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.

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.

Plantar fasciitis(PF)is a primary cause of heel pain(HP).Platelet-rich plasma(PRP),as an emerging biological treatment method,possesses unique biological characteristics,showing significant dual therapeutic advantages in suppressing inflammation and promoting tissue repair.This article reviews the pathogenesis of PF,the biological characteristics of PRP and its application in pain management and functional prognosis assessment of PF,particularly focusing on PRP in improving plantar fascia thickness(PFT).

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.

Objective:To study the influence of methyltransferases like 3(METTL3)on the radiosensitivity of oral squamous cell carcinoma cells(OSCCs).Methods:The apoptosis level of OSCCs CAL27,SCC9 and SCC15 treated with X-ray radiation doses of 2,4 and 8 Gy respectively was compared by flow cytometry,the expression of methylated gene RNA and protein in the cells were examined by qRT-PCR and Western blot.m6A in the cells was quantified by LC/LC-MS method.qRT-PCR and Western blot were used to investigate the expression of methylated gene RNA and protein in the cells.Flow cytometry was used to examine the cell apoptosis level of CAL27 and SCC15 cells treated with METTL3 overexpression and knockdown respectively.The clone forma-tion of CAL27 and SCC15 cells after knockdown and overexpression of target genes followed by radiation treatment was observed by clonogenic assays.Results:The apoptosis rate of all the cell lines increased with the increase dose of radiation at each dose,CAL27 cells showed the highest and SCC15 showed the lowerst apoptosis rate.The RNA and protein expression levels of METTL3 in CAL27 were significantly lower than those of SCC15.m6A quantification showed that the methylation modification in CAL27 cells was lower than that in SCC15.The expression of METTL3 was increased in CAL27 and SCC15 cells after radiation treatment.Knockdown of METTL3 increaced the apoptosis rate and decreased the clonogenesity,overession of METTL3 the decreaced the ap optosis rate and increased the clonogenecity of the cells.Conclusion:Regulation of METTL3 can affect the radiotherapy sensitivity of OSCCs,METTL3 may become a new target for radiosensitization of OSCCs.

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 develop evaluation indicators for care ability of caregivers in home-based palliative care based on the Farran caregiver skills model.Methods:Based on the Farran caregiver skills model, a preliminary evaluation index system was constructed through theoretical analysis, literature review, and semi-structured interviews. From July to October 2024, experts in the field were selected to conduct expert consultations, revise and improve the index system, and determine the weight of the indicators through the analytic hierarchy process.Results:A total of two rounds of expert consultations were conducted. The effective response rates for the first and second rounds of expert consultation questionnaires were 90.00% (18/20) and 100.00% (18/18), respectively. In the two rounds of expert consultations, 15 experts (83.33%) and 3 experts (16.67%) respectively proposed revision suggestions. In the two rounds of consultation, the expert authority coefficients were 0.931 and 0.936, respectively, and the Kendall coefficient of concordance were 0.152~0.283、0.183~0.269 ( P<0.05). The final evaluation indicators for care ability of caregivers in home-based palliative care included four first-level indicators, 12 second-level indicators, and 45 third-level indicators. Conclusions:The evaluation indicators for care ability of caregivers in home-based palliative care developed are highly scientific and reliable, and can provide a reference for the evaluation of family caregiver care ability and the formulation of training programs.

Objective:To investigate the correlation of combined detection of p16 and Rb with high-risk human papilloma virus (HR-HPV) infection in non-oropharyngeal squamous cell carcinoma (NOPSCC) of the head and neck.Methods:A total of 68 NOPSCC cases of the head and neck (23 cases of the nasal cavity and paranasal sinuses and 45 cases of larynx) with complete clinical and pathological data, diagnosed at the Beijing Tongren Hospital, Capital Medical University, Beijing, China from November 2013 to December 2023, were collected. The expression of p16 and Rb was detected using immunohistochemistry of the EnVision two-step method, while the HR-HPV mRNA expression was detected using in situ hybridization. The concordance, sensitivity, and specificity of p16 alone and the combined detection of p16 and Rb for detecting HR-HPV infection were analyzed.Results:Among the 68 patients with NOPSCC, 53 were male and 15 were female, with a median age of 63.5 (range, 57.3 to 66.8) years. 41 patients had a smoking history and 27 did not. 33 patients had an early T stage (T1/T2) and 35 had advanced T stage (T3/T4). 14 patients had lymph node metastasis and 2 had distant metastasis. Histological types included 62 cases of keratinized squamous cell carcinoma, 5 cases of non-keratinized squamous cell carcinoma, and 1 case of basal-like squamous cell carcinoma. 25 cases were positive for p16. Among the 25 cases, 16 cases were positive for Rb, and 6 cases were positive for HR-HPV mRNA. 43 cases were negative for p16, including 38 cases positive for Rb and no cases positive for HR-HPV mRNA. The concordance between p16 and HR-HPV mRNA expression was poor ( Kappa=0.285, P=0.001), with a sensitivity of 100.0% and specificity of 69.4%. In contrast, the combined detection of p16+/Rb- showed high concordance with HR-HPV mRNA expression ( Kappa=0.719, P<0.001), with a sensitivity of 100.0% and specificity of 95.2%. Conclusions:In NOPSCC of the head and neck, the combined detection of p16 and Rb may be used as a marker for assessing HR-HPV infection. Recognizing the p16+/Rb- expression pattern in NOPSCC can improve the specificity of HR-HPV detection.

Plantar fasciitis(PF)is a primary cause of heel pain(HP).Platelet-rich plasma(PRP),as an emerging biological treatment method,possesses unique biological characteristics,showing significant dual therapeutic advantages in suppressing inflammation and promoting tissue repair.This article reviews the pathogenesis of PF,the biological characteristics of PRP and its application in pain management and functional prognosis assessment of PF,particularly focusing on PRP in improving plantar fascia thickness(PFT).

Patients with severe periodontal disease often involve multidisciplinary therapy.This paper reports a case of adult patients with severe periodontitis who was treated by orthodontics,restoration,and periodontics.The space between upper central incisors was closed,aesthetics and periodontal conditions were significantly improved.