Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To analyze the distribution characteristics of 9 hypertension drug related gene polymorphisms in the population of essential hypertension(EH)in Xi'an area,providing an objective basis for personalized treatment.Methods A total of 306 EH patients who visited the Shaanxi Provincial Armed Police Force Hospital from January 2022 to December 2023 were selected as the research subjects.The PCR melting curve method was used to detect 9 hypertension drug related gene polymorphisms,their genotype and allele distribution frequency were analyzed,and the correlations of gene polymorphism among patients of different genders,ages,and hypertension grading groups were compared.Results Among 306 patients,the distribution frequencies of each gene were consistent with Hardy Weinberg equilibrium(x2=0.153～2.941,all P＞0.05).Mutation rates of various gene were as follows:SLCO1B1 c.388A＞G,ADRB1 c.1165G＞C,MTHFR C677T,ADD1 c.1378G＞T,CYP2D6 c.100C＞T,ACE I/D,CYP3A5 c.806-4288C＞T,SLCO1B1 c.521T＞C,AGTR1 c.1166A＞C and CYP2C9 c.1075A＞C were 77.29％,73.20％,56.54％,48.37％,50.82％,35.13％,29.41％,11.76％,7.68％and 3.43％,respectively,and CYP2C9 c.403C＞T had no mutation.Comparing with patients of different genders,the mutation rate of SLCO1B1 c.388A＞G genotype and allele mutations in male group were higher than those in the female group(x2=5.221,8.237),the mutation rate of CYP2D6 c.100C＞T genotype and allele in the female group were higher than those in the male group(x2=5.093,9.661),the mutation rate of ACE I/D allele in the male group was higher than that in the female group(x2=6.118,8.032),with significant differences(all P＜0.05).The mutation rates of CYP2C9 c.1075A＞C,SLCO1B1 c.388A＞G,CYP2D6 c.100C＞T genotypes and alleles in the middle-aged and young age group were higher than those in the elderly group,and the differences were statistically significant(x2=11.683,10.243;9.003,9.803;10.617,9.931,all P＜0.05).There was no significant difference in the comparison of other genotypes and alleles among different gender and age groups and in the frequency of genotype and allele mutations among different hypertension grading groups(x2=1.321～7.733,1.031～5.198,all P＞0.05).Conclusion The distribution of gene polymorphisms related to antihypertensive drugs in the Xi'an area was related to the gender and age of EH patients.Thus,the genotype testing of antihypertensive drugs may have important guiding significance for personalized medication treatment of EH patients.

Objective To evaluate the short-term efficacy and safety of percutaneous liver puncture for local management of portal vein thrombosis(PVT).Methods Variations in thrombus,blood flow,and laboratory examination results were observed before and after percutaneous liver puncture in 197 patients with PVT,and the occurrence of comorbidities was recorded and followed up for one year after treatment.Results After treatment,the thrombus in the main portal vein vessels almostly disappeared in 119 patients(60.41％)with PVT,the thrombus had a significant reduction in 57 patients(28.93％),and the thrombus had a smaller change or an increase in 21 patients(10.66％);146 patients(74.11％)had smooth blood flow in the main portal vein vessels,29 patients(14.72％)showed significant improvement in blood flow,and 22 patients(11.17％)showed no significant improvement or worsening of blockage.The mean portal venous pressure was significantly lower than that before treatment(P＜0.001);thrombin time,activated partial thromboplastin time,and prothrombin time were prolonged compared to those before thrombolysis(P＜0.001),and fibrinogen were reduced compared to those before thrombolysis(P＜0.001).A total of 35 patients(17.77％)occured comorbidities during treatment.One year after treatment,196 patients(99.49％)with PVT survived,of which thrombus essentially disappeared in 141(71.94％),thrombus stabilized(or decreased)in 42(21.43％),and thrombus increased in 13(6.63％).Conclusion percutaneous liver puncture for local management of PVT is effective and reliable in the short-term and requires standardized management of the entire process.

Objective To evaluate the efficacy and safety of intravascular lithotripsy(IVL)in the treatment of coronary artery calcification in patients with acute coronary syndrome(ACS)and chronic coronary syndrome(CCS).Methods In a retrospective study,patients with coronary artery calcified lesions who underwent IVL treatment at the Department of Cardiology,Second Affiliated Hospital of Xi'an Jiaotong University between February 2023 and June 2024 were enrolled.Among them,22 patients in ACS group and 25 patients in CCS group.The differences in baseline data,complication,clinical success rate and major cardiovascular adverse events(MACE)in patients followed one month after the procedure were compared between the two groups.Results In the ACS group,21 stent implantations were successful(95.5％success rate),while in the CCS group,25 cases were successful(100.0％success rate),showing no statistically significant difference between the two groups(P=0.468).There was one case of intraoperative IVL balloon rupture in the ACS group(1/22;4.5％),while in the CCS group,three cases were observed(3/25;12.0％).Additionally,one case in the ACS group(1/22;4.5％)with slow blood flow after IVL calcification modification.No instances of IVL-related vessel dissection or target vessel rupture occurred between the two groups,and there was no statistically significant difference in intraoperative complications(all P＞0.05).There was no significant difference in the MACE(9.1％vs.4.0％,P=0.593)between the two groups for follow up of one month.Conclusions The technique of IVL is a safe and effective treatment option for patients with ACS or CCS who have coronary artery calcification lesions.

Objective To evaluate the efficacy and safety of intravascular lithotripsy(IVL)in the treatment of coronary artery calcification in patients with acute coronary syndrome(ACS)and chronic coronary syndrome(CCS).Methods In a retrospective study,patients with coronary artery calcified lesions who underwent IVL treatment at the Department of Cardiology,Second Affiliated Hospital of Xi'an Jiaotong University between February 2023 and June 2024 were enrolled.Among them,22 patients in ACS group and 25 patients in CCS group.The differences in baseline data,complication,clinical success rate and major cardiovascular adverse events(MACE)in patients followed one month after the procedure were compared between the two groups.Results In the ACS group,21 stent implantations were successful(95.5％success rate),while in the CCS group,25 cases were successful(100.0％success rate),showing no statistically significant difference between the two groups(P=0.468).There was one case of intraoperative IVL balloon rupture in the ACS group(1/22;4.5％),while in the CCS group,three cases were observed(3/25;12.0％).Additionally,one case in the ACS group(1/22;4.5％)with slow blood flow after IVL calcification modification.No instances of IVL-related vessel dissection or target vessel rupture occurred between the two groups,and there was no statistically significant difference in intraoperative complications(all P＞0.05).There was no significant difference in the MACE(9.1％vs.4.0％,P=0.593)between the two groups for follow up of one month.Conclusions The technique of IVL is a safe and effective treatment option for patients with ACS or CCS who have coronary artery calcification lesions.

OBJECTIVES: To establish a method for the detection of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples by liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: The blood samples were treated with 1-butyl-3-methylimidazolium hexafluorophosphate as an extraction solvent. The samples were extracted by ultrasound-assisted extraction and separated by ZORBAX Eclipse Plus C18, 95Å column. The mobile phase A aqueous solution containing 0.1% formic acid and 10 mmol/L ammonium acetate, and mobile phase B mixed organic solvent containing acetonitrile/methanol (V_acetonitrile∶V_methanol=2∶3) were used for gradient elution at the flow rate of 1.00 mL/min. An electrospray ion source in positive mode was used for detection in the multiple reaction monitoring. RESULTS: The linearities of carbamazepine and its metabolites 10,11-dihydro-10,11-epoxycarbamazepine and 10,11-dihydro-10-hydroxycarbamazepine in blood samples were good within the corresponding range, with correlation coefficients (r) greater than 0.995 6. The limits of detection were 3.00, 0.40 and 1.30 ng/mL, respectively. The limit of quantitation were 8.00, 1.00 and 5.00 ng/mL, respectively. The extraction recoveries ranged from 76.00% to 106.44%. The relative standard deviations of the intra-day and inter-day precisions were less than 16%. Carbamazepine and its main metabolite 10,11-dihydro-10,11-epoxycarbamazepine were detected in blood samples of death cases with a mass concentration of 2.71 μg/mL and 252.14 ng/mL, respectively. CONCLUSIONS This method has high sensitivity and good selectivity, which is suitable for the detection of carbamazepine and its metabolites in blood samples, and can be used for carbamazepine-related forensic identifications.
Chromatography, Liquid/methods* ; Tandem Mass Spectrometry ; Methanol ; Carbamazepine/analysis* ; Benzodiazepines/analysis* ; Solvents ; Chromatography, High Pressure Liquid ; Solid Phase Extraction

ω-transaminases are able to catalyze the reversible transfer of amino groups between diverse amino compounds (such as amino acids, alkyl amines, aromatic amines) and carbonyl compounds (such as aldehydes, ketones, ketoacids). ω-transaminases exhibit great application prospects in the field of chiral amine biosynthesis because of their desirable properties, such as wide range of substrates, high stereoselectivity, and mild catalytic conditions. It is therefore important for China to develop efficient, specific, and environment-friendly chiral amine production technologies with independent intellectual property rights, which is of great significance for the development of pharmaceutical, pesticide, and material industries. This review systematically summarizes the Chinese patents regarding ω-transaminase filed by Chinese institutions in the recent decade. The development of ω-transaminase resource, enzymatic property improvement by protein engineering, application in chiral amine synthesis, and development of production technologies are elaborated. This review will shed light on further basic and application studies of ω-transaminase.
Transaminases/genetics* ; Amino Acids ; China ; Aldehydes ; Amines

The threat of fungal diseases is increasingly rigorous. The clinically invasive fungal infections remain a main cause of morbidity and mortality in certain high-risk groups, especially in critical patients or immunocompromised patients. In drug therapy, the problems of off-target toxicity and antifungal drug resistance are still challenging. With the wide application of biomaterials and nanotechnology, more nanomedicine studies have been carried out on antifungal drugs, such as the amphotericin B liposome which greatly reduced the renal toxicity of drugs has been successfully marketed. For the unique physical and chemical properties, the nano-drug delivery system possessed great potential in improving the bioavailability, reducing the side effects of drugs, increasing the stability of drugs, and achieving cells or tissue-specificity through the modification. This review summarized the applications and limitations of antifungal drugs. Some nanomedicines were summarized in discussion oriented around the antifungal therapy, including liposomes, niosomes, lipid nanoparticles, polymer nanoparticles, microemulsion, dendrimers, inorganic nanocarriers. Nanotechnology and nano-drug delivery system provide promising strategies for the research and development of new formulations that can improve antifungal activity and possibly overcome antifungal drug resistance.

The zearalenone hydrolase (ZHD101) derived from Clonostachys rosea can effectively degrade the mycotoxin zearalenone (ZEN) present in grain by-products and feed. However, the low thermal stability of ZHD101 hampers its applications. High throughput screening of variants using spectrophotometer is challenging because the reaction of hydrolyzing ZEN does not change absorbance. In this study, we used ZHD101 as a model enzyme to perform computation-aided design followed by experimental verification. By comparing the molecular dynamics simulation trajectories of ZHD101 at different temperatures, 32 flexible sites were selected. 608 saturated mutations were introduced into the 32 flexible sites virtually, from which 12 virtual mutants were screened according to the position specific score and enzyme conformation free energy calculation. Three of the mutants N156F, S194T and T259F showed an increase in thermal melting temperature (ΔTm>4 °C), and their enzyme activities were similar to or even higher than that of the wild type (relative enzyme activity 95.8%, 131.6% and 169.0%, respectively). Molecular dynamics simulation analysis showed that the possible mechanisms leading to the improved thermal stability were NH-π force, salt bridge rearrangement, and hole filling on the molecular surface. The three mutants were combined iteratively, and the combination of N156F/S194T showed the highest thermal stability (ΔTm=6.7 °C). This work demonstrated the feasibility of engineering the flexible region to improve enzyme performance by combining virtual computational mutations with experimental verification.
Computer-Aided Design ; Edible Grain ; Enzyme Stability ; Hydrolases/metabolism* ; Hypocreales/enzymology* ; Protein Engineering ; Zearalenone