This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective:To analyze the clinical features and prognosis of patients with lymphoplasmacytic lymphoma/Waldenstr?m macroglobulinemia (LPL/WM) transformed into diffuse large B-cell lymphoma (DLBCL) .Methods:This study retrospectively analyzed the clinical data of five patients with LPL/WM transformed to DLBCL diagnosed and treated at a multicenter hospital in Hunan Province from December 2020 to April 2023. Clinical manifestations, treatment regimens, and therapeutic efficacy before and after the transformation were compared.Results:Of the five patients, four were male and one was female, with a median age of 64.0 (57.0–80.0) years, all of whom had abnormally increased β 2-microglobulin levels at diagnosis, and two were combined with increased lactate dehydrogenase levels. The MYD88 L265P mutation was detected in 4 patients, whereas 1 carried the FAT1 and NOTCH1 mutations, and none demonstrated CXCR4 mutations. Three patients were negative for the TP53 mutation, and two were not tested. Before transformation, three patients were treated with Bruton tyrosine kinase inhibitor therapy, and one patient was treated with the bendamustine plus rituximab regimen. All patients eventually transformed into non-growth center-derived DLBCL, with a median time to conversion of 11.8 (4.0–19.0) months, and most of them presented with weight loss, lymph node enlargement, splenomegaly, and extranodal involvement. Posttransformation, the patients were mainly treated with the rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP) regimen, with an optimal outcome of partial remission. Disease progression occurred in 4 of the patients, with a median overall survival of 16.8 (10.0–26.0) months. Conclusion:Transformation from LPL/WM to DLBCL is rare. Patients should remain highly vigilant for transformation if they develop rapidly enlarging lymph nodes and/or newly involved lymph nodes, worsening systemic symptoms, and declining body mass. R-CHOP regimen may induce a partial response in some cases; however, the overall prognosis remains poor.

The gut microbiota is generally thought in regulating the body's metabolism and immune function.The imbalance of gut microbiota is related to the occurrence and development mechanisms of acute and chronic lung dis-eases,resulting from lung injury.The"gut-lung axis"pays a main role in various ways in the occurrence of lung injury,including intestinal barrier dysfunction,reduced diversity of gut microbiota,decreased secretion of beneficial metabolites,translocation of gut microbiota and metabolites to the lungs,immune damage to the body and lungs,increased inflammatory response in the lungs.

Objective:To analyze the characteristics of transabdominal bowel ultrasound (TBUS) in immune checkpoint inhibitor-related colitis (IRC) and their correlation with endoscopic manifestations.Methods:A cross-sectional study was conducted. Clinical data from 10 patients with IRC treated at Peking Union Medical College Hospital from January 2022 to January 2024 were collected. The ulcerative colitis endoscopic index of severity (UCEIS) and Limberg classification were used to assess the severity of colonoscopy and TBUS examinations, respectively. Kendall's tau-b method was applied for correlation analysis between UCEIS scores and Limberg classification.Results:All the 10 patients were male with a median age of 65 years (59-74 years). The majority had lung cancer (8 patients) and all were in advanced stages, with 6 patients in stage Ⅲ and 4 in stage Ⅳ. They all received anti-programmed death 1 (PD-1) /anti-programmed death ligand 1 (PD-L1) combined with chemotherapy, among whom 2 patients were combined with anti-angiogenic drug treatment. The median time from the first immunotherapy to the onset of IRC was 1.50 (0.25-12.00) months; the median time from IRC treatment to clinical symptom relief to G1 was 2.45 (0.50-8.00) weeks. Nine patients were in the active phase, mainly G3 (8 patients) ; 1 was in the remission phase after treatment. TBUS showed that among the 9 active IRC patients, the entire colon was mainly involved (7 patients), with combined small intestine involvement (3 patients) ; the main manifestations were thickening of the bowel wall, with the thickest bowel wall being 7.0 (5.0-8.0) mm, mainly located in the sigmoid colon (3 patients) and descending colon (3 patients) ; increased bowel wall blood flow signals (Limberg classification 2-4) occurred in 7 patients; 3 active patients had perienteric fat wrapping, and 2 had blurred bowel wall stratification. The Kendall's tau-b correlation coefficient r between the entire colon UCEIS scores and Limberg classification was 0.891 ( P = 0.003), and the Kendall's tau-b correlation coefficient r between the colon segment UCEIS scores and Limberg classification was 0.690 ( P < 0.001) . Conclusion:During the active phase, the left colon of IRC is more severe in TBUS, which mainly manifests as the thickening bowel wall and increased blood flow signals, and the TBUS has good correlation with colonoscopy evaluation.

Objective:To analyze the characteristics of transabdominal bowel ultrasound (TBUS) in immune checkpoint inhibitor-related colitis (IRC) and their correlation with endoscopic manifestations.Methods:A cross-sectional study was conducted. Clinical data from 10 patients with IRC treated at Peking Union Medical College Hospital from January 2022 to January 2024 were collected. The ulcerative colitis endoscopic index of severity (UCEIS) and Limberg classification were used to assess the severity of colonoscopy and TBUS examinations, respectively. Kendall's tau-b method was applied for correlation analysis between UCEIS scores and Limberg classification.Results:All the 10 patients were male with a median age of 65 years (59-74 years). The majority had lung cancer (8 patients) and all were in advanced stages, with 6 patients in stage Ⅲ and 4 in stage Ⅳ. They all received anti-programmed death 1 (PD-1) /anti-programmed death ligand 1 (PD-L1) combined with chemotherapy, among whom 2 patients were combined with anti-angiogenic drug treatment. The median time from the first immunotherapy to the onset of IRC was 1.50 (0.25-12.00) months; the median time from IRC treatment to clinical symptom relief to G1 was 2.45 (0.50-8.00) weeks. Nine patients were in the active phase, mainly G3 (8 patients) ; 1 was in the remission phase after treatment. TBUS showed that among the 9 active IRC patients, the entire colon was mainly involved (7 patients), with combined small intestine involvement (3 patients) ; the main manifestations were thickening of the bowel wall, with the thickest bowel wall being 7.0 (5.0-8.0) mm, mainly located in the sigmoid colon (3 patients) and descending colon (3 patients) ; increased bowel wall blood flow signals (Limberg classification 2-4) occurred in 7 patients; 3 active patients had perienteric fat wrapping, and 2 had blurred bowel wall stratification. The Kendall's tau-b correlation coefficient r between the entire colon UCEIS scores and Limberg classification was 0.891 ( P = 0.003), and the Kendall's tau-b correlation coefficient r between the colon segment UCEIS scores and Limberg classification was 0.690 ( P < 0.001) . Conclusion:During the active phase, the left colon of IRC is more severe in TBUS, which mainly manifests as the thickening bowel wall and increased blood flow signals, and the TBUS has good correlation with colonoscopy evaluation.

Objective:To systematically integrate the qualitative research results on the exercise experience and needs of patients with Parkinson's disease at home and abroad, and to provide a reference for formulating exercise management plans that are in line with the feelings of patients with Parkinson's disease.Methods:Computer retrieval was conducted in databases including China National Knowledge Infrastructure, Wanfang Data, VIP, China Biology Medicine disc, Web of Science, PubMed, Cochrane Library, Medline, Embase, and ProQuest for qualitative studies on the exercise experience of patients with Parkinson's disease. The retrieval time limit was from the establishment of the databases to August 8, 2024.Results:A total of 14 articles were included, and 34 research results were extracted. Similar research results were grouped into 11 new categories and integrated into 4 integrated results, namely the incentive factors for patients with Parkinson's disease to participate in exercise, the perceived benefits of patients with Parkinson's disease in exercise, the perceived difficulties of patients with Parkinson's disease in exercise, and the needs of patients with Parkinson's disease to participate in exercise.Conclusions:Exercise has a positive effect on improving the physical and mental conditions of patients with Parkinson's disease. Medical staff should fully consider the needs of patients and formulate safe and reasonable exercise plans to improve the motor life ability of patients with Parkinson's disease.

Objective:To summarize ICU acquired weakness (ICU-AW) assessment tools from both domestic and international sources, providing a reference for healthcare providers in evaluating ICU-AW.Methods:Using Arksey and O'Malley's framework for scope reviews, a computer search was conducted in PubMed, Web of Science, Embase, Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Database, VIP, and China Biology Medicine disc for relevant information on ICU-AW assessment tools. The search period was from the establishment of the databases to March 31, 2024. Two researchers independently summarized and analyzed the included literature.Results:A total of 14 articles were included, of which seven focused on the development/construction of prediction models, and seven were related to assessment tools, involving 17 different ICU-AW assessment tools.Conclusions:Researchers should develop and construct ICU-AW risk assessment tools with low bias risk and high clinical applicability based on existing ICU-AW assessment tools, providing effective instruments for the precise health management of ICU patients.

Objective:To systematically integrate the qualitative research results on the exercise experience and needs of patients with Parkinson's disease at home and abroad, and to provide a reference for formulating exercise management plans that are in line with the feelings of patients with Parkinson's disease.Methods:Computer retrieval was conducted in databases including China National Knowledge Infrastructure, Wanfang Data, VIP, China Biology Medicine disc, Web of Science, PubMed, Cochrane Library, Medline, Embase, and ProQuest for qualitative studies on the exercise experience of patients with Parkinson's disease. The retrieval time limit was from the establishment of the databases to August 8, 2024.Results:A total of 14 articles were included, and 34 research results were extracted. Similar research results were grouped into 11 new categories and integrated into 4 integrated results, namely the incentive factors for patients with Parkinson's disease to participate in exercise, the perceived benefits of patients with Parkinson's disease in exercise, the perceived difficulties of patients with Parkinson's disease in exercise, and the needs of patients with Parkinson's disease to participate in exercise.Conclusions:Exercise has a positive effect on improving the physical and mental conditions of patients with Parkinson's disease. Medical staff should fully consider the needs of patients and formulate safe and reasonable exercise plans to improve the motor life ability of patients with Parkinson's disease.

Objective:To summarize ICU acquired weakness (ICU-AW) assessment tools from both domestic and international sources, providing a reference for healthcare providers in evaluating ICU-AW.Methods:Using Arksey and O'Malley's framework for scope reviews, a computer search was conducted in PubMed, Web of Science, Embase, Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Database, VIP, and China Biology Medicine disc for relevant information on ICU-AW assessment tools. The search period was from the establishment of the databases to March 31, 2024. Two researchers independently summarized and analyzed the included literature.Results:A total of 14 articles were included, of which seven focused on the development/construction of prediction models, and seven were related to assessment tools, involving 17 different ICU-AW assessment tools.Conclusions:Researchers should develop and construct ICU-AW risk assessment tools with low bias risk and high clinical applicability based on existing ICU-AW assessment tools, providing effective instruments for the precise health management of ICU patients.