Intrathecal liproxstatin-1 delivery inhibits ferroptosis and attenuates mechanical and thermal hypersensitivities in rats with complete Freund's adjuvant-induced inflammatory pain.

Previous studies have confirmed the relationship between iron-dependent ferroptosis and a peripheral nerve injury-induced neuropathic pain model. However, the role of ferroptosis in inflammatory pain remains inconclusive. Therefore, we aimed to explore whether ferroptosis in the spinal cord and dorsal root ganglion contributes to complete Freund's adjuvant (CFA)-induced painful behaviors in rats. Our results revealed that various biochemical and morphological changes were associated with ferroptosis in the spinal cord and dorsal root ganglion tissues of CFA rats. These changes included iron overload, enhanced lipid peroxidation, disorders of anti-acyl-coenzyme A synthetase long-chain family member 4 and glutathione peroxidase 4 levels, and abnormal morphological changes in mitochondria. Intrathecal treatment of liproxstatin-1 (a ferroptosis inhibitor) reversed these ferroptosis-related changes and alleviated mechanical and thermal hypersensitivities in CFA rats. Our study demonstrated the occurrence of ferroptosis in the spinal cord and dorsal root ganglion tissues in a rodent model of inflammatory pain and indicated that intrathecal administration of ferroptosis inhibitors, such as liproxstatin-1, is a potential therapeutic strategy for treating inflammatory pain.

Systemic immune inflammatory index is an independent predictor for the requirement of decompressive craniectomy in large artery occlusion acute ischemic stroke patients after mechanical thrombectomy.

Background and purpose: Following mechanical thrombectomy (MT), patients with large artery occlusive acute ischemic stroke (LAO-AIS) often have cerebral herniation due to its complications, resulting in poor prognosis. Decompressive craniectomy (DC) can markedly improve patient prognosis. This study aimed to verify the predictive value of clinical parameters such as the systemic immune-inflammatory index (SII) for DC in patients with LAO-AIS after MT. Methods: Clinical data of a total of 173 patients with LAO-AIS treated with MT between January 2020 and January 2022 were retrospectively analyzed. Patients receiving DC were grouped into an experimental group or a control group (no DC). The patients were randomly divided into the training set (n = 126, 75%) and validation set (n = 43, 25%). Multivariate logistic regression was used to construct a nomogram predictive model. Results: The SII value in the experimental group (median: 2851.1×109/L) was significantly higher than that in the control group (median: 1898.6 × 109/L) (P = 0.019). Receiver operating characteristic (ROC) analyses showed that the best cutoff value of the SII was 2505.7 × 109/L with a sensitivity of 55%, a specificity of 75.8%, and an area under the curve (AUC) of 0.649. Multivariate logistic regression indicated that the SII was an independent predictor for performing DC in patients with LAO-AIS after MT (OR = 3.579, 95% CI = 1.360-9.422, P = 0.01). The AUC was 0.728 in the training set and 0.583 in the validation set. The average error of the calibration curve was 0.032 in the training set and 0.023 in the validation set. The average error was relatively small and consistent in the training set and validation set. The C-index of the nomogram was 0.804 suggesting good accuracy. Conclusions: The SII at admission is an independent predictor for the requirement of DC in patients with LAO-AIS after MT. The SII-based nomogram helps doctors make decisions on whether DC is needed timely and rationally, and thereby may improve the prognosis of these patients.

Feasibility and effectiveness of unintended pregnancy prevention with low-dose mifepristone combined with misoprostol before expected menstruation.

STUDY QUESTION: What is the efficacy of maintaining or restoring non-pregnant status with low-dose mifepristone combined with misoprostol administered before expected menstruation? SUMMARY ANSWER: Low-dose mifepristone and misoprostol administered at the time of expected menstruation was effective and safe in maintaining or restoring non-pregnant status, with no obvious menstrual disturbance. WHAT IS KNOWN ALREADY: Menstrual regulation involves the medical or mechanical stimulation of uterine sloughing in women with up to 2-3 weeks of menstrual delay. Low-dose mifepristone plus misoprostol is efficacious for termination of ultra-early pregnancy (≤ 35 days of amenorrhoea) with no obvious menstrual disturbance. STUDY DESIGN, SIZE, DURATION: A total of 678 women fulfilled all criteria and were recruited. Seventeen women dropped out after deciding to remain pregnant and 11 others were lost to follow-up. Thus, data from 650 women who completed the procedure were included in analyses. Participants were enrolled at any time during their menstrual cycle and administered medication 1 day before expected menstruation. The end of the study was defined on a per-patient basis as the date of completion of the post-treatment menstrual cycle. The primary outcome was the efficacy of abortion induction (for pregnant women) or menstrual regulation (for non-pregnant women). PARTICIPANTS, SETTING, METHODS: Women with regular menstrual cycles (25-35 days) were voluntarily recruited for this study between February 2012 and December 2014. Serum ß-hCG was measured before mifepristone intake. Mifepristone (50 mg) was administered orally 1 day before expected menstruation and 200 µg misoprostol was administered orally on the day of expected menstruation. Efficacy, disturbance in bleeding patterns in the treatment and post-treatment cycles, satisfaction with the treatment, and subsequent contraception preference were analysed. MAIN RESULTS AND THE ROLE OF CHANCE: Retrospective analysis of serum ß-hCG levels at admission indicated that 23.3% (158/678) of the women were pregnant. The success rate for pregnancy termination was 98.6% (136/138). Two women (1.5%, 2/138) had ongoing pregnancy that was subsequently terminated surgically. The overall bleeding induction rate within 7 days was 98.3% (639/650), with 100% (138/138) in pregnant participants and 97.9% (501/512) in non-pregnant participants. Most pregnant and non-pregnant participants experienced no significant menstrual disturbance during the treatment [96.3% (131/136) versus 97.6% (489/501)] or post-treatment [97.8% (133/136) versus 98.4% (493/501)] menstrual cycle. The general rate of satisfaction with the treatment was 96.7% (618/639). Generally, 36.0% (230/639) of participants preferred to use the regimen as a routine contraception method versus the 64.0% (409/639) who preferred to use it as a remedy for pregnancy prevention after unprotected sex (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: Study participants were recruited from a single region; further studies should include participants from multiple centres in different cities and nations. Given the uncertain efficacy of regimen reuse, the assessment of efficacy was based solely on the first treatment administration. Studies with larger samples and long-term follow-up may provide more data on whether repeated use of this regimen hampers its efficacy. WIDER IMPLICATIONS OF THE FINDINGS: Menstrual regulation with low-dose mifepristone and misoprostol at expected menstruation can be efficacious and highly acceptable to maintain or restore non-pregnant status, which may have potential for routine contraception.

"Old" metal oxide affinity chromatography as "novel" strategy for specific capture of cis-diol-containing compounds.

The metal oxide affinity chromatography (MOAC) materials have been extensively used for extraction of phosphate compounds in the past decade. Actually, some of these materials also possess adsorption affinity towards cis-diol-containing compounds, which was seldom explored in separation field so far. Here we present the proof-of-concept study to evaluate the feasibility of expanding MOAC for specific capture of cis-diol biomolecules. Benefitting from the high commercialisation of the metal oxide materials, such MOAC strategy possesses several advantages, like synthesis-free, low cost and high expandability. Firstly, the recognition of adenosine against 2'-deoxyadenosine was performed using zirconium oxide and cerium oxide, two typical commercial MOAC materials. The results showed that efficient adsorption and elution could be achieved easily by pH switching from basic to acidic. The isotherm curves demonstrated the adsorption process fitted well with Freundlich isotherm model and was spontaneous at room temperature (ΔG(0)<0) with an exothermic nature (ΔH(0)<0). Afterwards, the highly efficient and selective enrichment of various model cis-diol biomolecules, including ribonucleosides, glycopeptides and glycoproteins, was achieved using this MOAC strategy. Finally, the endogenous ribonucleosides and modified ribonucleosides were successfully purified from human urine sample, which demonstrated the potential application of MOAC materials in the enrichment of target compounds from complex biological samples. Besides the excellent performance of extraction for cis-diol-containing compounds, equally important is that these materials are commercially available with low cost, which makes the MOAC a promising strategy for the study of cis-diol biomolecules in metabolomics and proteomics.