the Thbs4-BMSCs group were significantly higher than those in the model group and BMSCs group (VEGF protein:P<0.01 and P<0.05). The mRNA expression of VEGF and Ang-1 were significantly up-regulated, the differences were statistically significant(VEGF mRNA:all P<0.01;Ang-1:P<0.01 and P<0.05). The expression of p-Smad2/3 protein in the Thbs4-BMSCs group was significantly higher than that in the model group and the BMSCs treatment group (all P<0.01). The expression of p-Smad2/3 protein was significantly decreased after the addition of p-Smad2/3 pathway inhibitor, the differences were statistically significant (P<0.05). Conclusions Thbs4-BMSCs transplantation can effectively promote angiogenesis in diabetic rats with hind limb ischemia, and the effect of angiogenesis may be related to the activation of Smad2/3 signaling pathway.