Objective To develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

Objective:To observe effectiveness of combining diffusion tensor imaging (DTI) with motor evoked potentials (MEPs) in evaluating the upper limb motor functioning of stroke survivors.Methods:Thirty-seven stroke survivors with upper limb motor dysfunction were selected. At the 4th, 12th and 24th week after their onset, each was were assessed using Fugl-Meyer Upper Limb (FMA-UE) scoring, the National Institutes of Health stroke scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index (BI) and hemiplegic hand function classification. DTI was also applied and MEPs were measured. The patients were divided into an MEP positive group and an MEP negative group according to the existence of the MEP waveform. The DTI and MEP parameters were correlated with the FMA-UE scores, linear regressions were evaluated and a receiver operating characteristics curve was prepared to estimate the utility of DTI in predicting hand function. The sensitivity and specificity of MEPs in predicting hand function recovery were evaluated.Results:The asymmetry index (FAa) of the average anisotropy score of the posterior limb of the internal capsule and the FAa of the cerebral peduncle were both significantly correlated with the FMA-UE scores at the 12th and 24th weeks. The best cut-off points for predicting functional recovery of a patient′s hand were 0.155 for the FAa of the posterior limb of the internal capsule and 0.145 for the cerebral peduncle. Among the 37 patients, the MEPs of 8 (the MEP positive group) could be extracted, and their hand functions recovered completely. The sensitivity of the MEPs in predicting the complete recovery of hand function was 80% with 100% specificity. The linear regression analysis showed 77% prediction accuracy for the FAa and MEPs of the cerebral peduncle for upper limb motor function at the 24th week after onset. In the MEP negative group, two patients completely recovered their hand function, with one′s FAa less than 0.145, and the other′s more than 0.145. When the MEP was negative, the sensitivity of DTI in predicting the recovery of hand function was 50% with 81.5% specificity.Conclusions:DTI combined with MEPs can be used as an index to evaluate the prognosis of upper limb motor function in stroke patients.

The Diagnosis-Intervention Packet(DIP)payment exerts notable effects on hospitals' economic operations.As centralized hubs of high-quality medical resources,tertiary hospitals face a functional mismatch with the provision of services for primary care diseases.By analyzing the admission and payment practices for primary care diseases in sample hospitals in Henan Province,it identifies key challenges,including inadequate alignment between healthcare payment reform policies and management systems,weak foundational capabilities in hospital health insurance informatization,and insufficient awareness of health insurance policies among medical staff.It is recommended that hospitals should strengthen communication and coordination with health insurance administration agencies to foster positive interactions between healthcare providers and insurers;continuously advance in-house health insurance informatization and enhance data governance capabilities;improve strategic awareness and innovate value-based health insurance management models.

Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Objective To develop and validate an efficient and simple liquid chromatography with tandem mass spectrometry(LC-MS/MS)method for determination of polymyxin E in human plasma,and apply the established method in therapeutic drug monitoring(TDM)of polymyxin E.Methods The LC-MS/MS platform was based on AB SCIEX HPLC-4500MD system.Gradient elution was performed with 0.2％formic acid in water and 0.2％formic acid in acetonitrile.Phenomenex Kinetex XB-C18 column(100 mm × 2.1 mm,2.6 μm)were used.The analytes were detected by electrospray ionization(ESI)positive multiple reaction monitoring mode.The ion pairs for analytes(polymyxins E1,E2)and internal standard(polymyxins B1)were m/z 390.7→101.3,m/z 386.0→101.2,and m/z 402.3→101.2,respectively.Plasma samples were processed with protein precipitation method.Results Polymyxin E1 and E2 showed good linearity in the range of 0.031 2-6.24 mg/L and 0.006 15-1.23 mg/L,respectively.The within-run accuracy of polymyxin E1 and E2 in plasma ranged from 89.4％to 99.8％and 91.5％to 108.2％,respectively,while the between-run accuracy ranged from 91.8％to 104.7％and 95.6％to 105.2％,respectively.The within-run precision of polymyxin E1 and E2 in plasma ranged from 4.9％to 8.9％and 2.8％to 8.5％,respectively,while the between-run precision ranged from 4.1％to 7.6％and 4.2％to 9.8％,respectively.The average internal standard normalized matrix effect factors of polymyxins E1 and E2 were 96.9％-111.2％and 106.1％-112.8％in blank plasma samples from 6 different sources,102.5％-106.8％and 98.8％-105.2％in lipemic plasma,respectively,107.8％-108.9％and 106.9％-1 07.4％in hemolyzed plasma,respectively.The precision of matrix effects was less than 15.0％.The average recovery rate was 102.9％-107.5％for polymyxin E1 and E2,and 107.0％for internal standard polymyxin B1.The precision was less than 3.7％.Conclusions In this study,a simple and efficient LC-MS/MS method was established for determination of polymyxin E1 and E2 in human plasma,which is reliable in the therapeutic drug monitoring and pharmacokinetic study of polymyxin E.

Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7％of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.

Objective:To observe effectiveness of combining diffusion tensor imaging (DTI) with motor evoked potentials (MEPs) in evaluating the upper limb motor functioning of stroke survivors.Methods:Thirty-seven stroke survivors with upper limb motor dysfunction were selected. At the 4th, 12th and 24th week after their onset, each was were assessed using Fugl-Meyer Upper Limb (FMA-UE) scoring, the National Institutes of Health stroke scale (NIHSS), the modified Rankin Scale (mRS), the Barthel Index (BI) and hemiplegic hand function classification. DTI was also applied and MEPs were measured. The patients were divided into an MEP positive group and an MEP negative group according to the existence of the MEP waveform. The DTI and MEP parameters were correlated with the FMA-UE scores, linear regressions were evaluated and a receiver operating characteristics curve was prepared to estimate the utility of DTI in predicting hand function. The sensitivity and specificity of MEPs in predicting hand function recovery were evaluated.Results:The asymmetry index (FAa) of the average anisotropy score of the posterior limb of the internal capsule and the FAa of the cerebral peduncle were both significantly correlated with the FMA-UE scores at the 12th and 24th weeks. The best cut-off points for predicting functional recovery of a patient′s hand were 0.155 for the FAa of the posterior limb of the internal capsule and 0.145 for the cerebral peduncle. Among the 37 patients, the MEPs of 8 (the MEP positive group) could be extracted, and their hand functions recovered completely. The sensitivity of the MEPs in predicting the complete recovery of hand function was 80% with 100% specificity. The linear regression analysis showed 77% prediction accuracy for the FAa and MEPs of the cerebral peduncle for upper limb motor function at the 24th week after onset. In the MEP negative group, two patients completely recovered their hand function, with one′s FAa less than 0.145, and the other′s more than 0.145. When the MEP was negative, the sensitivity of DTI in predicting the recovery of hand function was 50% with 81.5% specificity.Conclusions:DTI combined with MEPs can be used as an index to evaluate the prognosis of upper limb motor function in stroke patients.

The Diagnosis-Intervention Packet(DIP)payment exerts notable effects on hospitals' economic operations.As centralized hubs of high-quality medical resources,tertiary hospitals face a functional mismatch with the provision of services for primary care diseases.By analyzing the admission and payment practices for primary care diseases in sample hospitals in Henan Province,it identifies key challenges,including inadequate alignment between healthcare payment reform policies and management systems,weak foundational capabilities in hospital health insurance informatization,and insufficient awareness of health insurance policies among medical staff.It is recommended that hospitals should strengthen communication and coordination with health insurance administration agencies to foster positive interactions between healthcare providers and insurers;continuously advance in-house health insurance informatization and enhance data governance capabilities;improve strategic awareness and innovate value-based health insurance management models.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveTo construct an animal model of respiratory syncytial virus（RSV）-infected pneumonia suitable for preclinical studies. MethodsThe virulence of RSV to the four cell lines was observed by cytopathic effect （CPE）， and 50% tissue culture infective dose（TCID₅₀） was calculated. Twenty BALB/c mice were randomly divided into a normal group and a model group. Six BALB/c-hIGF1R mice served as the humanized IGF1R model group. Except for the normal group， the other groups received intranasal RSV infection on days 1 and 3 to establish a viral pneumonia model. The efficacy of establishing an RSV-induced pneumonia animal model based on humanized insulin-like growth factor 1 receptor （IGF1R） mice was evaluated by measuring organ indices， peripheral blood lymphocyte percentages， pulmonary pathology and imaging， and pulmonary viral load. Additionally， ten BALB/c mice served as normal group， and thirty-two BALB/c-hIGF1R mice were randomly assigned to humanized IGF1R model group， ribavirin group （82.5 mg·kg^-¹·d^-¹）， and high and low dose groups of Lianhua Qingwen （3.3 mg·kg^-¹·d^-¹ ， 1.65 mg·kg^-¹·d^-¹）， with 8 mice per group. The viral load in lung tissue was measured after ribavirin and Lianhua Qingwen intervention， and the model was applied to the evaluation of anti-RSV drugs. ResultsIn the lungs of the humanized IGF1R model group， large solid and diffuse ground-glass shadows were seen， and the lung volume was significantly increased （P<0.01）. The lung index was significantly increased （P<0.01）， and both the spleen index and thymus index were significantly decreased （P<0.01）. The percentages of CD3⁺ and CD4⁺T cells were significantly decreased （P<0.05）， and there was a large amount of inflammation and stasis in the perivascular area of the lung tissue， which was predominantly characterized by lymphocytes. The endothelium of blood vessels was partially detached， with a small number of eosinophils. After infecting BALB/c-hIGF1R mice with RSV， the expression of viral nucleic acids in the lung tissue of the mice was significantly increased， with significant differences compared with the normal group （P<0.01）. The expression of viral nucleic acids in the ribavirin group and the high and low dose groups of Lianhua Qingwen was significantly reduced， with significant differences compared with the normal group （P<0.01）. ConclusionHumanized IGF1R mice are more susceptible to respiratory SVC， and the animal model of RSV-infected pneumonia based on humanized IGF1R mice was successfully constructed， which is suitable for the evaluation of anti-RSV drugs.