Objective: To establish a method for determining the molecular weight and molecular weight distribution of Poly(Lactide-co-Glycolide Acid) (PLGA) using Size Exclusion Chromatography-Refractive Index-Multiangle Laser Light Scattering (SEC-RI-MALLS) and Size Exclusion Chromatography-Refractive Index (SEC-RID), and to compare the results obtained from these two methods.
Methods: For SEC-RI-MALLS, tetrahydrofuran was used as the mobile phase, Shodex GPC KF-803L was employed as the chromatographic column with a flow rate of 1 mL·min^-1, column temperature at 30 ℃, and an injection volume of 100 μL. For SEC-RID, tetrahydrofuran was also used as the mobile phase, Agilent PLgel 5 μm MIXD-D was used as the chromatographic column with a flow rate of 1 mL·min^-1, column temperature at 30 ℃, differential detector temperature at 35 ℃, and an injection volume of 20 μL. The molecular weight and molecular weight distribution were calculated using Agilent’s GPC software. The newly established methods were validated methodologically, and the molecular weight and molecular weight distribution of 13 batches of samples were determined.
Results: The precision, accuracy, stability, and repeatability tests for SEC-RI-MALLS showed RSD values of 1.35%, 1.58%, 1.53%, and 1.26%, respectively. The SEC-RID method exhibited good linearity (r=0.999 9), with RSD values for precision, accuracy, stability, and repeatability tests (n=6) of 2.05%, 1.62%, 1.30%, and 2.97%, respectively. The results obtained from SEC-RI-MALLS were lower than those from SEC-RID, and the molecular weight distribution coefficient was smaller, but the results from the paired T-test performed with the value measured by SEC-RID method and the value measured by SEC-RI-MALLS method multiplied a conversion coefficient of 1.5 showed no significant difference between the two methods.
Conclusion: Both methods are stable and reliable, and can be used for the determination of PLGA molecular weight and molecular weight distribution based on the specific situations.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Objective To investigate the correlation between preoperative N-terminal pro-B-type natriuretic peptidogen(NT-proBNP)levels and early postoperative outcomes in elderly and critically ill pa-tients with hip fractures.Methods A total of 593 elderly and critically ill patients with hip fractures from January 2018 to April 2021 were selected,including 189 males and 404 females,aged≥65 years,BMI 12.0-35.5 kg/m2,ASA physical status Ⅱ-Ⅳ.General preoperative information,intraoperative and post-operative discharge outcomes of patients were retrospectively obtained by the electrical clinical medical record system or telephone follow-up.The receiver operator characteristic(ROC)curve of preoperative plas-ma NT-proBNP and postoperative 30-day death was plotted,and the corresponding optimal cut-off value was 1 765.0 pg/ml.According to NT-proBNP values,the patients were divided into two groups:low-ratio group(NT-proBNP≤1 765.0 pg/ml,group L,n = 463)and high-ratio group(NT-proBNP＞1 765.0 pg/ml,group H,n = 130).The correlation between different plasma concentrations of NT-proBNP before surgery and ICU length of stay,total length of stay,postoperative complications,and 30-day mortality rate were an-alyzed using univariate and multivariate logistic regression analysis.Results Compared with group L,age,preoperative comorbidities with coronary heart disease,arrhythmia,chronic heart failure,lung disease,and chronic kidney disease,as well as mortality within 30 days after surgery were significantly increased in group H(P＜0.05).The multivariate logistic regression analysis showed that high preoperative plasma NT-proBNP concentration was positive correlation with postoperative ICU length of stay(OR = 1.215,95%CI 1.073-1.375,P = 0.020)and 30-day mortality rate(OR = 32.696,95%CI 7.158-149.338,P＜0.001).Conclusion High preoperative plasma NT-proBNP concentration is positive correlation with postoperative ICU hospitalization timeand 30-day mortality.

At present , methamphetamine has become a major hidden danger in global public health safety. In order to judge methamphetamine addicts and methamphetamine abstainers more scientifically and reliably, this study analyzed the endogenous metabolites in plasma, serum and urine of methamphetamine addicts, methamphetamine abstainers and healthy volunteers by highly sensitive high-throughput liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) analytical instrument. The obtained metabolomic data were processed by univariate analysis (t-test) and multivariate analysis (PLS-DA and OPLS-DA) and eligible potential biomarkers were then screened.The identified biomarkers set enrichment analysis to find the connection between metabolites and metabolic pathways.Multivariate statistical results showed that methamphetamine acute group, recovery group and healthy group were clearly separated.3, 18 and 6 regulated metabolites were identified in serum, plasma and urine, respectively, suggesting that lipid metabolism was abnormal in methamphetamine acute group, and that fatty acid metabolism, sulfate/sulfite metabolism and sex hormone metabolism were abnormal in methamphetamine recovery group.The selected potential biomarkers in this study provide the possibility for scientific judgment of the clinical stage of methamphetamine detoxification.

Objective:To learn about the knowledge, attitude and behavior of brucellosis and brucellosis infection in Tongyu County, Jilin Province, and to provide a reference for the formulation of prevention and control measures in relocated poverty alleviation and relocation areas.Methods:Using a multi-stage sampling method, three townships, Xianghai Township, Wulanhua Town and Xinhua Town were selected in Tongyu County, where the incidence of brucellosis is high in Jilin Province; then Miren, Huimin, Longjing, Xinfeng and Dayou villages from the three townships were surveyed. A face-to-face questionnaire survey was conducted among the villagers to collect the knowledge, attitude and behavior of brucellosis; and blood samples were collected from the villagers according to the principle of informed consent for brucellosis serological tests, and according to the "Diagnostic criteria for Brucellosis (WS 269-2007)" for diagnosis.Results:A total of 274 questionnaires were distributed and 244 valid questionnaires were collected with a recovery rate of 89.05%. Among them, 233 people had heard of brucellosis, accounting for 95.49%. The total awareness rate of knowledge related to brucellosis prevention and control was 39.29% (2 205/5 612), of which the total awareness rate of "knowledge related to brucellosis prevention" was 71.99% (527/732), and the total awareness rate of "knowledge related to human infection with brucellosis" was 38.08% (1 115/2 928), and the total awareness rate of "knowledge about brucellosis in animals" was 28.84% (563/1 952). A total of 90.13% (21/233) people supported the brucellosis prevention and control plan (such as free screening for brucellosis, publicity and education, immunization, culling, etc.), and 61.54% (48/78) of the people would take the initiative to buy protective equipment. The contact rates of livestock through assisted feeding and slaughtering were 27.46% (67/244) and 11.48% (28/244), respectively, and the total protection rates of sheep pens cleaning and slaughtering were 30.91% (102/330) and 21.43% (30/140), respectively. In terms of brucellosis infection, a total of 1 confirmed case, 1 latent infection and 37 suspected cases were found.Conclusions:The awareness rate of "knowledge related to brucellosis prevention" in Tongyu County is generally good, but the awareness rate of "knowledge about brucellosis in animals" is low, and the protection rate of some brucellosis prevention and control behaviors is poor. Health and epidemic prevention departments should carry out targeted health education, improve and optimize propaganda methods in order to improve the protection level of the general population and reduce the risk of brucellosis infection.

The waste water-based epidemiology is an important technique to fight against drug abuse by analyzing the concentration of illicit drugs in urban sewage, which can monitor the abuse of drugs.An SPE-UPLC-MS/MS method was developed for the analysis of 12 common drugs and their metabolites involving amphetamine and morphine.It was shown that the best result was achieved when hydrochloric acid/ acetonitrile (5∶95) was added to acidify the sample during the concentration process, guaranteeing the anti-across contamination of the analysis of organic nitrogen basic trace components, and improve the stability, specificity, and accuracy of the method.The optimized method meets the analytical requirements of complex sewage samples, and has been successfully applied to the assessment of urban drug abuse through sewage analysis.

A novel method was developed for the content assay and related substances determination of neomycin sulfate by high performance liquid chromatography combined with pulsed amperometric detection(HPLC-PAD). The HPLC was performed on Thermo AcclaimTMAmG C18(4. 6 mm×150 mm, 3 μm). The mobile phase consisted of aqueous solution with 2% trifluoroacetic acid containing 0. 01% pentafluoropropionic acid and 0. 6%NaOH. The pulsed amperometric detector was operated with aquadruple-potential waveform for the detection. Neomycin B, Neomycin C and thirteen related substances were adequately separated by the established HPLC conditions. The limits of detection(LOD)and quantification(LOQ)of neomycin B and neomycin C were both 1. 75 ng and 3. 5 ng, respectively. Good linearities of neomycin B and neomycin C were found in their respective ranges which their correlation coefficients were greater than 0. 998 5. The established method is characterized by high specificity, sensitivity and wide range of linearity which has a good application prospect and provides the basis for improving the standard and quality control of neomycin sulfate.

To identify the related substances of fusidic acid by LC-MS,separation was performed on an Agilent Extend-C18column(150 mm ×4. 6 mm,3. 5 μm)by linear gradient elution with a mobile phase consisting of methanol,acetonitrile and formic acid. Electrospray positive ionization high resolution TOF/MS was used for the determination of the accurate mass and elemental composition of parent ions of the related substances;triple qua-drupole tandem mass was employed for the mass spectra determination of the product. The structures of the related substances were then figured out through the elucidation of the fragment ions. Fusidic acid and its related sub-stances were adequately separated under the established HPLC conditions. Nineteen major related substances of fusidic acid were detected and speculated by hyphenated techniques. Eleven of them were recorded in European Pharmacopoeia,while the others have not been previously reported. The established LC-MS method is effective for the separation and identification of the related substances of fusidic acid and the results are useful for its storage conditions and quality assurance.

Simple and sensitive methods were developed for the determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma or whole blood by hyphenated ultra-performance li-quid chromatography-mass spectrometry (UPLC-MS/MS). Indapamide-d3, perindopril-d4 and perindo-prilat-d4 were used as the internal standards. The separation was performed on a Thermo BDS Hypersil C18column (4.6 mm × 100 mm, 2.4 μm) for indapamide and perindopril simultaneously following a protein precipitation pretreatment of the biosamples. The separation of perindoprilat was achieved in-dependently on a phenomenex PFP column (4.6 mm × 150 mm, 5 μm). All the analytes were quantitated with positive electrospray ionization and multiple reactions monitoring mode. The assay exhibited a linear range of 1–250 ng/mL for indapamide, 0.4–100 ng/mL for perindopril and 0.2–20 ng/mL for peri-ndoprilat. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, recovery, reproducibility, stabilities and matrix effects, and successfully applied to the pharmacokinetic study of perindopril tert-butylamine/indapamide compound tablets in Chinese healthy volunteers and the comparative pharmacokinetic study between plasma and whole blood.