The once-weekly combination of rifapentine and isoniazid (3HP regimen) is a preferred treatment for latent tuberculosis infection (LTBI). Although generally well tolerated, rare but severe systemic adverse reactions may occur. We report the case of a 57-year-old woman receiving once-weekly rifapentine, isoniazid, and pyridoxine for LTBI who developed recurrent chest pain, generalized weakness, nausea, and vomiting within a short time after taking each weekly dose. The evaluation demonstrated multiorgan involvement, including acute liver injury, hyperbilirubinemia, hyperferritinemia, markedly elevated lactate dehydrogenase (LDH), undetectable haptoglobin, thrombocytopenia, and acute kidney injury. An extensive evaluation for infectious, cardiac, hematologic, and hepatic etiologies was unrevealing. The temporal relationship to medication administration, recurrence with re-exposure, and improvement following discontinuation of the rifapentine and isoniazid regimen supported a diagnosis of severe drug-induced hypersensitivity with hepatic, hematologic, renal, and systemic inflammatory involvement. The patient was managed with supportive care, resulting in progressive improvement of laboratory abnormalities, although renal recovery remained incomplete at discharge. This case highlights a rare but clinically significant multiorgan adverse reaction associated with the 3HP regimen. Clinicians should maintain a high index of suspicion for drug-induced hypersensitivity in patients who develop recurrent systemic symptoms after dosing, as early recognition and prompt discontinuation of therapy may prevent significant morbidity.

Patients with acute leukemia are immunocompromised and highly susceptible to infections. Central nervous system (CNS) tuberculoma is a rare but serious complication in this population, particularly among those undergoing treatment for hematological malignancies. Early diagnosis is often challenging due to non-specific symptoms. We report the case of a 28-year-old female recently diagnosed with CALLA-positive B-cell acute lymphoblastic leukemia, who presented with a two-month history of low-grade fever. Induction chemotherapy was initiated; however, during the third week, she developed new-onset seizures. A computed tomography scan of the brain revealed a heterogeneous ring-enhancing lesion in the right parietal lobe. Magnetic resonance imaging with spectroscopy demonstrated characteristic lipid peaks, supporting the diagnosis of a tuberculoma. Antitubercular therapy comprising rifampicin, isoniazid, pyrazinamide, and ethambutol, along with pyridoxine and dexamethasone, was commenced. The patient showed a favorable response, with resolution of fever and no recurrence of seizures. This case underscores the importance of considering CNS tuberculosis in the differential diagnosis of unexplained neurological symptoms and fever in patients with acute leukemia, particularly in tuberculosis-endemic regions. Prompt recognition and treatment can lead to favorable outcomes.

Whey contains abundant nutrients and bioactive compounds with health benefits, but functional peptides and metabolites in Dairy fan whey (Whey generated during dairy fan processing, DFW) remain underexplored. Therefore, this study identifies DFW nutritional profile and bioactivity via peptidomics, nontargeted metabolomics, and in vitro experiments. The results showed that a variety of bioactive peptides were identified, including antioxidant peptides and angiotensin-converting enzyme (ACE) inhibitory peptides. Four antioxidant peptides interact with Keap1 via hydrogen bonds and salt bridges, thereby exerting antioxidant effects and regulating the Keap1-Nrf2/ARE pathway. In vitro assays confirmed that DFW scavenged DPPH, ABTS, and hydroxyl radicals, demonstrating strong antioxidant activity. Additionally, 919 metabolites were identified in DFW and conventional whey (W), including 15 characteristic compounds such as 4-aminobutyric acid, histamine, and pyridoxine. These characteristic metabolites exhibit antioxidant, anti-inflammatory, and immunoregulatory activities. Compared with W, DFW contains more characteristic nutrients. Overall, this study provides a theoretical basis for the high-value utilization of DFW.

Isoniazid (INH) is a potent bactericidal antibiotic used in the treatment of tuberculosis. Treatment with INH therapy has a risk of toxicity, which can be acute or chronic. Acute toxicity manifests as neurological symptoms. Consumption of 2 g of INH can predispose a patient to acute toxicity; while chronic toxicity usually presents as hepatotoxicity and peripheral neuropathy.  There are 2 known syndromes of hepatotoxicity:  1. Mild type manifesting as transient and asymptomatic elevation in serum aminotransferase levels. 2. Severe acute hepatitis which can sometimes be fatal[1]. Peripheral neuropathy is secondary to a deficiency of vitamin B6 (pyridoxine).

A young adult female presented with recurrent sputum smear-positive pulmonary tuberculosis (TB) despite completing four prior courses of standard first-line anti-tubercular therapy. She presented with progressive breathlessness, productive cough and intermittent fever. Imaging revealed bilateral upper lobe fibrocavitary disease with cystic bronchiectasis. Repeated molecular testing confirmed Mycobacterium tuberculosis without rifampicin or isoniazid resistance. Therapeutic drug monitoring (TDM), though not routinely recommended in TB management, was undertaken in view of recurrent disease and showed undetectable rifampicin and subtherapeutic isoniazid concentrations, pointing towards impaired absorption or altered pharmacokinetics as the likely cause of recurrence. The patient was treated with a higher-dose fixed-dose combination regimen supplemented with pyridoxine, probiotics, vitamin D and nutritional support. After 6 months, she showed symptomatic improvement, weight gain, sputum conversion and reduced respiratory symptoms. This case emphasises the importance of identifying alternative causes of recurrence and supports the role of TDM in patients with recurrent drug-sensitive TB.

Toxoplasma gondii infection remodels the gut microbiome, yet its impact on microbial vitamin biosynthetic potential and host redox metabolism remains unclear. Here, we integrated mouse gut metagenomes with publicly available metagenome-assembled genomes (MAGs) to construct a genome-resolved atlas of B-vitamin and vitamin K2 biosynthesis. From 45,697 MAGs, we curated 4,771 representative genomes, of which 2,682 met high-quality criteria (completeness ≥90%, contamination <5%). Functional annotation identified 229,717 vitamin-related genes corresponding to 177 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs across de novo pathways for eight B vitamins, thiamine (B1), riboflavin (B2), niacin (B3), pantothenate (B5), pyridoxine (B6), biotin (B7), folate (B9), cobalamin (B12), and vitamin K2. Among the high-quality genomes, 1,665 encoded complete de novo pathways for at least one vitamin, highlighting functional specialization and community-level complementarity. Transcripts per million-normalized metagenomic read counts revealed significant differences in KEGG ortholog abundances across six of the nine vitamin pathways. Reanalysis of metagenomic data from infected mice (acute, chronic, and control; n = 10 per group) revealed a stage-dependent reduction in α-diversity of vitamin biosynthesis pathways during acute infection, and a clear β-diversity separation from chronic and control groups. Core niacin biosynthesis genes (nadB, nadA, nadC) displayed phylum-specific redistribution, indicating selective remodeling of microbial NAD[+] precursor production under infection-induced metabolic stress. These results suggest that T. gondii infection disrupts cooperative vitamin biosynthetic networks while specifically modulating niacin pathways linked to host NAD[+] metabolism.

Tuberculosis (TB) remains a major global public health problem. According to the World Health Organization (WHO) Global Tuberculosis Report 2025, an estimated 10.7 million people developed TB and approximately 1.23 million died from the disease in 2024. China continues to face a high burden of both TB and multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). The introduction and expanded use of new and repurposed anti-tuberculosis drugs, including bedaquiline and linezolid, together with accumulating evidence supporting all-oral shorter regimens, have resulted in evidence-based uses that are not yet fully reflected in current Chinese prescribing information. Meanwhile, off-label doses, treatment durations, and alternative uses of established anti-tuberculosis drugs and repurposed anti-infective agents, including isoniazid, rifamycins, fluoroquinolones, and carbapenems, are common in patients with complex drug resistance, drug intolerance, or other special clinical conditions. Standardized guidance is therefore needed within evidence-based, legal, and safety-monitoring frameworks.Building on the Expert Consensus on Off-Label Use of Anti-Tuberculosis Drugs (2023 Update), the Tuberculosis Branch of the Chinese Medical Association developed this guideline using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach and the Reporting Items for Practice Guidelines in Healthcare (RIGHT) statement. Focusing on 13 commonly used anti-tuberculosis drugs, the guideline systematically evaluates evidence regarding off-label indications, dosing, treatment duration, routes of administration, target populations, and safety monitoring. Comprehensive literature searches were conducted from database inception through June 10, 2025, and a total of 25 recommendations were formulated. Major updates in this guideline address newly approved and repurposed drugs and all-oral shorter regimens, optimized dosing and alternative applications of established agents, treatment considerations for children and patients with extrapulmonary tuberculosis, local drug administration, drug-safety monitoring, and therapeutic drug monitoring (TDM). The guideline aims to provide practical, standardized, and evidence-based recommendations to support the rational and safe off-label use of anti-tuberculosis drugs in clinical practice.The 25 recommendations are summarized as follows.Recommendation 1: Off-label use of anti-tuberculosis drugs should be supported by adequate medical evidence and limited to situations in which no appropriate approved alternative is available. Appropriate review and informed consent are required (1, B).Recommendation 2: An individualized safety monitoring plan should be developed according to drug-specific toxicities, patient characteristics, concomitant medications, and potential drug-drug interactions (1, B).Recommendation 3: High-dose isoniazid may be considered for patients with low-level isoniazid resistance and as a component of selected shorter regimens for MDR/RR-TB when isoniazid is likely to retain activity (2, C).Recommendation 4: Isoniazid, 10-15 mg/kg once daily, may be used for MDR/RR-TB with low-level resistance and retained activity (2, B). In selected cases of severe or refractory TBM, or when CNS exposure is inadequate, higher isoniazid dosing may be used; for children/adolescents, 15-20 mg/kg once daily with pyridoxine, toxicity monitoring, and TDM as needed (2, C).Recommendation 5: Local isoniazid administration may be cautiously and individually considered in selected cases as an adjunct to standardized systemic therapy, following specialist evaluation and appropriate safety monitoring (2, D).Recommendation 6: Where available, TDM may be considered for patients receiving high-dose isoniazid or those with an inadequate response, suspected malabsorption, clinically important drug interactions, a high risk of hepatotoxicity, or altered pharmacokinetics. NAT2 genotype-inferred acetylator phenotype may support individualized dose adjustment together with TDM, efficacy, and safety assessments (2, B).Recommendation 7: Off-label rifampicin use includes a 3-month regimen of isoniazid and rifampicin (3HR) (1, B) or a 4-month regimen of rifampicin (4R) (2, B) for tuberculosis preventive treatment; individualized high-dose use in TBM or investigational use in drug-susceptible pulmonary tuberculosis (2, C); local administration as adjunct therapy only (2, D); and use during pregnancy, including early pregnancy, after individualized benefit-risk assessment (2, C).Recommendation 8: Based on pharmacokinetic and safety data from Chinese populations, the 3H2P2 regimen-isoniazid 500-600 mg, plus rifapentine, 450-600 mg, twice weekly for 3 months-is recommended for tuberculosis preventive treatment (1, B).Recommendation 9: Levofloxacin is a key drug for fluoroquinolone-susceptible MDR/RR-TB (1, B); it may also be used for rifampicin-susceptible, isoniazid-resistant TB (2, D) or as an individualized alternative when first-line drugs cannot be used (2, C).Recommendation 10: Levofloxacin may be used in children of any age with MDR/RR-TB, and when first-line drugs cannot be used, as an individualized alternative for drug-susceptible TB. Dosing should be adjusted according to age and body weight, accompanied by appropriate safety monitoring (2, B).Recommendation 11: Oral levofloxacin administered once daily for 6 months is recommended for eligible close contacts of patients with MDR/RR-TB after active TB has been excluded and fluoroquinolone susceptibility of the source case has been assessed (1, B).Recommendation 12: Moxifloxacin may be used in fluoroquinolone-susceptible MDR/RR-TB (1, B). In drug-resistant TBM, individualized use may be considered, but 800 mg/day should not be routinely used (2, D). ECG and electrolyte monitoring is recommended during prolonged or high-dose use or concomitant QT-prolonging therapy (1, C).Recommendation 13: Fluoroquinolone TDM may be considered during high-dose or prolonged treatment or when drug exposure is uncertain. Levofloxacin Cmax 8-12 mg/L and moxifloxacin Cmax 3-5 mg/L are empirical reference ranges rather than fixed targets (2, B).Recommendation 14: Off-label linezolid use includes MDR/RR-TB, including pre-XDR-TB and XDR-TB (1, B); drug-resistant or refractory tuberculous meningitis (2, D); and eligible non-severe extrapulmonary MDR/RR-TB (2, C). Adults typically receive 600 mg once daily; children receive age-and weight-based dosing, with duration determined by the regimen (1, C).Recommendation 15: During prolonged linezolid treatment, monitoring should be performed for myelosuppression, optic and peripheral neuropathy, and lactic acidosis. The dose should be reduced, treatment interrupted, or linezolid discontinued according to toxicity severity, and concomitant serotonergic medications should be avoided whenever possible (1, B).Recommendation 16: TDM should be considered during prolonged linezolid treatment, particularly in patients with an inadequate response, serious toxicity, organ dysfunction, extreme body weight, or clinically important drug interactions (2, B).Recommendation 17: Contezolid may be considered as an alternative for patients with MDR/RR-TB who cannot tolerate linezolid or are at high risk of linezolid toxicity due to baseline myelosuppression, neurologic disease, or other factors, when an oxazolidinone is required to construct an effective regimen (2, D).Recommendation 18: Off-label clofazimine use includes longer MDR/RR-TB regimens as a WHO group B drug and selected 6-and 9-month regimens: its duration should follow the complete regimen and fluoroquinolone susceptibility results (1, B).Recommendation 19: Patients receiving clofazimine should be counseled regarding discoloration of the skin, mucosa, and body fluids and they should be monitored for gastrointestinal toxicity and Fridericia-corrected QT interval (QTcF) prolongation (1, B).Recommendation 20: Bedaquiline is a core drug for MDR/RR-TB. Off-label use includes adult RR-TB (2, C), children of any age with MDR/RR-TB (2, D), treatment beyond 24 weeks (2, C), use during pregnancy after benefit-risk assessment (2, C), and extrapulmonary MDR/RR-TB (2, C).Recommendation 21: During bedaquiline treatment, monitoring should be performed for QTcF prolongation, hepatic dysfunction, and other adverse reactions. More frequent ECG monitoring is recommended for older patients, those with underlying heart disease or electrolyte abnormalities, and those receiving concurrent QT-prolonging medications (1, B).Recommendation 22: Off-label delamanid use includes adult RR-TB as part of an appropriate combination regimen (2, C), children of any age with MDR/RR-TB (2, D), treatment extending beyond 24 weeks (2, C), use during pregnancy after benefit-risk assessment (2, C), and extrapulmonary MDR/RR-TB (2, C). Monitoring of QTcF interval, electrolytes, and serum albumin is required; its use should be avoided if the baseline serum albumin is <28 g/L (1, B).Recommendation 23: Amikacin may be considered for selected MDR/RR-TB, retreatment TB, or TB requiring regimen modification due to drug intolerance, and for severe, refractory, or drug-resistant TBM during the intensive phase (2, C). Local administration may be used as adjunctive therapy in selected cases (2, D).Recommendation 24: Monitor renal function, urinalysis, and auditory/vestibular function during amikacin treatment. Adjust the dose or dosing interval for renal impairment. TDM is advised when available, particularly for high-risk or prolonged treatment, to support individualized dosing (1, B).Recommendation 25: Meropenem or imipenem/cilastatin, each combined with clavulanate, may be considered as a Group C option for MDR/RR-TB when Group A and B drugs cannot form an effective regimen (2, D). In drug-resistant, severe, or refractory TBM, individualized use may be considered only when other effective options are unavailable; meropenem is preferred for children and patients at high risk of seizures (2, D).

Background/Objectives: Micronutrient deficiencies are common in inflammatory bowel disease (IBD) and contribute to anemia, impaired wound healing, neurologic injury, and adverse disease outcomes. Major societies, including ESPEN, ACG, and ECCO, recommend nutritional and micronutrient assessment in patients with IBD, yet few studies describe how comprehensively these recommendations are applied during hospitalization. This study aimed to characterize inpatient testing practices for vitamins B1, B6, B12, and zinc in hospitalized IBD patients, quantify deficiency frequency among those tested, and identify gaps between guideline-recommended and actual micronutrient assessment. Methods: A retrospective chart review was performed on adults with Crohn's disease (CD) or ulcerative colitis (UC) hospitalized for an IBD flare at a tertiary care center. Demographics, comorbidities, and deficiency-associated clinical features were recorded. Yield was defined as the proportion of tested patients meeting institutional deficiency thresholds. Yield for each non-B12 micronutrient was compared with B12 as an internal benchmark. Results: Among 356 patients (285 CD, 71 UC), inpatient micronutrient testing was markedly imbalanced: B12 was tested in 97.2%, whereas B6, B1, and zinc were tested in only 34.8%, 30.6%, and 18.8%, respectively. Among those tested, deficiencies were common: B6 40.3%, zinc 32.8%, B1 22.9%, and B12 9.0%. Each non-B12 micronutrient yielded deficiency significantly more often per test than B12 (all p < 0.001), a testing-yield mismatch interpreted cautiously given selective testing of non-B12 nutrients. Deficiency frequencies did not differ significantly between CD and UC. Clinical contexts included tachycardia and edema (B1); elevated inflammatory markers and thromboembolism history (B6); anemia and neuropathy (B12); and diarrhea and hypoalbuminemia (zinc). Conclusions: Inpatient micronutrient assessment in IBD is heavily skewed toward B12, with B1, B6, and zinc under-tested despite a substantially higher yield of identified deficiency per test. This testing-yield mismatch represents a measurable implementation gap between guideline-recommended comprehensive assessment and actual inpatient practice; whether systematic panel-based assessment improves clinical outcomes warrants prospective evaluation.

Vitamin supplements are frequently utilized as adjunctive therapies in epilepsy care, yet the potential for toxic drug-nutrient interactions remains poorly defined. Using a pentylenetetrazol (PTZ) zebrafish seizure model, we conducted an exploratory screening of a multivitamin formulation containing vitamins B6, B9, D3, and E, together with CoQ10, in combination with common antiseizure medications (ASMs). This screening identified a severe, unexpected lethal interaction between pyridoxine (PN) and valproic acid (VPA). Co-exposure resulted in rapid, dose- and time-dependent mortality in both larval and adult zebrafish. Mechanistic investigations indicated that the calcium-dependent apoptosis, rather than necroptosis, contributes substantially to this toxicity. In vivo calcium imaging revealed marked cytosolic Ca[2+] accumulation, which was alleviated by calcium chelation and by pharmacological inhibition of endoplasmic reticulum Ca[2+] release through inositol 1,4,5-trisphosphate receptors and ryanodine receptors. PN/VPA co-exposure also caused pronounced cardiac dysfunction, characterized by reduced heart rate, ejection fraction, and cardiac output, together with apoptotic signals in cardiac tissue. Notably, no comparable cytotoxicity was observed in cultured zebrafish cardiomyocytes or mammalian cell lines, suggesting that organism-level or tissue-integrated factors may contribute to the observed toxicity. Supplemental pyridoxal 5'-phosphate (PLP) effectively rescued PN/VPA-induced mortality, supporting the possible involvement of altered vitamin B6/PLP-related cellular processes. Together, these results identify a previously unrecognized PN/VPA hazard and highlight the zebrafish as a sensitive in vivo platform for detecting complex drug-nutrient toxicities.

The effect of specific spacers added to the separation environment of capillary isotachophoresis in a hydrodynamically closed two-dimensional device hyphenated with tandem mass spectrometry is reported in this short communication. Combination of two spacers, here, 2-amino-2-hydroxymethyl-propane-1,3-diol and histidine, led to enhanced resolution of two model analytes (thiamine and pyridoxine) in model and real pharmaceutical samples (tablet drug dosage form). The addition of the spacers at relatively high concentration level (i.e., 20 µg/mL) caused no significant interference and suppression of the analytical signal in the mass spectrometry detection step. Eco-friendliness, practicality, and performance of the method were confirmed using the metric tools of the "White Analytical Chemistry." High repeatability of the separation process could broaden the application possibilities of the hydrodynamically closed capillary electrophoresis system.

Depression is a highly prevalent and serious mental disorder affecting populations worldwide. However, the traditional monoamine hypothesis does not fully account for its pathogenesis. In recent years, considerable attention has been directed toward the role of the NO-cGMP signaling pathway in the pathophysiology and treatment of depression.Nitric oxide (NO), a gaseous neurotransmitter, activates soluble guanylate cyclase (sGC), thereby increasing the level of the second messenger cyclic guanosine monophosphate (cGMP). In turn, this regulation modulates protein kinase G (PKG) and its downstream signaling cascades. This pathway has been implicated in synaptic plasticity, neurogenesis, and inflammatory responses.Substantial evidence indicates that abnormalities in the NO-cGMP pathway-observed both in patients with depression and in animal models-manifest as elevated NO levels, decreased cGMP content, and altered activities of related enzymes. These changes are thought to interact with multiple other signaling systems to jointly contribute to depressive pathophysiology.A variety of antidepressant drugs and natural products (e.g., vitamin C, pyridoxine, curcumin) have been shown to exert antidepressant effects through modulation of this pathway. Therapeutic strategies targeting this pathway-including NO donors, sGC activators, and phosphodiesterase (PDE) inhibitors-exhibit therapeutic potential.The present review comprehensively summarizes the molecular mechanisms of the NO-cGMP signaling pathway, its role in the pathogenesis of depression, and targeted treatment strategies, with the aim of providing a theoretical foundation for the development of novel antidepressants.

Rice, a global staple, often lacks essential nutrients due to milling, leading to micronutrient deficiencies or "hidden hunger." This study aimed to optimize the fortification of rice analogues with essential vitamins, focusing on nutrient retention during cooking. Using cold extrusion technology, rice analogues were produced from a mixture of rice flour, sodium alginate (1%), water (30%), and a nutrient ready mix (NRM) in varying proportions: low-dose (100%), intermediate-dose (125%), and High-dose (150%) of recommended levels. The fortification level was statistically optimized using Design Expert software, with high-dose fortification (150% NRM) yielding the highest cooking retention, achieving a desirability value of 0.961. Post-cooking, the fortified rice analogues retained significant levels of key vitamins, including vitamin A (4713.76 ± 64.65 µg RE/kg), thiamine (6.67 ± 0.01 mg/kg), riboflavin (84.03 ± 0.54 mg/kg), niacin (447.18 ± 0.01 mg/kg), pyridoxine (33.21 ± 1.12 mg/kg), and folic acid (4.52 ± 0.04 mg/kg). Retention rates varied across vitamins, with thiamine showing lowest retention (6.7-7.1% after extrusion and cooking), while riboflavin exhibited the highest stability (64.3-74.7% retention after extrusion and cooking) demonstrating its relative heat stability. Other vitamins showed intermediate retention rates: vitamin A (10.1-12.4%), niacin (28.6-36.7%), pyridoxine (15.5-22.1%) and folic acid (44.2-60.4%). By blending these fortified analogues with raw rice at a 1:50 ratio produced vitamin-fortified rice that meets nutritional standards. This optimized fortification process offers a viable solution to combat hidden hunger by enhancing the nutritional value of rice without altering traditional dietary habits.