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.

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.

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.

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).

Clinical and Laboratory Characteristics, Neuroimaging Alternations and Treatment Response of 25 HIV-Negative General Paresis Patients.

Purpose: General paresis is a common type of neurosyphilis featuring progressive cognitive deterioration. The lack of a golden standard of diagnosis and its nonspecific clinical manifestations resulted in a high rate of misdiagnoses. This study aims to investigate the clinical, laboratory and radiological presentations of general paresis and enrich its knowledge for timely diagnoses. Patients and methods: The study collected hospitalized patients admitted for general paresis from September 2002 to November 2022. Their socio-demographical and medical status, clinical presentations, cognitive assessments, laboratory and radiographical manifestations and treatment information were collected retrospectively. Results: A total of 20 males and 5 females were included. Patients' ages ranged from 30 to 66 years (average 50.3 years). The average and median time for diagnosing general paresis was 14.1 months and 10.0 months respectively. The most frequent initial symptom is memory deterioration (68.0%). Impaired calculative ability and memory deterioration were the most frequent cognitive anomalies, as found in 50% and 45.4% of subjects during examination. The mean and median scores of MoCA was 16.7 and 17 respectively. Serological tests revealed positive TPPA for all patients and a median RPR titer at 1:64 positive. All CSF samples with TPPA and FTA-ABS results reported positivity. The MRI manifestations of general paresis include patchy or speckled hyperintensities (70.8%) and cerebral atrophy (45.8%). The most common lesioned sites in MRI were the ventricular and paraventricular area (50.0%) and temporal lobes (45.8%). For treatment, penicillin-based anti-syphilitic plans were adopted in 17 patients (68.0%). Conclusion: The clinical features and radiological alternations of general paresis patients often exhibited diverse and nonspecific alternations. However, some specific clinical manifestations and auxiliary examinations can provide meaningful clues for the identification and differential diagnosis of this disease.

A Neglected Narrative in the COVID-19 Pandemic: Epidemiological and Clinical Impacts of the COVID-19 Outbreak on Syphilis.

The COVID-19 pandemic has profoundly changed our lives. While healthcare resources were redistributed and mobilized to focus on dealing with the COVID-19 crisis, there have been unmet medical needs of patients with other diseases such as syphilis, weaving an integral but neglected component of the pandemic story. In different countries, the epidemiology of newly reported syphilis underwent diverse changes during the COVID-19 pandemic. Asymptomatic cases experienced the largest decline in number. From the perspective of transmission, on one hand, the implementation of lockdown measures led to a higher degree of abstinence and sex distancing in many countries, thereby reducing the transmission of syphilis. On the other hand, vertical transmission was reported to have increased significantly during COVID-19. Meanwhile, the volume of STI clinic capacity declined, and STI staff were redeployed to facilitate the contact tracing of COVID-19. As a result, many STI centers converted traditional in-person clinical services to telemedicine and self-testing. However, syphilis testing and clinical treatment cannot fully adapt to this conversion. In syphilis diagnosis, COVID-19 infection and vaccination were reported to cause false positivity in syphilis serological tests. Diverse cutaneous manifestations of COVID-19 could resemble the skin lesions in syphilis patients, requiring differential diagnosis from clinicians. As for the post-pandemic years, consequent to service interruptions and diagnosis delays, a surge in the number of confirmed cases of syphilis is expected. The COVID-19 pandemic has also been a meaningful lesson for the control and prevention of infectious diseases. The experience in combating COVID-19 has underscored the importance of maintaining a robust and well-supported medical system for the provision of sexual health services and better healthcare equality even during eras of crisis, not least for syphilis patients.

Assessing the quality of care for skin malignant melanoma on a global, regional, and national scale: a systematic analysis of the global burden of disease study from 1990 to 2019.

Malignant melanoma (MM) is a highly aggressive form of skin cancer with increasing global incidence rates, particularly in developed countries. Variations in the prevalence and quality of care provided to patients with melanoma exist across different regions and across different sex and age. Assessing the global burden of melanoma and evaluating the quality of care can provide valuable insights for developing targeted interventions in certain underperforming regions and improving patient outcomes. This study aimed to systematically analyze the Global Burden of Disease Study from 1990 to 2019 to assess the quality of care for skin malignant melanoma on a global scale. We conducted a comprehensive literature review and extracted data on melanoma incidence, mortality, and disability-adjusted life years (DALYs) from the Global Burden of Disease Study. We incorporated these variables using principal component analysis (PCA) to form an informative single variable of quality of care index (QCI) and analyzed its spatial-temporal variations as well as disparities across age, sex and socio-demographic index (SDI). The overall Quality of Care Index (QCI) for melanoma improved from 82.81 in 1990 to 91.29 in 2019. The QCI score showed a positive correlation with socioeconomic status across regions. Australia ranked highest in QCI (99.96), while Central African Republic, and Kiribati had the lowest scores. China and Saudi Arabia showed significant QCI improvement, while the QCI of the Democratic People's Republic of Korea, Zimbabwe, and Guam decreased from 1990 to 2019. The highest QCI scores were observed in the age groups of 20-39 years old (93.40-94.65). Gender disparities narrowed globally in these three decades, but lower Socio-demographic Index (SDI) regions showed increased gender inequities. Our findings highlighted the spatial-temporal variations in the quality of care of MM as well as its disparities across different SDI levels, age groups and sex. These findings offer valuable insights and guidance for implementing focused interventions and resource allocation to enhance the quality of care and overall outcomes for MM worldwide, especially for underperforming regions.

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.

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.

Screening and characterization estrogen receptor ligands from Arnebia euchroma (Royle) Johnst. via affinity ultrafiltration LC-MS and molecular docking.

Arnebiae Radix (dried root of Arnebia euchroma (Royle) Johnst.) is a traditional Chinese medicine (TCM) used to treat macular eruptions, measles, sore throat, carbuncles, burns, skin ulcers, and inflammations. The Arnebiae Radix extract can exert anti-breast cancer effects through various mechanisms of action. This study aimed to rapidly screen potential estrogen receptor (estrogen receptor α and estrogen receptor ß) ligands from the Arnebiae Radix extract. In this study, an analytical method based on affinity ultrafiltration coupled with UHPLC-Q-Exactive Orbitrap mass spectrometry was established for rapidly screening and identifying estrogen receptor ligands. Then, bindings of the components to the active site of estrogen receptor (estrogen receptor α and estrogen receptor ß) were investigated via molecular docking. Moreover, surface plasmon resonance (SPR) experiments with six compounds were performed to verify the affinity. As a result, a total of 21 ligands were screened from Arnebiae Radix using affinity ultrafiltration. Among them, 14 and 10 compounds from Arnebiae Radix showed affinity with estrogen receptor α and estrogen receptor ß, respectively. All of those ligands could have a good affinity for the multiple amino acid residues of the estrogen receptor based on molecular docking. In addition, six compounds display the great affinity by SPR. The method established in the study could be used to rapidly screen estrogen receptor ligands in Traditional Chinese medicine. The results demonstrated that the affinity ultrafiltration-UHPLC-Q-Exactive Orbitrap mass spectrometry method not only aids in the interpretation of the potential bioactive components and possible mechanisms of action of Arnebiae Radix but also provides a further effective basis for the quality control of this valuable herb medicine.

Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) A.C. Sm. by UHPLC-Q-Exactive Orbitrap Mass spectrometry and assessment of their antioxidant and anti-inflammatory activities.

Kadsua coccinea (K. coccinea) has long been used as a fruit and folk medicine; however, the composition of its leaves and the activities of its constituents have been seldom studied. A total of 98 chemical constituents, including 53 phenolic acids, 41 flavonoids, and 4 lignans, were identified from the plant of kadsua coccinea by UHPLC-Q-Exactive Orbitrap Mass spectrometry. All these chemicals were reported for the first time in leaves, and 95 of them have been reported for the first time in the plant of kadsua coccinea. The biological potential of extracts of K. coccinea leaves (EKL) was evaluated by in vitro antioxidant assay and anti-inflammatory assay. EKL are composed of polysaccharides (60%), polyphenols (26%), and proteins (11%). EKL present decent potent •OH and DPPH scavenging abilities and Fe2+ chelating ability. They also inhibit the secretion of NO, reduce the level of Cox2 in proteins, inhibit the secretion of pro-inflammatory cytokines, such as IL-2 and IL-6, and promote the secretion of anti-inflammatory cytokine IL-10. These results displayed significant antioxidant and anti-inflammatory activities of EKL, which will be very beneficial for further development and investigation of kadsua coccinea leaves.

Rapid Characterization and Action Mechanism of the Antidiabetic Effect of Diospyros lotus L Using UHPLC-Q-Exactive Orbitrap MS and Network Pharmacology.

Diospyros lotus L, F. Ebenaceae, is an edible fruit that is widely distributed in China and other Asian countries. Presently, Diospyros lotus L can be used to treat patients with diabetes; however, its chemical composition and pharmacological profiles remain to be elucidated. This study investigated the potential bioactive compounds of Diospyros lotus L and their mechanisms of action using LC-MS and network pharmacology analysis. First, the components of Diospyros lotus L were identify using a reliable strategy for UHPLC-Q-Exactive Orbitrap mass spectrometry combined with parallel reaction monitoring (PRM) in the negative ion mode. Second, a network pharmacology study, including target gene prediction and functional enrichment, was applied to screen the main quality markers of Diospyros lotus L and explore its potential mechanism for the treatment of diabetes. The results showed that a total of 159 compounds were identified from Diospyros lotus L, among which, 140 were reported for the first time. Furthermore, 40 active components, such as quercetin, luteolin, and kaempferol, were proposed as active components of Diospyros lotus L for the treatment of diabetes based on network pharmacology analysis. In addition, 92 relevant antidiabetic targets were mainly related to positive regulation of transcription from the RNA polymerase II promoter, extracellular space, and protein binding, suggesting the involvement of TNF, PI3K-Akt, and HIF-1 signaling pathways in the antidiabetic effect of Diospyros lotus L. Our results may provide a useful approach to identify potential active components and molecular mechanisms of Diospyros lotus L for the treatment of diabetes.

Anti-cancer Research on Arnebiae radix-derived Naphthoquinone in Recent Five Years.

BACKGROUND: In recent years, many naphthoquinone compounds with anticancer activity have been identified in Arnebiae Radix, and some of them have the potential to be developed into anticancer drugs. OBJECTIVE: This article aimed to provide a comprehensive overview of the anticancer effects of naphthoquinone compounds through a detailed review of literature and Chinese patents, and discuss their potential to be developed as anticancer drugs for clinical application. METHODS: Research papers were collected through the databases of PubMed, Cnki and SciDirect using keyword searches "naphthoquinone compounds" and "anticancer". The keywords of "shikonin" and "shikonin derivatives" were also used in PubMed, Cnki and SciDirect databases to collect research articles. The Chinese patents were collected using the Cnki patent database. RESULTS: Naphthoquinone compounds have been found to possess anti-cancer activity, and their modes of action are associated with inducing apoptosis, inhibiting cancer cell proliferation, promoting autophagy in cancer cells, anti-cancer angiogenesis and inhibition of cell adhesion, invasion and metastasis, inhibiting glycolysis and inhibiting DNA topoisomerase activity. CONCLUSION: Most of the naphthoquinone compounds show effective anti-cancer activity in vitro. The structure modification of naphthoquinone aims to develop anti-cancer drugs with high efficacy and low toxicity.

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.

Proteomic profiling reveals Arl6ip-1 as a candidate target in cancer-induced bone pain rat model after oxycodone treatment.

Treatment of cancer-induced bone pain (CIBP) is challenging in clinics. Oxycodone is used to treat CIBP. However, the lack of understanding of the mechanism of CIBP limits the application of oxycodone. In this study, proteomic profiling of oxycodone-treated spinal dorsal cord of rats with CIBP was performed. Briefly, a total of 3519 proteins were identified in the Sham group; 3505 proteins in the CIBP group; and 3530 proteins in the CIBP-OXY treatment group. The 2-fold cut-off value was used as the differential protein standard for abundance reduction or increase (p < 0.05). Significant differences were found in the abundance of 16 proteins between Sham and CIBP group; 11 proteins in the CIBP group had increased abundance while 5 proteins had reduced abundance. Furthermore, fifteen proteins with differential abundance were identified between the CIBP group and the OXY group. Compared with the CIBP group, there were six increased abundances and nine reduced abundances in the OXY group. In addition, a reduced expression of ADP-ribosylation factor-like 6 binding factor 1 (Arl6ip-1), an endoplasmic reticulum protein that has an important role in cell conduction and material transport, was found in the CIBP group compared with the Sham group. Its expression increased after the administration of OXY. Proteomics results were further verified by Western-blot. Fluorescent staining revealed that Arl6ip-1 co-localized with spinal dorsal horn neurons, but not with astrocytes or microglia. Based on the observed results, we believe that Arl6ip-1 may be a potential drug target for OXY treatment of CIBP rats.

Predisposing factors for predicting the therapeutic response of adenomyosis after uterine artery embolization: serum CA125 levels and accompanying endometriosis.

PURPOSE: We aimed to identify predisposing factors that could help predict the therapeutic response of adenomyosis after uterine artery embolization (UAE). METHODS: This was a retrospective, single-center study of patients admitted to the hospital for adenomyosis between 2013 and 2015. Sixty-eight patients with adenomyosis who underwent UAE with tris-acryl gelatin microspheres were divided into two groups based on their therapeutic response (complete or incomplete necrosis of lesions), and pre- and postprocedural pelvic magnetic resonance imaging (MRI) data. Patients were followed up for 12 months after UAE. Improvements in dysmenorrhea and menorrhagia were evaluated based on the symptom relief criteria. Improvement rates in both groups were analyzed and compared. Multivariate logistic regression analysis was used to identify the predisposing factors from retrospectively gathered baseline data that might affect the therapeutic response, including MRI features, clinical symptoms, biochemical index, and accompanying diseases of adenomyosis. Then, a prognostic model was established, and the receiver operating characteristic (ROC) curve of identified factors was drawn to determine their predictive value. RESULTS: Following UAE, 46 patients (67.6%) showed complete necrosis, while 22 patients (32.4%) showed incomplete necrosis. At 12-month follow-up, dysmenorrhea symptom improvement was seen in 94.7% of complete necrosis and 50% of incomplete necrosis group (P < 0.001); menorrhagia symptom improvement was seen in 96.2% of complete necrosis and 57.1% of incomplete necrosis groups (P = 0.004). Multivariate logistic regression analysis determined serum cancer antigen 125 (CA125) levels (odds ratio [OR], 1.006; 95% confidence interval [CI], 1.002-1.010; P = 0.005) and accompanying endometriosis (OR, 6.869; 95% CI, 1.881-25.016; P = 0.004) as predisposing factors. The areas under the ROC curve of CA125, endometriosis, and these two indicators combined were 0.785, 0.708, and 0.845, which corresponded to sensitivities of 95.5%, 66.7%, and 68.2% and specificities of 52.2%, 80.0%, and 87.0% at optimal cutoff values, respectively. CONCLUSION: Symptom relief of dysmenorrhea and menorrhagia for patients with complete necrosis was significantly better than that for patients with incomplete necrosis. Serum CA125 levels and accompanying endometriosis can effectively distinguish complete necrosis from incomplete necrosis.