飞秒激光辅助超声乳化联合Ahmed青光眼引流阀植入术治疗合并难治性青光眼的白内障

目的：评估飞秒激光辅助超声乳化联合Ahmed青光眼引流阀植入术治疗合并难治性青光眼的白内障的有效性和安全性。

方法：回顾性病例对照研究。2019-10/2021-10入院合并难治性青光眼的白内障患者53例53眼，依据自愿选择分为飞秒激光辅助白内障超声乳化(FLACS)组26例26眼和常规白内障超声乳化(CPCS)组27例27眼。两组分别行FLACS和CPCS联合Ahmed青光眼引流阀植入术。比较两组患者术中超声乳化能量释放量(CDE)、有效超声时间(EPT)的差异和术前与术后抗青光眼药物数量的变化，以及术后观察不同时期(1d，1wk，1、3mo)在提高最佳矫正视力(BCVA)，降低眼压、角膜内皮细胞损伤程度和手术并发症及成功率状况。

结果：FLACS组术中CDE和EPT明显低于CPCS组(t=8.50、5.16； P<0.01、=0.001)。两组术后抗青光眼药物较术前均明显减少(t=9.12、7.76； P=0.011、0.016)，但两组间无差异(t=1.79，P=0.082)。两组术后BCVA均较术前改善，眼压均较术前降低(P<0.05)。FLACS组在术后早期(1d，1wk)BCVA的改善较CPCS组更显著(t=9.74、8.49； P=0.008、0.012)，但在术后1、3mo的BCVA改善程度并无不同(t=0.62、0.44； P=1.415、2.021)。CPCS组在术后随访不同时期的角膜内皮细胞损伤较FLACS组更明显(P<0.05)。术后随访的不同时期FLACS组和CPCS组在控制眼压方面无差异(F_组间=0.64，P_组间=0.421)。FLACS组的手术并发症发生率27%(7/26)较CPCS组89%(24/27)低(χ²=20.95，P<0.01)，其中角膜水肿(8% vs 41%)、前囊撕裂(0 vs 11%)在FLACS组中明显低于CPCS组，后囊破裂(0 vs 7%)、玻璃体脱出(0 vs 4%)及人工晶状体偏位(0 vs 7%)也均发生在CPCS组。但两组的治疗总成功率相近(P=28.718)。

结论：飞秒激光辅助超声乳化联合Ahmed青光眼引流阀植入术可充分发挥联合手术的精准微创可控优势，帮助合并难治性青光眼的白内障患者有效降低眼压及更早获得视力恢复。     

Shikonin from Chinese herbal medicine induces GSDME-controlled pyroptosis in tumor cells

ObjectiveTo investigate the potential anti-tumor mechanisms of naphthoquinone compound shikonin (SKN) extracted from the root of Chinese herbal medicine plant lithospermum (Lithospermum erythrorhizon Sieb. & Zucc.).MethodsWe first observed that SKN treatment led to swelling and bubbles in HeLa cells that were similar to the phenotype of cell pyroptosis. Subsequently, the HeLa cells experienced a pyroptotic process with SKN, and this was then assessed using lactate dehydrogenase (LDH) release and propidium iodide (PI)/Hoechst double staining experiments. Pyroptosis is defined as gasdermin-mediated programmed necroptosis. To identify the potential pyroptosis machinery, two strategies were utilized that included a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 screening experiment and a pyroptosis reconstitution assay executed by each of the five known gasdermins (GSDMA-E). Moreover, endogenous cleavage was also detected in a panel of tumor cell lines.ResultsCompared with the control, both the LDH release and PI/Hoechst double-staining experiments suggested that SKN induced perforation and enhancement of the permeability of the cell membranes that resulted in pyroptosis in HeLa cells (P = .028 and P = .032, respectively). In addition, the reconstitution assays in human embryonic kidney 293T (HEK-293T) cells and endogenous cleavage assays in HeLa cells indicated that the pyroptosis was controlled by GSDME. In addition, we also found SKN could trigger pyroptosis in a panel of tumor cell lines in which the cellular morphologies were proportional to the GSDME expression levels. Additionally, the cleavage of GSDME was also detected, and this was indicative of a similar GSDME-mediated mechanism.ConclusionOur study not only explained the molecular mechanism of cytotoxicity of SKN to various tumor cells, but also provided additional information for the potential clinical application of natural naphthoquinone compounds against cancer.     

Induction of tumor cell autosis by myxoma virus-infected CAR-T and TCR-T cells to overcome primary and acquired resistance

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Potentilla anserine L. polysaccharide protects against cadmium-induced neurotoxicity

Cadmium is a toxic metal that can damage the brain and other organs. This study aimed to explore the protective effects of Potentilla anserine L. polysaccharide (PAP) against CdCl₂-induced neurotoxicity in N2a and SH-SY5Y cells and in the cerebral cortex of BALB/c mice. In addition, we aimed to identify the potential mechanisms underlying these protective effects. Relative to CdCl₂ treatment alone, pretreatment with PAP prevented the reduction in cell viability evoked by CdCl₂, decreased rates of apoptosis, promoted calcium homeostasis, decreased ROS accumulation, increased mitochondrial membrane potential, inhibited cytochrome C and AIF release, and prevented the cleavage of caspase-3 and PARP. In addition, PAP significantly decreased the CdCl₂-induced phosphorylation of CaMKII, Akt, and mTOR. In conclusion, PAP represents a potential therapeutic agent for the treatment of Cd-induced neurotoxicity, functioning in part via attenuating the activation of the mitochondrial apoptosis pathway and the Ca²⁺-CaMKII-dependent Akt/mTOR pathway.     

Are we missing reverse TRALI? – A real world experience from a tertiary care oncology centre in India

Transfusion related acute lung injury (TRALI) is a rare but potentially fatal pulmonary complication of transfusion that presents as acute hypoxemia and non-cardiogenic pulmonary oedema, developing during or within six hours of transfusion. Majority of the cases reported are due to transfusion of plasma rich blood components containing antibodies to human leukocyte antigen (anti-HLA) or human neutrophil antigen (anti-HNA). Rarely, anti-HLA or anti-HNA in recipients against transfused donor leukocyte antigens, cause TRALI by a reverse mechanism. Herein, we report three cases of suspected TRALI following transfusions of buffy coat derived granulocytes and peripheral blood stem cells. Three patients with hematological malignancies developed pulmonary symptoms after transfusions of leukocyte rich blood components. All cases showed findings of bilateral pulmonary infiltrates at chest radiography and patients were managed accordingly; however, all three expired within seven days of transfusion due to progressive respiratory deterioration. The patients were transfusion dependent for a long time and had received multiple non-leukoreduced blood components in the past. Clinical findings in all three cases indicate the possibility of reverse TRALI. Although, patients’ anti-HLA or anti-HNA antibodies concordance with donors’ cognate antigens (HLA and HNA) was not confirmed; yet these three cases suggest that reverse pathogenesis of TRALI is not as infrequent as reported in the literature. However, reverse TRALI has not been confirmed as the presence and nature of antibodies in the transfused recipient were not investigated due to the non availability of immunodiagnostic tests in India.     

Newly recruited intraepithelial Ly6A+CCR9+CD4+ T cells protect against enteric viral infection

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Review of clinical characteristics,immune responses and regulatory mechanisms of hepatitis E-associated liver failure

Hepatitis E virus (HEV) is the most common cause of acute liver failure (LF) and one of the most common factors causing acute injury in acute-on-chronic LF (ACLF). When HEV-related LF occurs, a series of changes take place in both the intrahepatic environment and extrahepatic microenvironment. The changed types and distribution of immune cells (infiltrating macrophages and increased lymphocytes) in liver tissue, as well the increased proinflammatory cytokines and chemokines in the blood, indicate that the occurrence and progression of HEV-related LF are closely related to immune imbalance. The clinical features and immune reaction in the body during HEV-related acute LF (ALF) and ACLF are complicated. This review highlights recent progress in elucidating the clinical manifestations of HEV-associated ALF and ACLF and discusses the corresponding systemic immune changes and possible regulatory mechanisms.