Explore the vast range of titles available.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by hyperinflammation and organ failure, with a high mortality rate. Current first-line treatments for adult patients have limited efficacy and significant toxicity. The novel selective histone deacetylase inhibitor (HDACi), chidamide, has shown promise in preclinical studies for the potential treatment of HLH. An open-label, single-center study was conducted to evaluate the efficacy and safety of chidamide in combination with etoposide and glucocorticoids for the treatment of HLH in adult patients. Seventeen patients who fulfilled at least five of the eight HLH-2004 criteria were enrolled and treated with the combination therapy. The primary outcome was overall response rate (ORR), and secondary outcomes included survival, safety and tolerability, and changes in laboratory indicators. A total of 17 HLH patients who met the inclusion criteria were enrolled in this study, with a male to female ratio of 1.8:1. The age range at enrollment was 31 to 71 years old, with a median age of 52 years old. The ORR was 76.5% (13/17 patients), with a complete response (CR) rate of 17.6% (3/17 patients) and a partial response (PR) rate of 58.8% (10/17 patients). The median overall survival (OS) was not achieved, with OS at 6 months and 12 months being 81% and 65%, respectively. The median progression free survival (PFS) was not achieved, with PFS at 6 months and 12 months being 68% and 55%, respectively. Hematologic toxicities is the most common. Safety profile was favorable, with very few cases of grade 3/4 toxicities observed. The results showed that the levels of sCD25, platelets, aspartate aminotransferase, lactate dehydrogenase, and albumin in these patients were significantly improved 3 weeks after treatment. The addition of chidamide to etoposide and glucocorticoids may be a promising new treatment option for patients with HLH, with a high ORR, manageable safety profile, and significant improvement in laboratory indicators. Further research is needed to confirm these findings and determine the optimal dosing and duration of therapy.

Germline HAVCR2 mutation has been reported to be associated with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) leading to Hemophagocytic lymphohistiocytosis (HLH). Several studies have indicated that HAVCR2 mutation can cause HLH even in the absence of lymphoma, though the exact mechanism remains unclear. In this article, we reported five cases of HAVCR2 mutation-associated HLH. Our analysis revealed an elevated level of IL-1RA in the serum of these patients. Furthermore, we investigated the potential mechanisms underlying HLH associated with HAVCR2 mutation based on changes in cytokine levels. Our findings suggest that HAVCR2 mutation may represent a distinct genetic defect underlying HLH, differing from traditional primary HLH.

Background Myelin sheath is a crucial accessory to the functional nerve-fiber unit, its disruption or loss can lead to axonal degeneration and subsequent neurodegenerative diseases (NDs). Notwithstanding of substantial progress in possible molecular mechanisms underlying myelination, there is no therapeutics that prevent demyelination in NDs. Therefore, it is crucial to seek for potential intervention targets. Here, we focused on the transcriptional factor, signal transducer and activator of transcription 1 (Stat1), to explore its effects on myelination and its potential as a drug target. Methods By analyzing the transcriptome data obtained from Schwann cells (SCs) at different stages of myelination, it was found that Stat1 might be involved in myelination. To test this, we used the following experiments: (1) In vivo, the effect of Stat1 on remyelination was observed in an in vivo myelination mode with Stat1 knockdown in sciatic nerves or specific knockdown in SCs. (2) In vitro, the RNA interference combined with cell proliferation assay, scratch assay, SC aggregate sphere migration assay, and a SC differentiation model, were used to assess the effects of Stat1 on SC proliferation, migration and differentiation. Chromatin immunoprecipitation sequencing (ChIP-Seq), RNA-Seq, ChIP-qPCR and luciferase activity reporter assay were performed to investigate the possible mechanisms of Stat1 regulating myelination. Results Stat1 is important for myelination. Stat1 knockdown in nerve or in SCs reduces the axonal remyelination in the injured sciatic nerve of rats. Deletion of Stat1 in SCs blocks SC differentiation thereby inhibiting the myelination program. Stat1 interacts with the promoter of Rab11-family interacting protein 1 (Rab11fip1) to initiate SC differentiation. Conclusion Our findings demonstrate that Stat1 regulates SC differentiation to control myelinogenic programs and repair, uncover a novel function of Stat1, providing a candidate molecule for clinical intervention in demyelinating diseases.

The band level landscape in quantum dots is of great significance toward achieving stable and efficient electroluminescent devices. A series of quantum dots with specific emission and band structure of the intermediate layer is designed, including rich CdS (R-CdS), thick ZnSe (T-ZnSe), thin ZnSe (t-ZnSe) and ZnCdS (R-ZnCdS) intermediate alloy shell layers. These quantum dots in QLEDs show superior performance, including maximum current efficiency, external quantum efficiencies and a T50 lifetime (at 1000 cd/m2) of 47.2 cd/A, 11.2% and 504 h for R-CdS; 61.6 cd/A, 14.7% and 612 h for t-ZnSe; 70.5 cd/A, 16.8% and 924 h for T-ZnSe; and 82.0 cd/A, 19.6% and 1104 h for R-ZnCdS. Among them, the quantum dots with the ZnCdS interlayer exhibit deep electron confinement and shallow hole confinement capabilities, which facilitate the efficient injection and radiative recombination of carriers into the emitting layer. Furthermore, the optimal devices show a superior T50 lifetime of more than 1000 h. The proposed novel methodology of quantum dot band engineering is expected to start a new way for further enhancing QLED exploration.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, complicated and life threatening hyperinflammatory syndrome that maybe triggered by various infectious agents, malignancies and rheumatologic disorders. Early diagnosis and identification of the cause is essential to initiate appropriate treatment and improve the quality of life and survival of patients. The recently developed Onco-mNGS technology can be successfully used for simultaneous detection of infections and tumors. In the present study, 92 patients with clinically confirmed HLH were etiologically subtyped for infection, tumor and autoimmunity based on CNV and microbial data generated by Onco-mNGS technology, and a predictive model was developed and validated for the differential diagnosis of the underlying disease leading to secondary HLH. Furthermore, the treatment outcomes of patients with HLH triggered by EBV infection and non-EBV infection were evaluated, respectively. The current study demonstrated that the novel Onco-mNGS can identify the infection and malignancy- related triggers among patients with secondary HLH. A random forest classification model based on CNV profile, infectious pathogen spectrum and blood microbial community was developed to better identify the different HLH subtypes and determine the underlying triggers. The prognosis for treatment of HLH patients is not only associated with CNV, but also with the presence of pathogens and non- pathogens in peripheral blood. Higher CNV burden along with frequent deletions on chromosome 19, higher pathogen burden and lower non-pathogenic microbes were prognosis factors that significantly related with unfavorable treatment outcomes. Our study provided comprehensive knowledge in the triggers and prognostic predictors of patients with secondary HLH, which may help early diagnosis and appropriate targeted therapy, thus improving the survival and prognosis of the patients.

Within the evolving landscape of cancer immunotherapy, the so-called tail-of-the-curve effect has emerged as a distinctive and clinically relevant phenomenon, defined by the persistence of disease remission long after discontinuation of therapy and thereby reflecting the durability of antitumour immune responses. Immunotherapy has become an indispensable component of systemic treatment for advanced non-small-cell lung cancer (NSCLC), with immune checkpoint inhibitor (ICI)-based combinations-particularly those incorporating anti-angiogenic agents-demonstrating not only robust but also durable clinical benefit across multiple settings. Against this backdrop, we describe the clinical course of a patient with invasive adenocarcinoma of the left upper lobe who underwent surgical resection followed by adjuvant pemetrexed-cisplatin chemotherapy. Two years later, an isolated perihilar recurrence was treated with radical radiotherapy in combination with recombinant human endostatin (Endostar) as a radiosensitizer, after which the patient received four further cycles of the original chemotherapy regimen and subsequently transitioned to pemetrexed maintenance. Thirteen months into maintenance therapy, brain metastases were detected; at this juncture, the patient received whole-brain radiotherapy together with combined sintilimab and Endostar therapy. Although systemic treatment was discontinued after 18 months, the patient maintained disease control for an additional 36 months, consistent with a pronounced tail-of-the-curve effect. This case raises the possibility of integrating ICIs, anti-angiogenic therapy, and focal radiotherapy to elicit durable survival benefit in patients with chemotherapy-refractory, unresectable advanced NSCLC, and further highlights the clinical significance of the immunotherapy-associated tail effect.

We reported a case of a 19‐year‐old male patient with central nervous system symptoms as the main clinical manifestations, and multiple intracranial and abdominal occupying lesions visualized by imaging examinations, who was initially misdiagnosed as NK/T‐cell lymphoma but poorly responsive to the treatment. Finally, he was diagnosed as familial hemophagocytic lymphohistiocytosis type‐2 by genome sequencing, perforin test and pedigree study. The patient survived well after allogeneic hematopoietic stem cell transplantation. Central nervous system symptoms could be the main clinical manifestations in patients with primary hemophagocytic lymphohistiocytosis , whose early‐stage manifestations of blood system were usually atypical, easily leading to misdiagnosis. In clinical practice, primary hemophagocytic lymphohistiocytosis should be considered in patients with central nervous system symptoms and unknown causes. The combination of rapid immunological function test and genome sequencing contributes to the diagnosis of primary hemophagocytic lymphohistiocytosis.

Extranodal natural killer/T‐cell lymphoma, nasal type (ENKL) is a rare peripheral T‐cell lymphoma that predominantly occurs in Asian and South American populations. The treatment of ENKL has been a challenge for a long time. This study was conducted to compare the clinical efficacy and safety of cisplatin, dexamethasone, gemcitabine, and pegaspargase (DDGP) and methotrexate, dexamethasone, ifosfamide, L‐asparaginase, and etoposide (SMILE) regimens for relapsed/refractory ENKL and explore the prognostic factors. From October 2014 to July 2019, 54 patients with relapsed/refractory ENKL who received DDGP or SMILE chemotherapy were retrospectively assessed in this study. Thirty‐one patients received DDGP chemotherapy and 23 patients received SMILE chemotherapy. A higher complete response rate was observed in patients treated with DDGP regimen (61.3% vs. 30.4%, P = 0.025). The DDGP group (95% confidence interval (CI) of 5‐year progression‐free survival (PFS): 24.6–66.2%; 95% CI of 5‐year overall survival (OS): 8.5–91.7%) was also significantly associated with longer 5‐year PFS and 5‐year OS (P = 0.008 for 5‐year PFS, P = 0.023 for 5‐year OS). More serious leucopenia (P = 0.021), neutropenia (P = 0.041), and allergy (P = 0.040) were observed in the SMILE group. Post‐treatment Epstein–Barr virus (EBV)‐DNA status (P = 0.001 for PFS, P = 0.018 for OS) was identified as a significant prognostic factor for PFS and OS in multivariate analysis. The present research suggested that compared with SMILE chemotherapy, DDGP chemotherapy can significantly improve the response and survival of relapsed/refractory ENKL with better tolerance. Post‐treatment EBV‐DNA status was identified as a significant prognostic factor for PFS and OS in relapsed/refractory ENKL.

Background Constipation is a common complication after stroke that can severely influence a patient’s quality of life and rehabilitation. Treatments for constipation after stroke vary. Acupuncture may improve spontaneous bowel movements, quality of life, and clinical symptoms. The study seeks to assess the preliminary effects of acupuncture on constipation after an ischemic stroke. Methods/design This is a prospective randomized controlled pilot trial design in which 120 eligible patients will be randomly allocated to one of three groups. The acupuncture group ( n  = 40) will receive acupuncture and routine care, the medication group ( n  = 40) will receive mosapride citrate and routine care, and the control group ( n  = 40) will receive only routine care for ischemic stroke. Patients will be recruited 2 weeks to 6 months after stroke onset and will receive the intervention continuously over 4 weeks, with a follow-up period of 4 additional weeks. Adverse events will be recorded to assess the safety and tolerability of acupuncture for constipation after an ischemic stroke. The primary outcome will be the change in the weekly mean number of complete spontaneous bowel movements. Secondary outcomes will include any change in the weekly mean number of spontaneous bowel movements, mean stool consistency scores, mean straining scores during defecation, and frequency of laxative use. All outcome measures will be assessed at inception, after the intervention (4 weeks), and at the follow-up (8 weeks). Discussion This study will provide evidence of the preliminary effects and inform future sample size calculations for studies of acupuncture for constipation following an ischemic stroke. These findings will inform subsequent large-scale randomized controlled trials. Trial registration ISRCTN, 22214747 . Registered on 17 August 2015.

Pile-supported embankments are typically composed of soil-rock mixtures. within these structures, while the soil arching effect is crucial for effective load transfer, it remains incompletely understood, particularly when the impact of various loading conditions needs to be considered. This study investigates this problem using a 1 g physical experimental modeling approach. Subsequently, a DEM model for a full-scale pile-supported embankment of high-speed railways, accounting for multiple pile interactions, is established with proper model calibration. Numerical simulations are conducted to explore the load transfer mechanism and soil arching processes under self-weight, embankment preloading, and train-induced dynamics influences. The findings indicate that under self-weight, fully developed soil arching structures can be achieved with a sufficiently high embankment height, although they can diminish as the soil-pile relative displacement increases. However, during embankment preloading processes, represented by static loading, pressure can be transferred from pile caps to subsoil regions, potentially compromising the integrity of soil arching structures. Train-induced dynamics effects are modeled as cyclic loading inputs, revealing that an increase in loading frequency leads to weakened dynamic pressure fluctuation for both pile caps and subsoil regions, with a limited impact on the valley values of the pressures. Additionally, a higher loading frequency corresponds to smaller accumulated loading plate settlements.