Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients.

The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing (NGS). Our findings showed that a TP_rate cut-off of 0.033 demonstrated superior diagnostic performance for syphilis, with a specificity of 92.3% and a sensitivity of 71.4% (AUROC = 0.92). This diagnosis model predicted that 20 out of 92 serofast patients had a persistent low-level infection. Based on these predictions, re-treatment was administered to these patients and its efficacy was evaluated. The results showed a statistically significant decrease in RPR titers in the prediction-positive group compared to the prediction-negative group after re-treatment (p < 0.05). These findings provide evidence for the existence of T. pallidum under serofast status and support the use of intensive treatment for serofast patients at higher risk in clinical practice.

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).

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.

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.

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.

[A Retrospective Study of Ph Negative Adolescent and Young Adults with Acute B Lymphoblastic Leukemia in Two Centers].

OBJECTIVE: To analyze the therapeutic efficacy of different consolidation therapies after induction remission on Ph negative adolescent and young adults with acute B lymphoblastic leukemia, and to explore the effect of different risk factors on prognosis. METHODS: The treatment and efficacy of 80 Ph negative B-ALL in patients of 16-39 years old in the Hematology Department of 301(65 cases) and 309(15 cases) hospital from 1999 to 2016 are retrospectively analyzed. The patients received combined induction chemotherapy of 4 or 5 chemotherapeutic drugs (VDCLP/ VDLP/ DOLP/ IOLP). After remission patients received consolidation protocols of 3-5 cycls, and then received allo-HSCT or haploidentical HSCT. The median follow-up time was 29 (6-153) months. RESULTS: HSCT was carried out after CR1. The 5-year OS and EFS of allo-HSCT group(n=29) was (73±16)% and (67±17)%, respectively, while those of haploidentical-HSCT group(n=20) were (53±22)% and (53±22)%, respectively, and those of pediatric-inspired protocols(n=31) was (63±17)% and (50±18)%, respectively. The difference between OS and EFS in 3 group was not statistically significant(P>0.05). The re-remission rate of recurrent patients was (50±23)%. On the one side, the cumulative incidence of TRM of pediatric-inspired protocol was better than that of HSCT (P<0.05). On the other side, the cummulative incidence of relapse (CIR) of pediatric-inspired protocol was poorer than that of HSCT, yet without significant difference (P>0.05). The median remission time of CR2 in patients was 14(2-36) months. Univariate and multivariate analysis were performed in 65 patients, and showed an abnormal result of CD13 or CD33 positive, CD22 negative, indicating a poor prognosis(P<0.05). CONCLUSION: In the adolescent and young adult patients with Ph- B-ALL treated by pediatric-inspired protocols, the survival time is similar with that in allo-HSCT group. However, more prospective clinical studies of random control test(RCT) should be carried out.

Adjunctive targeted contrast-enhanced ultrasonography for the work-up of Breast Imaging Reporting and Data System category 3 and 4 lesions.

INTRODUCTION: The assessment and management of Breast Imaging Reporting and Data System category 3 and 4 lesions (BI-RADS 3 and 4 lesions respectively) present numerous challenges for breast radiologists and physicians due to the ambiguity in the classification guidelines. Different imaging modalities have been investigated for their ability to provide additional aid in classification and management. The aim of this study was to evaluate the utility of targeted contrast-enhanced ultrasonography (CEUS) as an adjunctive modality to mammography plus conventional ultrasound (MG + US) in the decision of whether further diagnostic work-up is needed for BI-RADS 3 and 4 lesions. METHODS: A total of 37 MG + US-detected BI-RADS 3 lesions and 60 MG + US-detected BI-RADS 4 lesions were analysed by targeted CEUS and biopsied. The effectiveness of CEUS in distinguishing benign from malignant entities among the breast lesions was evaluated by using the histological results of biopsied samples as the gold standard. RESULTS: Two BI-RADS 3 and 14 BI-RADS 4 lesions were diagnosed as true-positive findings by targeted CEUS, with negative predictive values (NPVs) of 100% and 89.2% respectively. CONCLUSIONS: Owing to the high NPV of targeted CEUS, a negative diagnosis of MG + US-detected BI-RADS 3 lesions by targeted CEUS can be helpful in avoiding unnecessary biopsies. However, targeted CEUS cannot be used to exclude patients with BI-RADS 4 lesions from further diagnostic work-up.

[Clinic Outcome of Allogeneic Stem Cell Transplantation in 45 Patients with MDS].

OBJECTIVE: To investigate the clinical features and prognosis of patients with myelodysplastic syndrome (MDS) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 45 patients with MDS and transformed acute myeloid leukemia (tAML) who received allo-HSCT between January 2009 and December 2014 were enrolled in this study. The effects of different conditioning regimens, donor and chemotherapy before transplantation on the clinical outcome were analyzed retrospectively. RESULTS: The median follow-up time for these patients was 54.6 months (ranged from 1 to 72.1 months), the 4-year cumulative overall survival (OS) and disease-free survival (DFS) rates were 77.1% and 62.1%, respectively. In myeloblative conditioning group and reduced intensity conditioning group, the 3-year cumulative OS rate was 69% and 68.6% (HR = 1.0, P = 0.984), respectively, the 3-year cumulative relapse rate was 17.6% and 33.3% (HR = 3.389, P = 0.162). The 100-day cumulative rate of aGVHD (38.6%) in HLA-identical nonsibling group was similar to HLA identical sibling group (37%) (HR = 1.089, P = 0.885); meanwhile the similar 3-year commulative OS rate was achieved in the 2 groups (72.7% and 70%) (HR = 0.952, P = 0.942). Among 26 patients with RAEB-2 and t-AML, the 2-year cumulative OS were 66.7% and 58.3% (HR = 1.265, P = 0.750) and 2-year cumulative relapse rates were 20.0% and 12.5% (HR = 0.417, P = 0.477) in non-chemotherapy and CR post-chemotherapy subgroups. The 1-year cumulative OS rate was 53.5% and 84.8% in the group with or without aGVHD. The patients with aGVHD had higher transplantation related mortality (TRM) compared with patients without aGVHD (HR = 15.0, P =0.011). CONCLUSION: The reduced intensity conditioning doesn't reduce OS rate in patients with MDS, and elderly patients can benefit from it. The OS rate is similar between HLA-identical sibling and HLA-identical nonsibling allo-HSCT. The chemotherapy before transplantation cannot prolong the survival of MDS patients.

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.

[Secondary antifungal prophylaxis in hematological malignancy patients with previous invasive fungal disease].

Invasive fungal disease (IFD) causes a high morbidity and mortality in patients with hematological malignancies. Reactivation of IFD after chemotherapy or hematopoietic stem cell transplantation (HSCT) is very common and associated with poor prognosis. Secondary antifungal prophylaxis (SAP) is effective in preventing IFD recurrence. With effective SAP, a history of IFD is not an absolute contraindication to allogeneic HSCT or continuation of high-dose chemotherapy. In recent years, a variety of antifungal drugs such as voriconazole, itraconazole, AmB and caspofungin have been found to be effective for SAP. However, its management during granulocytopenia and immunosuppression remains challenging. This review summarizes the current status of SAP in patients with hematological malignancies.

Langerhans cell sarcoma arising from the root of tongue: a rare case.

Langerhans cell sarcoma (LCS), a rare malignant disease with markedly malignant cytological features and poor outcome, originates from Langerhans cells and most commonly affects the lymph nodes, skin, and bone. This paper presents the case of a 58-year-old female with LCS at the root of her tongue, with neither local recurrence nor distant metastasis observed during 47 months of follow up following radiotherapy for more than one month after complete tumor resection. Histological and immunophenotypic tests revealed that the malignant tumor cells were positive for S-100 protein, CD1a, and LCA, and partially positive for CD3ε. By contrast, the tumor cells were negative for langenin, CD30, HMB45, PCK, CK5/6, and P63. Their Ki-67proliferation index ranged from 30% to 40%. This neoplasm was diagnosed as LCS according to the classification of WHO2008. This work is the first report on LCS arising from the root of tongue. This rare case may serve as a reference for future clinical studies.

Treatment of uterine arteriovenous malformation by myometrial lesion resection combined with artery occlusion under laparoscopy: a case report and literature review.

Uterine arteriovenous malformation (AVM) is an uncommon, potentially life-threatening condition, and the primary therapeutic method is embolization. We describe a case of a 36-year-old woman with acquired uterine AVM accompanied by abnormal vaginal bleeding. The diagnosis was established by Doppler flow ultrasonography combined with magnetic resonance arteriography. Because this uterine AVM was extensive and multiple, uterine arterial embolization could not be considered. We therefore employed a combined method under laparoscopy, in which the uterine arteries were first occluded, then uterine myometrial lesions were resected and abnormal pelvic blood vessels were ablated. Finally, the uterus was reconstructed with an intact uterine cavity. Abnormal vaginal bleeding was successfully stopped after operation, but amenorrhea due to uterine adhesions occurred. This method is suitable for the treatment of uterine AVM with extensive and multiple lesions, but it should be chosen cautiously for women of reproductive age with AVM and fertility requirement.

[Influence of P2Y12 receptor inhibitor on pain threshold and spinal p38MAPK in rat bone cancer pain model].

OBJECTIVE: To investigate the role of P2Y12 receptor in rat bone cancer pain model and its influence on p38MAPK (Mitogen-activated protein kinase). METHOD: A total of forty female SD rats, weighting 200 - 250 g, were randomly divided into 5 groups (n = 8): normal group (group N), sham group (group S), vehicle group (group DA), cancer group (group A), and analgesia group (group MA). Rats in group N were untreated, rats in group S were injected with Hank's solution 10 µl into the left tibial metaphysis; rats in group DA, group A and group MA were injected with Walker 256 cancer cells (10 µl, 2×107 cells/ml) into the left tibial metaphysic to establish the model of bone cancer pain. Catheterization was simultaneously made in four groups between L3 and L4 vertebra except group N. Saline (0.9%, 15 µl) was injected in group S and group A, DMSO (5%, 15 µl) was injected in group DA, and MRS2395 (400 pmol/µl, 15 µl) was injected in group MA on day 9 to 12 post-inoculation. Mechanical withdrawal thresholds were measured on left hind paw before and every 10 min after intrathecal injection. Rats were euthanized after measuring mechanical withdrawal threshold at day 12 post-inoculation. L4-6 sections of spinal cord were collected to determine the expression of p-p38MAPK by immunohistochemistry and immunofluorescent. RESULT: Compared to that in group N (36.1 g ± 4.0 g) and group S (38.9 g ± 5.2 g), mechanical withdrawal thresholds in group MA (19.8 g ± 5.0 g) were decreased on day 9 post-inoculation (P < 0.01), and the expression of p-p38MAPK in spinal cord was increased on day 12 (P < 0.01). Compared to that in group DA (17.7 g ± 3.0 g) and group A (19.1 g ± 2.5 g), mechanical withdrawal threshold in group MA was obviously increased after intrathecal injection, peaked at (26.5 g ± 4.7 g) (P < 0.05); compared with group DA (number 43.4 ± 3.8, IOD 569 ± 27) and group A(number 45.0 ± 2.6, IOD 594 ± 22), the expression level of p-p38MAPK in spinal cord in group MA at day 12 was significantly decreased (number 20.9 ± 2.2, IOD 246 ± 25) (P < 0.01); Mechanical withdrawal threshold in group MA was still lower than group N and group S, while the expression of p-p38MAPK was higher than group N (number 9.9 ± 2.4, IOD 82 ± 28) and group S (number 10.9 ± 2.2, IOD 109 ± 25) (P < 0.01). Immunofluorescent showed that p-p38MAPK was colocalized with microglia in spinal dorsal horn, but not with neurons and astrocytes. CONCLUSIONS: These results demonstrate rat bone cancer pain could partially relieved after intrathecal injection of P2Y12 receptor inhibitor MRS2395 through inhibiting the phosphorylation of p38MAPK in spinal dorsal horn.

Antiallodynic effects of propentofylline Elicited by interrupting spinal glial function in a rat model of bone cancer pain.

The activation of microglia and astrocytes in the spinal cord is involved in the progress of cancer pain. Propentofylline (PPF), a glial modulating agent, alleviates pain hypersensitivity in neuropathic pain models. The present study investigated the potential roles of PPF in a preclinical rat model of bone caner pain established by inoculating Walker 256 cells into the left tibia. At day 9 postinoculation, single administration of PPF (10 µg/10 µl, i.t.) significantly but transiently suppressed mechanical allodynia induced by bone cancer. Repeated application of PPF (10 µg/10 µl, i.t., once daily from days 9 to 12) persistently relieved mechanical allodynia on the side ipsilateral to surgery. Immunohistochemistry and ELISA showed that microglia and astrocytes in the spinal cord were activated, and the production of glia-derived proinflammatory cytokines interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) markedly increased at day 12 postinoculation in the cancer group. Intrathecal injection of PPF (10 µg/10 µl) significantly inhibited the activation of spinal glial cells and the expression of proinflammatory cytokines. These results suggest that the glial modulating agent PPF has antiallodynic effects on bone cancer pain and has potential utility for clinical treatment of cancer pain.

Differential diagnosis of metastasis from non-metastatic lymph nodes in cervical cancers: pilot study of diffusion weighted imaging with background suppression at 3T magnetic resonance.

BACKGROUND: Diffusion weighted imaging with background suppression (DWIBS) is potentially useful in detecting metastatic lymph nodes. This study aimed to evaluate the efficacy of DWIBS at 3T magnetic resonance (MR) for diagnosing metastatic lymph nodes in cervical cancer. METHODS: This retrospective study included 25 patients with cervical cancer who underwent MR examination and were treated by hysterectomy and lymphadenectomy. The metastatic and non-metastatic lymph nodes were histologically proven by operation. Apparent diffusion coefficient (ADC) values, long-axis diameters, short-axis diameters, ratio of short- to long-axis diameters of all the identifiable lymph nodes were measured and compared. RESULTS: Twenty-five primary tumor lesions, 17 metastatic lymph nodes and 140 non-metastatic lymph nodes were pathologically confirmed in 25 cases with cervical cancer. The difference of ADC values between primary tumor lesions, metastatic and non-metastatic lymph nodes were statistically significant (F = 7.93, P = 0.001). There was no statistically significant difference between primary tumor lesions of cervical cancer and metastatic lymph nodes (t = -0.75, P = 0.456), and the difference between primary tumor lesions and non-metastatic lymph nodes was statistically significant (t = 4.68, P < 0.001). The ADC values, long-axis diameters, short-axis diameters, ratio of short- to long-axis diameters of metastatic and non-metastatic lymph nodes were (0.86 ± 0.36) × 10(-3) mm(2)/s vs. (1.12 ± 0.34) × 10(-3) mm(2)/s, (1.51 ± 0.41) cm vs. (1.19 ± 0.36) cm, (1.16 ± 0.35) cm vs. (0.77 ± 0.22) cm, 0.78 ± 0.17 vs. 0.68 ± 0.19 respectively, and statistically significant difference existed between two groups. CONCLUSIONS: DWIBS at 3T MR has the distinct advantages in detecting pelvic lymph nodes of cervical cancer. Quantitative measurement of ADC values could reflect the degree of restriction of diffusion of metastatic and non-metastatic lymph nodes. The combination of size and ADC value would be useful in the accurate diagnosis of metastatic lymph nodes.