Zhen-Wu-Tang ameliorates lupus nephritis by diminishing renal tissue-resident memory CD8+ T cells via suppressing IL-15/STAT3 pathway.

Zhen-Wu-Tang (ZWT), a conventional herbal mixture, has been recommended for treating lupus nephritis (LN) in clinic. However, its mechanisms of action remain unknown. Here we aimed to define the immunological mechanisms underlying the effects of ZWT on LN and to determine whether it affects renal tissue-resident memory T (TRM) cells. Murine LN was induced by a single injection of pristane, while in vitro TRM cells differentiated with IL-15/TGF-ß. We found that ZWT or mycophenolate mofetil treatment significantly ameliorated kidney injury in LN mice by decreasing 24-h urine protein, Scr and anti-dsDNA Ab. ZWT also improved renal pathology and decreased IgG and C3 depositions. In addition, ZWT down-regulated renal Desmin expression. Moreover, it lowered the numbers of CD8+ TRM cells in kidney of mice with LN while decreasing their expression of TNF-α and IFN-γ. Consistent with in vivo results, ZWT-containing serum inhibited TRM cell differentiation induced by IL-15/TGF-ß in vitro. Mechanistically, it suppressed phosphorylation of STAT3 and CD122 （IL2/IL-15Rß）expression in CD8+ TRM cells. Importantly, ZWT reduced the number of total F4/80+CD11b+ and CD86+, but not CD206+, macrophages in the kidney of LN mice. Interestingly, ZWT suppressed IL-15 protein expression in macrophages in vivo and in vitro. Thus, we have provided the first evidence that ZWT decoction can be used to improve the outcome of LN by reducing CD8+ TRM cells via inhibition of IL-15/IL-15R /STAT3 signaling.

Land conversion to agriculture induces taxonomic homogenization of soil microbial communities globally.

Agriculture contributes to a decline in local species diversity and to above- and below-ground biotic homogenization. Here, we conduct a continental survey using 1185 soil samples and compare microbial communities from natural ecosystems (forest, grassland, and wetland) with converted agricultural land. We combine our continental survey results with a global meta-analysis of available sequencing data that cover more than 2400 samples across six continents. Our combined results demonstrate that land conversion to agricultural land results in taxonomic and functional homogenization of soil bacteria, mainly driven by the increase in the geographic ranges of taxa in croplands. We find that 20% of phylotypes are decreased and 23% are increased by land conversion, with croplands enriched in Chloroflexi, Gemmatimonadota, Planctomycetota, Myxcoccota and Latescibacterota. Although there is no significant difference in functional composition between natural ecosystems and agricultural land, functional genes involved in nitrogen fixation, phosphorus mineralization and transportation are depleted in cropland. Our results provide a global insight into the consequences of land-use change on soil microbial taxonomic and functional diversity.

The TOPK Inhibitor HI-TOPK-032 Enhances CAR T-cell Therapy of Hepatocellular Carcinoma by Upregulating Memory T Cells.

Chimeric antigen receptor (CAR) T cells are emerging as an effective antitumoral therapy. However, their therapeutic effects on solid tumors are limited because of their short survival time and the immunosuppressive tumor microenvironment. Memory T cells respond more vigorously and persist longer than their naïve/effector counterparts. Therefore, promoting CAR T-cell development into memory T cells could further enhance their antitumoral effects. HI-TOPK-032 is a T-LAK cell-originated protein kinase (TOPK)-specific inhibitor that moderately represses some types of tumors. However, it is unknown whether HI-TOPK-032 works on hepatocellular carcinoma (HCC) and whether it impacts antitumoral immunity. Using both subcutaneous and orthotopic xenograft tumor models of two human HCC cell lines, Huh-7 and HepG2, we found that HI-TOPK-032 significantly improved proliferation/persistence of CD8+ CAR T cells, as evidenced by an increase in CAR T-cell counts or frequency of Ki-67+CD8+ cells and a decrease in PD-1+LAG-3+TIM-3+CD8+ CAR T cells in vivo. Although HI-TOPK-032 did not significantly suppress HCC growth, it enhanced the capacity of CAR T cells to inhibit tumor growth. Moreover, HI-TOPK-032 augmented central memory CD8+ T cell (TCM) frequency while increasing eomesodermin expression in CD8+ CAR T cells in tumor-bearing mice. Moreover, it augmented CD8+ CAR TCM cells in vitro and reduced their expression of immune checkpoint molecules. Finally, HI-TOPK-032 inhibited mTOR activation in CAR T cells in vitro and in tumors, whereas overactivation of mTOR reversed the effects of HI-TOPK-032 on CD8+ TCM cells and tumor growth. Thus, our studies have revealed mechanisms underlying the antitumoral effects of HI-TOPK-032 while advancing CAR T-cell immunotherapy.

Oligotrophic microbes are recruited to resist multiple global change factors in agricultural subsoils.

An increasing number of anthropogenic pressures can have negative effects on biodiversity and ecosystem functioning. However, our understanding of how soil microbial communities and functions in response to multiple global change factors (GCFs) is still incomplete, particularly in less frequently disturbed subsoils. In this study, we examined the impact of different levels of GCFs (0-9) on soil functions and bacterial communities in both topsoils (0-20 cm) and subsoils (20-40 cm) of an agricultural ecosystem, and characterized the intrinsic factors influencing community resistance based on microbial life history strategy. Our experimental results showed a decline in soil multifunctionality, bacterial diversity, and community resistance as the number of GCFs increased, with a more drastic reduction in community resistance of subsoils. Specifically, we observed a significantly positive relationship between the oligotroph/copiotroph ratio and community resistance in subsoils, which was also verified by the negative correlation between 16S rRNA operon (rrn) copy number and community resistance. Structural equation modeling further revealed the direct effects of community resistance in promoting the ecosystem functioning, regardless of top- and subsoils. Therefore, these results suggested that subsoils may recruit more oligotrophic microbes to enhance their originally weaker community resistance under multiple GCFs, which was essential for maintaining sustainable agroecological functions and services. Overall, our study represents a significant advance in linking microbial life history strategy to the resistance of belowground microbial community and functionality.

Methotrexate and electrostimulation cooperate to alleviate the relapse of psoriasiform skin inflammation by suppressing memory T cells.

Methotrexate (MTX) is an immunosuppressant used to treat autoimmune diseases, including psoriasis. However, like other immunosuppressants, MTX alone does not prevent their recurrence. Electrostimulation (ES) has been utilized to treat some inflammatory disorders without any major side-effect. But it remains unknown if ES alone, or together with MTX, ameliorates autoimmune disease relapse: a sticky medical problem. In particular, the mechanisms underlying ES action remain unclear. The objective of this study was to determine an impact of ES and/or MTX on psoriasis relapse and their potential cooperation. We found that regional ES, but not MTX, ameliorated psoriasiform skin inflammation recurrence. Interestingly, treatment with both MTX and ES further prevented psoriasis recurrence compared to ES alone. Moreover, ES downregulated potassium channel Kv1.3 on T-cells and reduced CD4+/CD8+ effector memory (TEM) and CD8+ skin-resident memory T (TRM) cells, while ES plus MTX further decreased CD8+ TEM/TRM cells compared to ES alone. However, ES failed to further attenuate psoriasis recurrence or suppress T cell memory in Kv1.3-deficient mice, whereas lack of Kv1.3 itself ameliorated psoriasis relapse by shrinking T cell memory pool. Importantly, ES moderately inhibited T-cell proliferation in vitro. ES also reduced human CD8+ TRM cells and attenuated human skin lesions in humanized mice grafted with lesional skin from patients with recurrent psoriasis, with an enhanced efficacy in mice treated with both ES and MTX. Thus, ES and MTX cooperated to prevent psoriasis relapse by reducing T-cell memory via targeting potassium channel Kv1.3. Our studies may be implicated for treating human psoriasis.

The neglected roles of adjacent natural ecosystems in maintaining bacterial diversity in agroecosystems.

A central aim of community ecology is to understand how local species diversity is shaped. Agricultural activities are reshaping and filtering soil biodiversity and communities; however, ecological processes that structure agricultural communities have often overlooked the role of the regional species pool, mainly owing to the lack of large datasets across several regions. Here, we conducted a soil survey of 941 plots of agricultural and adjacent natural ecosystems (e.g., forest, wetland, grassland, and desert) in 38 regions across diverse climatic and soil gradients to evaluate whether the regional species pool of soil microbes from adjacent natural ecosystems is important in shaping agricultural soil microbial diversity and completeness. Using a framework of multiscales community assembly, we revealed that the regional species pool was an important predictor of agricultural bacterial diversity and explained a unique variation that cannot be predicted by historical legacy, large-scale environmental factors, and local community assembly processes. Moreover, the species pool effects were associated with microbial dormancy potential, where taxa with higher dormancy potential exhibited stronger species pool effects. Bacterial diversity in regions with higher agricultural intensity was more influenced by species pool effects than that in regions with low intensity, indicating that the maintenance of agricultural biodiversity in high-intensity regions strongly depends on species present in the surrounding landscape. Models for community completeness indicated the positive effect of regional species pool, further implying the community unsaturation and increased potential in bacterial diversity of agricultural ecosystems. Overall, our study reveals the indubitable role of regional species pool from adjacent natural ecosystems in predicting bacterial diversity, which has useful implication for biodiversity management and conservation in agricultural systems.

MiR-124-3p mediates gastric cancer cell ferroptosis induced by an anti-cancer drug polyphyllin I.

Background: Ferroptosis is an emerging type of regulated cell death and associated with antitumoral therapy, while some microRNAs have been shown to regulate the tumorigenesis and cancer progression. Meanwhile, polyphyllin I (PPI) has exhibited antitumoral effects by promoting cancer cell apoptosis and ferroptosis. However, it is unclear whether PPI induces cancer cell ferroptosis by regulating microRNAs. Methods: We used two gastric cancer cell lines (AGS and MKN-45) to set up a tumor model of the nude mice, which were then treated daily with PPI to measure the cancer growth in vitro and in vivo. Ferroptosis was measured using immunofluorescence staining and flow cytometric analysis according to levels of intracellular ROS, lipid ROS and ferrous ions. Moreover, NRF2 expression was measured by Western blotting. In some experiments, the mimics or inhibitors of miR-124-3p were used to further confirm its involvement in PPI-induced cancer cell ferroptosis. Results: Here we found that miR-124-3p mediated cancer ferroptosis and tumor repression induced by PPI since PPI increased miR-124-3p expression in gastric cancer cells and promoted their ferroptosis, whereas inhibition of miR-124-3p mostly abolished the effects of PPI on tumor growth, ferroptosis and NRF2 expression. Moreover, miR-124-3p mimics promoted cancer cell ferroptosis by downregulating NRF2 through directly targeting 3'-UTR region of NRF2, confirming a role for miR-124-3p in regulating PPI-induced ferroptosis. Conclusion: PPI exerts its antitumoral effects on the gastric cancer by promoting cell ferroptosis via regulating miR-124-3p. Our findings have clinical implications for cancer chemotherapy.

Agricultural tillage practice and rhizosphere selection interactively drive the improvement of soybean plant biomass.

Rhizosphere microbes play key roles in plant growth and productivity in agricultural systems. One of the critical issues is revealing the interaction of agricultural management (M) and rhizosphere selection effects (R) on soil microbial communities, root exudates and plant productivity. Through a field management experiment, we found that bacteria were more sensitive to the M × R interaction effect than fungi, and the positive effect of rhizosphere bacterial diversity on plant biomass existed in the bacterial three two-tillage system. In addition, inoculation experiments demonstrated that the nitrogen cycle-related isolate Stenotrophomonas could promote plant growth and alter the activities of extracellular enzymes N-acetyl- d-glucosaminidase and leucine aminopeptidase in rhizosphere soil. Microbe-metabolites network analysis revealed that hubnodes Burkholderia-Caballeronia-Paraburkholderia and Pseudomonas were recruited by specific root metabolites under the M × R interaction effect, and the inoculation of 10 rhizosphere-matched isolates further proved that these microbes could promote the growth of soybean seedlings. Kyoto Encyclopaedia of Genes and Genomes pathway analysis indicated that the growth-promoting mechanisms of these beneficial genera were closely related to metabolic pathways such as amino acid metabolism, melatonin biosynthesis, aerobactin biosynthesis and so on. This study provides field observation and experimental evidence to reveal the close relationship between beneficial rhizosphere microbes and plant productivity under the M × R interaction effect.

Diagnostic value of IL-22, IL-23, and IL-17 for NK/T cell lymphoma.

NK/T cell lymphoma (NKTCL) is a common blood cancer, and early diagnosis of this disease is crucial. This study is aimed to investigate the roles of IL-17, IL-22 as well as IL-23 for the diagnosis of NKTCL. Sixty-five patients with NKTCL were included and the blood samples were collected, and sixty healthy objectives served as the controls. Serums of the patients and controls were collected. The expression levels of IL-17, IL-22, and IL-23 were examined using enzyme-linked immunosorbent (ELISA) assay. The receiver operator characteristic (ROC) curve was drawn for determining the potential diagnostic value of these cytokines. The serum levels of IL-17 (156.0 ± 67.75 pg/mL), IL-22 (39.98 ± 23.88 pg/mL), and IL-23 (43.05 ± 25.69 pg/mL) were all markedly increased in NKTCL patients (P<0.001); ROC analysis showed the serum level of IL-17, IL-22, and IL-23 could serve as the potential diagnostic biomarker for NKTCL with high sensitivity and specificity. The AUC of IL-17 was 0.9487 (95% confidence interval (CI), 0.9052 to 0.9922). Area under the curve (AUC) of IL-22 was 0.7321 (95% CI, 0.6449 to 0.8192). The AUC of IL-23 was 0.7885 (95% CI, 0.7070 to 0.8699). Our data indicated that IL-17, IL-22, and IL-23 were all increased in NKTCL and may function as potential diagnostic biomarkers for NKTCL.

Corrigendum: Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis.

[This corrects the article DOI: 10.3389/fphar.2023.1145407.].

Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis.

Background: Ferroptosis is a new form of regulated cell death characterized by the accumulation of iron-dependent lipid peroxides and membrane damages. Recent studies have identified an important role for cancer cell ferroptosis in antitumor therapy. On the other hand, polyphyllin I (PPI) has been reported to exert antitumor effects on some types of cancers. However, it remains unknown whether or not PPI regulates cancer cell ferroptosis. Methods: Two types of human gastric cancer cells (AGS and MKN-45) were used to establish tumor xenograft models in nude mice that were treated with polyphyllin I (PPI) to observe tumor growth, while cells also were cultured for in vitro studies. Ferroptosis, based on the intracellular ROS/lipid ROS production and accumulation of ferrous ions, was detected using a fluorescence microscope and flow cytometer, while the expression of NRF2/FTH1 was measured using Western blotting assays. Results: Here we found that PPI inhibited the gastric cancer growth in vivo and in vitro while increasing the intracellular reactive oxygen species (ROS)/lipid peroxides and ferrous ions in the gastric cancer cells. PPI also decreased the levels of nuclear factor erythroid 2-related factor 2 (NRF2) and ferritin heavy chain 1 (FTH1) in gastric cancer cells in vitro. Moreover, liproxstain-1, an inhibitor of cell ferroptosis, mostly reversed the cell ferroptosis and tumor growth arrest induced by PPI. Finally, the effects of PPI on cancer cell ferroptosis were diminished by the overexpression of NRF2. Conclusion: For the first time, our results have demonstrated that PPI exerts its antitumor activity on the gastric cancer by, at least partially, inducing cancer cell ferroptosis via regulating NRF2/FTH1 pathway. These findings may be implicated for clinical replacement therapy of the gastric cancer.

Indigenous microbial community governs the survival of Escherichia coli O157:H7 in constructed wetlands.

The survival pattern of Escherichia coli O157:H7 (E. coli O157:H7) and its regulatory factors in natural environments have been widely studied. However, there is little information about the survival of E. coli O157:H7 in artificial environments, especially in wastewater treatment facilities. In this study, a contamination experiment was performed to explore the survival pattern of E. coli O157:H7 and its central control factors in two constructed wetlands (CWs) under different hydraulic loading rates (HLRs). The results showed that the survival time of E. coli O157:H7 was longer in the CW under the higher HLR. Substrate ammonium nitrogen and available phosphorus were the main factors that influenced the survival of E. coli O157:H7 in CWs. Despite the minimal effect of microbial α-diversity, some keystone taxa, such as Aeromonas, Selenomonas, and Paramecium, governed the survival of E. coli O157:H7. In addition, the prokaryotic community had a more significant impact on the survival of E. coli O157:H7 than the eukaryotic community. The biotic properties had a more substantial direct power on the survival of E. coli O157:H7 than the abiotic factors in CWs. Collectively, this study comprehensively disclosed the survival pattern of E. coli O157:H7 in CWs, which is an essential addition to the environmental behavior of E. coli O157:H7, providing a theoretical basis for the prevention and control of biological contamination in wastewater treatment processes.

Preparation and characterization of flexible laminated composites impregnated with TPU/SiO2 for static puncture resistance.

At present, people face the danger of various occupational exposures, resulting in the rapid development of protective composites among which puncture-resistant materials are an essential component. In this article, composites impregnated with polyester polyurethane (TPU)/SiO2 are used to improve static puncture resistance. Different types of TPU and different concentrations of SiO2 in the impregnation solution are selected. The mechanical and wearing-related properties of composites are systematically explored and analyzed. The results show that static puncture resistance and tensile strength are improved after impregnation. Meanwhile, the composites can still maintain a good water-vapor transmission rate. The air permeability, tearing strength, elongation at break and flexibility of the composites decrease slightly. This study provides a novel and feasible strategy to prepare a flexible composite with high static puncture resistance as well as excellent wearability which is a desirable candidate as a garment accessory or gaket protecting the human body from puncture risk.

The neglected role of micronutrients in predicting soil microbial structure.

Predicting the distribution patterns of soil microbial communities requires consideration of more environmental drivers. The effects of soil micronutrients on composition of microbial communities are largely unknown despite micronutrients closely relating to soil fertility and plant communities. Here we used data from 228 agricultural fields to identify the importance of micronutrients (iron, zinc, copper and manganese) in shaping structure of soil microbial communities (bacteria, fungi and protist) along latitudinal gradient over 3400 km, across diverse edaphic conditions and climatic gradients. We found that micronutrients explained more variations in the structure of microbial communities than macronutrients in maize soils. Moreover, micronutrients, particularly iron and copper, explained a unique percentage of the variation in structure of microbial communities in maize soils even after controlling for climate, soil physicochemical properties and macronutrients, but these effects were stronger for fungi and protist than for bacteria. The ability of micronutrients to predict the structure of soil microbial communities declined greatly in paddy soils. Machine learning approach showed that the addition of micronutrients substantially increased the predictive power by 9-17% in predicting the structure of soil microbial communities with up to 69-78% accuracy. These results highlighted the considerable contributions of soil micronutrients to microbial community structure, and advocated that soil micronutrients should be considered when predicting the structure of microbial communities in a changing world.

Core phylotypes enhance the resistance of soil microbiome to environmental changes to maintain multifunctionality in agricultural ecosystems.

Agricultural ecosystems are facing increasing environmental changes. Revealing ecological stability of belowground organisms is key to developing management strategies that maintain agricultural ecosystem services in a changing world. Here, we collected soils from adjacent pairs of maize and rice fields along large spatial scale across Eastern and Southeast China to investigate the importance of core microbiota as a predictor of resistance of soil microbiome (e.g. bacteria, fungi and protist) to climate changes and nutrient fertilization, and their effect on multiple ecosystem functions, representing key services for crop growth and health in agro-ecosystems. Soil microbiome in maize soils exhibited stronger resistance than that in rice soils, by considering multiple aspects of the resistance index, for example, community, phylogenetic conservation and network complexity. Community resistance of soil microbiome showed a geographic pattern, with higher resistance at lower latitudes, suggesting their stronger resistance in warmer regions. Particularly, we highlighted the role of core phylotypes in enhancing the community resistance of soil microbiome, which was essential for the maintenance of multifunctionality in agricultural ecosystems. Our results represent a significant advance in linking core phylotypes to community resistance and ecosystem functions, and therefore forecasting agro-ecosystems dynamics in response to ongoing environmental changes. These suggest that core phylotypes should be considered a key factor in enhancing agricultural sustainability and crop productivity under global change scenarios.

Tug1 Acts on ERK12 Signaling Pathway to Aggravate Neuronal Damage after Acute Ischemic Stroke.

Approximately 85% of stroke patients suffer from ischemic stroke, which has a high incidence and difficult prognosis. It has become one of the leading causes of death in middle-aged and elderly people and seriously threatens human health. This study mainly considers the role of lncRNA tug 1 on the ERK 12 signaling pathway to enhance neuronal damage after acute ischemic stroke. In the experiment, the middle cerebral artery occlusion (MCAO) model was constructed using the thread embolization method. The real-time quantitative RT-CR method was used to detect the relative transcriptional activity of TG1, GAS5 and SM22a genes in tissues. The relative expression level of SM22a protein in tissues was detected by the immune-histochemical method. Twenty-four hours after cerebral infarction, the nerve function, cerebral infarction area and ERK1/2 protein expression level of cerebral cortex on the side of cerebral infarction were detected in each group. The experimental results showed that the successful animal behavior scores of the MCAO model in the normal saline control group and Pepstatin A interference group were 1 point 25, 2 points 17 and 3 points 18. The results show that lncRNA tug1 can enhance the neuronal damage of the ERK12 signaling pathway after acute ischemic stroke. lncRNATUGl plays an important role after OGD/RX and can accelerate cell apoptosis. If the expression of lncRNATUGl is inhibited, the number of apoptosis is significantly reduced.

Salvianolic acid B attenuates membranous nephropathy by activating renal autophagy via microRNA-145-5p/phosphatidylinositol 3-kinase/AKT pathway.

The abnormal proliferation and inflammatory response of the mesangial cells play a crucial role in the progression of membranous nephropathy (MN). Herein, this study aimed to investigate the therapeutic effect of Salvianolic acid B (SalB) on MN-induced mesangial abnormalities and its underlying mechanisms. MN models were established in cationic bovine serum albumin-induced Sprague-Dawley rats and lipopolysaccharide-induced human mesangial cells (HMCs). Following SalB and microRNA-145-5p antagomir treatment, kidney function was investigated by 24-hours urine protein, serum creatinine, and blood urea nitrogen. Pathological changes of kidney were investigated by Periodic acid Schiff staining. CD68 and IgG were detected by immunofluorescence in glomerulus. Mesangial autophagosomes were observed by transmission electron microscope. MicroRNA-145-5p inhibitor, mimic, LY294002, and SalB were used to treat with HMCs. In kidney and HMCs, IL-1 ß, IL-2, IL-6, TNF-α and microRNA-145-5p was detected by quantitative real-time PCR. Phosphatidylinositol 3-kinase (PI3K), phosphorylated AKT, AKT, beclin1, and microtubule-associated protein light chain 3 (LC3) levels were detected by Western blot. HMCs proliferation and cycle were detected by Cell Counting Kit-8 and flow cytometry. LC3 were detected by LC3-dual-fluorescent adenovirus in HMCs. Our results showed that SalB significantly ameliorated kidney function and pathological changes. Furthermore, it significantly alleviated proliferation, inflammation and activated autophagy in mesangial cells. Moreover, microRNA-145-5p antagomir accentuated MN while microRNA-145-5p inhibitor and LY294002 encouraged proliferation and inflammation through PI3K/AKT pathway in HMCs. Collectively, our study demonstrated that SalB activated renal autophagy to reduce cell proliferation and inflammation of MN, which was mediated by microRNA-145-5p to inhibit PI3K/AKT pathway, and ultimately attenuated MN.

Long-Term Effect of ß-Blocker Use on Clinical Outcomes in Postmyocardial Infarction Patients: A Systematic Review and Meta-Analysis.

Background: Prior studies provided inconsistent results regarding long-term effect of ß-blocker use on clinical outcomes in postmyocardial infarction (MI) patients. Methods: We searched for articles regarding long-term effect of ß-blocker use on clinical outcomes in patients after MI and published them before July 2021 in the databases as follows: PubMed, Web of Science, MEDLINE, EMBASE, and Google Scholar. STATA 12.0 software was used to compute hazard ratios (HRs) and their 95% confidence intervals (CIs). Results: The study indicated that ß-blocker group had significantly lower long-term all-cause mortality, cardiovascular mortality, major adverse cardiac events (MACEs) in post-MI patients, compared to no ß-blocker group (all-cause mortality: HR, 0.67; 95% CI: 0.56-0.80; cardiovascular mortality: HR, 0.62; 95% CI: 0.49-0.78; MACE: HR, 0.87; 95% CI: 0.75-1.00). The study indicated no significant long-term effect of ß-blocker use on risk of hospitalization for heart failure (HF), risk of recurrent MI, risk of stroke, and risk of repeat revascularization in post-MI patients (risk of hospitalization for HF: HR, 0.82; 95% CI: 0.58-1.16; risk of recurrent MI: HR, 0.93; 95% CI: 0.78-1.11; risk of stroke: HR, 0.94; 95% CI: 0.79-1.12; risk of repeat revascularization: HR, 0.91; 95% CI: 0.80-1.04). Conclusions: The meta-analysis demonstrated significant long-term effects of ß-blocker use on all-cause mortality, cardiovascular mortality, and risk of MACE in post-MI patients, whereas no significant long-term effect was shown on risk of hospitalization for HF, risk of recurrent MI, risk of stroke, and risk of repeat revascularization in post-MI patients.

Clinical profile and outcome of non-HIV-infected patients with cryptococcal meningitis and malignancy.

BACKGROUND: Cryptococcal meningitis (CM) can coexist with malignancy in patients not infected by human immunodeficiency virus (HIV). The purpose of this study was to evaluate the clinical characteristics and therapeutic outcomes of non-HIV-infected patients with CM with malignancy. METHODS: The study cohort comprised 320 patients diagnosed with CM from January 2013 to May 2019. Malignancy was diagnosed based on the medical history, imaging findings, and pathological findings. One-hundred-and-four patients also underwent positron emission computed tomography (PET-CT) examination to enable the early detection of possible malignancies. The demographics, clinical characteristics, and outcomes were analyzed. RESULTS: Twelve patients with CM with malignancies were found. Seven were patients with CM who had a history of malignancies (CM in malignancy; CIM), while five patients had malignancies detected after being diagnosed with CM (malignancy in CM; MIC). The patients with CM with malignancies, especially MIC, were older than those without malignancies. The outcome was similar for patients with CIM and patients with CM without malignancy, but was extremely poor for patients with MIC. PET-CT examination suggested malignancy in five of 104 patients, with malignancy finally confirmed in four of five patients. CONCLUSIONS: Compared with the general population, the rate of solid malignancies was increased in patients with CM, especially older adults. The presence of malignancies and timing of discovery were closely related to the outcome of patients with CM. Thus, it is necessary to screen for malignancies in older adults with CM. PET-CT might be useful for early malignancy screening of patients with CM.