OBJECTIVE To establish a method for simultaneously determining three anti-tuberculosis drugs in the plasma of patients with spinal tuberculosis and apply it in clinical practice. METHODS LC-MS/MS method was established for the quantitative determination of the concentrations of isoniazid， rifampicin and pyrazinamide in the plasma of patients with spinal tuberculosis， using diphenhydramine as the internal standard. The determination was carried out using Chemalink CM-C18T column， with mobile phase consisting of 0.1% formic acid-methanol solution （gradient elution）， at the flow rate of 0.4 mL/min and an injection volume of 2 μL. Multiple reaction monitoring was conducted using an electrospray ionization source in positive ion mode. The ion pairs used for quantitative analysis were m/z 138.0→121.0（ for isoniazid）， m/z 823.3→791.3（ for rifampicin）， m/z 124.1→ 79.0 （for pyrazinamide）， and m/z 256.0→167.0 （for diphenhydramine）. Fifty-three patients diagnosed with spinal tuberculosis in Qinghai Provincial People’s Hospital from January 2023 to June 2025 were selected， and the plasma concentrations of isoniazid， rifampicin and pyrazinamide in these patients were measured using the above method. RESULTS The linear ranges for isoniazid， rifampicin and pyrazinamide were 0.5-16， 2-64， and 2.5-80 μg/mL， respectively （r≥0.998 7）. The accuracy ranged from 90.20% to 108.64% （n＝5）. RSDs for intra-day precision were all less than 6.63% （n＝5）， while those for inter-day precision were all less than 8.42% （n＝3）. The matrix effects ranged from 88.60% to 115.41% （n＝5）. The relative deviations in the stability tests were all within the ±15% range， and the carry-over effect did not interfere with the determination. The results of clinical application showed that the mean plasma drug concentrations of isoniazid， rifampicin and pyrazinamide in patients with spinal tuberculosis were （3.62±2.80）， （8.55±4.57）， and （20.12±6.56） μg/mL， respectively. The incidences of plasma drug concentrations falling below the effective peak concentrations were 49.06%， 58.49% and 60.38%， respectively. CONCLUSIONS The method established in this study is rapid， accurate， and demonstrates good stability， making it suitable for clinical monitoring of the plasma concentrations of isoniazid， rifampicin and pyrazinamide in patients with spinal tuberculosis.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Dental trauma is a common oral condition in children. For single-type trauma to young permanent teeth, timely treatment often results in a high survival rate for both the teeth and the pulp. However, in cases of complex dental trauma or when supernumerary teeth are impacted near the apex of the injured tooth, the prognosis is less predictable. This article reports a case of root fracture in an immature maxillary permanent central incisor combined with impacted supernumerary tooth in the apical region. After supernumerary tooth extraction and pulp revascularization therapy, the case demonstrated a good treatment outcome over a nearly 10-year follow-up period.
Child ; Humans ; Incisor/injuries* ; Maxilla ; Tooth Extraction ; Tooth Fractures/complications* ; Tooth Root/injuries* ; Tooth, Impacted/surgery* ; Tooth, Supernumerary/surgery*

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Permeability is one of the determinants of intestinal absorption and oral bioavailability. The non-cell-based permeation model is a kind of in vitro permeability measurement tool, which has the advantages of high efficiency, low cost, stable property, easy to use and customizable. According to the barrier type, non-cell-based permeation model can be divided into biomimetic barriers containing (phosphate) lipids and non-biomimetic barriers without lipids. Biomimetic permeation models include parallel artificial membrane permeability assay, vesicle-based permeation assay and PermeaPad®. Non biomimetic permeation models include Hollow fiber membrane models based on polyether sulfone materials. In foreign countries, the application of these four barriers for different purposes is gradually becoming a hot spot in drug absorption research. However, in China, there are only more applied studies on PMAPM and few published applied studies on the other three barriers. In order to meet the development needs of insoluble drug formulations, the author summarized the permeability devices and permeability calculation methods, searched the application of non-cell-based permeation model in the permeability of BSCⅡ drugs in recent years, and summarized the characteristic applications of three Biomimetic permeation models and hollow fiber membranes.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Objective:To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China.Methods:The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function.Results:The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M ( Q 1, Q 3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) μg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95% CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion:Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

With the aging population, the burden of diseases such as atrial fibrillation and venous thrombosis is gradually increasing. Anticoagulant therapy has a positive significance in preventing ischemic stroke, pulmonary embolism, and other related conditions in these patients. However, anticoagulant therapy can have the opposite effect on diseases caused by intracranial hemorrhage, such as falls in the elderly, cerebrovascular accidents, and car accidents. It is still difficult to determine whether and when to restart anticoagulation after cerebral hemorrhage. Although most studies have shown that restarting anticoagulant therapy can reduce stroke risk without significantly increasing bleeding risk, they are mostly based on observational studies, so more high-quality research is needed to guide clinical decision-making. This article reviews the research progress on restart anticoagulation, aiming to provide some assistance for clinical applications.

Objective:To analyze the distribution and drug resistance of pathogens of bacterial bloodstream infection in patients with hematological diseases in the Department of Hematology of Tianjin Medical University General Hospital, and to provide etiological data for clinical empirical anti-infection treatment.Methods:A retrospective analysis was conducted on the general clinical information, pathogenic bacteria and drug susceptibility test results of patients with hematological diseases diagnosed with bacterial bloodstream infection by menstrual blood culture in our center from January 2016 to December 2022.Results:Patients included 498 inpatients, with a total of 639 bacterial strains. Among the patients, 86.9% patients had malignancies, and 76.7% had agranulocytosis. Symptoms of concurrent infections, including those of the respiratory tract, oral mucosa, skin and soft tissues, and abdominal sources were observed in 68.3% patients. Gram-negative bacteria (G -) accounted for 79.0% of the isolated bacteria, and gram-positive bacteria (G +) accounted for 21.0%. The top five isolated pathogens were Klebsiella pneumoniae (22.5%), Escherichia coli (20.8%), Pseudomonas aeruginosa (15.0%), Enterococcus faecium (5.5%), and Stenotrophomonas maltophilum (5.0%). Escherichia coli exhibited a decreasing trend of resistance to quinolones, cephalosporins, and carbapenems. Klebsiella pneumoniae exhibited increasing rates of resistance to quinolones and cephalosporins between 2016 and 2018, but the rated decreased after 2019. The resistance rate to carbapenems exhibited by Pseudomonas aeruginosa was approximately 20%. Carbapenem-resistant strains of Pseudomonas aeruginosa strains were first detected in 2017, with a peak resistance rate of 35.7%, detected in 2019. A 60.0% resistance rate to methicillin was observed in methicillin-resistant coagulase-negative staphylococci (MRCNS), and one case of linezolid-resistant MRCNS was detected. Conclusions:Pathogenic bacteria of bacterial bloodstream infections were widely distributed in our center, and precautions are warranted against carbapenem resistant P. aeruginosa and Klebsiella pneumoniae.

Objective: To investigate the rifampicin resistance status and its influencing factors among elderly patients with pulmonary tuberculosis in Changzhou City, Jiangsu Province, so as to provide the basis for improving drug-resistant pulmonary tuberculosis prevention and control strategies. Methods: Patients aged over 60 years with pulmonary tuberculosis treated in tuberculosis designated hospital was selected. Demographic information, history of previous disease, history of diagnosis and treatment and drug sensitivity test were collected. Rifampicin resistance among elderly patients with pulmonary tuberculosis and its influencing factors was analyzed. Results: Totally 249 elderly patients with pulmonary tuberculosis were included, with an average of (69.75±4.36) years. There were 147 males and 102 females, with a gender ratio of 1.44∶1. There were 183 treatment-naïve patients (73.49%) and 66 retreated patients (26.51%). Rifampicin resistance was found in 21 cases, with a drug resistance rate of 8.43%. Among them, there were 7 treatment-naïve patients (3.83%), and 14 retreated patients (21.21%). Multivariable logistic regression analysis showed that retreated elderly patients with pulmonary tuberculosis had a higher risk of rifampicin resistance (OR=10.551, 95%CI: 1.344-82.857). Conclusion The rifampicin resistance rate of 249 elderly patients with pulmonary tuberculosis was 8.43% and was associated with the type of treatment.