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 investigate the association between serum C-X-C motif chemokine ligand 14(CXCL14)level and carotid atherosclerotic plaques(CAP)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 262 patients with T2DM(T2DM group)and 131 healthy individuals(control group)who underwent physical examinations in Ganzhou Municipal Hospital from January 2022 to February 2025 were selected at a ratio of 2∶1.T2DM patients were further divided into CAP group(112 cases)and non-CAP group(150 cases)based on the presence or absence of CAP.Serum CXCL14 level was measured using enzyme-linked immunosorbent assay.The correlation between serum CXCL14 level and clinical characteristics in CAP patients was analyzed.The association between serum CXCL14 level and CAP in T2DM patients was assessed using multivariate Logistic regression and restricted cubic spline(RCS)regression.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of serum CXCL14 level for CAP in T2DM patients.Results The serum CXCL14 level of patients in T2DM group was significantly higher than that in control group(P＜0.05).The age of patients in CAP group was significantly older than that in non-CAP group,and the course of diabetes mellitus was significantly longer than that in non-CAP group.The proportions of hypertension,fasting plasma glucose,fasting insulin,2-hour plasma glucose,glycosylated hemoglobin,homeostasis model assessment of insulin resistance index,low density lipoprotein cholesterol,hypersensitive C-reaction protein,interleukin-6,and CXCL14 level were all significantly higher than those in non-CAP group(P＜0.05).Multivariate Logistic regression analysis showed that after adjusting for general information,glycolipid metabolism indicators,and inflammatory indicators,higher CXCL14 level was an independent risk factor for CAP in patients with T2DM(P＜0.05).RCS regression analysis showed that after adjusting for general information,glycolipid metabolism indicators,and inflammatory indicators,the CXCL14 level was associated with the risk of CAP in T2DM patients,and presented a positive dose-response relationship(P＜0.05).The ROC curve showed that area under the curve of serum CXCL14 for evaluating CAP in T2DM patients was 0.772,and the sensitivity and specificity were 58.9％and 82.0％,respectively.Conclusion Elevated serum CXCL14 level is positively associated with an increased risk of CAP in patients with T2DM and has a high assessment efficiency for CAP in T2DM patients.

The study and control of elemental impurities are crucial for ensuring the quality and safety of drugs.The ICH has published the Q3D guideline as a globally harmonised approach for the research and control of elemental impurities in drugs.In accordance with the requirements of the ICH Q3D guideline for risk assessment and control of elemental impurities,how to carry out the development and validation of detecting methods for elemental impurities is important to analysts.In this research,the key points of ICP-AES and ICP-MS method development are summarized,including the determination of the types and limits of the elements to be measured,the selection of pretreatment methods,interferences and corrections;the validation requirements for the two methods in ICH Q2(R2)and different pharmacopoeial general rules are analyzed,and the evaluation methods of each validation experiments are compared in detail.This paper can provide a reference for the development and validation of detecting methods for elemental impurities,and research ideas for related research workers.

Objective:To investigate the effects of botulinum toxin A (BTX-A) injection on ocular surface in patients with blepharospasm and dry eye.Methods:In this prospective study, 56 patients (83 eyes) with essential blepharospasm who were treated with BTX-A in the Department of Ophthalmology of Jiaxing Hospital of Traditional Chinese Medicine from April 2020 to January 2022 were included. The patients were divided into blepharospasm with dry eye group (group A, 50 eyes) and simple blepharospasm group (group B, 33 eyes) according to whether they were accompanied by dry eye. The Oculus Keratograph was used to evaluate tear meniscus height (TMH), tear break-up time (BUT), ocular bulbar redness, and corneal fluorescein staining. The OPD-Scan III analyzer was used to measure the corneal surface regularity index. The Ocular Surface Disease Index and meibomian gland analysis were performed to diagnose dry eye before treatment. Paired t-tests and Wilcoxon signed-rank tests were conducted to analyze the data. In patients with unilateral conditions, the ocular surface data of the affected and healthy eyes were compared before treatment. The severity of blepharospasm was evaluated in both groups before treatment and 1 week after treatment. Results:Among the 56 patients, 57.1% (32/56) were diagnosed with dry eye. One week after BTX-A injection treatment, both groups demonstrated varying degrees of improvement in their conditions. In patients with unilateral blepharospasm, pre-treatment ocular surface examinations indicated that the affected eye had a lower tear BUT of (6.67 ± 3.86) seconds and a lower TMH of (0.18 ± 0.07) mm compared with the healthy eye, which showed (10.20 ± 5.95) seconds for BUT and (0.20 ± 0.05) mm for TMH ( t = -3.94, -2.44, both P < 0.05). Additionally, the ocular bulbar redness value was significantly higher in the affected eye [(1.75 ± 0.38)] than in the healthy eye [(1.65 ± 0.47), t = 2.16, P < 0.05]. After treatment, both groups exhibited significant increases in BUT and TMH compared with their pre-treatment values ( t = -6.27, -4.21, -2.56, -3.12, all P < 0.05). Furthermore, both groups showed significant decreases in ocular bulbar redness values compared with pre-treatment values ( t = 3.04, 3.32, both P < 0.05). In group A, the corneal fluorescein staining score post-treatment was significantly lower than the pre-treatment value ( Z = 2.10, P < 0.05). However, in group B, the FL score did not show a significant difference between pre-treatment and post-treatment. ( Z = 0.03, P > 0.05). There were also no significant differences in the surface regularity index between the two groups both before and after treatment ( t = 1.35, 0.65, both P > 0.05). Conclusions:Blepharospasm can affect the stability of the tear film on the ocular surface, and BTX-A injection can help relieve dry eye caused by essential blepharospasm.

Objective To investigate the association between serum C-X-C motif chemokine ligand 14(CXCL14)level and carotid atherosclerotic plaques(CAP)in patients with type 2 diabetes mellitus(T2DM).Methods A total of 262 patients with T2DM(T2DM group)and 131 healthy individuals(control group)who underwent physical examinations in Ganzhou Municipal Hospital from January 2022 to February 2025 were selected at a ratio of 2∶1.T2DM patients were further divided into CAP group(112 cases)and non-CAP group(150 cases)based on the presence or absence of CAP.Serum CXCL14 level was measured using enzyme-linked immunosorbent assay.The correlation between serum CXCL14 level and clinical characteristics in CAP patients was analyzed.The association between serum CXCL14 level and CAP in T2DM patients was assessed using multivariate Logistic regression and restricted cubic spline(RCS)regression.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of serum CXCL14 level for CAP in T2DM patients.Results The serum CXCL14 level of patients in T2DM group was significantly higher than that in control group(P＜0.05).The age of patients in CAP group was significantly older than that in non-CAP group,and the course of diabetes mellitus was significantly longer than that in non-CAP group.The proportions of hypertension,fasting plasma glucose,fasting insulin,2-hour plasma glucose,glycosylated hemoglobin,homeostasis model assessment of insulin resistance index,low density lipoprotein cholesterol,hypersensitive C-reaction protein,interleukin-6,and CXCL14 level were all significantly higher than those in non-CAP group(P＜0.05).Multivariate Logistic regression analysis showed that after adjusting for general information,glycolipid metabolism indicators,and inflammatory indicators,higher CXCL14 level was an independent risk factor for CAP in patients with T2DM(P＜0.05).RCS regression analysis showed that after adjusting for general information,glycolipid metabolism indicators,and inflammatory indicators,the CXCL14 level was associated with the risk of CAP in T2DM patients,and presented a positive dose-response relationship(P＜0.05).The ROC curve showed that area under the curve of serum CXCL14 for evaluating CAP in T2DM patients was 0.772,and the sensitivity and specificity were 58.9％and 82.0％,respectively.Conclusion Elevated serum CXCL14 level is positively associated with an increased risk of CAP in patients with T2DM and has a high assessment efficiency for CAP in T2DM patients.

Objective:To investigate the effects of botulinum toxin A (BTX-A) injection on ocular surface in patients with blepharospasm and dry eye.Methods:In this prospective study, 56 patients (83 eyes) with essential blepharospasm who were treated with BTX-A in the Department of Ophthalmology of Jiaxing Hospital of Traditional Chinese Medicine from April 2020 to January 2022 were included. The patients were divided into blepharospasm with dry eye group (group A, 50 eyes) and simple blepharospasm group (group B, 33 eyes) according to whether they were accompanied by dry eye. The Oculus Keratograph was used to evaluate tear meniscus height (TMH), tear break-up time (BUT), ocular bulbar redness, and corneal fluorescein staining. The OPD-Scan III analyzer was used to measure the corneal surface regularity index. The Ocular Surface Disease Index and meibomian gland analysis were performed to diagnose dry eye before treatment. Paired t-tests and Wilcoxon signed-rank tests were conducted to analyze the data. In patients with unilateral conditions, the ocular surface data of the affected and healthy eyes were compared before treatment. The severity of blepharospasm was evaluated in both groups before treatment and 1 week after treatment. Results:Among the 56 patients, 57.1% (32/56) were diagnosed with dry eye. One week after BTX-A injection treatment, both groups demonstrated varying degrees of improvement in their conditions. In patients with unilateral blepharospasm, pre-treatment ocular surface examinations indicated that the affected eye had a lower tear BUT of (6.67 ± 3.86) seconds and a lower TMH of (0.18 ± 0.07) mm compared with the healthy eye, which showed (10.20 ± 5.95) seconds for BUT and (0.20 ± 0.05) mm for TMH ( t = -3.94, -2.44, both P < 0.05). Additionally, the ocular bulbar redness value was significantly higher in the affected eye [(1.75 ± 0.38)] than in the healthy eye [(1.65 ± 0.47), t = 2.16, P < 0.05]. After treatment, both groups exhibited significant increases in BUT and TMH compared with their pre-treatment values ( t = -6.27, -4.21, -2.56, -3.12, all P < 0.05). Furthermore, both groups showed significant decreases in ocular bulbar redness values compared with pre-treatment values ( t = 3.04, 3.32, both P < 0.05). In group A, the corneal fluorescein staining score post-treatment was significantly lower than the pre-treatment value ( Z = 2.10, P < 0.05). However, in group B, the FL score did not show a significant difference between pre-treatment and post-treatment. ( Z = 0.03, P > 0.05). There were also no significant differences in the surface regularity index between the two groups both before and after treatment ( t = 1.35, 0.65, both P > 0.05). Conclusions:Blepharospasm can affect the stability of the tear film on the ocular surface, and BTX-A injection can help relieve dry eye caused by essential blepharospasm.

The study and control of elemental impurities are crucial for ensuring the quality and safety of drugs.The ICH has published the Q3D guideline as a globally harmonised approach for the research and control of elemental impurities in drugs.In accordance with the requirements of the ICH Q3D guideline for risk assessment and control of elemental impurities,how to carry out the development and validation of detecting methods for elemental impurities is important to analysts.In this research,the key points of ICP-AES and ICP-MS method development are summarized,including the determination of the types and limits of the elements to be measured,the selection of pretreatment methods,interferences and corrections;the validation requirements for the two methods in ICH Q2(R2)and different pharmacopoeial general rules are analyzed,and the evaluation methods of each validation experiments are compared in detail.This paper can provide a reference for the development and validation of detecting methods for elemental impurities,and research ideas for related research workers.

Objective To analyze the epidemiological characteristics of new elderly malignant tumor cases in Tongren City from 2018 to 2022, so as to provide a theoretical basis for the prevention and control of elderly malignant tumor in this area. Methods A retrospective analysis of the epidemiological characteristics of cases aged 60 and above who were first diagnosed with malignant tumors by pathology in our hospital from 2018 to 2022 was conducted based on the International Classification of Diseases (ICD-10). Results The incidence rate of elderly malignant tumors in Tongren City increased from 123.83/100 000 in 2018 to 126.14/100 000 in 2022, and the incidence rate showed a trend of first rising and then declining. The top five tumors in incidence rate are lung cancer, rectal cancer, liver cancer, stomach cancer and cervical cancer. The tumor order has changed over the years except lung cancer, which was the first. Lung cancer was the main high incidence tumor among the elderly of all ages. With the increase of age, the number of bladder cancer patients increases significantly, and the number of colon cancer patients also shows an upward trend. The prevalence rate of lung cancer（χ²=16.032，P=0.014) , liver cancer（χ²=8.099，P=0.030) , bladder cancer（χ²=11.274 , P=0.018) , and gastric cancer（χ²=19.387 , P=0.011) in elderly people of different sexes was generally higher in men than in women, and the difference was statistically significant (P<0.05). Conclusion Lung cancer , rectal cancer and liver cancer, as the malignant tumors with high case composition and rapid increase in the elderly, can be the focus of early screening and prevention of malignant tumors in the elderly in Tongren City, and men should pay more attention.

Objective To develop an expert consensus on artificial airway humidification care in critical adult patients(refer as"Consensus"hereafter)for a standardised procedure of artificial airway humidification.Methods Reviews of domestic and international literatures relevant to artificial airway humidification care in critical adult patients were conducted.Clinical experiences of medical and nursing experts were taken into consideration.Two rounds of expert consultations were conducted to finalise the Consensus.Results Various aspects were studied including concepts,targeted range of temperature and humidification,methods of humidification,selection of humidification liquid and methods for evaluation of humidification effectiveness.The Consensus was applicable to the management of humidification of artificial airway in critical adult patients.Conclusions The Consensus exhibits a certain level of scientific rigor and practical applicability.It serves as a theoretical basis and practical guide to clinical nursing personnel in the management of artificial airway humidification.

Objective To observe the effects of recombinant human B-type natriuretic peptide (rhBNP) on cardiac function and heart rate variability (HRV) in patients with heart failure after acute myocardial infarction (AMI). Methods One hundred and twenty patients with heart failure after AMI admitted to the Department of Cardiology of Cangzhou Central Hospital of Hebei Province from January 2015 to January 2018 were enrolled. The patients were divided into a conventional treatment group and an rhBNP treatment group according to random number table method, with 60 cases in each group. The two groups were treated according to the AMI guidelines, the conventional treatment group received west medicine anti-myocardial ischemia and anti-heart failure treatment; the rhBNP treatment group received rhBNP on the basis of routine treatment; the first load dose was 2 μg/kg intravenous injection impact treatment, followed by maintaining dose 8.5 ng·kg-1·min-1 intravenous drip for 7 days. The changes of hypersensitivity C-reactive protein (hs-CRP), N-terminal B-type natriuretic peptide precursor (NT-proBNP), left ventricular ejection fraction (LVEF) and HRV index were observed before and after treatment in the two groups [HRV indexes including the changes of average normal RR interval standard deviation (SDNN), the average value of the normal RR interval standard deviation (SDANN), the root mean square (RMSSD) of the adjacent RR interval difference, and the percentage of adjacent RR interval difference > 50 ms (PNN50)]; the incidences of adverse reactions in the two groups were observed. Results After treatment, the levels of hs-CRP and NT-proBNP in the two groups were significantly lower than those before treatment (all P < 0.05). LVEF, SDNN, SDANN, RMSSD and PNN50 were higher than those before treatment, and the changes of the above indicators in the rhBNP treatment group were more significant than those in the conventional treatment group [hs-CRP (mg/L): 6.2±3.3 vs. 11.8±5.5, NT-proBNP (ng/L): 2.5±2.0 vs. 6.4±4.3, LVEF: 0.49±0.02 vs. 0.44±0.04, SDNN (ms): 93.3±18.1 vs. 79.1±16.0, SDANN (ms): 87.3±17.8 vs. 70.9±14.9, RMSSD: 30.3±11.0 vs. 23.8±10.4, PNN50: (15.9±7.3)% vs. (9.6±5.5)%, all P < 0.05]; No significant adverse reactions occurred during the treatment of the two groups. Conclusion rhBNP can significantly improve the heart function of patients with heart failure after AMI, reduce the levels of inflammatory response indicators and improve HRV;since its clinical efficacy is good, and its application safe, it is worthy to promote its clinical use.