Objective To mine and analyze adverse drug events(ADEs)signals in minors using recombinant human growth hormone(rhGH),and to provide reference for clinically safe use of drugs.Methods Based on the the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the data of ADE reports related to rhGH from the third quarter of 2014 to the second quarter of 2024 were retrieved.The ADE reports were standardized and categorized using the Medical Dictionary for Regulatory Activities(MedDRA).The reporting odds ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)method were employed to mine and analyze ADE signals between rhGH and individuals under 18 years of age.Results A total of 33,642 ADE reports related to the use of rhGH in minors were retrieved.After excluding signals unrelated to ADEs(product issues,social issues,etc.),358 ADE signals were ultimately identified,involving 21 system organ lasses(SOCs).The most frequently reported ADEs were general disorders and administration site reactions(3,621 cases),as well as various laboratory test abnormalities(3,259 cases).Notably,ADE signals related to cardiovascular system tests,psychiatric disorders,and reproductive system and breast disorders,such as decreased serum creatinine,elevated alkaline phosphatase,reduced red blood cell distribution width,crying,aggression,and hypogonadism,were not documented in the drug package insert.Conclusion When administering rhGH to minors,in addition to monitoring common ADEs such as changes in blood glucose levels and scoliosis,attention should also be given to potential ADEs,including alterations in hematological parameters,psychiatric issues,and reproductive system and breast disorders,to ensure medication safety.

Purpose To quantitatively compare the diffusion parameters of mono-and biexponential diffusion-weighted imaging models,and to obtain optimal sets of b-values in diffusion-weighted MRI for obtaining monoexponential apparent diffusion coefficient(ADC)close to perfusion-insensitive intravoxel incoherent motion(IVIM)model ADC(ADCIVIM)in identifying of pulmonary solid benign and malignant lesions.Materials and Methods IVIM was performed in 40 patients with solid nodule and masse in Xi'an Gaoxin Hospital from July 2021 to August 2022 using a 3.0T MR imager.Two experienced diagnostic radiologists subjectively evaluated the IVIM images.A single index model was used to calculate ADC values(ADC0-1 000,ADC20-1 000,ADC50-1 000,ADC80-1 000,ADC150-1 000,ADC300-1 000,ADC500-1 000,ADC300,500,1 000,ADC300,800,1 000,ADC300,500,ADC300,800 and ADC300,1 000).The reference standard ADCIVIM value were calculated using a double-exponential model.The physician's measurements between two physicians were measured.The malignant and benign groups were compared and receiver operator characteristic curve for all parameters were analyzed.Results The measurement consistency of ADC values under b value sets and ADCIVIM was very good,and the intraclass correlation coefficient was more significant than 0.75.The differences between ADCIVIM and ADC values in each b group were statistically significant(t=-6.016--2.500,all P<0.05).The area under the curve(AUC)of ADCIVIM was the largest(0.906),with an optimal threshold of 1.271×10-3 mm2/s,a sensitivity of 80.0%and a specificity of 93.0%.The diagnostic efficacy close to ADCIVIM were ADC300,800(AUC=0.891),ADC50-1 000(AUC=0.827)and ADC300,800,1 000(AUC=0.795),respectively.The optimal threshold of ADC300,800 was 1.140×10-3 mm2/s,the sensitivity and specificity were 80.0%and 93.7%,respectively.Conclusion Combining b-values 300 s/mm2 and 800 s/mm2 is recommended as routine scanning parameters for identifying the insensitive monoexponential ADC between benign and malignant solid pulmonary lesions.

Purpose To explore the value of quantitative parameters(T2* value,R2* value)of three-dimensional multi-echo ultrashort echo time technique for the differential diagnosis of benign and malignant pulmonary nodules and masses(PNMs).Materials and Methods The MRI data of 68 patients with PNMs in Xi'an Gaoxin Hospital from July 2021 to October 2022 were retrospectively analyzed,and PNMs were grouped into benign(34 cases)and malignant(34 cases)categories using histopathology or clinical follow-up as the reference standard.Two observers respectively outlined the regions of interest on three-dimensional multi-echo ultrashort echo time-T2* and R2* maps,and quantitatively measured the T2* and R2* values.The intraclass correlation coefficient(ICC)was used to evaluate the consistency of the measured values.Differences in the above indicators between the two groups of PNMs were analyzed,and their diagnostic efficacy was assessed.The predictive probability of the combined two indicators was computed,the receiver operating characteristic curve was plotted,and the area under the curve(AUC)was calculated.Results The measurement results of each parameter of PNMs in the benign and malignant groups by the two observers were consistent(ICC>0.75).The T2* value of the malignant group was higher than that of the benign group(Z=-5.158,P<0.001),and the R2* value was lower than that of the benign group(Z=-4.845,P<0.001),and the differences were statistically significant.The AUC of the T2* value was 0.864(95%CI 0.775-0.953,P<0.001),with a maximum Youden index of 0.677,a threshold of 9.675 ms,a sensitivity of 76.5%,and a specificity of 91.2%.The AUC of the R2* value was 0.842(95%CI 0.746-0.937,P<0.001),with a maximum Youden index of 0.647,and a threshold of 109.15/s,with a sensitivity of 73.5%and a specificity of 91.2%.The AUC of the combined diagnosis of T2* and R2* values was 0.867(95%CI 0.779-0.955,P<0.001),with a maximum Youden index of 0.677,a sensitivity of 82.4%,and a specificity of 85.3%.There was no statistically significant difference in the pairwise comparison of T2* values,R2* values,and their combined AUC(all P>0.05).Conclusion The T2* value and R2* value of the three-dimensional multi-echo ultrashort echo time technique,as well as the combination of the two indicators,are all helpful in differentiating benign and malignant PNMs,providing imaging support for the preoperative non-invasive and precise differentiation of PNMs and optimizing clinical diagnosis and treatment decisions.

Purpose To explore the value of quantitative parameters(T2* value,R2* value)of three-dimensional multi-echo ultrashort echo time technique for the differential diagnosis of benign and malignant pulmonary nodules and masses(PNMs).Materials and Methods The MRI data of 68 patients with PNMs in Xi'an Gaoxin Hospital from July 2021 to October 2022 were retrospectively analyzed,and PNMs were grouped into benign(34 cases)and malignant(34 cases)categories using histopathology or clinical follow-up as the reference standard.Two observers respectively outlined the regions of interest on three-dimensional multi-echo ultrashort echo time-T2* and R2* maps,and quantitatively measured the T2* and R2* values.The intraclass correlation coefficient(ICC)was used to evaluate the consistency of the measured values.Differences in the above indicators between the two groups of PNMs were analyzed,and their diagnostic efficacy was assessed.The predictive probability of the combined two indicators was computed,the receiver operating characteristic curve was plotted,and the area under the curve(AUC)was calculated.Results The measurement results of each parameter of PNMs in the benign and malignant groups by the two observers were consistent(ICC>0.75).The T2* value of the malignant group was higher than that of the benign group(Z=-5.158,P<0.001),and the R2* value was lower than that of the benign group(Z=-4.845,P<0.001),and the differences were statistically significant.The AUC of the T2* value was 0.864(95%CI 0.775-0.953,P<0.001),with a maximum Youden index of 0.677,a threshold of 9.675 ms,a sensitivity of 76.5%,and a specificity of 91.2%.The AUC of the R2* value was 0.842(95%CI 0.746-0.937,P<0.001),with a maximum Youden index of 0.647,and a threshold of 109.15/s,with a sensitivity of 73.5%and a specificity of 91.2%.The AUC of the combined diagnosis of T2* and R2* values was 0.867(95%CI 0.779-0.955,P<0.001),with a maximum Youden index of 0.677,a sensitivity of 82.4%,and a specificity of 85.3%.There was no statistically significant difference in the pairwise comparison of T2* values,R2* values,and their combined AUC(all P>0.05).Conclusion The T2* value and R2* value of the three-dimensional multi-echo ultrashort echo time technique,as well as the combination of the two indicators,are all helpful in differentiating benign and malignant PNMs,providing imaging support for the preoperative non-invasive and precise differentiation of PNMs and optimizing clinical diagnosis and treatment decisions.

Objective To mine and analyze adverse drug events(ADEs)signals in minors using recombinant human growth hormone(rhGH),and to provide reference for clinically safe use of drugs.Methods Based on the the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,the data of ADE reports related to rhGH from the third quarter of 2014 to the second quarter of 2024 were retrieved.The ADE reports were standardized and categorized using the Medical Dictionary for Regulatory Activities(MedDRA).The reporting odds ratio(ROR)method and Bayesian confidence propagation neural network(BCPNN)method were employed to mine and analyze ADE signals between rhGH and individuals under 18 years of age.Results A total of 33,642 ADE reports related to the use of rhGH in minors were retrieved.After excluding signals unrelated to ADEs(product issues,social issues,etc.),358 ADE signals were ultimately identified,involving 21 system organ lasses(SOCs).The most frequently reported ADEs were general disorders and administration site reactions(3,621 cases),as well as various laboratory test abnormalities(3,259 cases).Notably,ADE signals related to cardiovascular system tests,psychiatric disorders,and reproductive system and breast disorders,such as decreased serum creatinine,elevated alkaline phosphatase,reduced red blood cell distribution width,crying,aggression,and hypogonadism,were not documented in the drug package insert.Conclusion When administering rhGH to minors,in addition to monitoring common ADEs such as changes in blood glucose levels and scoliosis,attention should also be given to potential ADEs,including alterations in hematological parameters,psychiatric issues,and reproductive system and breast disorders,to ensure medication safety.

Purpose To quantitatively compare the diffusion parameters of mono-and biexponential diffusion-weighted imaging models,and to obtain optimal sets of b-values in diffusion-weighted MRI for obtaining monoexponential apparent diffusion coefficient(ADC)close to perfusion-insensitive intravoxel incoherent motion(IVIM)model ADC(ADCIVIM)in identifying of pulmonary solid benign and malignant lesions.Materials and Methods IVIM was performed in 40 patients with solid nodule and masse in Xi'an Gaoxin Hospital from July 2021 to August 2022 using a 3.0T MR imager.Two experienced diagnostic radiologists subjectively evaluated the IVIM images.A single index model was used to calculate ADC values(ADC0-1 000,ADC20-1 000,ADC50-1 000,ADC80-1 000,ADC150-1 000,ADC300-1 000,ADC500-1 000,ADC300,500,1 000,ADC300,800,1 000,ADC300,500,ADC300,800 and ADC300,1 000).The reference standard ADCIVIM value were calculated using a double-exponential model.The physician's measurements between two physicians were measured.The malignant and benign groups were compared and receiver operator characteristic curve for all parameters were analyzed.Results The measurement consistency of ADC values under b value sets and ADCIVIM was very good,and the intraclass correlation coefficient was more significant than 0.75.The differences between ADCIVIM and ADC values in each b group were statistically significant(t=-6.016--2.500,all P<0.05).The area under the curve(AUC)of ADCIVIM was the largest(0.906),with an optimal threshold of 1.271×10-3 mm2/s,a sensitivity of 80.0%and a specificity of 93.0%.The diagnostic efficacy close to ADCIVIM were ADC300,800(AUC=0.891),ADC50-1 000(AUC=0.827)and ADC300,800,1 000(AUC=0.795),respectively.The optimal threshold of ADC300,800 was 1.140×10-3 mm2/s,the sensitivity and specificity were 80.0%and 93.7%,respectively.Conclusion Combining b-values 300 s/mm2 and 800 s/mm2 is recommended as routine scanning parameters for identifying the insensitive monoexponential ADC between benign and malignant solid pulmonary lesions.

A quantitative analysis method for ten principal components (phenylethanol, iridoids and triterpenes) of raw Ligustri Lucidi Fructus and its wine-steamed product was developed using liquid chromatography tandem triple quadrupole mass spectrometry (LC-QQQ-MS) to study their pharmacokinetic behavior in vivo. The results of methodological investigation were in accord with the criteria of biological analysis. After a single administration to rats of the water extracts of Ligustri Lucidi Fructus and its wine-steamed product, the plasma concentration of each component at different time points was measured and the pharmacokinetic parameters were determined. The AUC_{0-24 h} and C_max of the phenylethanol components (salidroside, tyrosol, hydroxytyrosol) were the greatest, suggesting that these components are the main pharmacological substances of Ligustri Lucidi Fructus. In addition, the t_max values of the eight major components were even lower with administration of the wine-steamed product, suggesting that these components are rapidly absorbed. However, the t_max values of specnuezhenide and oleanolic acid were greater with administration of the wine-steamed product, indicating that these two components were more slowly absorbed. A secondary peak phenomenon of tyrosol and hydroxytyrosol were observed in two sample groups, whereas the secondary peak phenomenon of salidroside occurred only with the wine-steamed product. This result suggests that the effect of wine-steamed product could persist for a long period. Meanwhile, the relative bioavailability of specnuezhenide and oleanolic acid was greater than 100% with administration of the wine-steamed product, consistent with the Traditional Chinese Medicine theory of the wine-steamed product being more effective than the raw material. The results reveal the different pharmacokinetic parameters and relative bioavailability of each component of Ligustri Lucidi Fructus and its wine-steamed product, and also demonstrate the variation and correlation of various components in vivo and in vitro, providing an experimental basis for the selection of quality control indexes, mechanisms of processing and the metabolic rule in vivo of Ligustri Lucidi Fructus. These experiments were approved by the Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medicine Science.

Triterpenoids are one of the most active constituents in Ligustri Lucidi Fructus, but only oleanolic acid has been mostly studied. In recent years, a growing number of studies have shown that other triterpenes from Ligustri Lucidi Fructus also have various biological activities, so it is necessary to build up a detailed profile of the triterpenoids in Ligustri Lucidi Fructus. The chromatographic separation was performed on a C_(18) column(4.6 mm×250 mm, 5 μm) with mobile phase of methanol-acetonitrile-0.2% formic acid for gradient elution. The detection wavelength was set at 210 nm, with a flow rate of 0.5 mL·min~(-1), and the column temperature of 25 ℃. The HPLC fingerprint of triterpenoids in Ligustri Lucidi Fructus was built by testing 21 batches of samples from different sources. The structures of the total 15 common chromatographic peaks were elucidated with UHPLC-ESI-Orbitrap-MS/MS technique and six of them were identified as tormentic acid, pomolic acid, maslinic acid, botulin, oleanolic acid and ursolic acid by comparison to the reference substances. Under the same chromatographic condition, four main triterpenes(podocarboxylic acid, hawthorn acid, oleanolic acid and ursolic acid) were quantified and the results of system adaptability and methodology investigation all met the requirements of content determination. Meanwhile, with oleanolic acid(A) as the internal reference substance, quantitative analysis of multi-components by single marker(QAMS) method was used to analyze the above four components. The relative correction factor of oleanolic acid(B), hawthorn acid(C) and ursolic acid(D) to oleanolic acid was f_(B/A)=1.12, f_(C/A)=1.02 and f_(D/A)=0.88, respectively, and the relative retention values of these three to oleanolic acid was RRV_(B/A)=0.46, RRV_(C/A)=0.70 and RRV_(D/A)=1.03, respectively. The contents determined by two methods were similar. In conclusion, the method built in this paper is proved to be simple, reliable and specific for the simultaneous qualitative and quantitative analysis of the triterpenoids in Ligustri Lucidi Fructus, which can lay foundation for further assays of the triterpenoids in Ligustri Lucidi Fructus and the relative products.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Fruit ; Ligustrum ; Tandem Mass Spectrometry ; Triterpenes

This paper reviewed the literatures of TCM treating diabetes mellitus and pulmonary tuberculosis from two aspects, Chinese patent medicine and TCM decoctions, which showed that TCM therapy can control blood sugar levels, improve clinical symptoms such as cough, expectoration and wheezing, promote pulmonary tuberculosis lesion absorption, cavity closure and sputum vaginal discharge, and improve patients' quality of life.

Objective:To explore the correlation between the level of heart rate deceleration (DC), serum homocysteine(Hcy), the scope and extent of coronary artery lesion in coronary heart disease patients with hypertension.Methods:From January 2019 to October 2019, 103 coronary heart disease patients with hypertension who were diagnosed and hospitalized in cardiovascular department of Binzhou Central Hospital were selected as coronary heart disease(CHD) group, and 52 patients with simple hypertension were selected as control group.The serum Hcy levels of the two groups were measured and analyzed.The DC value and the difference of the two groups were analyzed.The degree of coronary artery lesion was evaluated by the number of coronary artery lesion and Gensini score.The relationship between DC, Hcy and the degree of coronary artery lesion was analyzed.Results:Compared with the control group, the DC value of CHD group was significantly lower [(6.02±1.97)ms vs.(4.97±1.59)ms, t=-3.989, P<0.05], and the serum Hcy level was increased [(11.46±4.38)μmol/L vs.(16.79±6.31)μmol/L, t=4.260, P<0.05]. In the CHD group, the DC values and Gensini scores of the patients with single vessel lesion, double vessel lesions and three vessel lesions were (5.52±1.34)ms, (5.06±1.29)ms, (4.39±1.19)ms, (21.35±17.10)points, (26.93±18.18)points, (49.39±30.14)points, respectively.The DC value of patients with three vessel lesions was lower than that of patients with single vessel lesion( F=7.349, P<0.05), and the Gensini score was higher( F=13.487, P<0.05). There were no statistically significant differences in DC value and Gensini score between patients with three vessel lesions and those with two vessel lesions and those with single vessel lesion( P>0.05). The serum Hcy levels of patients with single, double and three vessel lesions were (14.67±5.97)μmol/L, (15.85±6.29)μmol/L and (16.97±7.13)μmol/L, respectively.The difference among the three groups was statistically significant ( F=12.427, P<0.05). There was a negative correlation between DC and Gensini score( r=-0.310, P<0.05), and a positive correlation between serum Hcy and Gensini score( r=0.369, P<0.05). Conclusion:The DC value and Hcy level in coronary heart disease patients with hypertension are significantly decreased, which are closely related to the degree of coronary artery lesion.