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.

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

Objective To analyze the epidemiological characteristics of reported imported malaria cases in Zhengzhou City from 2016 to 2020, so as to provide insights into the management of imported malaria in the city. Methods All data pertaining to cases with definitive diagnosis of malaria in Zhengzhou City from 2016 to 2020 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China, including individual demographic data, and malaria onset, initial diagnosis and definitive diagnosis data. All data were descriptively analyzed. The duration from malaria onset to initial diagnosis, from initial diagnosis to definitive diagnosis and from onset to definitive diagnosis was compared among cases. In addition, the diagnoses of imported malaria cases in which definitive diagnosis was made were compared with the reexaminations by Zhengzhou Municipal Malaria Diagnosis Reference Laboratory. Results A total of 302 cases with definitive diagnosis of malaria were reported in Zhengzhou City from 2016 to 2020, and all were imported cases, with Plasmodium falciparum malaria as the predominant type (230 cases, 76.2%). There were 293 malaria cases imported from Africa (293 cases, 97.0%), which mainly included Nigeria (48 cases, 15.9%), Angola (40 cases, 13.2%), and the Democratic Republic of the Congo (29 cases, 9.6%). There was no obvious seasonality found in the date of malaria onset and time of reporting malaria. The ratio of male to female malaria cases was 49.3:1, and there were 103 cases (34.1%) with the current residency address in Zhengzhou City, 193 cases (63.9%) with the current residency address in other cities of Henan Province and 6 cases (2.0%) in other provinces of China. There were 271 cases (89.7%) seeking initial diagnosis in medical institutions, and the diagnostic accuracy of malaria was 56.6% (171/302) at initial diagnosis institutions. A total of 122 cases (40.4%) sought medical care on the day of malaria onset, and 252 cases (86.4%) within 3 days; however, only 22 cases (7.3%) were definitively diagnosed on the day of onset, and 162 cases (53.6%) diagnosed within 3 days. There were no significant differences between malaria cases seeking initial diagnosis at medical institutions and disease control and prevention institutions in terms of the duration from malaria onset to initial diagnosis (Z = −1.663, P > 0.05), from initial diagnosis to definitive diagnosis (Z = −0.413, P > 0.05) or from malaria onset to definitive diagnosis (Z = −0.838, P > 0.05). The median duration (interquartile range) from initial diagnosis to definitive diagnosis of malaria was 3.00 (2.00), 3.00 (6.00), 2.00 (4.00) d and 1.00 (1.00) d among cases seeking medical care at township-level and lower, county-, city- and province-level medical institutions, and the median duration from initial diagnosis to definitive diagnosis of malaria was significantly longer among cases seeking medical care at township-level and lower medical institutions than at city (Z = −3.286, P < 0.008 33) and province-level medical institutions (Z = −9.119, P < 0.008 33), while the median duration from initial diagnosis to definitive diagnosis [1.00 (3.00) d vs. 2.00 (4.00) d; Z = −4.099, P < 0.016] and from malaria onset to definitive diagnosis [3.00 (4.00) d vs. 4.00 (5.00) d; Z = −2.868, P < 0.016] among malaria cases with the current residency address in Zhengzhou City was both shorter than in other cities of Henan Province. The diagnostic accuracy was 89.1% (269/302) among malaria cases in which definitive diagnosis was made, and the accuracy of malaria reexaminations was 94.0% (284/302) in Zhengzhou Municipal Malaria Diagnosis Reference Laboratory. Conclusions P. falciparum malaria was predominant among reported imported malaria cases in Zhengzhou City from 2016 to 2020, and these imported malaria cases were predominantly diagnosed at medical institutions; however, the diagnostic capability of malaria is poor in township-level and lower medical institutions. Strengthening the collaboration between medical institutions and disease control and prevention institutions and improving the diagnostic capability building at medical institutions are recommended to consolidate malaria elimination achivements.

Objective To investigate the epidemiological characteristics of malaria and implementation of the “1-3-7” approach in malaria elimination in Yunnan Province, so as to provide the data support for the development of post-elimination surveillance interventions. Methods All data pertaining to malaria cases in Yunnan Province from 2014 to 2019 were captured from the Notifiable Disease Reporting System of Chinese Center for Disease Control and Prevention, and the changes in the epidemic situation of malaria were analyzed during the 5-year period. In addition, the core indexes regarding the “1-3-7” approach in malaria elimination of Yunnan Province from 2014 to 2019 were retrieved from the Malaria Control System in the Parasitic Disease Information Reporting System, and all changes in the indexes were descriptively analyzed. Results During the period from 2014 to 2019, a total of 2 283 malaria cases were reported in Yunnan Province, including 1 927 cases with vivax malaria, 326 cases with plasmodium malaria, 29 cases with other species of malaria, and one case with unidentified species. There were 64 local cases, 2 219 overseas imported cases. Among the 2 283 malaria cases, the male/female ratio was 4.58∶1, and 80.25% of the cases were aged from 15 to 50 years. Farmer (70.00%) was the predominant occupation, and 76.70% (1 751/2 283) of the cases were identified in 25 border counties (districts). Malaria cases were reported in each month during the 5-year period, and the number of malaria cases increased from April, peaked on May to July, and started to decline on August. From 2014 to 2019, the reporting rate of malaria cases within 24 hours upon diagnosis was 100%, and the detection of malaria cases was 99.69% (2 276/ 2 283) in the laboratory, with a 99.65% (2 275/2 283) rate of definite diagnosis. In addition, the percentage of individual epidemiological investigations within 3 days was 100.00% (2 283/2 283), and the number of epidemic foci survey and treatment within 7 days was 576 during the 3-year period from 2017 to 2019. The goal of malaria elimination was achieved in Yunnan Province on June, 2020. Conclusions Malaria has been eliminated in Yunnan Province, and management of overseas imported malaria is the primary challenge to consolidate the malaria elimination achievements in the future. However, the approach in malaria elimination remains to be maintained, and the role of the Yunnan Provincial Malaria Diagnostic Reference Laboratory requires to be strengthened.

OBJECTIVES: To investigate the clinical characteristics and risk factors for severe events of coronavirus disease 2019 (COVID-19) in elderly patients. METHODS: Retrospective analysis was performed on the clinical data of all elderly COVID- 19 patients treated in Changsha Public Health Treatment Center from January 17, 2020 to March 15, 2020, which included basic diseases, symptoms, test results, and other clinical characteristics, and prognostic indicators such as severity of illness, length of hospital stay, virus shedding time and mortality rate. The differences in clinical characteristics and prognostic indicators between elderly, middle-aged, and young COVID-19 patients were also analyzed. Logistic regression model was used to conduct univariate and multivariate analysis of risk factors for developing severe events in elderly COVID-19 patients; receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction efficacy. RESULTS: Of the 230 COVID-19 adult patients, 34 were young patients (14.8%), 136 were middle-aged patients (59.1%), and 60 were elderly (26.1%). Among the 60 elderly patients, 23 were male (38.3%) and 37 were female (61.7%), with a medium age of 66 years old. Common symptoms were fever (66.7%), cough (50.0%), and fatigue (41.7%). C reactive protein (CRP) was increased significantly. The proportion of severe cases was 31.7%, and mortality was 1.7%. The median length of hospitalization and median virus shedding time were 18.5 days and 21 days, respectively. Compared with the young and the middle-aged patients, the elderly had a higher proportion of hypertension, diabetes, and cardiovascular diseases, more common shortness of breath, higher proportions of pneumonia and severe cases (all <0.05), and the decreased lymphocyte count and lymphocyte percentage (both <0.05), as well as higher CRP and erythrocyte sedimentation rate (ESR) levels (both <0.05). Compared with non-severe cases, severe elderly patients demonstrated higher CRP and aspartate aminotransferase (AST) levels (all <0.05), the reduced lymphocyte count (<0.05), and the prolonged length of hospitalization and virus shedding duration (both <0.05). Univariate logistic regression analysis indicated that the lymphocytes proportion, CRP and AST levels were significantly correlated with the risk for developing severe events in elderly COVID-19 patients (all <0.05). Multivariate logistic regression found that severe events in elderly patients with COVID-19 were significantly correlated with CRP level (OR=1.041, =0.013). ROC curve analysis revealed that the area under the curve (AUC) for CRP to diagnose severe events in elderly COVID 19 patients was 0.851. CONCLUSIONS The proportion of severe cases in elderly COVID-19 patients is higher than that in young and middle-aged patients. CRP level has a good predictive value for the possibility of severe events in elderly COVID-19 patients.
Adult ; Aged ; Betacoronavirus ; C-Reactive Protein ; analysis ; China ; Comorbidity ; Coronavirus Infections ; diagnosis ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; physiopathology ; Retrospective Studies ; Risk Factors

Biorefinery technologies provide promising solutions to achieve sustainable development facing energy and environment crisis, while abundant sugar feedstock is an essential basis for biorefinery industries. Photosynthetic production of sucrose with cyanobacteria is an alternative sugar feedstock supply route with great potentials. Driven by solar energy, cyanobacteria photosynthetic cell factory could directly convert carbon dioxide and water into sucrose, and such a process could simultaneously reduce carbon emissions and supply sugar feedstocks. Here we introduced the history and updated the state-of-the-art on development of cyanobacteria cell factories for photosynthetic production of sucrose, summarized the progress and problems on mechanisms of sucrose synthesis, metabolic engineering strategies and technology expansions, and finally forecasted the future development direction in this area.
Carbon Dioxide ; Cyanobacteria ; Metabolic Engineering ; Photosynthesis ; Sucrose