Interactions between flue gas desulfurization gypsum and biochar on water infiltration characteristics and physicochemical properties of saline-alkaline soil.

The application of flue gas desulfurization gypsum (FGDG) improves the soil structure, reduces soil pH, and accelerates soil salt leaching. Biochar amendment to soil can affect the soil infiltration rate, increase soil porosity, decrease soil bulk density, and enhance the water retention capacity. This study investigated the interactive effect of FGDG and biochar on water infiltration characteristics and physicochemical properties as well as determined the optimal amendment rate as a saline-alkaline soil conditioner. Seven experimental schemes were designed, and the newly reclaimed cultivated soil from Pingtan Comprehensive Experimental Zone in Fujian Province, China, was used in an indoor soil column experiment to simulate soil infiltration. Five models were employed to describe the infiltration process. The power function was used to represent the dynamic process of the wetting front. The conclusions of this study are as follows: (1) there was a reduction in the infiltration capacity of saline-alkaline soil (sandy soil) in each treatment, and the application of FGDG alone had the highest inhibition effect compared to the control (CK). The Kostiakov model provides the best fit for the experimental data of soil cumulative infiltration. (2) All treatments increased the total porosity and water content of saline-alkali soil, with the combined application of FGDG and biochar found to be more effective. (3) The application of FGDG alone or in combination with biochar decreased the pH and increased the electrical conductivity of the saline-alkali soil significantly, with the combined application having the most significant effect. In contrast, soil amended with biochar alone had minimal effect on the pH and EC of the soil. (4) The best improvement ratio was achieved with the F1B2 combination (75 g/kg FGDG + 30 g/kg biochar).

Prevalence And Correlation Analysis Between Post-Traumatic Stress Disorder And Analgesic Use In Survivors Of ICU In China.

Objectives: To investigate the prevalence of post-traumatic stress disorder in intensive care unit survivors, and disorder's correlation with analgesia use. METHODS: The single-centre retrospective cohort study was conducted at the First Affiliated Hospital of Jinan University, China, and comprised data from February 2021 to January 2022 related to patients of either gender aged =18 years who were admitted to the intensive care unit and were successfully transferred out to the general ward. Post- traumatic stress disorder Checklist-Civilian Version scale was used for follow-up within one month of getting transferred out of intensive care. Data was analysed using Empower Stats. RESULTS: Of the 121 patients with mean age 54.34±18.19 years, 52(43%) were positive for post-traumatic stress disorder; 32(61.5%) males and 20(38.5%) females with mean age 54.48±19.56 years.The remaining 69(57%) patients were negative; 40(58%) males and 29(42%) females with mean age 54.23±17.24 years (p>0.05). The positive rate of re- experiencing symptoms was noted in 68(56.20%) patients. Analgesia usage was positive in 61(50.4%) cases and negative in 60(49.6%) cases. Compared to the non-analgesic group, the risk of post-traumatic stress disorder occurrence in the analgesic group wassignificantly high (p=0.018). The duration of analgesia usage 24-48h was also significant (p=0.017). CONCLUSIONS: There was a high prevalence of post-traumatic stress disorder in intensive care unit survivors, which was affected by the use of analgesicsin intensive care settings.

Nitrogeniibacter mangrovi gen. nov., sp. nov., a novel anaerobic and aerobic denitrifying betaproteobacterium and reclassification of Azoarcus pumilus as Aromatoleum pumilum comb. nov.

Denitrification is a vital link in the global bio-nitrogen cycle. Here, we isolated a strain (M9-3-2T) that is a novel benzo[a]pyrene (BaP)-tolerant, anaerobic and aerobic denitrifying bacterium from a continuous BaP-enrichment cultured mangrove sediment. In silico comparative genomics and taxonomic analysis clearly revealed that strain M9-3-2T (=MCCC 1K03313T=JCM 32045T) represents a novel species of a novel genus named as Nitrogeniibacter mangrovi gen. nov., sp. nov., belonging to family Zoogloeaceae, order Rhodocyclales. In addition, the species Azoarcus pumilus is transferred into genus Aromatoleum and named Aromatoleum pumilum comb. nov. The predominant respiratory quinone of strain M9-3-2T was ubiquinone-8 and the major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, three unidentified phospholipids and three unidentified aminophospholipids. In this study, the capacity of strain M9-3-2T to eliminate nitrate was detected under anaerobic and aerobic conditions, and the removal rates of nitrate were 6.1×10-6 µg N/l/h/cell and 3×10-7 µg N/l/h/cell, respectively. Our results suggested that strain M9-3-2T could play an important role in the nitrogen removal regardless of the presence of oxygen in natural or/and man-made ecosystems.

Simultaneous quantification and rat pharmacokinetics of formononetin-7-O-ß-d-glucoside and its metabolite formononetin by high-performance liquid chromatography-tandem mass spectrometry.

Formononetin-7-O-ß-d-glucoside has been proved to have significant anti-inflammatory effect. To evaluate its rat pharmacokinetics, a rapid, sensitive, and specific liquid chromatography-tandem mass spectrometry method has been developed and validated for the quantification of formononetin-7-O-ß-d-glucoside and its main metabolite formononetin in rat plasma. Samples were pretreated using a simple protein precipitation and the chromatographic separation was performed on a C18 column by a gradient elution using a mobile phase consisting of water and acetonitrile both containing 0.1% formic acid. Both analytes were detected using a tandem mass spectrometer in positive multiple reaction monitoring mode. The assay showed wide linear dynamic ranges of both 0.10-100 ng/mL, with acceptable intra- and inter-batch accuracy and precision. The lower limits of quantification were both 0.10 ng/mL using 50 µL of rat plasma for two analytes. The method has been successfully used to investigate the oral pharmacokinetic profiles of both analytes in rats. After oral administration of formononetin-7-O-ß-d-glucoside at the dose of 50 mg/kg, it was rapidly absorbed in vivo and metabolized to its metabolite formononetin. The plasma concentration-time profiles both showed double-peak phenomena, which would be attributed to the strong enterohepatic circulation of formononetin-7-O-ß-d-glucoside.

[Analysis of genetic and clinical characteristics of nine cases of myelodysplastic syndrome with near tetraploid/tetraploidy karyotype].

OBJECTIVE: To explore the genetic and clinical characteristics of near-tetraploidy/tetraploidy karyotype (NT/T) in patients with myelodysplastic syndrome (MDS). METHODS: Cytogenetic findings of 1576 inpatients with primary MDS were retrospective analyzed, among which 9 were diagnosed with NT/T. Clinical data including gender, age, morphology, genetic feature and prognosis were analyzed. RESULTS: The prevalence of MDS patients with NT/T (NT/T-MDS) among all cases was 0.57%. Karyotyping analysis suggested that eight MDS patients had sole NT/T, while the remainder one had a complex karyotype. In addition to the typical morphology of MDS, NT/T-MDS had unique morphology including huge blast, double-nuclear cell and irregular nuclear membrane. One NT/T-MDS patient gave up therapy, and the remaining eight underwent the first course of treatment, albeit with poor prognosis. Only one patient had complete remission, one had partial remission, three had no remission; and three had converted to acute myeloid leukemia. CONCLUSION: NT/T-MDS is rare and has unique morphology. Generally, NT/T-MDS patients have poor prognosis. However, NT/T cannot be simply classified as high-risk group, but with consideration whether they have affected particular chromosomal structures as well as other clinical data.

Sphingosinithalassobacter portus gen. nov., sp. nov., a novel member of the family Sphingomonadaceae isolated from surface seawater.

A Gram-stain-negative strain, designated FM6T, was isolated from surface seawater sampled at the port in Xiamen, PR China. Strain FM6T showed less than 96.3 % 16S rRNA gene sequence similarity to the type strains of species with validly published names. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain FM6T belonged to the family Sphingomonadaceae and was closely related to species of the genera Sphingomonas (96.3 %) and Stakelama (96.0 %). Ubiquinone-10 was the predominant respiratory quinone. Cells were motile with a single polar flagellum. Growth occurred at temperatures from 20 to 45 °C (optimum, 30 °C), at pH values between pH 6.0 and 8.0 (optimum, pH 7.0) and in 0-4.0 % (w/v) NaCl (optimum, 1.0-1.5 %). Predominant polar lipids were sphingoglycolipid, phosphatidylcholine, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, five unidentified glycolipids and five unidentified polar lipids. The major fatty acids were summed feature 8 (containing C18 : 1ω7c and/or C18 : 1ω6c). The DNA G+C content of the type strain was 63.8 mol%. On the basis of the results of phylogenetic analysis, combined with phenotypic and chemotaxonomic data, strain FM6T is considered to represent a novel species in a new genus in the family Sphingomonadaceae for which the name Sphingosinithalassobacter portus gen. nov., sp. nov. is proposed. The type strain of Sphingosinithalassobacter portus gen. nov., sp. nov. is FM6T (=MCCC 1K03501T=JCM 32714T).

Mangrove Sediment Microbiome: Adaptive Microbial Assemblages and Their Routed Biogeochemical Processes in Yunxiao Mangrove National Nature Reserve, China.

Microorganisms play important roles in mangrove ecosystems. However, we know little about the ecological implications of mangrove microbiomes for high productivity and the efficient circulation of elements in mangrove ecosystems. Here, we focused on mangrove sediments located at the Yunxiao National Mangrove Reserve in southeast China, uncovering the mangrove microbiome using the 16S rRNA gene and shotgun metagenome sequencing approaches. Physicochemical assays characterized the Yunxiao mangrove sediments as carbon (C)-rich, sulfur (S)-rich, and nitrogen (N)-limited environment. Then phylogenetic analysis profiling a distinctive microbiome with an unexpected high frequency of Chloroflexi and Nitrospirae appeared to be an adaptive characteristic of microbial structure in S-rich habitat. Metagenome sequencing analysis revealed that the metabolic pathways of N and S cycling at the community-level were routed through ammonification and dissimilatory nitrate reduction to ammonium for N conservation in this N-limited habitat, and dissimilatory sulfate reduction along with polysulfide formation for generating bioavailable S resource avoiding the biotoxicity of sulfide in mangrove sediments. In addition, methane metabolism acted as a bridge to connect C cycling to N and S cycling. Further identification of possible biogeochemical linkers suggested Syntrophobacter, Sulfurovum, Nitrospira, and Anaerolinea potentially drive the coupling of C, N, and S cycling. These results highlighting the adaptive routed metabolism flow, a previously undescribed property of mangrove sediment microbiome, appears to be a defining characteristic of this habitat and may significantly contribute to the high productivity of mangrove ecosystems, which could be used as indicators for the health and biodiversity of mangrove ecosystems.

Different Height Forms of Spartina alterniflora Might Select Their Own Rhizospheric Bacterial Communities in Southern Coast of China.

In the southernmost part of coast of China, two height forms of Spartina alterniflora, tall and short, have invaded Leizhou Peninsula within the last decade. However, the effect of different height forms of Spartina alterniflora on plant-microbe interaction has not been clarified. Here, the community structures of rhizosphere bacteria and the abundance of N- and S-cycling functional genes associated with selected S. alterniflora were investigated in the field and a common garden. The community structure of tall-form S. alterniflora was distinct from short-form S. alterniflora at OTU level in the field, even after transplantation into a common garden. The abundance of bacterial amoA, nirS, and nosZ in tall S. alterniflora was significantly greater than those in short S. alterniflora in the field; however, this difference disappeared in a 1-year common garden experiment. These results suggested that compared with the tall-form S. alterniflora, the rhizosphere of short-form S. alterniflora harbored fewer nitrification-denitrification related microorganisms, which might benefit from conserving N in an N limited habitat. Together, our results suggested that tall- and short-form S. alterniflora can host their specific rhizosphere microbial communities and had different strategies of N usage via selecting the composition of rhizosphere bacterial assemblages, which in turn might determine the growth and invasiveness of S. alterniflora in its introduced range.

Subacute combined degeneration of the spinal cord is associated with tripterygium glycoside tablet usage.

BACKGROUND: Subacute combined degeneration (SCD) is a neurodegenerative disease caused by vitamin B12 deficiency. The lesions mainly involve the posterior cord, lateral cord, and peripheral nerves. Occasionally, the lesions also involve brain white matter and optic nerves in severe cases. Reports of drug-induced impaired absorption and metabolism of vitamin B12 resulting in SCD are scarce. INTRODUCTION: A patient developed SCD after long-term use of tripterygium glycoside tablets in the treatment of glomerulonephritis. However, after discontinuation and vitamin B12 treatment with tripterygium glycoside tablet, the symptoms of SCD were significantly resolved. CONCLUSION: Drug-induced SCD is a less commonly reported cause of the disease. Tripterygium glycoside tablets can induce adverse reactions in the digestive system, causing damage to absorption and metabolism of vitamin B12. Physicians should be aware of the possibility of tripterygium glycoside tablet-induced SCD after excluding more common causes such as inadequate dietary intake and impaired absorption due to gastrointestinal diseases or genetic disorders.

Zhengella mangrovi gen. nov., sp. nov., a novel member of family Phyllobacteriaceae isolated from mangrove sediment.

A Gram-negative strain, designed X9-2-2T, was isolated from mangrove sediment in Yunxiao Mangrove National Nature Reserve, China. Strain X9-2-2T showed less than 96.2 % 16S rRNA gene sequence similarity to type strains of species with validly published names. Phylogenetic analysis based on 16S rRNA gene sequences and rpoB protein sequences revealed that strain X9-2-2T formed a distinct monophyletic clade within the family Phyllobacteriaceae and clustered distantly with the genera Aliihoeflea, Phyllobacterium and Hoeflea. Cells of X9-2-2T were rod-shaped, motile with subpolar or lateral flagella and facultative anaerobic. Optimal growth occurred at 30-37 °C, at pH 7 and in the presence of 2 % NaCl. The DNA G+C content of strain X9-2-2T was 64.9 mol%. The major fatty acids were summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c 56.0 %), iso -C17 : 0 (9.1 %) and C12 : 0 (6.6 %). The predominant respiratory quinone was ubiquinone-10 and the major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylmonomethylethanolamine, an unidentified aminolipid and two unidentified polar lipids. According to its morphology, physiology, fatty acid composition and 16S rRNA gene signature nucleotide patterns, strain X9-2-2T represents a novel species of a novel genus in the family Phyllobacteriaceae, for which the name Zhengella mangrovi gen. nov., sp. nov. is proposed. The type strain is X9-2-2T (=MCCC 1K03307T=JCM 32107T).

Molecular and stable isotopic evidence for the occurrence of nitrite-dependent anaerobic methane-oxidizing bacteria in the mangrove sediment of Zhangjiang Estuary, China.

Nitrite-dependent anaerobic methane oxidation (n-damo), which is mediated by "Candidatus Methylomirabilis oxyfera-like" bacteria, is unique in linking the carbon and nitrogen cycles. However, the niche and activity of n-damo bacteria in the mangrove ecosystem have not been confirmed. Here, we report the occurrence of the n-damo process in the mangrove wetland of the Zhangjiang Estuary, China. The widespread occurrence of n-damo bacteria in mangrove wetland was confirmed using real-time quantitative polymerase chain reaction (qPCR) assay, which showed that the abundance of Methylomirabilis oxyfera-like bacterial 16S rRNA and pmoA genes ranged from 2.43 × 106 to 2.09 × 107 and 2.07 × 106 to 3.38 × 107copies per gram of dry soil in the examined sediment cores. The highest amount of targeting genes was all detected in the upper layer (0-20 cm). Phylogenetic analyses of n-damo bacterial 16S rRNA and pmoA genes illustrated the depth-specific distribution and high diversity of n-damo bacteria in the mangrove wetland. Stable isotope experiments further confirmed the occurrence of n-damo in the examined mangrove sediments, and the potential n-damo rates ranged from 25.93 to 704.08 nmol CO2 per gram of dry soil per day at different depths of the sediment cores, with the n-damo being more active in the upper layer of the mangrove sediments. These results illustrate the existence of active M. oxyfera-like bacteria and indicate that the n-damo process is a previously overlooked microbial methane sink in the mangrove wetlands.

Altererythrobacter mangrovi sp. nov., isolated from mangrove sediment.

A Gram-stain-negative, facultative anaerobic, yellow-pigmented, rod-shaped, non-flagellum and non-motile bacterial strain, designed C9-11T, was isolated from mangrove sediment in Zhangzhou, Fujian Province, China. Growth was observed at temperatures from 15 to 37 °C (optimum 30 °C), at salinities from 0 to 4 % (optimum 0.5-2 %) and at pH from 6 to 8 (optimum 7). Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain C9-11T was a member of the genus Altererythrobacter. Strain C9-11T was related most closely to Altererythrobacter oceanensis Y2T (96.8 % 16S rRNA gene sequence similarity), followed by Altererythrobacter marinus H32T (96.5 %). The G+C content of the genomic DNA was 63.5 mol%. The dominant fatty acids were C18 : 1ω7c (41.6 %), C17 : 1ω6c (15.4 %), 11-methyl C18 : 1ω7c (8.1 %), summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c 7.4 %) and C16 : 0 (6.2 %). The predominant respiratory quinone was ubiquinone-10 and the major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and sphingoglycolipid. According to its morphology, physiology, fatty acid composition and 16S rRNA gene sequence analysis, strain C9-11Tbelongs to genus Altererythrobacter, but can readily be distinguished from recognized species. Strain C9-11T is proposed as the type strain of a novel species of the genus Altererythrobacter, for which the nameAltererythrobactermangrovi sp. nov (=MCCC 1K03311T=JCM 32056T) is proposed.

Mangrovitalea sediminis gen. nov., sp. nov., a member of the family Alteromonadaceae isolated from mangrove sediment.

A Gram-stain-negative, facultative anaerobic and oligotrophic, rod-shaped, and motile with single polar flagellum bacterial strain, designed M11-4T was isolated from mangrove sediment in Yunxiao Mangrove National Nature Reserve, China. Growth was observed at temperatures from 10 to 40 °C (optimum 30 °C), at salinities from 0.5 to 6 % (optimum 2-3 %), and at pH from 5 to 8 (optimum 6). Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain M11-4T shared highest sequence similarity with the genus Marinobacter(92.5-95.0 %) and represented a distinct phylogenetic lineage in the family Alteromonadaceae. The G+C content of the genomic DNA was 58.2 mol%. The dominant fatty acids were C16 : 0, C16 : 0 N-alcohol, summed feature 9 (comprising iso-C17 : 1ω9c and/or C16 : 0 10-methyl) and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). The predominant respiratory quinone was ubiquinone-9 and the major polar lipids were diphosphatidylglycerol; phosphatidylethanolamine; phosphatidylglycerol and an unidentified aminophospholipid. According to its morphology, physiology, fatty acid composition and 16S rRNA gene sequence analysis, the strain M11-4T should be assigned as a novel species of a novel genus for which the name Mangrovitalea sediminis gen. nov., sp. nov. is proposed. The type strain of Mangrovitalea sediminis is M11-4T (=MCCC 1K03312T=JCM 32104T).

Immunostimulation by cytosine-phosphate-guanine oligodeoxynucleotides in combination with IL-2 can improve the success rate of karyotype analysis in chronic lymphocytic leukaemia.

PURPOSE: To assess whether immunostimulatory cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODN) combined with interleukin-2 (IL-2) improves the number of mitotic metaphases and the detection rate of chromosomal abnormalities in chronic lymphocytic leukaemia (CLL). MATERIALS AND METHODS: Bone marrow specimens were collected from 36 patients with CLL. CLL cells were cultured with CpG-ODN type DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Conventional culture without the immunostimulant served as the control group. The incidence of genetic abnormalities was measured by fluorescence in situ hybridisation (FISH) using a panel of five specific probes: D13S25 (13q14.3), RB1 (13q14), P53 (17p13), ATM (11q22.3) and CSP12 (trisomy 12, +12). RESULTS: In the control group, chromosome analysis achieved a success rate of only 22.2, and 11.1% of abnormal karyotypes were detected. After immunostimulation with DSP30 plus IL-2, chromosome analysis achieved a success rate of up to 91.6, and 41.6% of abnormal karyotypes were detected. FISH analysis detected 77.7% of abnormalities. FISH combined with CpG-ODN DSP30 plus IL-2 improved the detection rate of chromosomal abnormalities in CLL to 83.3%. CONCLUSION: CpG-ODN DSP30 combined with IL-2 is effective in improving the detection rate of chromosomal abnormalities in CLL cells. This combination with FISH analysis is conducive to increasing the detection rate of genetic abnormalities in CLL.

[Application of fluorescent in situ hybridization in primary diagnosis of aplastic anemia by morphology].

OBJECTIVE: To investigate the clinical application of fluorescent in situ hybridization (FISH) for the differential diagnosis of myelodysplastic syndromes (MDS) and aplastic anemia (AA). METHODS: A FISH kit capable of detecting the chromosomal abnormalities related to MDS was used to analyze 94 patients who were suspected to have AA by bone marrow morphology. RESULTS: Cytogenetic abnormalities were detected in 11 of the 94 patients, which included trisomy 8 (5 cases), 20q- (1 case) and -Y (1 case). There were 4 cases related to MDS, which included 3 cases of 5q-, in which 1 case carry 20q- at the same time, and 7q- (1 case). No significant difference was found between the MDS and AA groups in terms of age, sex or routine blood examination including absolute neutrophil count, hemoglobin content and platelet count. CONCLUSION: FISH can detect certain cytogenetic abnormalities related to MDS in patients morphologically diagnosed as AA.

[Pathogenetic mechanism for a female patient with hemophilia A].

OBJECTIVE: To explore the pathogenetic mechanism for a female patient affected with hemophilia A (HA). METHODS: Potential genetic defect was detected with inverse shifting-polymerase chain reaction (IS-PCR). The pattern of X chromosome inactivation was determined with a human androgen receptor assay (HUMARA assay). G-banded karyotyping was carried out to exclude potential chromosome aberrations. RESULTS: IS-PCR showed that the defect of FVIII gene was the distal type of intron 22 inversion. The HUMARA assay showed that the X chromosome inactivation was non-random, and that the mother's X chromosome activity was lower than that of the father's X chromosome which has carried the inverted FVIII gene. No abnormalities were found with G-banded chromosomes. CONCLUSION: The prevalence of female HA patient may be caused by non-random inactivation of X chromosomes.

New light on ω-3 polyunsaturated fatty acids and diabetes debate: a population pharmacokinetic-pharmacodynamic modelling and intake threshold study.

OBJECTIVE: ω-3 polyunsaturated fatty acids (PUFA) are a key modifiable factor in the intervention of type 2 diabetes, yet recommendations for dietary consumption of ω-3 PUFA in type 2 diabetes remain ambiguous and controversial. Here, we revisit the subject in the light of population pharmacokinetic-pharmacodynamic (PPK-PD) modeling and propose a threshold for intake. RESEARCH DESIGN AND METHODS: Plasma levels of ω-3 PUFA and glycosylated hemoglobin (HbA1c) were measured as pharmacokinetic and pharmacodynamic indicator, respectively. The nonlinear mixed effect analysis was used to construct a PPK-PD model for ω-3 PUFA and to quantify the effects of FADS gene polymorphism, age, liver and kidney function, and other covariables. RESULTS: Data from 161 patients with type 2 diabetes in the community were modeled in a two-compartment model with primary elimination, and HDL was a statistically significant covariate. The simulation results showed that HbA1c showed a dose-dependent decrease of ω-3 PUFA plasma level. A daily intake of ω-3 PUFA at 0.4 g was sufficient to achieve an HbA1c level of 7% in more than 95% of patients. CONCLUSIONS: PPK/PD modeling was proposed as a multilevel analytical framework to quantitatively investigate finer aspects of the complex relationship between ω-3 PUFA and type 2 diabetes on genetic and non-genetic influence factors. The results support a beneficial role for ω-3 PUFA in type 2 diabetes and suggested the intake threshold. This new approach may provide insights into the interaction of the two and an understanding of the context in which changes occur.

Effectiveness of novel ß-lactams for Pseudomonas aeruginosa infection: A systematic review and meta-analysis.

BACKGROUND: Novel ß-lactams have in vitro activity against Pseudomonas aeruginosa (PA), but their clinical performances and the selection criteria for practical use are still not clear. We aimed to evaluate the efficacy of novel ß-lactams for PA infection in various sites and to compare the efficacy of each agent. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science for randomized controlled trials that used novel ß-lactams to treat PA infection. The primary outcomes were clinical cure and favorable microbiological response. Subgroup analyses were performed based on drug type, drug resistance of pathogens, and site of infection. Network meta-analysis was carried out within a Bayesian framework. RESULTS: In all studies combined (16 randomized controlled trials), novel ß-lactams indicated comparable performance to other treatment regimens in both outcome measures (relative risk = 1.04; 95% confidence interval 0.94-1.15; P = .43) (relative risk = 0.97; 95% confidence interval 0.81-1.17; P = .76). Subgroup analyses showed that the efficacy of ceftolozane-tazobactam (TOL-TAZ), ceftazidime-avibactam (CAZ-AVI), imipenem-cilastatin-relebactam, and cefiderocol had no apparent differences compared to control groups among different infection sites, drug types and drug resistance of PA. In network meta-analysis, the results showed no statistically significant differences between TOL-TAZ, CAZ-AVI, and cefiderocol. CONCLUSIONS: TOL-TAZ, CAZ-AVI, imipenem-cilastatin-relebactam, and cefiderocol are not inferior to other agents in the treatment of PA infection. Their efficacy is also comparable between TOL-TAZ, CAZ-AVI, and cefiderocol.

Efficacy of MUC1-targeted CAR-NK cells against human tongue squamous cell carcinoma.

Introduction: The clinical efficacy of CAR-NK cells against CD19-expressing blood cancers has been demonstrated, and they have shown potential for treating solid tumors as well. However, the efficacy of CAR-NK cells for treating human oral tongue squamous cell carcinoma (OTSCC) has not been examined. Methods: We assessed MUC1 expression in human OTSCC tissue and a cell line using immunohistochemistry and immunofluorescence. We constructed NK cells that express CAR targeted to MUC1 from pluripotent stem cells (iPSC-derived MUC1-targeted CAR-NK cells) and evaluated their effectiveness against OTSCC in vitro using the xCELLigence Real-Time Cell Analysis system and CCK8 assay, and in vivo by measuring xenograft growth daily in BNDG mice treated with MUC1-targeted CAR-NK cells. As controls, we used iPSC-derived NK cells and NK-free media, which were CAR-free and blank, respectively. Results: MUC1 expression was detected in 79.5% (66/83) of all OTSCC patients and 72.7% (24/33) of stage III and IV. In stage III and IV MUC1 positive OTSCC, 63.6% (21/33) and 48.5% (16/33) patients had a MUC1-positive cancer cell rate of more than 50% and 80%, respectively. The iPSC-derived MUC1-targeted CAR-NK cells exhibited significant cytotoxicity against MUC1-expressing OTSCC cells in vitro, in a time- and dose-dependent manner, and showed a significant inhibitory effect on xenograft growth compared to both the iPSC-derived NK cells and the blank controls. We observed no weight loss, severe hematological toxicity or NK cell-mediated death in the BNDG mice. Conclusion: The MUC1-targeted CAR-NK cells had significant efficacy against human OTSCC, and their promising therapeutic response warrants further clinical trials.

Efficacy of the induced pluripotent stem cell derived and engineered CD276-targeted CAR-NK cells against human esophageal squamous cell carcinoma.

Introduction: Chimeric antigen receptor natural killer (CAR-NK) cells have been found to be successful in treating hematologic malignancies and present potential for usage in solid tumors. Methods: In this study, we created CD276-targeted CAR-expressing NK cells from pluripotent stem cells (iPSC CD276-targeted CAR-NK cells) and evaluated their cytotoxicity against esophageal squamous cell carcinoma (ESCC) using patient-specific organoid (PSO) models comprising of both CD276-positive and CD276-negative adjacent epithelium PSO models (normal control PSO, NC PSO) as well as primary culture of ESCC cell models. In addition, in vitro and in vivo models such as KYSE-150 were also examined. iPSC NK cells and NK-free media were used as the CAR-free and NK-free controls, respectively. Results: The positive CD276 staining was specifically detected on the ESCC membrane in 51.43% (54/105) of the patients of all stages, and in 51.35% (38/74) of stages III and IV. The iPS CD276-targeted CAR-NK cells, comparing with the iPS NK cells and the NK-free medium, exhibited specific and significant cytotoxic activity against CD276-positive ESCC PSO rather than CD276-negative NC PSO, and exhibited significant cytotoxicity against CD276-expressing cultured ESCC cells, as well as against CD276-expressing KYSE-150 in vitro and in BNDG mouse xenograft. Discussion: The efficacy of the iPSC CD276-targeted CAR-NK cells demonstrated by their successful treatment of CD276-expressing ESCC in a multitude of pre-clinical models implied that they hold tremendous therapeutic potential for treating patients with CD276-expressing ESCC.