UNASSIGNED: To investigate the clinical efficacy of dexamethasone (Dex) combined with isoniazid in tuberculous meningitis (TBM) and its effect on peripheral blood T cell subsets.
UNASSIGNED: A total of 235 patients with TBM were divided into the control group (117 cases) and the observation group (118 cases). Both groups were given conventional treatment, the control group was further given isoniazid, and the observation group was further given Dex combined with isoniazid. The therapeutic effect and improvement of clinical symptoms were evaluated, peripheral blood T lymphocyte subsets and neurological function were observed, and patients\' prognosis was evaluated.
UNASSIGNED: The total effective rate of the observation group was higher. The recovery time of cerebrospinal fluid (CSF) pressure, CSF protein content, CSF cell count, and hospital stays in the observation group were shorter. The duration of cervicogenic headache, fever, vomiting, and coma in the observation group was shorter. CD3+ and CD4+/CD8+ proportions in the observation group were higher, and CD8+ proportion was lower. The NIHSS score and MRS score of the observation group were lower, as well as the incidence of adverse reactions.
UNASSIGNED: Dex combined with isoniazid alleviates clinical symptoms and neurological abnormalities and regulates peripheral blood T cell subsets in TBM.

暂无摘要。

BACKGROUND: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety.
METHODS: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators.
RESULTS: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD  - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544).
CONCLUSIONS: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results.
BACKGROUND: Retrospectively registered in PROSPERO  https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .

The design of single-atom nanozymes with dual active sites to increase their activity and for the detection and degradation of contaminants is rare and challenging. In this work, a single-atom nanozyme (FeCu-NC) based on a three-dimensional porous Fe/Cu dual active site was developed as a colorimetric sensor for both the quantitative analysis of isoniazid (INH) and the efficient degradation of levofloxacin (LEV). FeCu-NC was synthesized using a salt template and freeze-drying method with a three-dimensional hollow porous structure and dual active sites (Fe-Nx and Cu-Nx). In terms of morphology and structure, FeCu-NC exhibits excellent peroxidase-like activity and catalytic properties. Therefore, a colorimetric sensor was constructed around FeCu-NC for sensitive and rapid quantitative analysis of INH with a linear range of 0.9-10 μM and a detection limit as low as 0.3 μM, and the sensor was successfully applied to the analysis of INH in human urine. In addition, FeCu-NC promoted the efficient degradation of LEV by peroxymonosulfate activation, with a degradation rate of 90.4% for LEV at 30 min. This work sheds new light on the application of single-atom nanozymes to antibiotics for colorimetric sensing and degradation.

BACKGROUND: Tuberculosis (TB), one of the deadliest infectious diseases globally, is increasingly exacerbated in China by the emergence of resistant Mycobacterium tuberculosis (MTB) strains. Drug-resistant TB, including mono-drug resistant TB, multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB), presents significant public health challenges.
METHODS: We conducted a systematic literature review from January 2010 to February 2024 using databases such as PubMed, Embase, Web of Science, and Google Scholar. Our focus was on empirical data related to drug resistance patterns in newly diagnosed TB cases. Non-empirical studies were excluded through meticulous filtering. For meta-analysis, we used Review Manager (RevMan) 5.2 and assessed evidence quality using the Newcastle-Ottawa Scale (NOS).
RESULTS: Our search strategy identified 40 studies that met the inclusion criteria, encompassing a total sample size of 87,667 participants. Among new TB cases, the estimated prevalence of MDR-TB in China was 6.9% (95% CI: 5.6-8.1%). Prevalence rates for mono-drug resistance to first-line anti-TB medications were as follows: isoniazid at 18.2% (95% CI: 16.4-20.6%), rifampicin at 10.5% (95% CI: 8.6-12.8%), and ethambutol at 5.7% (95% CI: 4.1-7.3%). The prevalence of streptomycin resistance, a former first-line anti-TB drug, was 17.1% (95% CI: 14.6-19.1%). The prevalence of other types of mono-drug resistance was 15.2% (95% CI: 13.9-17.3%), and for XDR-TB, it was 0.9% (95% CI: 0.6-1.4%).
CONCLUSIONS: The high prevalence of drug-resistant TB in China poses a significant public health challenge. There is an urgent need for targeted interventions and continued surveillance to combat the spread of drug-resistant TB.

BACKGROUND: This study aimed to analyze the risk factors associated with isoniazid-resistant and rifampicin-susceptible tuberculosis (Hr-TB) in adults.
METHODS: The clinical data of 1,844 adult inpatients diagnosed with culture-positive pulmonary tuberculosis (PTB) in Nanjing Second Hospital from January 2019 and December 2021 were collected. All culture positive strain from the patient specimens underwent drug susceptibility testing (DST). Among them, 166 patients with Hr-TB were categorized as the Hr-TB group, while the remaining 1,678 patients were classified as having drug-susceptible tuberculosis (DS-TB). Hierarchical logistic regression was employed for multivariate analysis to identify variables associated with Hr-TB.
RESULTS: Multivariate logistic regression analysis revealed that individuals with diabetes mellitus (DM) (OR 1.472, 95% CI 1.037-2.088, p = 0.030) and a history of previous tuberculosis treatment (OR 2.913, 95% CI 1.971-4.306, p = 0.000) were at higher risk of developing adult Hr-TB, with this risk being more pronounced in male patients. Within the cohort, 1,640 patients were newly treated, and among them, DM (OR 1.662, 95% CI 1.123-2.461, p = 0.011) was identified as risk factors for Hr-TB.
CONCLUSIONS: Diabetes mellitus is a risk factor for Hr-TB in adults, and the contribution of diabetes as a risk factor was more pronounced in the newly treatment or male subgroup. And previous TB treatment history is also a risk factor for Hr-TB in adults.

BACKGROUND: Over-consumption of drugs can result in drug-induced liver damage (DILI), which can worsen liver failure. Numerous studies have shown the significant role ferroptosis plays in the pathophysiology of DILI, which is typified by a marked imbalance between the generation and breakdown of lipid reactive oxygen species (ROS). The content of peroxynitrite (ONOO-) rapidly increased during this process and was thought to be a significant marker of early liver injury. Therefore, the construction of fluorescence probe for the detection and imaging of ONOO- holds immense importance in the early diagnosis and treatment of ferroptosis-mediated DILI.
RESULTS: We designed a probe DILI-ONOO based on the ICT mechanism for the purpose of measuring and visualizing ONOO- in ferroptosis-mediated DILI processes and associated studies. This probe exhibited significant fluorescence changes with good sensitivity, selectivity, and can image exogenous and endogenous ONOO- in cells with low cytotoxicity. Using this probe, we were able to show changes in ONOO- content in ferroptosis-mediated DILI cells and mice models induced by the intervention of acetaminophen (APAP) and isoniazid (INH). By measuring the concentration of ferroptosis-related indicators in mice liver tissue, we were able to validate the role of ferroptosis in DILI. It is worth mentioning that compared to existing alanine transaminase (ALT) and aspartate aminotransferase (AST) detection methods, this probe can achieve early identification of DILI prior to serious liver injury.
CONCLUSIONS: This work has significant reference value in researching the relationship between ferroptosis and DILI and visualizing research. The results indicate a strong correlation between the progression of DILI and ferroptosis. Additionally, the use of DILI-ONOO shows promise in investigating the DILI process and assessing the effectiveness of medications in treating DILI.

Development of metal-free nanozymes has raised concern for their extensive applications in photocatalysis and sensing fields. As novel metal-free nanomaterials, covalent organic frameworks (COFs) have engendered intense interest in the construction of nanozymes due to their structural controllability and molecular functionality. The formation of the molecular arrangement by embedding orderly donor-acceptors (D-A) linked in the framework topology to modulate material properties for highly efficient enzyme mimicking activity is of importance but challenging. Here, a strong D-A type of COF was designed and synthesized by integrating electron donor units (pyrene) and electron acceptor units (phenanthroline), named Py-PD COF. Using experiments and theoretical calculations, the introduction of a phenanthroline ring endowed the Py-PD COF with a narrowed band gap, and efficient charge transfer and separation. Further, the Py-PD COF exhibited a superior light-responsive oxidase-mimicking characteristic under visible light irradiation, which could catalyze the oxidation of 3,3\',5,5-tetramethylbenzidine (TMB) and give the corresponding evolution of color. The nanoenzymatic activity of the Py-PD COF was light-regulated, which offers a fascinating advantage because of its high efficiency and spatial controllability. Based on previously mentioned characteristics, an \"on-off\" sensing platform for the colorimetric analysis of isoniazid (INH) could be constructed with a good linear relationship (2-100 μM) and a low limit of detection (1.26 μM). This research shows that not only is Py-PD COF an environmentally friendly compound for the colorimetric detection of INH, but it is also capable of providing the interesting D-A type COF-based material for designing an excellent nanozyme.

A robust and easily manufactured high-strength and long-term release hydrazone-based isoniazid acrylic (HIA) bone cement is reported. The mechanical strength of HIA bone cement is similar to that of normal polymethyl methacrylate (PMMA) bone cement, far surpassing that of traditional isoniazid-containing antibiotic-loaded bone cement (INH bone cement). Isoniazid is connected to the bone cement through bioorthogonal hydrazone chemistry, and it possesses release properties superior to those of INH bone cement, allowing for the sustained release of isoniazid for up to 12 weeks. In vivo and in vitro studies also indicate that HIA cement exhibits better biocompatibility than INH bone cement. The results of this study not only signify progress in the realm of antimicrobial bone cement for addressing bone tuberculosis but also enhance our capacity to create and comprehend high-performing antimicrobial bone cement.

Personalized medicine aims to effectively and efficiently provide customized drugs that cater to diverse populations, which is a significant yet challenging task. Recently, the integration of artificial intelligence (AI) and three-dimensional (3D) printing technology has transformed the medical field, and was expected to facilitate the efficient design and development of customized drugs through the synergy of their respective advantages. In this study, we present an innovative method that combines AI and 3D printing technology to design and fabricate customized capsules. Initially, we discretized and encoded the geometry of the capsule, simulated the dissolution process of the capsule with classical drug dissolution model, and verified it by experiments. Subsequently, we employed a genetic algorithm to explore the capsule geometric structure space and generate a complex multi-layer structure that satisfies the target drug release profiles, including stepwise release and zero-order release. Finally, Two model drugs, isoniazid and acetaminophen, were selected and fused deposition modeling (FDM) 3D printing technology was utilized to precisely print the AI-designed capsule. The reliability of the method was verified by comparing the in vitro release curve of the printed capsules with the target curve, and the f2 value was more than 50. Notably, accurate and autonomous design of the drug release curve was achieved mainly by changing the geometry of the capsule. This approach is expected to be applied to different drug needs and facilitate the development of customized oral dosage forms.