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*

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 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.

Objective:To explore the protective mechanism of tea polyphenols (TP) on mouse oral cancer.Methods:A total of 50 mice were divided into control group, model group, TP group, Selisistat group, TP+ Selisistat group, with 10 mice in each group. The control group was gavaged with physiological saline, while the model group, TP group, Selisistat group, and TP+ Selisistat group were gavaged with 300 mg/L 4-NQO to establish a mouse oral cancer model. Physiological saline, 200 mg/kg TP, 0.01 mg/kg Selisistat, and 200 mg/kg TP+ 0.01 mg/kg Selisistat were gavaged respectively. The weight changes of each group of mice were compared; HE staining was used to observe the morphology of mouse oral tumor tissue; Enzyme linked immunosorbent assay was used to detect the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in serum; Immunoblotting and immunohistochemistry were used to detect the expression of silencing information regulatory factor (Sirt1) and nuclear factor E2 related factor 2 (Nrf2) proteins in mouse oral tissues.Results:Compared with the control group, the model group mice had a decrease in body weight [(23.19±1.36)g], a decrease in serum SOD level [(91.64±8.75)U/ml], an increase in MDA level [(5.18±0.46)nmol/ml], a decrease in Sirt1 (0.38±0.05) and Nrf2 (0.36±0.05) protein expression in oral tissue, and an increase in Nrf2 acetylation level (0.84±0.11) (all P<0.05). Compared with the model group, the TP group mice had an increase in body weight [(25.28±1.25)g], elevated serum SOD levels [(121.24±10.68)U/ml], decreased MDA levels [(3.89±0.42)nmol/ml], increased expression of Sirt1 (0.61±0.09) and Nrf2 (0.58±0.06) proteins in oral tissue, and decreased Nrf2 protein acetylation levels (0.39±0.05); The Selisistat group mice showed a decrease in body weight [(21.41±1.07)g], a decrease in serum SOD levels [(72.16±7.43)U/ml], an increase in MDA levels [(5.87±0.41)nmol/ml], a decrease in Sirt1 (0.23±0.04) and Nrf2 protein (0.24±0.03) expression in oral tissue, and an increase in Nrf2 acetylation levels (1.12±0.14) ( P<0.05). The body weight [(23.32±1.27)g], serum SOD levels [(92.58±8.13)U/ml], and oral Sirt1 (0.41±0.06) and Nrf2 (0.38±0.05) protein expression in the TP+ Selisistat group mice were higher than those in the Selisistat group, while MDA [(5.11±0.38)nmol/ml] and Nrf2 acetylation levels (0.82±0.09) were lower than those in the Selisistat group (all P<0.05). Conclusions:Tea polyphenols can alleviate oral tissue damage and alleviate oxidative stress in mice with oral cancer, and their mechanism may be related to the upregulation of the Sirt1/Nrf2 pathway.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

BACKGROUND:Compound Shengmai Chenggu capsule has good therapeutic effects on early steroid-induced osteonecrosis of the femoral head,but the exact mechanism of treatment is not fully understood. OBJECTIVE:To observe the effect of compound Shengmai Chenggu capsule on fucosyltransferase 8,osteogenic gene and Wnt/β-catenin in bone tissue of rats with steroid-induced osteonecrosis of the femoral head. METHODS:Sixty Sprague-Dawley rats were randomized into blank group,model group,low-,middle-,and high-dose drug groups(n=12 per group).In the latter four groups,animal models of steroid-induced osteonecrosis of the femoral head were established by subcutaneous injection of imiquimod(once every 2 weeks,2 times in total)and gluteal muscle injection of methylprednisolone(once a week,4 times in total).The low-,middle-and high-dose drug groups were given 1.89,3.78 and 7.56 g/kg per day compound Shengmai Chenggu capsule solution by gavage respectively on the second day after the last modeling.The same amount of saline was given by gavage to the model group.Administration lasted 8 weeks.After the administration,micro-CT scan,histological staining,compression test,RT-qPCR and western blot were performed on the femoral head. RESULTS AND CONCLUSION:Micro-CT scan results showed that compared with the blank group,trabecular volume fraction,trabecular number and trabecular thickness were significantly decreased(P<0.05),while trabecular separation was increased in the model group(P<0.05).Compared with the model group,the compound Shengmai Chenggu capsule could increase trabecular volume fraction,trabecular number and trabecular thickness(P<0.05),and decrease trabecular separation(P<0.05)in a dose-dependent manner.Hematoxylin-eosin staining results showed that compared with the model group,the rate of empty bone lacunae was reduced in a dose-dependent group in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups(P<0.05).Immunohistochemical staining results showed that compared with the blank group,the protein expression of fucosyltransferase 8,Runx2 and bone morphogenetic protein 2 was reduced in the model group(P<0.05);compared with the model group,the compound Shengmai Chenggu capsule increased the protein expression of fucosyltransferase 8,Runx2 and bone morphogenetic protein 2 in a dose-dependent manner(P<0.05).Results from the compression test showed that there was a dose-dependent increase in the maximum load and elastic modulus of the femoral head in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups compared with the model group(P<0.05).RT-qPCR and western blot results showed that the mRNA and protein expressions of fucosyltransferase 8,Runx2,alkaline phosphatase,osteocalcin,osteoblast-specific transcription factor and bone morphogenetic protein 2 were decreased in the model group compared with the blank group(P<0.05);compared with the model group,there was a dose-dependent increase in the mRNA and protein expressions of the above indicators in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups compared with the model group(P<0.05).Compared with the blank group,the mRNA and protein expression of Wnt2,low-density lipoprotein receptor-related protein 5 and β-catenin were decreased(P<0.05)and the mRNA and protein expressions of glycogen synthase kinase 3β were increased(P<0.05)in the model group;compared with the model group,there was a dose-dependent increase in the mRNA and protein expressions of Wnt2,low-density lipoprotein receptor-related protein 5 and β-catenin(P<0.05)but a dose-dependent decrease in the mRNA and protein expressions of lycogen synthase kinase 3β(P<0.05)in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups.To conclude,the mechanism by which the compound Shengmai Chenggu capsule treats steroid-induced osteonecrosis of the femoral head may activate the Wnt/β-catenin signaling pathway through the up-regulation of fucosyltransferase 8,thereby promoting bone formation.

Objective:To explore whether there is a solution to the trilemma of health policy,and to reveal whether the health policy and policy portfolio can simultaneously improve the"health","wealth"and"equity"of residents.Methods:The study constructs a dynamic stochastic general equilibrium model and indicator estimation procedure that includes human health capital,and used Bayesian model comparison method to determine reasonable model settings.Using numerical simulation methods,by adjusting the corresponding parameters,it also simulates the policy effect of implementing comprehensive medical supervision policy and medical quality management policy separately,as well as the policy effects of combining these two policies.Results:Simply implementing comprehensive medical supervision policy may lead to the deviation of health outcomes from health affordability and financing equity,and simply implementing medical quality management policy may lead to the deviation of health affordability from health outcomes and financing fairness,and the combination of these two policies can effectively solve the trilemma of health policy.Conclusion:The problem of health policy trilemma is not unsolvable,and the mutual deviation of"health","wealth"and"equity"can be reconciled through reasonable policy combination design.

Objective:To explore whether there is a solution to the trilemma of health policy,and to reveal whether the health policy and policy portfolio can simultaneously improve the"health","wealth"and"equity"of residents.Methods:The study constructs a dynamic stochastic general equilibrium model and indicator estimation procedure that includes human health capital,and used Bayesian model comparison method to determine reasonable model settings.Using numerical simulation methods,by adjusting the corresponding parameters,it also simulates the policy effect of implementing comprehensive medical supervision policy and medical quality management policy separately,as well as the policy effects of combining these two policies.Results:Simply implementing comprehensive medical supervision policy may lead to the deviation of health outcomes from health affordability and financing equity,and simply implementing medical quality management policy may lead to the deviation of health affordability from health outcomes and financing fairness,and the combination of these two policies can effectively solve the trilemma of health policy.Conclusion:The problem of health policy trilemma is not unsolvable,and the mutual deviation of"health","wealth"and"equity"can be reconciled through reasonable policy combination design.