OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Objective To rapidly evaluate the effectiveness,safety and economy of edaravone in treating acute ischemic stroke(AIS),and to provide the evidence-based basis for clinical decision-making.Methods PubMed,Embase,Web of Science,Cochrane Library,CNKI and WanFang Data databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies of edaravone in the treatment of AIS from the inception to October 1,2024.Two reviewers independently screened the literature,extracted data,evaluated the quality,summarized the results,and qualitatively described and analyzed the results.Results A total of 12 literature were included,involving 9 systematic reviews/Meta-analysis and 3 pharmacoeconomic studies.In terms of efficacy,edaravone alone or in combination with conventional therapy(alteplase,ozagrel)increased efficiency,improved short-term neurological deficit scores and improved patients'ability to perform activities of daily living compared with placebo or conventional therapy(alteplase,ozagrel)(P＜0.05).There was no significant difference in the incidence of adverse reactions between edaravone and placebo,routine treatment,or other neuroprotectants(P＞0.05).Combined with alteplase,it could reduce the incidence of intracranial hemorrhage compared to alteplase alone(P＜0.05),with no statistically significant difference in all-cause mortality(P＜0.05).Pharmacoeconomic studies showed that,edaravone does not have a cost-effectiveness advantage in the short term,but it may have a cost-effectiveness advantage from limited long-term studies.Conclusion Edaravone is effective and safe in the treatment of AIS,but there is limited research evidence and the conclusion still needs to be confirmed by further studies and clinical trials,and the economics need to be further evaluated.

Heart failure is a severe manifestation or advanced stage of various heart diseases,with high mortality and readmission rates.The 2024 guidelines for the diagnosis and treatment of heart failure,which are on the 2018 guidelines,combined with new evidence and China's national conditions,provide a comprehensive and systematic description and recommendation on the classification,diagnosis,prevention,treatment,comorbidity,and management of heart failure.This article reviewed the update of the therapeutic drugs section.

Objective To rapidly evaluate the efficacy,safety and economics of empagliflozin in the treatment of type 2 diabetes mellitus(T2DM)and to provide evidence-based medical evidence for clinical decision.Methods PubMed,Embase,the Cochrane Library,CNKI,Wangfang,VIP database and major health technology assessment(HTA)websites were searched from the construction of the databases to Nov 30th,2022.Two researchers independently screened,extracted the data,evaluated the quality and analyzed the results according to inclusion and exclusion criteria.Results A total of 23 literatures were included,including 3 HTA reports,10 systematic review/Meta-analyses and 10 pharmacoeconomic studies.The results of efficacy showed that empagliflozin reduced HbA1c,blood pressure,body weight and all-cause mortality compared with the control group.Safety studies showed that empagliflozin was generally well tolerated,and significantly reduced MACEs and the relative risk of the renal primary outcomes,but increased the risk of genital infections and electrolyte abnormality compared with placebo and other oral antidiabetic drugs.The economic evaluation results showed that empagliflozin was more cost-effective in high risk patients with comorbid cardiovascular or kidney disease.Conclusion Empagliflozin is effective and safe in the treatment of T2DM,but the pharmacoeconomic studies focusing on chinese populations are urgently needed.

Cystatin, a cysteine protease inhibitor found in many parasites, plays important roles in immune evasion. This study analyzed the molecular characteristics of a cystatin from Fasciola hepatica (FhCystatin) and expressed recombinant FhCystatin (rFhcystatin) to investigate the immune modulatory effects on lipopolysaccharide-induced proliferation, migration, cytokine secretion, nitric oxide (NO) production, and apoptosis in mouse macrophages. The FhCystatin gene encoded 116 amino acids and contained a conserved cystatin-like domain. rFhCystatin significantly inhibited the activity of cathepsin B. rFhCystatin bound to the surface of mouse RAW264.7 cells, significantly inhibited cell proliferation and promoted apoptosis. Moreover, rFhCystatin inhibited the expression of cellular nitric oxide, interleukin-6, and tumor necrosis factor-α, and promoted the expression of transforming growth factor-β and interleukin-10. These results showed that FhCystatin played an important role in regulating the activity of mouse macrophages. Our findings provide new insights into mechanisms underlying the immune evasion and contribute to the exploration of potential targets for the development of new drug to control F. hepatica infection.

ObjectiveTo investigate the correlation between systemic immune-inflammation index (SII) and prognosis in patients with hepatic alveolar echinococcosis. MethodsA retrospective analysis was performed for the clinical data of 242 patients who were admitted to Department of Hepatopancreatobiliary Surgery, Qinghai University Affiliated Hospital, from January 2015 to December 2018 and underwent surgery for hepatic alveolar echinococcosis, and SII was calculated. The chi-square test was used for comparison of categorical data between two groups, and a Spearman correlation analysis was performed. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value of SII; the Kaplan-Meier method was used to plot survival curves and analyze overall survival time in the two groups, and the log-rank test was used for comparison of survival rates between the two groups; univariate and multivariate Cox regression analyses were used to identify the influencing factors for the prognosis of patients with hepatic alveolar echinococcosis. ResultsThe Spearman correlation analysis showed that SII was positively correlated with the postoperative fatality rate of patients with hepatic alveolar echinococcosis (r=0.267, P＜0.001). The ROC curve showed that the optimal cut-off value of SII before surgery was 758.92, and based on this, 242 patients with hepatic alveolar echinococcosis were divided into low SII (SII ≤758.92) group with 126 patients and high SII (SII ＞758.92) group with 116 patients. The low SII group had 1-, 3-, and 5-year survival rates of 98.20%, 88.47%, and 6610%, respectively, and the high SII group had 1-, 3-, and 5-year survival rates of 90.80%, 53.05%, and 27.40%, respectively. The low SII group had a cumulative survival rate of ＞50% and a mean survival time of 55.584 months (95% confidence interval［CI］: 53550-57.617), while the high SII group had a cumulative survival rate of ＜50%, a mean survival time of 39.384 months (95% CI: 35.070-43.698), and a median survival time of 43 months (95% CI: 34.694-51.306). The low SII group had a significantly better survival rate than the high SII group, and there was a significant difference in overall survival rate between the two groups (χ2=46.979, P＜005). The univariate analysis showed that SII ＞758.92 (hazard ratio ［HR］=5.907, 95% CI: 3.386-10.306, P=0.001) was an influencing factor for the overall survival time of patients with hepatic alveolar echinococcosis, and the multivariate Cox regression analysis showed that preoperative peripheral blood SII (HR=3.507, 95% CI: 1.911-6.435, P=0.001) was an independent risk factor for the overall survival rate of patients with hepatic alveolar echinococcosis. ConclusionPreoperative SII level is clearly correlated with the prognosis of patients with hepatic alveolar echinococcosis and can thus be used as a clinical indicator to evaluate the prognosis of patients. The higher the peripheral blood SII before surgery, the worse the prognosis of patients.

ObjectiveTo investigate related factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and to establish a nomogram model for predicting the risk of stone recurrence after surgery based on independent risk factors. MethodsA retrospective analysis was performed for the clinical data of 144 patients with gallstones who underwent endoscopic minimally invasive gallbladder-preserving cholecystolithotomy in Qinghai University Affiliated Hospital from January 2012 to January 2018, and according to postoperative stone recurrence, the patients were divided into non-recurrence group and recurrence group. The chi-square test was used for comparison of categorical data between two groups. LASSO and logistic regression analyses were used to analyze independent risk factors for postoperative stone recurrence, and the corresponding nomogram prediction model was plotted according to regression coefficient. The calibration curve was plotted to evaluate the reliability of the predictive nomogram; Harrell consistency index was used to quantify the discriminatory performance of the predictive nomogram; the receiver operating characteristic (ROC) curve was used to evaluate the sensitivity, specificity, and area under the ROC curve (AUC) of this predictive nomogram. ResultsAll 144 patients underwent successful endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, among whom 14 patients (9.7%) experienced stone recurrence after surgery. The multivariate analysis showed that family history (odds ratio ［OR］= 3.245, 95% confidence interval ［CI］: 0.752-13567, P=0.104), regular diet (OR=3.752, 95% CI: 1.067-14.141, P=0.041), stone homogeneity (OR=5.871, 95% CI: 1636-25.390, P=0.010), and medication compliance (OR=0.225, 95% CI: 0.057-0.799, P=0.024) were independent risk factors for recurrence. The nomogram model had an index of concordance (C-index) of 0.835 (95% CI: 0.732-0.938) in the modeling sample and 0.7925 in the verification sample, suggesting that the nomogram model in this study had good accuracy and discrimination. The predictive nomogram had an AUC of 0.835, suggesting that this nomogram had a relatively high predictive value. ConclusionFamily history, regular diet, stone homogeneity, and medication compliance are independent risk factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and the nomogram constructed based on these independent risk factors may help to predict the risk of postoperative stone recurrence.

Objective To screen out significant differential genes for predicting the effect of neoadjuvant chemotherapy (NAC) and select the most suitable breast cancer patients for NAC. Methods A total of 60 breast cancer patients' samples before and after NAC were collected for high-throughput RNA-Seq. We selected AHNAK, CIDEA, ADIPOQ and AKAP12 as the candidate genes that related to tumor chemotherapeutic resistance. We analyzed the correlation of AHNAK, CIDEA, ADIPOQ, AKAP12 expression levels with the effect of NAC by logistic regression analysis, constructed a prediction model and demonstrated the model by the nomogram. Results AHNAK, CIDEA, ADIPOQ and AKAP12 expression were up-regulated in the residual tumor tissues of non-pCR group after NAC(P < 0.05). Compared with pCR group, non-pCR group presented higher expression levels of AHNAK, CIDEA, ADIPOQ and AKAP12 (P < 0.05). The high expression levels of AHNAK, CIDEA, ADIPOQ and AKAP12 significantly reduced the pCR rate of NAC for breast cancer (P < 0.05). Our prediction model which AHNAK, CIDEA, ADIPOQ and AKAP12 were involved in showed a good fitting effect with H1 test (χ²=6.3967, P=0.4945) and the ROC curve (AUC 0.8249, 95%CI: 0.722-0.9271). Conclusion AHNAK, CIDEA, ADIPOQ and AKAP12 may be novel marker genes for NAC effect on breast cancer. The efficacy prediction model based on this result is expected to be a new method to select the optimal patients of breast cancer for neoadjuvant chemotherapy.

Background: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Objective:To establish a competing risk model to predict the cumulative hazard risk probability of the outcomes (unhealed or hyperthyroidism recurrence) of Graves disease (GD) treated with 131I. Methods:From January 2020 to May 2021, 61 GD patients (13 males, 48 females; age (46.0±13.8) years) who received 131I treatment in Zhangzhou Affiliated Hospital of Fujian Medical University were enrolled. The outcomes of treatment were recovery, unhealed or hyperthyroidism recurrence (event 1), and hypothyroidism (event 2). Follow-up was started 1 month after 131I treatment and ended 1 year later. It was terminated in the following conditions: one of the two events occurred; no event occurred after 1 year of follow-up; the research deadline was up. The Fine-Gray test was used to analyze the factors related to event 1, and then the competitive risk model was established. Results:Thirty-nine patients had hypothyroidism, 17 patients were unhealed or had hyperthyroidism recurrence, 2 patients lost follow-up, and 3 patients had normal thyroid function after 1 year follow-up. Multivariate analysis showed that effective half-life (hazard ratio ( HR)=1.74, 95% CI: 1.10-2.75, β=0.55, P=0.019) and thyroid volume ( HR=1.12, 95% CI: 1.07-1.17, β=1.12, P<0.001) were risk factors for event 1, while the elasticity of thyroid was a protective factor ( HR=0.17, 95% CI: 0.06-0.54, β=-1.76, P=0.003). The C index of the nomogram constructed based on the multi-factor competitive risk model was 0.784(95% CI: 0.633-0.935). Conclusions:Thyroid volume, elastic value, and effective half-life are associated with treatment outcomes of 131I. The competitive risk model can predict the therapeutic outcomes of GD patients treated with 131I.