Objective To explore the effects of CYP2C19, CYP2C9 and CYP3A5 genotypes on the plasma concentration of voriconazole in children. Methods Collected blood samples from 50 hospitalized children with invasive fungal infections who received intravenous voriconazole from January 2020 to December 2020. High performance liquid chromatography was used to detect the blood trough concentration of voriconazole, and the time-of-flight mass spectrometry detection system was used to detect the genotypes of CYP2C19, CYP2C9 and CYP3A5, and the effects of children’s genotyping on the plasma concentration, efficacy and adverse reactions of voriconazole were analyzed. Results The total effective rate of 50 children with IFI was 84% （42/50 cases） after voriconazole treatment. The incidence of adverse reactions was 20% （10/50 cases）. The measured plasma concentration of voriconazole ranged from 0.56~7.62 μg/ml. Combined with the different mutation types of CYP2C19 gene loci, three metabolic activities were produced: fast, medium and slow, and the test results showed that there were 16 cases of fast metabolism, 27 cases of intermediate metabolism and 7 cases of slow metabolism. There was a significant difference in plasma concentrations among the three groups （F=15.359, P<0.001）, and the drug concentrations in the fast metabolic group were significantly lower than those in the intermediate metabolic and slow metabolic groups. The mutations of CYP2C9 and CYP3A5 had no significant effect on the plasma concentrations of the drugs, which were （F=2.213, P=0.086 and F=0.757, P=0.475）. Conclusion Voriconazole had significant efficacy in the treatment of invasive fungal infections in children, and the adverse reactions were mild. CYP2C19 genotype was significantly related to the rate of drug metabolism and was an important factor affecting blood drug concentration, the detection of drug concentration and genotype of voriconazole was helpful to adjust the effective drug dose clinically and would achieve more scientific and individualized treatment.

Objective:To analyze the clinical characteristics of adverse reactions caused by dinutuximab β for the treatment of neuro-blastoma(NB)in China and to provide safety evidence for the rational use of dinutuximab β in clinical practice.Methods:Clinical data were retrospectively collected from 16 pediatric patients with NB who had been treated with dinutuximab β at Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to November 2023,and the adverse reactions caused by dinutuximab β were summarized and analyzed.Results:The male-to-female ratio was 5:3 among the 16 children with NB.The retroperitoneum was the main initial site of involvement,accounting for 75%.Thirteen(81.25%)patients had high-risk NB.The adverse reactions caused by dinutuximab β mainly included decreased hemoglobin,fever,vomiting,and diarrhea.The inci-dence of adverse reactions was highest in the first course of treatment,and the median time of adverse reactions was 2-5 days.Conclu-sion:Targeted monitoring should be carried out at an early stage during dinutuximab β administration.Adverse reactions should be de-tected and managed early to ensure the safety of medication for children.

Objective To investigate the establishment and evaluation method of a rat model for cold asthma syndrome during the acute exacerbation phase of asthma.Methods Thirty-two rats were randomly allocated into four distinct groups:normal control group,asthma group,cold asthma group,and Shegan Mahuang Decoction group(SMD).While the normal control group was not subjected to any modeling procedures,the remaining groups were induced to develop asthma by a combination of intraperitoneal injections and atomized inhalation of ovalbumin sensitization solution.Furthermore,to emulate the traditional Chinese medicine syndrome of cold asthma,the cold asthma group and the SMD underwent an additional protocol involving"swimming,cold water consumption,and external cold stimulation."Commencing from the 14th day of the experiment,the SMD received daily gavage administration of Shegan Mahuang Decoction for a consecutive period of 14 days.The cold asthma rat model was comprehensively evaluated from both macroscopic and microscopic perspectives.Results ①Following model induction,both the asthma and cold asthma groups exhibited significant increases in asthmatic behavioral scores,sluggish weight gain,and airway hyperreactivity.Additionally,there was a notable rise in eosinophils(EOS)in the bronchoalveolar lavage fluid(BALF),decreased expression of aquaporin-5(AQP5)in lung tissue,and altered immune balances with reduced Th1/Th2 ratios and elevated Th17/Treg ratios in the spleen.Hemorheological changes included increased whole blood viscosity,relative high-shear,and low-shear indices,alongside a marked decline in erythrocyte aggregation index.The cold asthma group further displayed pronounced cold asthma symptoms,slower weight gain,and more significant increases in whole blood viscosity and low-shear relative index compared to the asthma group.②Administration of SMD alleviated asthmatic behaviors and traditional Chinese medicine syndrome manifestations in cold asthma rats,resulting in enhanced weight gain.SMD also mitigated airway hyperreactivity,reduced EOS percentage in BALF,and ameliorated lung tissue damage and inflammatory cell infiltration.The treatment increased AQP5 expression levels and rectified the immune imbalances of Th1/Th2 and Th17/Treg in cold asthma rats.Furthermore,SMD significantly lowered whole blood viscosity,relative high-shear,and low-shear indices in these rats.Conclusion The research effectively established a model for cold asthma syndrome in TCM through a method that integrates intraperitoneal injection,nebulized ovalbumin sensitization,and a triad of swimming,cold water intake,and external cold exposure.This model consistently displays the symptoms of cold asthma and corresponds with the microscopic pathological alterations seen in asthma,thereby validating the robustness of the model's creation process.

Objective To investigate the correlation of serum brain natriuretic peptide(BNP)and D-dimer levels with cardiac function in elderly patients with chronic heart failure(CHF).Methods A retrospective analysis was conducted on 91 elderly CHF patients(observation group)admitted in our hospital from January 2021 to November 2024.They were then classified into grade Ⅰ-Ⅱsubgroup(66 cases)and grade Ⅲ-Ⅳ subgroup 25 cases according to NYHA cardiac function grading.Another 84 healthy individuals who underwent physical examinations in our hospital dur-ing the same period were selected as the control group.The levels of serum BNP and D-dimer were detected.Multivariate logistic regression model was used to analyze the risk factors affecting the severity of cardiac function in elderly CHF patients,and Spearman correlation analysis was adopted to analyze the correlation between the levels and cardiac function in elderly patients with CHF.Results Serum D-dimer and BNP levels were significantly higher in the observation group than the control group(P＜0.01),and in the grade Ⅲ-Ⅳ subgroup than the grade Ⅰ-Ⅱ sub-group(P＜0.01).Multivariate logistic regression analysis revealed that age(OR=2.815,95％CI:1.501-5.281,P=0.001),BNP(OR=2.901,95％CI:1.458-5.772,P=0.003)and D-dimer(OR=2.872,95％CI:1.501-5.495,P=0.002)were independent influencing factors for cardiac function in elderly CHF patients(P＜0.01).Spearman correlation analysis showed that serum BNP and D-dimer were negatively correlated with cardiac function(r=-0.324,P=0.023;r=-0.285,P=0.035).Conclusion The serum levels of D-dimer and BNP are significantly increased in elderly CHF patients,and the two levels are related to cardiac function.

OBJECTIVE To deeply explore the in vivo pharmacodynamic substance basis of Zhigancao Decoction,a classic tradi-tional Chinese medicine formula,and provide scientific evidence for its rational application and development in modern clinical practice.METHODS Wistar rats were treated with 12.15 g·kg-1 Zhigancao Decoction by gavage.Rat plasma samples were collect-ed at 10 time points(5,15,30,60,120,240,360,480,600 and 720 min after administration)and rat heart(atrial and ventricu-lar)tissue samples were collected at 12 h after administration.Components in the plasma and heart samples were qualitatively identi-fied by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF/MS),and the distri-bution characteristics of Zhigancao Decoction in vivo were analyzed.At the same time,the time-concentration curve of the prototype components and metabolites in Zhigancao Decoction was drawn to observe the changes of blood drug concentration.RESULTS A total of 11 prototype components(Ajugol,Nicotiflorin,Isoschaftoside,4-Hydroxycinnamic acid,Rehmapicrogenin,4-Hydroxybenzoic acid,4′,7-Dihydroxyflavone,Calycosin,3′,4′,7-Trihydroxyflavone,Pinellic acid,Truxillic acid)and 7 metabolites were identified from the plasma samples of Zhigancao Decoction,mainly including flavonoids(flavonoids glycosides),organic acids,and iridoid glyco-sides,etc.Additionally,6 prototype components(Ajugol,Isoschaftoside,Rehmapicrogenin,4′,7-Dihydroxyflavone,Liquiritigenin,3′,4′,7-Trihydroxyflavone)and 3 metabolites were identified from the cardiac samples(the atrium and the ventricle showed the same results).The metabolic pathways mainly involved Phase Ⅰ metabolism and glucuronidation.CONCLUSION The prototype compo-nents and metabolites in plasma and heart tissue of Zhigancao Decoction is preliminarily determined,providing a reference for analyzing the active components of Zhigancao Decoction in heart tissue.

Objective:To investigate the diagnostic value and imaging features of high resolution magnetic resonance imaging(HR-MRI)in patients with lesions in carotid artery and intracranial artery.Methods:Sixty-nine patients with suspected lesions in carotid artery and intracranial artery who admitted to Handan Central Hospital from June 2021 to December 2023 were selected,and they underwent routine MRI and HR-MRI examinations.Digital subtraction angiography(DSA)examination was used as the"gold standard"to analyze the detection rates of different MRI examinations for lesions in carotid artery and intracranial artery.The diagnostic efficacy of them was calculated,and the HR-MRI imaging features of positive cases and negative patients were compared under the"gold standard".Results:For 69 patients with suspected lesions in carotid artery and intracranial artery,41 cases(59.42%)were confirmed by"gold standard"examination,and 31 positive cases were confirmed by routine MRI examination,and 35 positive cases were confirmed by HR-MRI examination,and 39 positive cases were confirmed by combined examination of routine MRI and HR-MRI.The results indicated that the accuracy,sensitivity,specificity,positive and negative predictive values of the combined examination of routine MRI and HR-MRI were respectively 88.41%,87.80%,89.29%,92.31%and 83.33%,all of which were higher than those of single image examination,and the differences were statistically significant(x2=5.459,7.329,6.216,6.395,6.141,P<0.05).The irregular shape,blurred boundary,high signal,plaque formation,intra-plaque bleeding,displacement of common carotid artery or vein,and calcification of lesion in HR-MRI imaging features of positive patients were significantly higher than those of negative patients,and the differences were statistically significant(x2=8.918,4.418,7.001,4.746,8.743,5.951,4.947,P<0.05),respectively.Conclusion:The detection rates both of routine MRI and HR-MRI are higher in patients with lesions in carotid artery and intracranial artery.However,the combined examination of them can improve the diagnostic sensitivity and specificity,and the morphology,boundary,signal and calcification foci of confirmed patients are more obvious in HR-MRI examination,which can provide reference for subsequent diagnosis and treatment.

OBJECTIVE To investigate the current status and causes of occupational exposures to needlestick inju-ries among healthcare workers who perform minimally invasive acupunctures of traditional Chinese medicine(TCM)so as to propose treatment countermeasures.METHODS A total of 95 cases who were involved in the oc-cupational exposures to needlestick injuries due to minimally invasive acupunctures and were treated in hospital in-fection management department of Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine from Jan.2020 to Dec.2024 were retrospectively investigated,and the risk factors for the occupational exposures were statistically analyzed.RESULTS The cases of operation-induced needlestick injuries accounted for 16.35％(95/581)among the total cases of occupational exposures due to the operation of minimally invasive acupunctures of TCM,standardized and advanced training doctors as well as interns were dominant among the occupational ex-posure cases.There were 69(72.63％)cases of acupuncture needle injuries,34(35.79％)of whom had the needlestick injuries during the process of withdrawal of needles.The result of data analysis showed that there were significant differences in age,occupation,working years,distribution of departments,autoimmunity,type of needlestick injury,link of stick injuries and treatment of occupational exposure with emergent screening(all P＜0.05).CONCLUSIONS The incidence of needlestick injuries is high among the health care workers who per-form the minimally invasive acupunctures of TCM,which should be attached great attention to.It is of great sig-nificance to standardize and modify the use procedure,use portable sharp boxes,intensify the safe operation skills for the health care workers with less experience,strengthen the teaching,focus on the autoimmunity,vaccinate in a timely manner,and effectively treat the occupational exposures so as to reduce the incidence of occupational ex-posures and the risk of infections.

Objective To summarize the characteristics of the constitution of orthopedic diseases among soldiers in a sea area,so as to provide the reference for the rational allocation of medical resources,the prevention and treatment of orthopedic diseases,and the improvement of naval medical support.Methods Medical records on injuries of the outpatient and emergency departments in a hospital ship from February 2021 to April 2022 were retrospectively analyzed.The number of varying orthopedic diseases was counted,and descriptive statistical analysis was conducted.Results A total of 200 cases were included in the statistical analysis.The top five diseases were chronic low back pain,knee pain,tibial contusion,wrist joint injury,and shoulder joint injury,and they accounted for 82%of the total orthopedic diseases.Conclusion The medical team stationed on hospital ships should be guided by actual medical needs of officers and soldiers on island,enhance the diagnosis and treatment of common orthopedic diseases,formulate scientific and reasonable prevention and treatment strategies.The allocation of medical materials and personnel should be in line with the spectrum of orthopedic diseases as far as possible to reduce non-combat casualty and strengthen the combat effectiveness of the army.

Objective To analyze the current status of occupational stress among primary and secondary school teachers, and explore the dose-response relationship between weekly work hours and occupational stress. Methods A total of 1 252 teachers from 13 primary and secondary schools in three prefecture-level cities of a central province of China were selected as the research subjects by the convenience sampling method. The Core Occupational Stress Scale was used to assess occupational stress levels of the teachers. Multivariate logistic regression analysis combined with restricted cubic spline models was applied to study the dose-response relationship between weekly work hours and occupational stress. Results The average weekly work hours were (55.3±15.9) hours, with 78.6% of teachers working more than 40.0 hours per week. The total score of occupational stress was (40.3±8.2) points, and the detection rate of occupational stress was 29.8%. Multivariate logistic regression analysis combined with restricted cubic spline models revealed a linear dose-response relationship in weekly work hours and occupational stress among teachers (P for overall trend <0.05, P for nonlinearity was 0.22). Result of age-stratified analysis showed that weekly work hours had a linear dose-response relationship with occupational stress risk in teachers aged 21-<31 and 31-<46 years (P for overall trend <0.05, P for nonlinearity was 0.71 and 0.27, respectively). However, no association was found between weekly work hours and occupational stress risk among teachers aged ≥46 years (P for overall trend =0.08, P for nonlinearity was 0.09). Conclusion There is a linear dose-response relationship between weekly work hours and occupational stress among primary and secondary school teachers in the province, with younger teachers being more susceptible to suffer occupational stress due to long working hours.

OBJECTIVE: To investigate the predictive value of oxygenation index (PaO₂/FiO₂) at intensive care unit (ICU) admission on 30-day mortality in patients with sepsis. METHODS: A retrospective study was conducted. Patients with sepsis who were hospitalized in the ICU of the Affiliated Hospital of Jining Medical University from April 2015 to October 2023 were enrolled. The demographic information, comorbidities, sites of infection, vital signs and laboratory test indicators at the time of admission to the ICU, disease severity scores within 24 hours of admission to the ICU, treatment process and prognostic indicators were collected. According to the PaO₂/FiO₂ at ICU admission, patients were divided into Q1 group (PaO₂/FiO₂ of 4.1-16.4 cmHg, 1 cmHg ≈ 1.33 kPa), Q2 group (PaO₂/FiO₂ of 16.5-22.6 cmHg), Q3 group (PaO₂/FiO₂ of 22.7-32.9 cmHg), and Q4 group (PaO₂/FiO₂ of 33.0-94.8 cmHg). Differences in the indicators across the four groups were compared. Multifactorial Cox regression analysis was used to assess the relationship between PaO₂/FiO₂ and 30-day mortality of patients with sepsis. The predictive value of PaO₂/FiO₂, sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) on 30-day prognosis of patients with sepsis was analyzed by receiver operator characteristic curve (ROC curve). RESULTS: A total of 1 711 patients with sepsis were enrolled, including 428 patients in Q1 group, 424 patients in Q2 group, 425 patients in Q3 group, and 434 patients in Q4 group. 622 patients died at 30-day, the overall 30-day mortality was 36.35%. There were statistically significant differences in age, body mass index (BMI), history of smoking, history of alcohol consumption, admission heart rate, respiratory rate, APACHE II score, SOFA score, Glasgow coma score (GCS), site of infection, Combined chronic obstructive pulmonary disease (COPD), blood lactic acid (Lac), prothrombin time (PT), albumin (Alb), total bilirubin (TBil), pH, proportion of mechanical ventilation, duration of mechanical ventilation, proportion of vasoactive medication used, and maximal concentration, length of ICU stay, hospital stay, incidence of acute kidney injury, in-hospital mortality, 30-day mortality among the four groups. Multivariate Cox regression analysis showed that after adjusting for confounding factors, for every 1 cmHg increase in PaO₂/FiO₂ at ICU admission, the 30-day mortality risk decreased by 2% [hazard ratio (HR) = 0.98, 95% confidence interval (95%CI) was 0.98-0.99, P < 0.001]. The 30-day mortality risk in the Q4 group was reduced compared with the Q1 group by 41% (HR = 0.59, 95%CI was 0.46-0.76, P < 0.001). The fitted curve showed that a curvilinear relationship between PaO₂/FiO₂ and 30-day mortality after adjustment for confounders. In the inflection point analysis, for every 1 cmHg increase in PaO₂/FiO₂ at PaO₂/FiO₂ < 28.55 cmHg, the risk of 30-day death in sepsis patients was reduced by 5% (HR = 0.95, 95%CI was 0.94-0.97, P < 0.001); when PaO₂/FiO₂ ≥ 28.55 cmHg, there was no statistically significant association between PaO2/FiO2 and the increase in the risk of 30-day death in sepsis (HR = 1.01, 95%CI was 0.99-1.02, P = 0.512). ROC curve analysis showed that the area under the curve (AUC) for the prediction of 30-day mortality by admission PaO₂/FiO₂ in ICU sepsis patients was 0.650, which was lower than the predictive ability of the SOFA score (AUC = 0.698) and APACHE II score (AUC = 0.723). CONCLUSION In patients with sepsis, PaO₂/FiO₂ at ICU admission is strongly associated with 30-day mortality risk, alerting healthcare professionals to pay attention to patients with low PaO₂/FiO₂ for timely interventions.
Humans ; Sepsis/mortality* ; Intensive Care Units ; Retrospective Studies ; Prognosis ; Hospital Mortality ; Oxygen ; Male ; Predictive Value of Tests ; Female ; Middle Aged ; Aged