OBJECTIVE To develop a method for the determination of tacrolimus （TAC） concentration in human whole blood and to apply it in clinical therapeutic drug monitoring. METHODS Whole blood samples were processed by protein precipitation with methanol. The determination was performed using liquid chromatography-tandem mass spectrometry （LC-MS/MS）， with ascomycin serving as the internal standard. Chromatographic separation was carried out on a Kinetex F5 100Å column with a mobile phase consisting of 0.1 mmol/L ammonium acetate containing 0.2 mmol/L formic acid and methanol. Gradient elution was performed at a flow rate of 0.4 mL/min. The injection volume was 5 μL. Detection was conducted using multiple reaction monitoring （ m / z 821.6→768.6 for TAC； m / z 809.4→756.1 for ascomycin） with an electrospray ionization source in positive ion mode. The study focused on 86 whole blood samples collected from 83 pedi atric patients who received TAC therapy at Children’s Hospital of Nanjing Medical University from September 1 to 30， 2025. The aforementioned method was employed to measure the TAC concentration in the whole blood samples. The correlation and agreement between the aforementioned method and the traditional enzyme multiplied immunoassay technique （EMIT） were evaluated through Spearman correlation analysis， Bland-Altman analysis， and Passing-Bablok regression analysis. RESULTS The linear range of TAC was 0.5-100 ng/mL； the evaluation results for accuracy， precision， extraction recovery， matrix effect， and stability tests all met the relevant requirements. Clinical application results showed that the median concentration of TAC in pediatric whole blood measured by LC-MS/MS and EMIT methods were 4.4 and 4.0 ng/mL， respectively. Moreover， the two methods exhibited a strong correlation （correlation coefficient of 0.848 1） and good agreement （average relative deviation of 6.5%）. CONCLUSIONS A reliable LC-MS/MS method for the determination of TAC concentration in human whole blood is successfully established. This method demonstrates strong correlation and good agreement with the EMIT method， making it suitable for clinical therapeutic drug monitoring.

BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

BACKGROUND: Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases. METHODS: A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity. RESULTS: After a mean follow-up time of 11.8 years, over 20 International Classification of Diseases, 10th Revision ( ICD-10 ) codes were showed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR] = 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR = 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR = 1.58, 95% CI: 1.14-2.17), gastritis (K29: HR = 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR = 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR = 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR = 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR = 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR = 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR = 1.50, 95% CI: 1.17-1.94; K44: HR = 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR = 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL. CONCLUSIONS This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.
Humans ; Male ; Female ; Middle Aged ; Cohort Studies ; Leukocytes/metabolism* ; Telomere/genetics* ; Proportional Hazards Models ; Adult ; Digestive System Diseases/genetics* ; Aged ; Risk Factors ; Telomere Shortening

The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

Objective To investigate the immediate therapeutic efficacy of Kuanxiong Aerosol on improving the angina pectoris in the patients complicated with intermediate coronary stenosis(ICS),and to observe its effect on resting full-cycle ratio(RFR),corrected TIMI(thrombolysis in myocardial infarction)frame count(CTFC)in angiography,and coronary serum inflammatory factors.Methods Sixty angina pectoris patients with ICS admitted to the Cardiovascular Department of Dade Road Hospital,Guangdong Provincial Hospital of Traditional Chinese Medicine from March 2023 to March 2024 were randomly divided into the trial group and the control group,with 30 patients in each group.The trial group was given four consecutive sprays of Kuanxiong Aerosol by sublingual spray,and the control group had no intervention but just was given the monitoring for 10 minutes.Before and after the intervention,the changes of coronary RFR,CTFC,Visual Analogue Scale(VAS)score of chest pain,and the serum levels of C-reactive protein(CRP),interleukin 6(IL-6)and lipoprotein-associated phospholipase A2(Lp-PLA2)in the two groups were observed.Moreover,the incidence of adverse reactions during the intervention in the two groups of patients was compared.Results(1)After the intervention,the coronary RFR value of the trial group was increased significantly compared with that before intervention(P<0.01),while the coronary RFR value of the control group was not increased significantly compared with that before intervention(P>0.05);the comparison between the two groups showed that the effect on increasing the coronary RFR value in the trial group was superior to that in the control group(P<0.05).(2)After intervention,the CTFC value of the trial group was significantly decreased compared with that before intervention(P<0.01),while the CTFC value of the control group was not significantly decreased compared with that before intervention(P>0.05);the intergroup comparison showed that the trial group tended to have a better effect on the decrease of CTFC value than the control group,but the difference being not statistically significant(P>0.05).(3)After the intervention,the chest pain VAS score of the trial group was significantly reduced compared with that before intervention(P<0.01),while the pre-and post-treatment changes of the score in the control group was not significant(P>0.05);the intergroup comparison showed that the decrease of the chest pain VAS score in the trial group was superior to that in the control group(P<0.01).In particular for immediate therapeutic efficacy,Kuanxiong Aerosol achieved the effective rate of 96.67%(29/30)for relieving chest pain 10 minutes after sublingual spraying,which was significantly superior to that of the control group[10.00%(3/30)],and the comparison between the two groups showed that the difference was statistically significant(P<0.001).(4)After the intervention,the Lp-LPA2 value of the trial group was decreased compared with that before intervention(P<0.05),while the CRP and IL-6 values of the trial group as well as the CRP,IL-6,and Lp-LPA2 values of the control group were all not significantly decreased compared with those before intervention(P>0.05).The intergroup comparison showed that the trial group's effect on the decrease of Lp-LPA2 value was significantly superior to that of the control group(P<0.05).(5)Before and after the intervention,no obvious changes of the general vital signs in the two groups were shown,no drug-related adverse occurred,either.Conclusion Kuanxiong Aerosol can immediately improve the coronary physiological function indicators of angina pectoris patients with ICS,increase the coronary flow rate,and inhibit inflammatory response of the coronary artery to some degree,thus to alleviate the symptoms of angina pectoris in patients with ICS.

Objective To explore the feasibility of prototype of flexible ultrasound array transducer for measuring intravascular diameter and blood flow velocity.Methods A prototype of flexible ultrasonic array transducer composed of a surface mount flexible ultrasonic array transducer(referred to as the transducer)and acquisition system was designed and fabricated.Doppler body model and vascular simulation control system was used to simulate human blood.Mindray M7 color multi-functional ultrasound diagnostic instrument(abbreviated as M7)and the prototype were adopted to detect pulse wave excitation mode,spectral morphology,echo signal time interval,blood flow velocity,etc.Taken the results of M7 as standards,the effectiveness of the prototype was evaluated.Then the inner diameter and flow velocity of left common carotid artery,left brachial artery and left radial artery of 20 healthy controls(HC)were measured respectively using M7 and the prototype,and the consistency of measurement results were analyzed to evaluate the accuracy of the prototype.The safety of the prototype was evaluated according to subjectively scoring the comfort level of HC applying the transducer and whether there was skin discomfort,injury,etc.after removing the transducer.Results The collected blood flow spectrum of the above vascular simulation control system acquire with the prototype were clear,and the spectral morphology,flow velocity,as well as echo signal time interval were basically consistent with those of M7.The consistency of the inner diameter of left common carotid artery,left brachial artery and left radial artery measured by the prototype and M7 in 20 HC were all very strong(ICC=0.919-0.992),while of flow velocities were moderate or very strong(ICC=0.524-0.831).The subjective score of comfort level of application of transducer was 3(2,3),and no skin discomfort occurred.Conclusion Flexible ultrasound array transducer technology could be used to measure intravascular diameter and blood flow velocity.

Objective:To analyze the iodine nutrition status and its related factors among adults aged 18 years and above in Zhejiang Province in 2022.Methods:A multistage stratified sampling method was used to select 4 320 adults aged 18 years and above from 16 on-site survey sites in Zhejiang Province for the study. A questionnaire was used to investigate the general demographic information and personal dietary characteristics of the study participants. Household edible salt and urine samples were collected to detect salt iodine content and urinary iodine level by using direct titration and cerium arsenate-catalyzed spectrophotometry, respectively, to evaluate the iodine nutritional status according to the standard. The multiple-ordered logistic regression model was used to analyze the factors influencing the urinary iodine concentration.Results:The age of the 4 320 study participants was (51.19±15.33) years, with males accounting for 44.44% (1 920). About 40.16% of adults (1 735) were from coastal areas and 56.37% (2 435) from urban areas. The salt iodine content, M ( Q1, Q3), of the 4 320 household edible salt samples was 21.10 (0.00, 24.16) mg/kg, including 1 662 non-iodized salt samples, 182 unqualified iodized salt samples and 2 476 qualified iodized salt samples. The rate of iodized salt coverage was 61.53%, and the rate of qualified iodized salt consumption was 57.31%. There was a statistically significant difference in the proportion of qualified iodized salt in adult households among different regions ( P<0.001), with the proportion of non-iodized salt gradually decreasing from coastal to inland areas ( χ 2trend=618.458, P<0.001). The urinary iodine concentration M ( Q1, Q3) was 137.60 (86.85, 210.60) μg/L in 4 320 adult urine samples, with the urinary iodine levels of<100, 100-199, 200-299, and≥300 μg/L accounting for 31.64% (1 367), 40.56% (1 752), 17.66% (763), and 10.14% (438), respectively. There was a nonlinear positive correlation between household salt iodine content and urinary iodine level in adults aged 18 years and above by using the χ 2 test for trend ( χ 2regression=231.10, P<0.001 and χ 2skew=28.81, P<0.001). Urinary iodine concentrations were higher in men than in women ( P=0.029) and higher in adults in rural areas than in urban areas ( P<0.001). There were statistically significant differences in the distribution of iodine nutritional status among adults of different ages, regions, and urban and rural areas (all P<0.001). The proportion of those with urinary iodine levels<100 μg/L gradually increased with age ( χ 2trend=37.493, P<0.001), and gradually decreased from coastal areas to inland areas ( χ 2trend=71.381, P<0.001). The results of the multiple-ordered logistic regression model analysis showed that compared with adults aged 18 to 44 years and male adults, those aged 45 to 59 years and female adults had lower urinary iodine levels, with OR (95% CI) of 0.75 (0.68-0.83) and 0.85 (0.76-0.95), respectively. Compared with adults in coastal and urban adults, those in sub-coastal, inland and rural adults had higher levels of urinary iodine, with OR (95% CI) of 1.89 (1.63-2.19), 2.02 (1.72-2.37) and 1.46 (1.28-1.66), respectively. Conclusion:The overall iodine nutrition level of adults aged 18 years and above in Zhejiang Province in 2022 is generally appropriate. However, there is a potential risk of iodine deficiency among adults in coastal areas.

Objective:To investigate the iodine nutrition status of pregnant women in Zhejiang Province, explore the impact of salt industry system reform on iodine nutrition level of pregnant women, and provide scientific basis for prevention and treatment of iodine deficiency disorders.Methods:From 2016 to 2021, a multi-stage stratified sampling method was used to select 100 pregnant women from 90 counties (cities, districts) in Zhejiang Province each year as survey subjects. Salt samples were collected from pregnant women's families, and one random urine sample was taken for salt iodine and urinary iodine level testing, respectively.Results:A total of 56 581 samples of household edible salt were collected from pregnant women, with a median salt iodine level of 23.20 mg/kg. Among them, 7 961 were non iodized salt, 45 803 were qualified iodized salt, and 2 817 were unqualified iodized salt. The iodized salt coverage rate was 85.93% (48 620/56 581), and the qualified iodized salt consumption rate was 80.95% (45 803/56 581). The proportion of non iodized salt increased from 10.05% (897/8 928) in 2016 to 15.09% (1 461/9 679) in 2021 (χ 2trend = 95.16, P < 0.001). A total of 56 581 urine samples were collected from pregnant women, with a median urinary iodine level of 130.50 μg/L. Among them, the proportions of urinary iodine levels < 150, 150 - 249, 250 - 499, and ≥500 μg/L were 58.32% (32 996/56 581), 27.24% (15 410/56 581), 12.24% (6 926/56 581), and 2.21% (1 249/56 581), respectively. The median urinary iodine level of pregnant women in inland areas was significantly higher than that in coastal areas ( Z = 19.15, P < 0.001). Furthermore, urinary iodine levels exhibited a non-linear decline as age increased (χ 2regression = 12.65, P < 0.001; χ 2partial = 22.65, P < 0.001) and as pregnancy progressed (χ 2regression = 37.28, P < 0.001; χ 2partial = 18.89, P < 0.001). Conclusions:The overall iodine nutrition status of pregnant women in Zhejiang Province is in a state of iodine deficiency (< 150 μg/L), and there is a greater risk in coastal areas compared to inland areas. However, in the context of the reform of the salt industry system, it is still necessary to strengthen the quality supervision of iodized salt, provide scientific iodine supplementation education, promote specialized iodized salt for pregnant women, and strengthen interventions for prevention and control of iodine deficiency disorders.

Objective To explore the feasibility of prototype of flexible ultrasound array transducer for measuring intravascular diameter and blood flow velocity.Methods A prototype of flexible ultrasonic array transducer composed of a surface mount flexible ultrasonic array transducer(referred to as the transducer)and acquisition system was designed and fabricated.Doppler body model and vascular simulation control system was used to simulate human blood.Mindray M7 color multi-functional ultrasound diagnostic instrument(abbreviated as M7)and the prototype were adopted to detect pulse wave excitation mode,spectral morphology,echo signal time interval,blood flow velocity,etc.Taken the results of M7 as standards,the effectiveness of the prototype was evaluated.Then the inner diameter and flow velocity of left common carotid artery,left brachial artery and left radial artery of 20 healthy controls(HC)were measured respectively using M7 and the prototype,and the consistency of measurement results were analyzed to evaluate the accuracy of the prototype.The safety of the prototype was evaluated according to subjectively scoring the comfort level of HC applying the transducer and whether there was skin discomfort,injury,etc.after removing the transducer.Results The collected blood flow spectrum of the above vascular simulation control system acquire with the prototype were clear,and the spectral morphology,flow velocity,as well as echo signal time interval were basically consistent with those of M7.The consistency of the inner diameter of left common carotid artery,left brachial artery and left radial artery measured by the prototype and M7 in 20 HC were all very strong(ICC=0.919-0.992),while of flow velocities were moderate or very strong(ICC=0.524-0.831).The subjective score of comfort level of application of transducer was 3(2,3),and no skin discomfort occurred.Conclusion Flexible ultrasound array transducer technology could be used to measure intravascular diameter and blood flow velocity.

Objective:To analyze the iodine nutrition status of children and adolescents and influencing factors in Zhejiang Province, providing scientific basis for optimizing iodine deficiency disorders (IDD) prevention and control strategies.Methods:In June 2022, a multistage stratified sampling method was used to divide 16 counties (cities, districts, abbreviated as counties) in Zhejiang Province into three categories based on their geographical locations (average distance from the coastline): coastal areas (including Dinghai District, Jiaojiang District, Sanmen County, Cixi City and Lucheng District), sub-coastal areas (including Wuxing District, Haining City, Linping District, Fuyang District and Fenghua District), and inland areas(including Suichang County, Changshan County, Shengzhou City, Jindong District, Dongyang City and Yongjia County). One county was selected from each category, and one township (street) was selected from each county. Two administrative villages (neighborhood committees) were selected from each township (street). Ten households including all children and adolescents aged 6-17 in each household were selected from each administrative village (neighborhood committee). Demographic information and personal dietary characteristics were collected via questionnaires, while household salt and a random urine sample were tested for iodine level. Trend analysis was conducted using a χ 2trend test, and a multivariate logistic stepwise regression model was used to analyze the influencing factors of urinary iodine levels. Results:A total of 755 children and adolescents aged 6-17 were selected, including 387 males (51.26%) and 368 females (48.74%), with an age of (11.24 ± 3.32) years. There were 269 children and adolescents in coastal areas (35.63%) and 409 children and adolescents in urban areas (54.17%). A total of 755 household salt samples were collected, with a median salt iodine concentration of 21.80 mg/kg. These included 263 non-iodized salt samples, 38 unqualified iodized salt samples, and 454 qualified iodized salt samples. The coverage rate of iodized salt was 65.17% (492/755), and the consumption rate of qualified iodized salt was 60.13% (454/755). The distribution of salt iodine quality among children and adolescents in different geographical locations showed statistically significant differences (χ 2 = 111.95, P < 0.001), with the proportion of non-iodized salt gradually decreasing from coastal areas to inland areas (χ 2trend = 90.17, P < 0.001). A total of 755 urine samples were collected, with a median urinary iodine concentration of 186.60 μg/L. The proportions of urinary iodine < 100, 100-199, 200-299, and ≥300 μg/L were 16.95% (128/755), 37.62% (284/755), 24.37% (184/755), and 21.06% (159/755), respectively. The χ 2trend test revealed a nonlinear positive correlation between salt iodine level and urinary iodine level (χ 2regression = 21.98, P < 0.001; χ 2partial = 6.96, P < 0.001). The frequency distribution of urinary iodine in children and adolescents from different geographical locations and between urban and rural areas showed statistically significant differences (χ 2 = 29.63, 16.56, P < 0.001). Among them, the proportion of children and adolescents with urinary iodine < 100 μg/L gradually decreasing from coastal areas to inland areas (χ 2trend = 6.15, P = 0.013). The results of multivariate logistic regression analysis revealed that sub-coastal regions, inland regions, and urban-rural regions ( OR = 1.57, 1.53, 1.64, 95% CI: 1.11-2.24, 1.03-2.27, 1.17-2.32, P < 0.05) were significantly associated with urinary iodine levels in children and adolescents aged 6-17. Conclusions:In 2022, the iodine nutrition of children and adolescents in Zhejiang Province is generally suitable, but there is a risk of iodine deficiency among coastal children and adolescents. Geographic location and urban/rural areas are influencing factors on iodine nutrition status of children and adolescents in Zhejiang Province.