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 effects of Zhuanggu Zhitong Capsules on JNK signaling molecules and their phosphorylated proteins in postmenopausal osteoporosis model female mice.Methods:The rats were divided into sham-operation group, blank group, model group, positive drug group, and Zhuanggu Zhitong Capsules group according to the random number table method, with 10 rats in each group. The model group, the positive drug group and the Zhuanggu Zhitong Capsules group were prepared by bilateral ovarian detomy to prepare a female mouse model of postmenopausal osteoporosis. The positive drug group was given 0.9 mg/kg of alendronate sodium, the Zhuanggu Zhitong Capsules group was given was Zhuanggu Zhitong Capsules 1.944 g/kg for gavage, and the blank group, sham-operation group, and model group were given the same volume of normal saline for gavage, once a day for a total of 13 weeks. Rat vaginal exfoliated cells were stained with Wright's staining; serum Omentin-1 and 25(OH)D 3 levels were determined by ELISA; renal tissue and femoral structure were observed by HE staining; JNK and p-JNK protein expressions were detected by immunohistochemical staining; JNK mRNA levels were detected by PCR. Results:Compared with the model group, the serum levels of 25(OH)D3 and Omentin-1 in the Zhuanggu Zhitong Capsules group and the positive drug group increased ( P<0.01), the mean gray values of JNK and p-JNK protein in bone and kidney tissues decreased ( P<0.01), and the mRNA levels of JNK in bone and kidney tissues decreased ( P<0.01). Conclusion:Zhuanggu Zhitong Capsules can effectively improve the bone microstructure of postmenopausal osteoporotic rats, and its mechanism may be related to the regulation of JNK signaling pathway.

Objective To discuss the application value of coronary CT angiography(CCTA)evaluation of morphological parameters of coronary chronic total occlusion(CTO)in guiding interventional therapy.Methods A total of 300 patients with coronary angiography-confirmed CTO in Jinhua Municipal People's Hospital from January 2021 to December 2023 were selected.All patients received CCTA examination before surgery.The morphological parameters of CCTA,including proximal morphology of occlusion segment,length of occlusion vessel,length of linear enhancement in occlusion segment,length of linear enhancement in occlusion segment/length of occlusion vessel,vascular linear enhancement in occlusion segment,vascular calcification in occlusion segment,vascular calcification area in occlusion segment ≥50％on cross section image,tortuous path of lesion(＞45°),collateral vessels and lesion of vascular opening,were recorded.The correlation between the above parameters and therapeutic results of percutaneous coronary intervention(PCI)was analyzed.Results There were 325 lesions in 300 patients with CTO,and 227 lesions(69.85％)were successfully treated by PCI and PCI treatment failed in 98 lesions(30.15％).The proximal blunt shape of occlusion segment,length of occlusion vessel,vascular calcification area of occlusion segment ≥50％on cross section image,and tortuous path of lesion(＞45°)in the failure group were significantly higher than those in the successful group(all P＜0.05),while the length of linear enhancement in occlusion segment,length of linear enhancement in occlusion segment/length of occlusion vessel and vascular linear enhancement in occlusion segment in the failure group were strikingly lower than those in the successful group(all P＜0.05).No obvious significant differences in other parameters existed between the two groups(all P＞0.05).Multivariate logistic regression analysis showed that the length of linear enhancement in occlusion segment(OR=1.975,95％CI:1.306-2.988),the length of linear enhancement in occlusion segment/length of occlusion vessel(OR=3.831,95％CI:1.332-11.017),and the linear enhancement in occlusion segment(OR=1.702,95％CI:1.007-2.879)were the valuable factors for predicting the success of PCI treatment(all P＜0.05).Conclusion CCTA evaluation of coronary CTO morphological parameters has a certain value in guiding interventional therapy.The length of linear enhancement in occlusion segment,the length of linear enhancement in occlusion segment/length of occlusion vessel,and the linear enhancement in occlusion segment are the useful factors for predicting the success of PCI treatment.

Objective To investigate the clinical characteristics and outcomes of Coronavirus Dis-ease 2019 in immunocompromised hosts.Methods A retrospective analysis was conducted on the clinical data of 230 hospitalized patients diagnosed with Coronavirus Disease 2019 at Nanjing Yimin Hospital from December 2022 to November 2023.The patients were divided into three groups based on their immune status:immunocompromised group(n=59),relatively immunocompromised group(n=129),and immunocompetent group(n=42).The clinical characteristics(such as clinical manifesta-tions,imaging features,and laboratory examinations)and outcomes(such as length of hospital stay and in-hospital mortality)were compared among three groups.Results Compared with there latively immunocompromised and immunocompetent groups,the immunocompromised group showed no obvious specific clinical manifestations.However,the proportions of patients with symptoms such as cough and expectoration were lower,and the occurrences of symptoms such as myalgia and fatigue were less fre-quent in the immunocompromised group(P＜0.05).The chest CT findings in the immunocompro-mised group also lacked specific changes,mainly presenting as subpleural ground-glass opacities and consolidations with multilobar distribution,but fibrotic changes were more common(P＜0.05).The proportion of patients with decreased absolute lymphocyte counts in the immunocompromised group was higher than that in the immunocompetent group,and the proportion of patients with elevated procalcitonin levels was higher than that in the other two groups(P＜0.05).The proportion of severe case sand the length of hospital stay in the immunocompromised group were higher and longer than those in the relatively immunocompromised and immunocompetent groups(P＜0.05).The in-hospital mortality rates in the immunocompromised,relatively immunocompromised,and immunocompetent groups were 10.17％,6.98％,and 2.38％,respectively,with no statistically significant difference(P＞0.05).Conclusion After Coronavirus Disease 2019,immunocompromised hosts do not show obvi-ous clinical and imaging features.However,they have a prolonged length of hospital stay,a signifi-cantly higher proportion of severe cases,and a tendency towards increased in-hospital mortality,which should be given high clinical attention.

Objective To study the root canal morphology of permanent mandibular anterior teeth and explore its correlation with the occurrence of three-rooted mandibular molars using cone beam computed tomographic(CBCT)imaging.Methods CBCT image data of 200 subjects were randomly collected from dental clinics.The root canal morphology of the mandibular anterior teeth was identified and classified by Vertucci's classification,and the root length and labio-lingual dimension at the tooth neck level were measured.The occurrence of three-rooted mandibular first molars was examined as well.The concurrence rates of double-canaled anterior teeth and three-rooted mandibular first molars at each side,and concurrence rates of bilateral double-canaled anterior teeth and three-rooted man-dibular first molars were calculated.Spearman correlation tests were applied to analyze the correlation between the double-canaled ante-rior teeth and three-rooted mandibular first molars,as well as the bilateral antimetric teeth.Results The incidence of double-canaled system was 10.4％,18.6％and 6.5％in mandibular central incisors,lateral incisors and canines,respectively;the bilateral concur-rence rates were 5.7％,11.1％and 3.0％,respectively,and Spearman correlation coefficients(rho)were 0.487,0.505 and 0.440(P＜0.01),respectively;gender difference and side difference were not detected(P＞0.05).The frequency of three-rooted mandibular first molars was 24.6％;gender difference was not detected(P＞0.05),while the incidence was significantly higher at the right side(29.0％)than the left side(20.3％)(P＜0.05).The bilateral concurrence rate was 17.4％,and a moderate correlation was detected(rho=0.666,P＜0.01).The concurrence rates between the double-canaled anterior teeth and three-rooted mandibular first molars at each side were very low(2.6％-7.6％),and Spearman correlation tests demonstrated that no correlation(P＞0.05)could be detected between them.Conclusion The lateral incisors exhibited the highest incidence of two root canals among the mandibular anterior teeth.Ad-ditionally,there was no significant corr-elation between three-rooted mandibular first molars and double-canaled mandibular anterior teeth.

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 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.