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 spectrometry(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 effects of edaravone-dexborneol combined with intravenous thrombolysis on cerebrovascular reserve capacity and inflammatory factors in patients with acute cerebral infarction.Methods From January 2023 to June 2024,100 patients diagnosed with acute cerebral infarction in our hospital were divided into research group(n=50)and conventional group(n=50)by random number table method.The conventional group received intravenous thrombolysis,while the research group was treated with edaravone-dexborneol in addition to intravenous thrombolysis.The efficacy was evaluated after 2 weeks of treatment;the neurological function scores(mRS and NIHSS),cerebrovascular reserve indicators[pulsatility index(PI),cerebrovascular reserve(CVR)],hemorheological indicators(platelet aggregation rate,red blood cell aggregation index),levels of inflammatory factors[matrix metalloproteinase(MMP)-9,monocyte chemoattractant protein(MCP)-1,intercellular adhesion molecule(ICAM)-1],and levels of neurological functional factors[neuron specific enolase(NSE),nerve growth factor(NGF),central nervous system specific protein(S100)β]before and after treatment were compared.Results After 2 weeks of treatment,the efficacy of the conventional group was 80.00％,the efficacy of the research group was 94.00％.And the therapeutic effect of research group was significantly higher than the conventional group(x2=4.332,P=0.037).After 4 weeks of treatment,the mRS score,NIHSS score,PI,platelet aggregation rate,red blood cell aggregation index,and serum levels of MCP-1,MMP-9,ICAM-1,NSE and S100β were significantly lower than those before treatment in the two groups,while the CVR and serum NGF levels were significantly higher than those before treatment(all P＜0.05).After 4 weeks of treatment,the mRS score,NIHSS score,PI,platelet aggregation rate,red blood cell aggregation index,and serum levels of MCP-1,MMP-9,ICAM-1,NSE and S100β were significantly lower in the research group than those in the conventional group(all P＜0.05),while the CVR and serum NGF level were significantly higher in the research group than those in the conventional group(all P＜0.05).Conclusion The combination of edaravone-dexborneol with intravenous thrombolysis can improve clinical efficacy,restore neurological function,enhance cerebrovascular reserve capacity,improve hemorheology,and reduce inflammatory factors in patients with acute cerebral infarction.

Objective To investigate the effects of edaravone-dexborneol combined with intravenous thrombolysis on cerebrovascular reserve capacity and inflammatory factors in patients with acute cerebral infarction.Methods From January 2023 to June 2024,100 patients diagnosed with acute cerebral infarction in our hospital were divided into research group(n=50)and conventional group(n=50)by random number table method.The conventional group received intravenous thrombolysis,while the research group was treated with edaravone-dexborneol in addition to intravenous thrombolysis.The efficacy was evaluated after 2 weeks of treatment;the neurological function scores(mRS and NIHSS),cerebrovascular reserve indicators[pulsatility index(PI),cerebrovascular reserve(CVR)],hemorheological indicators(platelet aggregation rate,red blood cell aggregation index),levels of inflammatory factors[matrix metalloproteinase(MMP)-9,monocyte chemoattractant protein(MCP)-1,intercellular adhesion molecule(ICAM)-1],and levels of neurological functional factors[neuron specific enolase(NSE),nerve growth factor(NGF),central nervous system specific protein(S100)β]before and after treatment were compared.Results After 2 weeks of treatment,the efficacy of the conventional group was 80.00％,the efficacy of the research group was 94.00％.And the therapeutic effect of research group was significantly higher than the conventional group(x2=4.332,P=0.037).After 4 weeks of treatment,the mRS score,NIHSS score,PI,platelet aggregation rate,red blood cell aggregation index,and serum levels of MCP-1,MMP-9,ICAM-1,NSE and S100β were significantly lower than those before treatment in the two groups,while the CVR and serum NGF levels were significantly higher than those before treatment(all P＜0.05).After 4 weeks of treatment,the mRS score,NIHSS score,PI,platelet aggregation rate,red blood cell aggregation index,and serum levels of MCP-1,MMP-9,ICAM-1,NSE and S100β were significantly lower in the research group than those in the conventional group(all P＜0.05),while the CVR and serum NGF level were significantly higher in the research group than those in the conventional group(all P＜0.05).Conclusion The combination of edaravone-dexborneol with intravenous thrombolysis can improve clinical efficacy,restore neurological function,enhance cerebrovascular reserve capacity,improve hemorheology,and reduce inflammatory factors in patients with acute cerebral infarction.

Objective To explore the medication rules of Professor Hua Baojin in the treatment of subsolid pulmonary nodules through retrospective analysis and data mining techniques. Methods The prescriptions of patients with subsolid pulmonary nodules who were diagnosed and treated by Professor Hua Baojin at Guang’anmen Hospital of the Chinese Academy of Chinese Medical Sciences from January 1, 2021 to December 31, 2024 were retrospectively collected. Data were imported into the Ancient and Modern Medical Case Cloud Platform for analysis of drug frequency, four natures and five flavors, meridian tropism, drug association, and hierarchical clustering. Results A total of 455 prescriptions were included, containing 205 kinds of traditional Chinese medicines, with a total frequency of 12048 times. Fifty-seven commonly used drugs were screened out, among which drugs with high frequencies included astragalus membranaceus (raw) and hawthorn fruit (charred). The nature of the drugs was mainly warm, cold, and neutral. The flavor of the drugs was mostly sweet, bitter, and pungent. The meridians they belonged to mainly included the lung, spleen, and liver meridians. Their efficacy was mainly tonifying deficiency, clearing heat, resolving phlegm, and relieving cough and asthma. Association analysis obtained 19 pairs of drug combinations, 21 groups of three-drug combinations, and four groups of four-drug combinations. Hierarchical clustering obtained 10 groups of drug combinations. Conclusion On the basis of the core pathogenesis of subsolid pulmonary nodule, Professor Hua applies the theory of regulating qi and detoxifying; regulating the qi of the liver, spleen, and lung; and detoxifying the toxins of phlegm and blood stasis, providing valuable experience for the clinical treatment of SSN.

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.

BACKGROUND:The traditional view is that proximal fibular fractures do not require fixation.Others and our research suggest that the proximal fibular structure plays an important role in the stability of the posterolateral structure of the knee joint,and its mechanism of action is worth studying. OBJECTIVE:To investigate the biomechanical effects of proximal fibular fractures on various structures of the knee joint in an extended state. METHODS:Finite element method was used to conduct simulated biomechanical experiments.A healthy young male volunteer was selected to establish a finite element model of the knee joint in an extended state using MRI and CT image data,and four proximal fibular shapes were simulated(Model A:intact,Model B:1 cm fracture below the fibular head,Model C:1 cm tip defect fracture from the proximal end of the fibula to the distal end,and Model D:2 cm bone defect from the proximal end of the fibula).A longitudinal concentrated load of 1 500 N was applied to the femoral shaft to compare and analyze the distribution and changing trend of the maximum equivalent stress and maximum first principal stress of each structure of the knee joint in an extended state under four working conditions. RESULTS AND CONCLUSION:(1)In Model A,the maximum equivalent stress in the tibial cartilage and lateral compartment of the meniscus was greater than that in the medial compartment,while the maximum first principal stress in the tibial plateau and medial compartment of the meniscus was greater than that in the lateral compartment.The maximum equivalent stress of the medial condyle of the femoral cartilage was greater than that of the lateral condyle,and the maximum first principal stress of the medial condyle of the femoral cartilage was greater than that of the medial condyle.(2)Compared to Model A,there was no significant difference in the magnitude and distribution of the maximum equivalent stress and maximum first principal stress in the cartilage and meniscus of Model C.(3)Compared to Model A,the maximum equivalent stress increase amplitude of Model B was in the order of medial tibial cartilage(14.9％),medial condyle of femoral cartilage(13.6％),and medial meniscus(6.6％).The maximum first principal stress increase amplitude was the medial meniscus(11.06％),the medial tibial cartilage(8.65％),and the medial condyle of the femoral cartilage(7.46％).The maximum equivalent stress increase amplitude of the ligament was as follows:popliteal arch ligament(33.2％)>anterior cruciate ligament(21.3％)>fibular collateral ligament(17％)>posterior cruciate ligament(14.3％)>anterior lateral collateral ligament(13.2％)>medial collateral ligament(10.1％).(4)Compared to Model A,the maximum equivalent stress increasing trend of Model D followed the medial tibial cartilage(19.5％),femoral cartilage medial condyle(17.9％),and medial meniscus(9.9％).The maximum first principal stress in sequence was the medial meniscus(14.04％),the medial tibial cartilage(13.03％),and the medial condyle of the femoral cartilage(11.37％).The increasing trend of maximum equivalent stress in ligaments was as follows:anterior cruciate ligament(25.2％)>posterior cruciate ligament(18.9％)>medial collateral ligament(18.5％)>anterior lateral collateral ligament(12.7％).(5)It is suggested that when the knee joint is extended,a 1 cm fracture below the fibular head and a 2 cm fibular tip bone defect have a significant impact on the structure of the medial ventricular cartilage,anterior cruciate ligament,and posterior lateral ligament complex.

Objective To investigate the effects of three-dimensional(3D)screws and circular plates on the biomechanical stability of Sanders ABⅢ calcaneal fractures.Methods Calcaneal computed tomography(CT)and magnetic resonance imaging(MRI)data from a 26-year-old volunteer were collected to establish a 3D finite element model of Sanders ⅢAB calcaneal fracture fixed with 3D screws and circular plates.A longitudinal load of 700 N was applied to compare the variations in the stress,displacement of the bone block,and internal fixation in the different models.Results Under 700 N longitudinal loads,the maximum displacement of the bone block and the maximum stress of the bone block and internal fixation were concentrated at the intersection of the posterior talar articular plane internal fixation and fracture line.The overall displacements of the bone blocks in the 3D screw and circular plate models were similar.Compared with the circular plate model,the maximum and average stresses of the bone block and internal fixation in the 3D screw model were lower,and the displacement and stress changes of the 3D screw model were closer to those of the complete calcaneal bone model.Conclusions In the fixation of Sanders ⅢAB calcaneal fractures,both 3D screw and circular plate fixation method can provide good stability.The biomechanical properties of the 3D screws were better than those of the circular plates,which is consistent with the biomechanical characteristics.

Objective:To explore the mediating effect of chronic disease self-efficacy between fatigue and social support in breast cancer patients undergoing chemotherapy.Methods:This study was a cross-sectional study. From July 2020 to April 2021, convenience sampling was used to select 376 patients with breast cancer undergoing chemotherapy in the Shandong Provincial Hospital Affiliated to Shandong First Medical University as the research object. The General Information Questionnaire, Fatigue Scale-14, Chronic Disease Self-Efficacy Scale and Social Support Rating Scale were used to investigate the patients. Structural equation modeling was used to test the mediating effect among variables. A total of 376 questionnaires were distributed, and 372 valid questionnaires were recovered, with a valid recovery rate of 98.94%.Results:Among 372 breast cancer patients undergoing chemotherapy, the total scores of the Fatigue Scale-14, Chronic Disease Self-Efficacy Scale and Social Support Rating Scale were (10.61±1.81) , (5.00±2.53) and (43.42±12.59) , respectively. Chronic disease self-efficacy was positively correlated with social support in breast cancer patients undergoing chemotherapy ( r=0.493-0.648, P<0.01) , and social support was negatively correlated with fatigue ( r=-0.703--0.234, P<0.01) , and self-efficacy was negatively correlated with fatigue ( r=-0.729--0.220, P<0.01) . Chronic disease self-efficacy played a partial mediating role between fatigue and social support in breast cancer patients undergoing chemotherapy (β=-0.335, P<0.01) , and the mediating effect accounted for 47.59% of the total effect. Conclusions:Social support can indirectly affect fatigue through chronic disease self-efficacy in breast cancer patients undergoing chemotherapy. Nurses should focus on improving the chronic disease self-efficacy and social support of breast cancer patients undergoing chemotherapy.

Objective:To synthesize 177Lu-prostate-specific membrane antigen (PSMA)-617 with domestic 177Lu (made in China), and explore its optimal labeling condition, biodistribution, stability, and safety. Methods:177Lu-PSMA-617 was prepared with domestic 177Lu by a manual method. The optimal labeling condition, radiochemical purity, stability ( in vivo and in vitro), lipid-water partition coefficient, and plasma protein binding rate were determined. The uptake rate of 177Lu-PSMA-617 was evaluated by using 22RV1 cells. Biodistribution and SPECT/CT imaging were performed on normal mice with imported 177Lu-PSMA-617 as control group. The blood routine test was performed to evaluate the safety. Results:The best labeling result of domestic 177Lu-PSMA-617 can be obtained under the following conditions: pH=4.5, 100 ℃ for 30 min. And the radiochemical purity was ≥99%. The product was stable in vivo and in vitro, with the radiochemical purity >95% in 72 h. The plasma protein binding rate was (35.3±5.3)%, the lipid-water partition coefficient was -2.27±0.06, and the specific uptake rate of domestic 177Lu-PSMA-617 by 22RV1 cells reached the highest in 1 h ((7.58±0.84)%), which was slightly lower than the imported 177Lu-PSMA-617 ((7.86±0.96)%), but there was no significant difference between them ( t=-0.439, P>0.05). The distribution and SPECT/CT imaging of normal mice showed that domestic and imported 177Lu-PSMA-617 in blood were cleared quite fast, and both of them were excreted mainly through the kidneys. No obvious adverse reactions were found in the toxicity test of domestic and imported 177Lu-PSMA-617. There was no obvious abnormality in blood routine and liver and kidney metabolism. Conclusion:The domestic 177Lu-PSMA-617 has many advantages, such as qualified quality control, good biological properties and safety, which support its potential application value in diagnosis of prostatic neoplasms.

Objective To detect levels of C?X?C chemokine receptor type 5 (CXCR5) and inducible costimulator(ICOS)in blister fluid of patients with bullous pemphigoid(BP), and to explore their significance in the pathogenesis of BP. Methods Blister fluid samples were collected from 15 patients with BP(experimental group)and 15 patients with second?degree burns(control group). Enzyme?linked immunosorbent assay(ELISA)was performed to detect the levels of CXCR5 and ICOS in the 2 groups. Results The level of CXCR5 was significantly higher in the experimental group than in the control group(219 ± 145.31 vs. 147 ± 23.83 ng/L, t=4.577, P<0.05), while no significant difference in the ICOS level was observed between the 2 groups (30.18 ± 14.86 vs. 21.43 ± 5.32 ng/L, t = 1.628, P > 0.05). Conclusion The expression of CXCR5 may be associated with the occurrence of BP, but further researches are needed to determine the relationship between ICOS and the occurrence of BP.