Analysing the causal relationship between potentially protective and risk factors and cutaneous melanoma: A Mendelian randomization study.

BACKGROUND: Previous observational studies reported altered melanoma risks in relation to many potential factors, such as coffee intake, smoking habits and photodamage-related conditions. Considering the susceptibility of epidemiological studies to residual confounders, there remains uncertainty about the actual causal roles of these reported factors in melanoma aetiology. OBJECTIVES: This study aims to investigate the causal association between cutaneous melanoma (CM) and previously reported factors: coffee intake, alcohol consumption, lifetime smoking, socioeconomic status (SES), ease of skin tanning, childhood sunburn and facial ageing, providing insight into its underlying aetiology and preventative strategies. METHODS: We utilized a two-sample MR analysis on data from the largest meta-analysis summary statistics of confirmed cutaneous melanoma including 30,134 patients. Genetic instrumental variables were constructed by identifying single nucleotide polymorphisms (SNPs) that associate with corresponding factors. Inverse variance weighted (IVW) was the primary MR method. For sensitivity and heterogeneity, MR Egger, weighted median, simple mode, weighted mode and MR Egger intercept tests were examined. RESULTS: Cutaneous melanoma risks were found to be elevated in association with a predisposition towards ease of skin tanning (IVW: OR = 2.842, 95% CI 2.468-3.274, p < 0.001) and with childhood sunburn history (IVW: OR = 6.317, 95% CI 4.479-8.909, p < 0.001). Repeated MR after removing potential confounders and outliers demonstrated resolved horizontal pleiotropy and statistically significant results that closely mirrored the initial findings. Other potential factors, such as coffee intake, alcohol consumption, smoking and socioeconomic status (SES), indicated insignificant effects on melanoma risk in the analysis, and therefore, our Mendelian randomization study does not support their roles in modifying melanoma risks. CONCLUSIONS: Our extensive MR analysis provides strong evidence of the causative role of ease of skin tanning and childhood sunburn history in elevating melanoma risk. Curtailing ultraviolet radiation (UVR) exposure may be the single best preventative strategy to reduce melanoma risk.

Spinal Nrf2 translocation may inhibit neuronal NF-κB activation and alleviate allodynia in a rat model of bone cancer pain.

Bone cancer pain (BCP) is a clinical pathology that urgently needs to be solved, but research on the mechanism of BCP has so far achieved limited success. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) has been shown to be involved in pain, but its involvement in BCP and the specific mechanism have yet to be examined. This study aimed to test the hypothesis that BCP induces the transfer of Nrf2 from the cytoplasm to the nucleus and further promotes nuclear transcription to activate heme oxygenase-1 (HO-1) and inhibit the activation of nuclear factor-kappa B (NF-κB) signalling, ultimately regulating the neuroinflammatory response. Von-Frey was used for behavioural analysis in rats with BCP, whereas western blotting, real-time quantitative PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect molecular expression changes, and immunofluorescence was used to detect cellular localization. We demonstrated that BCP induced increased Nrf2 nuclear protein expression with decreased cytoplasmic protein expression in the spinal cord. Further increases in Nrf2 nuclear protein expression can alleviate hyperalgesia and activate HO-1 to inhibit the expression of NF-κB nuclear protein and inflammatory factors. Strikingly, intrathecal administration of the corresponding siRNA reversed the above effects. In addition, the results of double immune labelling revealed that Nrf2 and NF-κB were coexpressed in spinal cord neurons of rats with BCP. In summary, these findings suggest that the entry of Nrf2 into the nucleus promotes the expression of HO-1, inhibiting activation of the NF-κB signalling pathway, reducing neuroinflammation and ultimately exerting an anti-nociceptive effect.

Lumbar Sympathetic Nerve Modulation Using Absolute Ethanol for the Treatment of Primary Lower-Extremity Hyperhidrosis: A Dose-Effect Pilot Study.

BACKGROUND Primary lower-extremity hyperhidrosis (PLEH) can be treated by CT-guided lumbar sympathetic nerve modulation using absolute ethanol. However, doses of ethanol that are too high can cause nerve injury, and doses that are too low have suboptimal results. The present study aimed to investigate the dose-effect relationship of CT-guided lumbar sympathetic nerve modulation with absolute ethanol for PLEH. MATERIAL AND METHODS The study was conducted at the First Affiliated Hospital of Jiaxing University between 07/2014 and 02/2017. Twenty participants were enrolled in each group. The doses of absolute ethanol were 2.0 ml in the R1 group, 2.5 ml in the R2 group, 3.0 ml in the R3 group, 3.5 ml in the R4 group, and 4.0 ml in the R5 group. Treatment effectiveness was assessed according to the time to complete hyperhidrosis relief: <10 min, effective; ≥10 min, non-effective. RESULTS The patient characteristics among the 5 groups were not statistically different (P>0.05). The onset time and time to complete hyperhidrosis relief decreased significantly with increasing dose of absolute ethanol (P<0.05). The effective rates in the 5 groups were 15.0%, 35.0%, 60.0%, 90.0%, and 100.0%, respectively. The ED50 and ED95 were 2.306 ml (95% CI: 2.003-2.512 ml) and 3.343 ml (95% CI: 3.051-3.962 ml), respectively. CONCLUSIONS This was the first dose-effect pilot study of consecutive PLEH patients treated by CT-guided lumbar sympathetic nerve modulation. CT-guided lumbar sympathetic nerve modulation with 2.306 ml (ED50) and 3.343 ml (ED95) of absolute ethanol showed treatment efficacy for PLEH. No complications were seen.

Astrocyte activation in the periaqueductal gray promotes descending facilitation to cancer-induced bone pain through the JNK MAPK signaling pathway.

Descending nociceptive modulation from the supraspinal structures has an important role in cancer-induced bone pain (CIBP). Midbrain ventrolateral periaqueductal gray (vlPAG) is a critical component of descending nociceptive circuits; nevertheless, its precise cellular and molecular mechanisms involved in descending facilitation remain elusive. Our previous study has shown that the activation of p38 MAPK in vlPAG microglia is essential for the neuropathic pain sensitization. However, the existence of potential connection between astrocytes and c-Jun N-terminal kinase (JNK) pathway in CIBP has not yet been elucidated. The following study examines the involvement of astrocyte activation and upregulation of p-JNK in vlPAG, using a CIBP rat model. Briefly, CIBP was mimicked by an intramedullary injection of Walker 256 mammary gland carcinoma cells into the animal tibia. A significant increase in expression levels of astrocytes in the vlPAG of CIBP rats was observed. Furthermore, stereotaxic microinjection of the astrocytic cytotoxin L-α-aminoadipic acid decreased the mechanical allodynia as well as established and reversed the astrocyte activation in CIBP rats. A significant increase in expression levels of p-JNK in astrocytes in vlPAG of CIBP rats was also observed. Moreover, the intrathecal administration of JNK inhibitors SP600125 reduced the expression of glial fibrillary acidic protein, while microinjection of the SP600125 decreased the mechanical allodynia of CIBP rats. These results suggested that CIBP is associated with astrocyte activation in the vlPAG that probably participates in driving descending pain facilitation through the JNK MAPK signaling pathway. To sum up, these findings reveal a novel site of astrocytes modulation of CIBP.

Correlation Between Computed Tomography Features and Clinical Presentation and Management of Isolated Superior Mesenteric Artery Dissection.

OBJECTIVES: To examine the correlation between computed tomography (CT) features and clinical presentation and to assess the management strategy for patients with isolated superior mesenteric artery (SMA) dissection. MATERIAL AND METHODS: Retrospective analysis of clinical records and CT findings of patients with isolated superior mesenteric artery dissection treated between 2012 and 2016. The relationship between CT features and clinical symptoms and treatment options was studied. Follow up CT images were reviewed and telephone interviews were conducted with patients. RESULTS: Sixty-nine patients with isolated SMA dissection (47 symptomatic and 22 asymptomatic) were evaluated. The dissection length in patients with Sakamoto type IV lesions was significantly longer than that in patients with other lesion types (83.0 ± 40.1 mm, p = .001). Compared with the asymptomatic group, the symptomatic group had longer dissections (63.5 ± 35.9 mm, p < .001) and lesser true lumen diameter (3.1 ± 1.7 mm, p = .044). Fifty-six patients were treated conservatively, of whom 31 showed clinical improvement and exhibited no morphological change during long-term follow up. CONCLUSIONS: In patients with isolated SMA dissection, clinical symptoms were related to the length of dissection and degree of true lumen stenosis. Conservative treatment was commonly employed and yielded favourable outcomes.

Primary antifungal prophylaxis: decrease of invasive fungal disease incidence and reduction of risk factors in haematological patients in a 5-year retrospective study.

BACKGROUND: Invasive fungal disease (IFD) is a major cause of morbidity and mortality in patients with haematological malignancies. AIM: To evaluate the efficacy and rationality of primary antifungal prophylaxis (PAP) in a 5-year real-life setting and choose an appropriate PAP strategy. METHODS: Clinical data of patients were retrospectively reviewed and IFD was diagnosed using the revised diagnostic criteria. The efficacy of PAP and the risk factors for IFD, especially the rationality of PAP, were evaluated. RESULTS: Of the 1340 patients enrolled, 749 patients received PAP (55.9%), and IFD occurred in 157 patients: 51 (6.8%) in the PAP group and 106 (17.9%) in the non-PAP group (P = 0.000). The IFD-related mortality was 10.1 and 29.7% in the PAP group and non-PAP group (P = 0.000) respectively. PAP was an independent protective factor for IFD (odds ratio = 0.183, 95% confidence interval: 0.122-0.274, P = 0.000) and could reduce the effect of risk factors, such as allogeneic haemopoietic stem cell transplantation, prolonged neutropenia and corticosteroid. The IFD incidence was not significantly different among different PAP regimens and PAP start time subgroups, and it was lowest (4.2%) when PAP started after a short period of neutropenia (1-10 days). CONCLUSION: PAP is necessary and efficient to prevent IFD in haematological patients, and the real-life PAP strategy is reasonable. Different drugs can be chosen, and it is better to start PAP as soon as neutropenia begins.

Evaluation of the sacral nerve plexus in pelvic endometriosis by three-dimensional MR neurography.

PURPOSE: To investigate the feasibility of three-dimensional MR neurography (3D MRN) for the sacral plexus using sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) sequences, and to demonstrate structural abnormalities in the pelvic nerve of women with pelvic endometriosis. MATERIALS AND METHODS: Twenty patients with pelvic endometriosis and 20 healthy controls were examined by contrast-enhanced 3D short time inversion recovery T2-weighted imaging (CE 3D STIR T2WI) SPACE sequences on 3 Tesla MRI. Image quality and diagnostic confidence of the sequences in identifying abnormalities of the sacral plexus were analyzed and compared with conventional three-plane images of 2D turbo-spin echo T2-weighted images (2D TSE T2WI). The changes in the sacral plexus caused by endometrial lesions were evaluated. RESULTS: The sacral plexus was clearly revealed in both healthy controls and patients with endometriosis on 3D STIR SPACE images. A good agreement was reached in the evaluation of both imaging quality (Kappa value [κ] = 0.73-1.00) and diagnostic confidence (κ = 0.66-0.81) when compared between the two independent readers. Abnormalities caused by endometriosis were identified in 17 patients, unilaterally in 10 patients, and bilaterally in 7 patients. Nerve fiber abnormalities of lumbar 5 (L5) were detected in 11 patients, of sacral 1 (S1) in 14 patients and of sacral 2 (S2) in 9 patients. CONCLUSION: CE 3D STIR SPACE sequences demonstrate its significant capacity to investigate and map the sacral plexus, and reveal the compression and adhesion of the sacral plexus nerve as a result of ectopic lesions. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:1225-1231.

Glial activation in the periaqueductal gray promotes descending facilitation of neuropathic pain through the p38 MAPK signaling pathway.

The midbrain ventrolateral periaqueductal gray (VL-PAG) is a key component that mediates pain modulation. Although spinal cord glial cells appear to play an important role in chronic pain development, the precise mechanisms involving descending facilitation pathways from the PAG following nerve injury are poorly understood. This study shows that cellular events that occur during glial activation in the VL-PAG may promote descending facilitation from the PAG during neuropathic pain. Chronic constriction nerve injury (CCI) was induced by ligature construction of the sciatic nerve in male Sprague-Dawley rats. Behavioral responses to noxious mechanical (paw withdrawal threshold; PWT) and thermal (paw withdrawal latency; PWL) stimuli were evaluated. After CCI, immunohistochemical and Western blot analysis of microglia and astrocytes in the VL-PAG showed morphological and quantitative changes indicative of activation in microglia and astrocytes. Intra-VL-PAG injection of microglial or astrocytic inhibitors attenuated PWT and PWL at days 7 and 14, respectively, following CCI. We also evaluated the effects of intra-VL-PAG administration of the phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) inhibitor SB 203580 at day 7 after CCI. This treatment abolished microglial activation and produced a significant time-dependent attenuation of PWT and PWL. Western blot analysis showed localized expression of p-p38 in the VL-PAG after CCI. P-p38 was expressed in labeled microglia of the VL-PAG but was not present in astrocytes and neurons on day 7 after CCI. These results demonstrate that CCI-induced neuropathic pain is associated with glial activation in the VL-PAG, which likely participates in descending pain facilitation through the p38 MAPK signaling pathway.

Hematopoietic stem cell transplantation for treatment of patients with leukemia concomitant with active tuberculosis infection.

BACKGROUND: Currently, hematopoietic stem cell transplantation is still an essential treatment approach for leukemia. However, patients with leukemia often have weakened immune function, especially more seriously compromised cellular immune response, and appear to be at greater risk for tuberculosis infection during the transplantation process. We aimed to investigate the efficacy and safety of hematopoietic stem cell transplantation for the treatment of patients with leukemia accompanying active tuberculosis infection. MATERIAL/METHODS: We retrospectively analyzed records of 7 consecutive patients who were diagnosed with leukemia concomitant with active tuberculosis infection and who underwent hematopoietic stem cell transplantation in our hospital from January 2006 to December 2012. RESULTS: Among these 7 patients (4 males and 3 females; median age: 38 years; range: 30-46 years), the mean duration of anti-TB treatment before transplantation was 3 months (range: 2-4.5 months). All patients acquired engraftment, with an implantation rate of 100%. After transplantation, the mean duration of anti-TB treatment was 12 months. All patients had response after receiving anti-TB treatment. One patient died of leukemia relapse 6 months after the transplantation, but no tuberculosis infection-related death was reported. CONCLUSIONS: Patients with leukemia concomitant with active tuberculosis infection can be treated with hematopoietic stem cell transplantation if they receive an effective anti-TB treatment regimen. The anti-TB treatment regimen had no effect against hematopoietic stem cell transplantation and was well-tolerated. All post-transplanted patients experienced no relapse of tuberculosis during the immune-suppression period. The findings in the present investigation deserve further in-depth study.

3T magnetic resonance diffusion tensor imaging in chronic kidney disease.

OBJECTIVE: To investigate the relationship of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values with renal function on 3T diffusion tensor imaging (DTI) in chronic kidney disease. MATERIALS AND METHODS: Twenty healthy volunteers and 29 patients with CKD underwent DTI. The relationship among ADC, FA, and renal function was analyzed. RESULTS: Cortical and medullary ADC and FA values of patients with chronic kidney disease were lower than those of healthy volunteers (P = 0.000). Both the renal ADC and FA values correlated inversely with serum creatinine and blood urea nitrogen (P < 0.05). CONCLUSION: DTI is a feasible and non-invasive means to reflect the severity of renal function damaged.

[Effects of intrathecal injection P2Y12 receptor inhibitor on interleukin-1 beta and interleukin-6 in spinal cord of rat bone cancer pain model].

OBJECTIVE: To explore the roles of P2Y12 receptor (P2Y12R) in bone cancer pain by observing the changes of inflammatory cytokines (IL-1ß, IL-6) after intrathecal injection (i.t.) of P2Y12R antagonist MRS2395. METHODS: Thirty-two female SD rats were randomly divided into 4 groups (n = 8 each): sham group (group S), MRS2395 group (group M), cancer group (group A) and cancer + MRS2395 group (group MA).Groups S and M received an injection of 10 µl Hank's solution into left tibia medullar cavity while groups A and MA had an injection of Walker 256 mammary cancer cells (10 µl, 2×10(7) cells/ml) into the same place. At Day 9-12 post-inoculation, groups S and A received an injection of saline (0.9%, 15 µl, i.t.) while groups M and MA had MRS2395 (400 pmol/µl, 15 µl, i.t.). Intrathecal catheterization between L3 and L4 was performed immediately after inoculating tumor cells by inserting a small tube into vertebral space. Mechanical withdrawal thresholds were measured on left hind paws before and during 10-minute intervals after dosing. Spinal cords (L4-L6 segments) were removed for determining the expressions of IL-1ß and IL-6 by enzyme-linked immunosorbent assay (ELISA) at Day 12 after drug delivery. RESULTS: At 20 min post-injection, mechanical withdrawal thresholds of groups S, M, A and MA were (34.2 ± 5.8), (34.4 ± 5.7), (21.0 ± 2.0) and (25.4 ± 2.3) g respectively at Day 9 post-inoculation (F = 18.679, P < 0.01); mechanical withdrawal thresholds of group A obviously decreased versus groups S and M; mechanical withdrawal thresholds in group MA increased obviously versus group A. The expressions of IL-1ß in groups S, M, A and MA were (74.0 ± 18.6), (98.4 ± 17.3), (253.5 ± 66.4) and (146.3 ± 22.3) pg/ml at Day 12 post-inoculation (F = 18.221, P < 0.01); compared with groups S and M, the expression of IL-1ß in group A showed a significant up-regulation. Likewise, the expressions of IL-6 were (377.4 ± 65.8), (331.6 ± 67.9), (856.1 ± 53.4) and (596.1 ± 34.9) pg/ml (F = 70.880, P < 0.01) respectively in groups S, M, A and MA; compared with groups S and M, the expression of IL-6 increased obviously in group A. There were significant decreases of IL-1ß and IL-6 in group MA versus group A. CONCLUSIONS: An intrathecal injection of MRS2395 may alleviate hyperalgesia and inhibit the up-regulated expression of spinal cord inflammatory cytokines in bone cancer rats. And P2Y12 receptor may be involved in the formation of bone cancer pain through regulating the expressions of IL-1ß and IL-6.

Outcomes of the transformation of follicular lymphoma to diffuse large B-cell lymphoma in the rituximab era: A population-based study.

BACKGROUND: Histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL) is a common complication of follicular lymphoma (FL) and is usually associated with a dismal outcome. However, the survival rate of these patients has improved over the last 20 years with the introduction of rituximab. This study aimed to access the outcome of transformation to DLBCL (t-DLBCL) from FL in a retrospective series that began after the widespread use of rituximab use. In addition, we also compared survival between t-DLBCL and primary DLBCL (p-DLBCL) in the same timeframe. METHODS: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with primary FL and patients with p-DLBCL between 2000 and 2020. Patients who had a subsequent diagnosis of DLBCL at least 2 months after FL diagnosis were identified as t-DLBCL. RESULTS: Finally, we identified 50,332 FL and 95,933 p-DLBCL. With a median follow-up of 119 months, 1631 patients developed t-DLBCL. The median time from FL diagnosis to t-DLBCL was approximately 4 years. The post-transformation survival (PTS) rate at 5 years was 49.6%, with a median PTS of 56 months. Older age, advanced stage, and early transformation were associated with worse PTS. Furthermore, t-DLBCL receiving chemotherapy or combined modality as initial therapy before HT was also associated with worse PTS, while the result was inverse when taking the impact of initial management strategy at HT into account. Taking t-DLBCL and p-DLBCL as a whole, comparable survival was observed between p-DLBCL and t-DLBCL receiving radiation or watch-and-wait as initial therapy prior to HT. CONCLUSION: The outcome of t-DLBCL in the rituximab era was better than historical series before the rituximab era. Due to the good prognosis, we did not recommend autologous stem cell transplantation for t-DLBCL receiving watch-and-wait or radiation as initial therapy before HT.

Post-marketing safety concerns with abrocitinib: a real-world pharmacovigilance analysis of the FDA adverse event reporting system.

BACKGROUND: Abrocitinib was newly approved for treatment of moderate-to-severe atopic dermatitis. The present study was to assess abrocitinib-related adverse events (AEs) using the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed to quantify the signals of abrocitinib-related AEs. RESULTS: A total of 3,177,744 reports of AEs were collected from the FAERS database, of which 1370 reports were identified with abrocitinib as the primary suspect drug. Abrocitinib-induced adverse events (AEs) occurred across 27 system organ classes (SOCs). A total of 68 preferred terms (PTs) with significant disproportionality, meeting the criteria of all four algorithms simultaneously, were identified. Unexpected significant AEs, such as increased blood cholesterol, venous embolism, hypoacusis, cellulitis, and tuberculosis, might also occur. The median onset time for abrocitinib-associated AEs was 182 days (interquartile range [IQR] 47-527 days). CONCLUSIONS: The results of this study were consistent with clinical observations. Additionally, unexpected safety signals for abrocitinib were identified, which provided supportive information for the safety profile of abrocitinib. Prospective clinical studies are warranted to validate these findings.

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.

Large-Scale Proteome Profiling Identifies Biomarkers Associated with Suspected Neurosyphilis Diagnosis.

Neurosyphilis (NS) is a central nervous system (CNS) infection caused by Treponema pallidum (T. pallidum). NS can occur at any stage of syphilis and manifests as a broad spectrum of clinical symptoms. Often referred to as "the great imitator," NS can be easily overlooked or misdiagnosed due to the absence of standard diagnostic tests, potentially leading to severe and irreversible organ dysfunction. In this study, proteomic and machine learning model techniques are used to characterize 223 cerebrospinal fluid (CSF) samples to identify diagnostic markers of NS and provide insights into the underlying mechanisms of the associated inflammatory responses. Three biomarkers (SEMA7A, SERPINA3, and ITIH4) are validated as contributors to NS diagnosis through multicenter verification of an additional 115 CSF samples. We anticipate that the identified biomarkers will become effective tools for assisting in diagnosis of NS. Our insights into NS pathogenesis in brain tissue may inform therapeutic strategies and drug discoveries for NS patients.

A case report of acute myeloid leukemia after liver transplantation.

Acute myeloid leukemia (AML) is a rare complication observed after liver transplantation and only a handful of cases have been reported until now. We report a case of acute promyelocytic leukemia (APL) after liver transplantation in a 50-year-old man. The case presentation was postodontectomy bleeding with an associative abnormal coagulation test 85 months after liver transplantation. A routine blood test, bone marrow test, chromosome analysis and examination of PML/RARα chimeric gene confirmed the diagnosis of APL and disseminated intravascular coagulation (DIC). Induction chemotherapy with all-trans retinoic acid, arsenic trioxide and daunorubicin was given to this patient and complete remission was achieved. The patient was subjected to DA (daunorubicin combined with cytarabine) and MA (mitoxantrone combined with cytarabine) regimens after remission induction to consolidate the chemotherapy for two courses of treatment, and subsequently subjected to arsenous acid chemotherapy on a periodic basis. Twenty-two months into the follow-up, sustained bone marrow remission was observed with the adapted treatment regimen.

A Bibliometric Analysis of Melanoma Treated with Vaccinations Research from 2013 to 2023: A Comprehensive Review of the Literature.

BACKGROUNDS: Melanoma is a malignant tumor that originates from melanocytes and is known for its aggressive behavior and high metastatic potential. In recent years, vaccine therapy has emerged as a promising approach for the treatment of melanoma, offering targeted and individualized immunotherapy options. In this study, we conducted a bibliometric analysis to assess the global research trends and impact of publications related to melanoma and vaccine therapy. METHODS: We retrieved relevant literature from the Web of Science database from the past decade (2013-2023) using keywords such as "melanoma", "vaccine therapy", and "cancer vaccines". We used bibliometric indicators including publication trends, citation analysis, co-authorship analysis, and journal analysis to evaluate the research landscape of this field. RESULTS: After screening, a total of 493 publications were included in the analysis. We found that melanoma and vaccine therapy have gained significant attention in the field of cancer immunotherapy, as evidenced by the numerous research output and increasing citation impact. The United States, China, and their organizations are the leading countries/institutes in terms of publication output, and collaborative research networks are prominent in this field. Clinical trials evaluating the safety and efficacy of vaccination treatment in melanoma patients are the focus of research. CONCLUSIONS: This study provide valuable insights into the novel research landscape of vaccine treatment of melanoma, which could inform future research directions and facilitate knowledge exchange among researchers in this field.

Rapid characterization of the potential active metabolites of diacerein in rat plasma based on UHPLC-Q-exactive orbitrap mass spectrometry and molecular docking.

Diacerein, a competently semisynthetic diacetyl derivative of anthraquinone, is a nonsteroidal anti-inflammatory drug, which has been used for treating osteoarthritis and preventing vascular diseases. However, previous investigation indicated that diacerein metabolites and its metabolic pathway in vivo was still unclear. In this research, an effective method was established based on ultra-high-performance liquid chromatography coupled with Q-Exactive-Orbitrap mass spectrometer and molecular docking to screen and detect the potential active metabolites of diacerein in rat plasma after oral administration. The data acquisition and processing methods including Full MS-ddMS2 combined with parallel reaction monitoring mode, extracted ion chromatogram and diagnostic fragment ions were adopted to detect and identify more infinitesimal and unknown diacerein metabolites in vivo. As a result, a total of 32 metabolites were detected and identified in rat plasma according to retention times, accurate mass, diagnostic fragment ions, and relevant drug biotransformation knowledge, among 31 metabolites were firstly reported in this study. Then, the relevant reactions in vivo such as deacetylation, hydroxylation, methylation, sulfate conjugation, glucuronidation, and their composite reactions, were all detected. Ultimately, the results of molecular docking showed that the metabolites of diacerein might have good affinity with IL-1 receptor in vivo. Among them, the metabolites M21 and M1 have the strongest binding affinity with IL-1 receptors, and could be considered as potential active metabolites of diacerein, which have an efficient effect on exerting pharmacological effects of diacerein in vivo. In conclusion, the study of diacerein metabolites in rat plasma expanded our understanding about the metabolism of diacerein in vivo and provided the significant foundation for further drug efficacy studies.

Pre-oxygenation with high-flow oxygen through the nasopharyngeal airway compared to facemask on carbon dioxide clearance in emergency adults: a prospective randomized non-blinded clinical trial.

INTRODUCTION: Before tracheal intubation, it is essential to provide sufficient oxygen reserve for emergency patients with full stomachs. Recent studies have demonstrated that high-flow nasal oxygen (HFNO) effectively pre-oxygenates and prolongs apneic oxygenation during tracheal intubation. Despite its effectiveness, the use of HFNO remains controversial due to concerns regarding carbon dioxide clearance. The air leakage and unknown upper airway obstruction during HFNO therapy cause reduced oxygen flow above the vocal cords, possibly weaken the carbon dioxide clearance. METHODS: Patients requiring emergency surgery who had fasted < 8 h and not drunk < 2 h were randomly assigned to the high-flow group, who received 100% oxygen at 30-60 L/min through nasopharyngeal airway (NPA), or the mask group, who received 100% oxygen at 8 L/min. PaO2 and PaCO2 were measured immediately before pre-oxygenation (T0), anesthesia induction (T1), tracheal intubation (T2), and mechanical ventilation (T3). The gastric antrum's cross-sectional area (CSA) was measured using ultrasound technology at T0, T1, and T3. Details of complications, including hypoxemia, reflux, nasopharyngeal bleeding, postoperative pulmonary infection, postoperative nausea and vomiting (PONV), and postoperative nasopharyngeal pain, were recorded. The primary outcomes were PaCO2 measured at T1, T2, and T3. The secondary outcomes included PaO2 at T1, T2, and T3, CSA at T1 and T3, and complications happened during this trial. RESULTS: Pre-oxygenation was administered by high-flow oxygen through NPA (n = 58) or facemask (n = 57) to 115 patients. The mean (SD) PaCO2 was 32.3 (6.7) mmHg in the high-flow group and 34.6 (5.2) mmHg in the mask group (P = 0.045) at T1, 45.0 (5.5) mmHg and 49.4 (4.6) mmHg (P < 0.001) at T2, and 47.9 (5.1) mmHg and 52.9 (4.6) mmHg (P < 0.001) at T3, respectively. The median ([IQR] [range]) PaO2 in the high-flow and mask groups was 404.5 (329.1-458.1 [159.8-552.9]) mmHg and 358.9 (274.0-413.3 [129.0-539.1]) mmHg (P = 0.007) at T1, 343.0 (251.6-428.7 [73.9-522.1]) mmHg and 258.3 (162.5-347.5 [56.0-481.0]) mmHg (P < 0.001) at T2, and 333.5 (229.9-411.4 [60.5-492.4]) mmHg and 149.8 (87.0-246.6 [51.2-447.5]) mmHg (P < 0.001) at T3, respectively. The CSA in the high-flow and mask groups was 371.9 (287.4-557.9 [129.0-991.2]) mm2 and 386.8 (292.0-537.3 [88.3-1651.7]) mm2 at T1 (P = 0.920) and 452.6 (343.7-618.4 [161.6-988.1]) mm2 and 385.6 (306.3-562.0 [105.5-922.9]) mm2 at T3 (P = 0.173), respectively. The number (proportion) of complications in the high-flow and mask groups is shown below: hypoxemia: 1 (1.7%) vs. 9 (15.8%, P = 0.019); reflux: 0 (0%) vs. 0 (0%); nasopharyngeal bleeding: 1 (1.7%) vs. 0 (0%, P = 1.000); pulmonary infection: 4 (6.9%) vs. 3 (5.3%, P = 1.000); PONV: 4 (6.9%) vs. 4 (7.0%, P = 1.000), and nasopharyngeal pain: 0 (0%) vs. 0 (0%). CONCLUSIONS: Compared to facemasks, pre-oxygenation with high-flow oxygen through NPA offers improved carbon dioxide clearance and enhanced oxygenation prior to tracheal intubation in patients undergoing emergency surgery, while the risk of gastric inflation had not been ruled out. TRIAL REGISTRATION: This trial was registered prospectively at the Chinese Clinical Research Registry on 26/4/2022 (Registration number: ChiCTR2200059192).

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.