OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

OBJECTIVE To analyze the medication needs of parents of pediatric children in our hospital regarding drug instructions， and explore improvement strategies， thereby providing a basis for clinically guiding the rational use of drugs in pediatric patients. METHODS A self-designed questionnaire was used to randomly select the parents of pediatric patients in the pediatric outpatient and emergency departments of our hospital from July 1st to September 30th， 2024. A randomized face-to-face survey was conducted regarding their willingness to read drug instructions， their current understanding status， and their needs. The survey results were then statistically analyzed. RESULTS A total of 300 questionnaires were distributed in this survey， and 299 valid questionnaires were recovered， with an effective recovery rate of 99.7%. Before medication， the parents who “always” and “often” read the drug instructions in detail accounted for 39.1% （117 respondents） and 35.1% （105 respondents）， respectively. Statistically significant differences were observed in the willingness to read drug instructions among respondents with varying educational levels and occupations （P＜0.05）. Among the 299 respondents， only 48 people （16.1%）“ fully understood” the drug instructions， and the average understanding score of all the respondents was （3.77±0.83） points. The stronger the respondents’ willingness to read drug instructions， the higher their understanding scores of drug instructions （P＜0.05）. A total of 256 respondents thought that drug instructions were of great help to themselves， and the average helpfulness rating score of all the respondents was （4.28±0.78） points. Under the conditions of varying ages， educational levels， occupations， and willingness to read drug instructions， statistically significant differences were observed in the scores representing the degree of helpfulness of drug instructions to the respondents （P＜0.05）. Respondents paid the most attention to content in drug instructions such as “dosage and administration method”，“ adverse reactions”， and “indications and therapeutic categories”. The most difficult sections for them to understand included “chemical structure and properties”， “pharmacological and toxicological effects” ， and “pharmacokinetics”， etc. The demographic characteristics of the respondents were not significantly associated with the content areas of drug instructions they most desired to see improved （P＞0.05）. Most respondents （86.0%） hoped to improve the instructions mainly by “simplifying professional terms to make them more accessible”. Others included “highlighting key information” （60.5%） and “providing more detailed medication guidance” （49.2%）， etc. CONCLUSIONS Parents of pediatric patients in our hospital have a high demand for drug instructions but low comprehension. The pharmacy department should make targeted improvements to drug instructions based on parents’ actual needs， helping them accurately obtain medication knowledge and reduce potential medication safety risks.

Objective:To investigate the association of serum apolipoprotein A1 (Apo-A1) and tumor abnormal protein (TAP) with recurrence risk after transurethral resection of bladder tumor (TURBT) in patients with bladder cancer.Methods:The data of 120 patients with bladder cancer who received TURBT treatment and were followed up in Xi′an Daxing Hospital from April 2018 to April 2021 were retrospectively collected. According to the recurrence data after 3 years of follow-up, the patients were divided into recurrence group (29 cases) and non-recurrence group (91 cases). Baseline data, serum Apo-A1, TAP levels and other laboratory indicators at the last preoperative examination were collected and compared between the two groups. Cox regression analysis was performed to determine the association of serum Apo-A1, TAP with recurrence in these patients after TURBT. The dose-response relationship between serum Apo-A1, TAP and risk of recurrence after TURBT in patients with bladder cancer was analyzed by restricted cubic spline method. The interaction of serum Apo-A1 and TAP on recurrence after TURBT in patients with bladder cancer was analyzed.Results:During the follow-up period of 3 years, the disease recurred in 29 patients, with recurrence time from 16 to 33 months, and with the median recurrence time of 25.00 (20.50, 29.50) months. The proportion of tumor TNM stageⅡ, tumor pathological grade G 2, non intravesical bacillus Calmette-Guérin perfusion after operation and serum Apo-A1, TAP, nuclear matrix protein 22, bladder tumor antigen levels in the recurrence group were higher than those in the non-occurrence group: 72.41% (21/29) vs. 50.55% (46/91), 34.48% (10/29) vs. 14.29% (13/91), 31.03% (9/29) vs. 12.09% (11/91), (29.45 ± 4.78) μg/L vs. (24.81 ± 4.25) μg/L, (165.37 ± 10.28) μm 2 vs. (156.33 ± 9.92) μm 2, (31.11 ± 5.21) μg/L vs. (28.29 ± 5.13) μg/L, (27.93 ± 4.18) μg/L vs. (25.57 ± 4.95) μg/L, and the differences were statistically significant ( P<0.05). Cox regression analysis showed that the recurrence after TURBT was related to the levels of serum Apo-A1, TAP and nuclear matrix protein 22 ( P<0.05). The results of restricted cubic spline analysis showed that there was a linear dose-response relationship between serum Apo-A1, TAP levels and the risk of recurrence after TURBT in patients with bladder cancer ( P<0.05). When serum Apo-A1≥25.50 μg/L and TAP≥159.20 μm 2, the risk of postoperative recurrence increased with the increase of their expression. There was a positive interaction between serum Apo-A1 and TAP on the recurrence after TURBT in patients with bladder cancer. The risk of recurrence in patients with high expression of both was 25.25 times that of patients with low expression of both, and the synergistic effect was 1.521 times that of the sum of the effects of the two alone. In the risk of tumor recurrence, 32.95% was caused by the interaction between the two. Conclusions:The risk of recurrence after TURBT in patients with bladder cancer may be related to the levels of serum Apo-A1 and TAP. Increase of the two levels may be a risk factor for postoperative recurrence, and there is a significant dose-response relationship between the two, and there is a positive interaction with tumor recurrence.

To analyze potential adverse drug events(ADEs) associated with ustekinumab and upadacitinib in the treatment of inflammatory bowel disease(IBD) based on an international authoritative database, thereby providing evidence for clinical medication safety.

Objective To generate and characterize natural killer cell (NK cell)-conditional Cd226 gene knockout mice using Cre-loxP technology, and to explore the role of CD226 on NK cells in alleviating intestinal inflammation in a murine model of ulcerative colitis (UC). Methods NK cell-conditional Cd226 gene knockout mice were generated by crossing loxP-flanked Cd226 mice with Ncr1-Cre mice via the Cre-loxP system. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used for genotyping. A UC model was established by dextran sulfate sodium (DSS) induction. Flow cytometry was performed to analyze CD226 expression levels on NK cells and the infiltration of related immune cells in colon tissues. Hematoxylin-eosin (HE) staining was performed to assess the degree of colonic inflammation. Results DNA gel electrophoresis and flow cytometry confirmed the successful generation of NK cell-specific Cd226 knockout mice. After conditional knockout of Cd226 in NK cells, inflammation in the UC mouse model was alleviated. Flow cytometry results showed a reduced proportion of NK cells in peripheral blood and the colon lamina propria, while HE staining demonstrated attenuated inflammatory responses. Conclusion Specific knockout of Cd226 in NK cells mitigates intestinal inflammation in UC mice by reducing NK cell numbers and inhibiting their pro-inflammatory functions.
Animals ; Colitis, Ulcerative/pathology* ; Killer Cells, Natural/metabolism* ; Mice, Knockout ; T Lineage-Specific Activation Antigen 1 ; Antigens, Differentiation, T-Lymphocyte/genetics* ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male

Objective:To investigate the association of serum apolipoprotein A1 (Apo-A1) and tumor abnormal protein (TAP) with recurrence risk after transurethral resection of bladder tumor (TURBT) in patients with bladder cancer.Methods:The data of 120 patients with bladder cancer who received TURBT treatment and were followed up in Xi′an Daxing Hospital from April 2018 to April 2021 were retrospectively collected. According to the recurrence data after 3 years of follow-up, the patients were divided into recurrence group (29 cases) and non-recurrence group (91 cases). Baseline data, serum Apo-A1, TAP levels and other laboratory indicators at the last preoperative examination were collected and compared between the two groups. Cox regression analysis was performed to determine the association of serum Apo-A1, TAP with recurrence in these patients after TURBT. The dose-response relationship between serum Apo-A1, TAP and risk of recurrence after TURBT in patients with bladder cancer was analyzed by restricted cubic spline method. The interaction of serum Apo-A1 and TAP on recurrence after TURBT in patients with bladder cancer was analyzed.Results:During the follow-up period of 3 years, the disease recurred in 29 patients, with recurrence time from 16 to 33 months, and with the median recurrence time of 25.00 (20.50, 29.50) months. The proportion of tumor TNM stageⅡ, tumor pathological grade G 2, non intravesical bacillus Calmette-Guérin perfusion after operation and serum Apo-A1, TAP, nuclear matrix protein 22, bladder tumor antigen levels in the recurrence group were higher than those in the non-occurrence group: 72.41% (21/29) vs. 50.55% (46/91), 34.48% (10/29) vs. 14.29% (13/91), 31.03% (9/29) vs. 12.09% (11/91), (29.45 ± 4.78) μg/L vs. (24.81 ± 4.25) μg/L, (165.37 ± 10.28) μm 2 vs. (156.33 ± 9.92) μm 2, (31.11 ± 5.21) μg/L vs. (28.29 ± 5.13) μg/L, (27.93 ± 4.18) μg/L vs. (25.57 ± 4.95) μg/L, and the differences were statistically significant ( P<0.05). Cox regression analysis showed that the recurrence after TURBT was related to the levels of serum Apo-A1, TAP and nuclear matrix protein 22 ( P<0.05). The results of restricted cubic spline analysis showed that there was a linear dose-response relationship between serum Apo-A1, TAP levels and the risk of recurrence after TURBT in patients with bladder cancer ( P<0.05). When serum Apo-A1≥25.50 μg/L and TAP≥159.20 μm 2, the risk of postoperative recurrence increased with the increase of their expression. There was a positive interaction between serum Apo-A1 and TAP on the recurrence after TURBT in patients with bladder cancer. The risk of recurrence in patients with high expression of both was 25.25 times that of patients with low expression of both, and the synergistic effect was 1.521 times that of the sum of the effects of the two alone. In the risk of tumor recurrence, 32.95% was caused by the interaction between the two. Conclusions:The risk of recurrence after TURBT in patients with bladder cancer may be related to the levels of serum Apo-A1 and TAP. Increase of the two levels may be a risk factor for postoperative recurrence, and there is a significant dose-response relationship between the two, and there is a positive interaction with tumor recurrence.

Objective To observe the expression of adhesion molecule CD226 on the small intestinal group 3 innate lymphoid cells (ILC3) in mice. Methods The bioinformatics was used to analyze the expression of CD226 on murine ILCs. Small intestinal mucosal lamina propria lymphocytes (LPL) were isolated from wild-type C57BL/6J mice, and the expression of CD226 on ILC1 and ILC3 was detected by flow cytometry. A mouse model of dextran sulfate sodium (DSS)-induced colitis was constructed to observe the changes in the expression of CD226 on ILC3. Results Both ILC1 and ILC3 in the mice small intestine expressed CD226 molecules; the proportion of ILC3 was reduced, while the expression level of CD226 on ILC3 was increased in the colitis model. Conclusion CD226 is expressed on the small intestines of mice, and although the proportion of ILC3 decreases in the DSS-induced colitis, the expression of CD226 on ILC3 increases.
Animals ; Mice ; Colitis/chemically induced* ; Immunity, Innate ; Intestine, Small ; Lymphocytes ; Mice, Inbred C57BL

OBJECTIVE To mine the adverse drug event （ADE） signals of sacituzumab govitecan and provide a reference for its clinical safety application. METHODS The data of sacituzumab govitecan-related ADE reports were collected from the FDA Adverse Event Reporting System （FAERS） database from April 1， 2020 to April 30， 2024. The reporting odds ratio（ROR） method， the United Kingdom Medicines and Healthcare Products Regulatory Agency comprehensive standard method （MHRA） and Bayesian confidence propagation neural network （BCPNN） method were used for data mining. Systematic organ classification （SOC） and preferred term （PT） in the ADE terminology set of version 27.0 of the Medical Dictionary for Regulatory Activities （MedDRA） were used for data classification and statistics. RESULTS A total of 753 ADE reports were obtained for sacituzumab govitecan， including 46 ADE signals， involving 12 SOCs， and 13 new suspicious ADE signals not recorded in the instructions. Top 5 PTs in terms of occurrence frequency were disease progression， death， diarrhea， off label use and inappropriate schedule of product administration. Top 5 PTs in terms of signal strength were febrile bone marrow aplasia， neutropenic colitis， disease progression， pulmonary sepsis， general physical condition abnormal. New ADE not recorded in the drug instructions included neutropenic sepsis， hepatic cytolysis， meningitis， aplasia， etc. CONCLUSIONS When using sacituzumab govitecan in clinical practice， special attention should be paid to ADE with highly reported cases and strong signal intensity， such as febrile neutropenia， febrile bone marrow aplasia， weight fluctuations， colitis. We should also be alert to new suspected ADE such as neutropenic sepsis， hepatic cytolysis， meningitis， and aplasia to ensure patient medication safety.

In order to evaluate the safety and effectiveness of endoscopic hemorrhoids treatment, a retrospective analysis was conducted on data of 166 patients with grade I to Ⅲ hemorrhoids who underwent endoscopic treatment in the First Affiliated Hospital of University of Science and Technology of China from January 2018 to June 2020 with complete follow-up data. There were 35 cases in the simple sclerotherapy group, 104 cases in the simple ligation group, and 27 cases in the ligation combined sclerotherapy group. The results showed that, no serious complications occurred in the 3 groups after surgery. In the simple ligation group and the ligation combined with sclerotherapy group, the incidence of postoperative anal pain [35.6% (37/104) and 33.3% (9/27), respectively,] and anal pendant distension [70.2% (73/104) and 70.4% (19/27), respectively] were higher, but symptoms could be tolerated or relieved after simple treatment. The satisfaction of patients in the 3 groups was all more than 90% before discharge, and the degree of operation acceptance was more than 95%. The effective rate of the 3 groups was above 90.0% at 3 months after surgery, At 12 months after surgery, the effective rate of the simple sclerotherapy group was the lowest [74.3% (26/35)], and the effective rate of the other two groups was still above 85.0%. In conclusion, minimally invasive treatment for internal hemorrhoids under endoscopy is safe and effective with effective improvement of symptoms, high postoperative satisfaction of patients and high degree of acceptance.

ObjectiveTo analyze the community structure and dynamics of parasitic fleas on the body surface of host animals and nested fleas in different seasons in the natural foci of wild rat plague in Yulong County，Yunnan Province， to explore the relationship between seasonal fluctuation of fleas and the prevalence of plague among animals， so as to provide evidence for plague prevention and control in the natural foci. MethodsNanxi Village， Huangshan Town， the core area of plague epidemic in Yulong County， was selected as the monitoring sample area in December 2019 （winter）， August 2020（summer）， October 2020（autumn） and March 2021（spring）. Host animals were captured by rattrap at night and rat nests were excavated for collecting parasitic fleas on host animals and rat nest fleas in different seasons. Excel 2010 and SPSS 26.0 software were used to analyze the data， and Chi square test was used to compare the rate. Community ecological indicators were used to analyze the community structure and species diversity of the host animals and their parasitic fleas. ResultsA total of 355 vector fleas were captured， belonging to 7 species of 5 genera in 2 families. 441 small animals were captured and 138 rat body fleas were detected with the flea infection rate of 14.51% and the flea index 0.31. 96 effective rat holes were excavated and 217 fleas were detected with the flea infection rate of 35.42% and the flea index 2.26. Among the four seasons， the flea infection rates of rat body and rat nests were higher in summer and winter， showing a significant difference in general （χ²=15.851， P<0.01； χ²=16.398， P<0.01）. The dominant species of flea community were Ctenophthalmus quadratus， Stenischia humilis， Neopsylla specialis and Frontopsylla spadix， with a dominance index of 0.434， 0.254， 0.180 and 0.110， respectively. The diversity and evenness of rat body fleas showed a distribution characteristic of decreasing， increasing and then decreasing again with season changes， and both were the highest in spring， while the ecological dominance showed an opposite trend. The diversity and evenness of rat nest fleas showed a distribution characteristic of increasing first and then decreasing in summer， autumn and winter， with the highest in autumn， while the ecological dominance was diametrically opposite. ConclusionThe fleas community structure is relatively stable in Yulong County， but the number of species in the community is unevenly distributed by seasons， and the status of dominant species is prominent. Local authorities should carry out timely preventive deratization and depulization measures according to the results of daily monitoring， so as to effectively avoid the prevalence and spread of plague among animals in plague foci.