Femtosecond Laser Assisted Chemical Ionization Mass Spectrometry: Toward Sub-ppq Detection Limits for Organic Molecules.

Ultrasensitive analysis of organic molecules is crucial for various fundamental research and applications. State-of-the-art techniques for this purpose can achieve detection limits of several hundred ppq (parts-per-quadrillion), while a higher sensitivity is pursued constantly. To achieve this goal, we develop femtosecond laser assisted chemical ionization for mass spectrometry. This technique combines the advantages of femtosecond laser ionization and chemical ionization, either of which enables subppt (parts-per-trillion) mass spectrometry analysis of organic molecules. The results demonstrate that the developed ionization technique, when employed in mass spectrometry, can surpass femtosecond laser ionization by more than 3 orders of magnitude in sensitivity, while still maintaining good versatility and the ability to work under ambient conditions. This work paves the way for subppq analysis of organic molecules in gas phase and even in ambient environments, which can open up new research fields for trace substance analysis in atmospheric environment, clinical diagnosis, biomedical studies, etc.

Diagnosing Tabes Dorsalis in HIV-Negative Patients: Clinical Features, Neuroimaging, and Laboratory Insights in the Modern Antibiotic Era.

Background: Tabes dorsalis is a late manifestation of neurosyphilis, characterized by progressive ataxia, lightning pains, loss of proprioception, and urinary incontinence. The absence of a definitive diagnostic standard and the non-specific clinical manifestations have led to a significant rate of misdiagnoses. Methods: Hospitalized patients with tabes dorsalis at Peking Union Medical College Hospital between January 2010 and December 2023 were reviewed. Results: A total of 13 patients were included, with 10 males and 3 females. The median age was 50 years (range, 34-64). The most frequent initial symptoms were limb numbness (30.8%) and lightning pains (30.8%). Eleven patients (84.6%) received misdiagnoses prior to the final diagnosis. The most frequently observed physical sign was positive Romberg's sign (84.6%). Notably, Argyll Robertson pupil was presented in 7 subjects (53.8%). Serological tests revealed positive rapid plasma regain (RPR) and Treponema pallidum particle agglutination (TPPA) for all patients. All CSF samples were TPPA-reactive. Intramedullary hyperintensity on T2-weighted imaging of spinal MRI was found in 5 patients (38.5%). All patients received anti-syphilitic treatment, with effective treatment recorded in five cases. Conclusion: This study underscores the importance of neurological symptoms and signs in diagnosing tabes dorsalis. Individuals with progressive ataxia and positive Romberg's sign should be closely monitored for potential neurosyphilis. Integrating clinical features, laboratory tests, and neuroimaging could reduce misdiagnosis and expedite the initiation of anti-syphilitic therapy.

Telomere length is associated with increased risk of cutaneous melanoma: a Mendelian randomization study.

RESULTS: The MR analysis using two TL GWAS datasets revealed strong and consistent evidence that long TL is causally associated with an increased risk of CM. The analysis of the Codd et al. dataset found that long TL significantly predicted an elevated risk of CM (IVW OR = 2.411, 95% CI 2.092-2.780, P = 8.05E-34). Similarly, the analysis of the Li et al. dataset yielded consistent positive results across all MR methods, providing further robustness to the causal relationship (IVW OR = 2.324, 95% CI 1.516-3.565, P = 1.11E-04). The study provides evidence for a causal association between TL and CM susceptibility, indicating that longer TL increases the risk of developing CM and providing insight into the unique telomere biology in melanoma pathogenesis. Telomere maintenance pathways may be a potential target for preventing and treating CM.

Topical calcineurin inhibitors as a double-edged sword in rosacea: A systematic review.

BACKGROUND: Rosacea is a chronic inflammatory disease mainly with skin or ocular manifestations. Topical calcineurin inhibitors, pimecrolimus and tacrolimus, can be used to treat rosacea. However, they can also induce rosacea-like eruptions. AIMS: This study systematically reviewed the double-edged sword effects of pimecrolimus and tacrolimus on rosacea. METHODS: Four databases were retrieved to search for articles on the effects of pimecrolimus and tacrolimus on rosacea, including Cochrane Library, Embase, PubMed, and Web of Science. Only English articles were included in the systematic review. Relevant data were collected, and the levels of evidence were evaluated. RESULTS: 28 articles published between 2001 and 2016 were included. 11 articles were about pimecrolimus as the treatment of rosacea, 4 articles were about the pimecrolimus-induced rosacea, 9 articles were about tacrolimus as the treatment of rosacea, and 4 articles were about tacrolimus-induced rosacea. Participants for each study ranged from 1 to 200. Several types of outcome measurements were used for these publications. CONCLUSIONS: Both pimecrolimus and tacrolimus might have double-edged sword effects on rosacea. Pimecrolimus and tacrolimus could be effective for rosacea. However, both of them could also induce rosacea. Larger, randomized, controlled studies on pimecrolimus and tacrolimus as the treatment of rosacea and studies on the mechanisms of pimecrolimus and tacrolimus in treating or inducing rosacea are needed. This systematic review emphasized the double-edged sword role of topical calcineurin inhibitors in rosacea, which may pave the way for future research.