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.

X-ray is usually used to determine anatomy and localization during conventional permanent pacemaker implantation.But X-ray exposure might induce radiation injury to fetus.In this paper,we reported 2 cases successful double cavity permanent pacemaker implantation in pregnant women woman at 13 weeks of gestation under the guidance of transthoracic echocardiography.The postoperative pacing parameters were good,the whole process was finished with zero radiation,and there were complications during pregnancy.Both cases resulted in full-term pregnancies and the natural delivery of healthy newborns.Pacemaker electrodes were in normal position as confirmed by post-delivery X-ray examinations.

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 evaluate the short-term outcomes of robot-assisted partial nephrectomy(RAPN)in the treatment of renal cell carcinoma(RCC)involving segmental renal vein invasion,and to summarize relevant diagnostic experience and surgical techniques.Methods A retrospective analysis was conducted on the clinicopathological data of 23 RCC patients who were found to have segmental renal vein invasion during RAPN at Sun Yat-sen University Cancer Center during 2022 and 2024.All procedures were performed by the same experienced urologic surgeon(＞1000 robotic cases).Preoperative computed tomography(CT)scans of all patients failed to reveal segmental renal vein invasion.Two experienced radiologists re-evaluated the imaging postoperatively.The clinical and pathological data of patients were analyzed to preliminarily explore the short-term efficacy,imaging,intraoperative findings and pathological characteristics.Results All surgeries were completed successfully via the transperitoneal approach with renal preservation.The median operation time was 151.0(125.5,182.0)min,and median blood loss was 180.0(100.0,300.0)mL;2 patients(8.7％)required intraoperative transfusion;3(13.0％)experienced postoperative complications,all of which were minor(Clavien-Dindo grade 1-2).Postoperative pathology confirmed venous invasion in 2 patients.The diagnostic rates of segmental renal vein invasion by the two radiologists were 47.8％(11/23)and 21.7％(5/23),respectively,with concordance in only 3 cases.During a mean follow-up of 9.1 months,1 patient developed iliac lymph node metastasis without local recurrence 12.4 months after surgery.After reoperation to remove the metastatic focus,the patient was treated with Axitinib combined with Toripalimab and has survived to date.The remaining patients were followed up for an average of 8.9 months,with no recurrence or metastasis observed.Conclusion Preoperative detection of segmental renal vein invasion in RCC is challenging,and pathological confirmation is often inconsistent with intraoperative findings.For RCC patients with intraoperatively identified segmental renal vein invasion,RAPN performed by experienced surgeons is feasible and safe on the premise of ensuring complete tumor resection,with favorable short-term oncologic outcomes.Long-term results require further follow-up.

Purpose This study aims to investigate the clinicopathological features of diffuse pulmonary menin-gotheliomatosis(DPM).Methods The clinical data of 10 patients with DPM undergoing video-assisted thoracic sur-gery(VATS)were collected,and their clinical and pathological characteristics were analyzed using immunohistochem-istry.Results The detection rate of DPM was 1.19‰,with 90％of the patients being female.DPM predominantly occurred in the age range of 40-60 years,with an average age at diagnosis of 50.7 years.Most patients had no smok-ing history.Pathological diagnosis combined with imaging findings was the main method for diagnosing DPM.80％of the patients were prone to concurrent early-stage invasive pulmonary adenocarcinoma.Laboratory indicators,including pulmonary function,were generally normal.Chest CT showed diffuse multiple ground-glass opacity or cystic nodules in both lungs,with the number of nodules in both lungs ranging from dozens to hundreds,and the maximum diameter of the nodules was 2-6 mm.The median volume and CT value of the pulmonary nodules were 35.32 mm3 and-566 HU,respectively.Pathological features mainly included multiple meningothelial-like nodules observed under the micro-scope.Immunophenotypically,CD56,EMA,PR,and vimentin were often positive.Conclusion DPM is a rare lung disease with no obvious clinical symptoms,and is more common in middle-aged and elderly women.Diffuse multiple nodules in both lungs are its main imaging features.Most DPM patients are complicated with lung adenocarcinoma,and regular follow-up is recommended.

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.

Purpose This study aims to investigate the clinicopathological features of diffuse pulmonary menin-gotheliomatosis(DPM).Methods The clinical data of 10 patients with DPM undergoing video-assisted thoracic sur-gery(VATS)were collected,and their clinical and pathological characteristics were analyzed using immunohistochem-istry.Results The detection rate of DPM was 1.19‰,with 90％of the patients being female.DPM predominantly occurred in the age range of 40-60 years,with an average age at diagnosis of 50.7 years.Most patients had no smok-ing history.Pathological diagnosis combined with imaging findings was the main method for diagnosing DPM.80％of the patients were prone to concurrent early-stage invasive pulmonary adenocarcinoma.Laboratory indicators,including pulmonary function,were generally normal.Chest CT showed diffuse multiple ground-glass opacity or cystic nodules in both lungs,with the number of nodules in both lungs ranging from dozens to hundreds,and the maximum diameter of the nodules was 2-6 mm.The median volume and CT value of the pulmonary nodules were 35.32 mm3 and-566 HU,respectively.Pathological features mainly included multiple meningothelial-like nodules observed under the micro-scope.Immunophenotypically,CD56,EMA,PR,and vimentin were often positive.Conclusion DPM is a rare lung disease with no obvious clinical symptoms,and is more common in middle-aged and elderly women.Diffuse multiple nodules in both lungs are its main imaging features.Most DPM patients are complicated with lung adenocarcinoma,and regular follow-up is recommended.

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 provide reference for improving the pre-prescription review system and reducing the occurrence of medication error by analyzing the drug-related problems(DRPs)in the pre-prescription review orders of pediatric outpatient clinics using the Pharmaceutical Care Network Europe(PCNE)classification system.METHODS The data of pre-prescription review orders were retrospectively collected from outpatient department of Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine from July 2022 to June 2023;DRPs in the pre-prescription review orders were classified and summarized by using the PCNE classification system(version 9.1),and then analyzed in terms of types and causes of issues,and the acceptance of interventions.RESULTS A total of 66 017 DRPs orders were included,involving 41 165 patients.The proportion of DRPs orders in children aged ≤5 years old was the highest(58.25％),followed by children aged 6-12 years old(33.52％);the department with the highest proportion of DRPs was internal medicine of pediatrics department(71.41％);the department with the highest incidence of DRPs was thoracic surgery department(9.73％);top three drug categories of DRPs orders were systemic anti-infective drugs(25.26％),Chinese patent medicines(24.74％)and respiratory drugs(22.38％).Referring to PCNE classification system,the types of DRPs mainly focused on treatment safety(64.86％);the reasons of DRPs orders mainly focused on dose selection(82.09％),of which 41.26％were due to excessive drug dosage;92.13％of interventions could be accepted and fully executed by doctors.CONCLUSIONS DRPs orders identified by the pre-prescription review system can be effectively analyzed by using PCNE classification system.Pharmacists should focus on medication use in children aged＜5 years old,update and develop personalized prescription review rules timely,and meet the rational needs of clinical medication for children.

Objective To evaluate the short-term outcomes of robot-assisted partial nephrectomy(RAPN)in the treatment of renal cell carcinoma(RCC)involving segmental renal vein invasion,and to summarize relevant diagnostic experience and surgical techniques.Methods A retrospective analysis was conducted on the clinicopathological data of 23 RCC patients who were found to have segmental renal vein invasion during RAPN at Sun Yat-sen University Cancer Center during 2022 and 2024.All procedures were performed by the same experienced urologic surgeon(＞1000 robotic cases).Preoperative computed tomography(CT)scans of all patients failed to reveal segmental renal vein invasion.Two experienced radiologists re-evaluated the imaging postoperatively.The clinical and pathological data of patients were analyzed to preliminarily explore the short-term efficacy,imaging,intraoperative findings and pathological characteristics.Results All surgeries were completed successfully via the transperitoneal approach with renal preservation.The median operation time was 151.0(125.5,182.0)min,and median blood loss was 180.0(100.0,300.0)mL;2 patients(8.7％)required intraoperative transfusion;3(13.0％)experienced postoperative complications,all of which were minor(Clavien-Dindo grade 1-2).Postoperative pathology confirmed venous invasion in 2 patients.The diagnostic rates of segmental renal vein invasion by the two radiologists were 47.8％(11/23)and 21.7％(5/23),respectively,with concordance in only 3 cases.During a mean follow-up of 9.1 months,1 patient developed iliac lymph node metastasis without local recurrence 12.4 months after surgery.After reoperation to remove the metastatic focus,the patient was treated with Axitinib combined with Toripalimab and has survived to date.The remaining patients were followed up for an average of 8.9 months,with no recurrence or metastasis observed.Conclusion Preoperative detection of segmental renal vein invasion in RCC is challenging,and pathological confirmation is often inconsistent with intraoperative findings.For RCC patients with intraoperatively identified segmental renal vein invasion,RAPN performed by experienced surgeons is feasible and safe on the premise of ensuring complete tumor resection,with favorable short-term oncologic outcomes.Long-term results require further follow-up.