Risk factors for Pneumocystis jirovecii pneumonia after kidney transplantation: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Pneumocystis jirovecii pneumonia (PJP), an opportunistic infection, often leads to an increase in hospitalization time and mortality rates in kidney transplant (KT) recipients. However, the risk factors associated with PJP in KT recipients remain debatable. Therefore, we conducted this meta-analysis to identify risk factors for PJP, which could potentially help to reduce PJP incidence and improve outcome of KT recipients. METHODS: We systematically retrieved relevant studies in PubMed, EMBASE, and the Cochrane Library up to November 2023. Pooled odds ratios (ORs) or mean differences (MDs) and the corresponding 95% confidence intervals (CIs) were calculated to assess the impact of potential risk factors on the occurrence of PJP. RESULTS: 27 studies including 42383 KT recipients were included. In this meta-analysis, age at transplantation (MD = 3.48; 95% CI = .56-6.41; p = .02), cytomegalovirus (CMV) infection (OR = 4.00; 95% CI = 2.53-6.32; p = .001), BK viremia (OR = 3.38; 95% CI = 1.70-6.71; p = .001), acute rejection (OR = 3.66; 95% CI = 2.44-5.49; p = .001), ABO-incompatibility (OR = 2.51; 95% CI = 1.57-4.01; p = .001), estimated glomerular filtration rate (eGFR) (MD = -14.52; 95% CI = -25.37- (-3.67); p = .009), lymphocyte count (MD = -.54; 95% CI = -.92- (-.16); p = .006) and anti-PJP prophylaxis (OR = .53; 95% CI = .28-.98; p = .04) were significantly associated with PJP occurrence. CONCLUSION: Our findings suggest that transplantation age greater than 50 years old, CMV infection, BK viremia, acute rejection, ABO-incompatibility, decreased eGFR and lymphopenia were risk factors for PJP.

Impact of cell wall polysaccharide modifications on the performance of Pichia pastoris: novel mutants with enhanced fitness and functionality for bioproduction applications.

BACKGROUND: Pichia pastoris is a widely utilized host for heterologous protein expression and biotransformation. Despite the numerous strategies developed to optimize the chassis host GS115, the potential impact of changes in cell wall polysaccharides on the fitness and performance of P. pastoris remains largely unexplored. This study aims to investigate how alterations in cell wall polysaccharides affect the fitness and function of P. pastoris, contributing to a better understanding of its overall capabilities. RESULTS: Two novel mutants of GS115 chassis, H001 and H002, were established by inactivating the PAS_chr1-3_0225 and PAS_chr1-3_0661 genes involved in ß-glucan biosynthesis. In comparison to GS115, both modified hosts exhibited a looser cell surface and larger cell size, accompanied by faster growth rates and higher carbon-to-biomass conversion ratios. When utilizing glucose, glycerol, and methanol as exclusive carbon sources, the carbon-to-biomass conversion rates of H001 surpassed GS115 by 10.00%, 9.23%, and 33.33%, respectively. Similarly, H002 exhibited even higher increases of 32.50%, 12.31%, and 53.33% in carbon-to-biomass conversion compared to GS115 under the same carbon sources. Both chassis displayed elevated expression levels of green fluorescent protein (GFP) and human epidermal growth factor (hegf). Compared to GS115/pGAPZ A-gfp, H002/pGAPZ A-gfp showed a 57.64% higher GFP expression, while H002/pPICZα A-hegf produced 66.76% more hegf. Additionally, both mutant hosts exhibited enhanced biosynthesis efficiencies of S-adenosyl-L-methionine and ergothioneine. H001/pGAPZ A-sam2 synthesized 21.28% more SAM at 1.14 g/L compared to GS115/pGAPZ A-sam2, and H001/pGAPZ A-egt1E obtained 45.41% more ERG at 75.85 mg/L. The improved performance of H001 and H002 was likely attributed to increased supplies of NADPH and ATP. Specifically, H001 and H002 exhibited 5.00-fold and 1.55-fold higher ATP levels under glycerol, and 6.64- and 1.47-times higher ATP levels under methanol, respectively, compared to GS115. Comparative lipidomic analysis also indicated that the mutations generated richer unsaturated lipids on cell wall, leading to resilience to oxidative damage. CONCLUSIONS: Two novel P. pastoris chassis hosts with impaired ß-1,3-D-glucan biosynthesis were developed, showcasing enhanced performances in terms of growth rate, protein expression, and catalytic capabilities. These hosts exhibit the potential to serve as attractive alternatives to P. pastoris GS115 for various bioproduction applications.

Extramedullary relapsed acute lymphoblastic leukemia presenting as asymptomatic acute kidney injury after hematopoietic stem cell transplantation.

Acute kidney injury (AKI) is a common complication in children with hematological malignancies. Although AKI due to infiltration of tumor cells in children is rare, it negatively impacts treatment outcomes and increases the risk of mortality. We introduce a case of a child with acute lymphoblastic leukemia (ALL) who experienced kidney relapse resulting in asymptomatic AKI after remission from treatment, to remind clinicians not to overlook the primary disease in clinical judgment. In cases of unexplained AKI, kidney biopsy should be performed when feasible to get an accurate diagnosis and scientific treatment. In brief, children with leukemia who have achieved remission after treatment still need regular monitoring of urine routine and kidney function.

Enhanced electrochemical performances based on ZnSnO3 microcubes functionalized in-doped carbon nanofibers as free-standing anode materials.

The binary composite, ZnSnO3 microcubes (ZSO MC) homogeneously parceled in an N-doped carbon nanofiber membrane (ZSO@CNFM), was synthesized via a mild hydrothermal, electrospinning and carbonization process as a flexible lithium-ion battery (LIB) anode material. The unique carbon-coating layer architecture of ZSO@CNFM not only plays a crucial role in alleviating the volume change of ZSO MC during lithium ion insertion/extraction processes, but also constructs a three-dimensional (3D) transport network with the help of interconnected carbon nanofibers (CNFs) to ensure the structural integrity of the material and promote the electrochemical reaction kinetics. Due to its good flexibility characteristics, the as-prepared ZSO@CNFM can be directly adopted as an anode material for LIBs without the use of copper foil, conductive carbon black and any binder. Electrochemical surveying results manifest that the optimal ZSO@CNFM electrode displays excellent cycling stability (582.6 mA h g-1 after 100 lithiation/delithiation cycles at 100 mA g-1), high coulombic efficiency (CE, 99.6% at 100th cycles), and superior rate performance (349.5 mA h g-1 at 2 A g-1). The good electrochemical properties can be ascribed to the synergistic effect of the high theoretical specific capacity of ZSO MC, favourable stability of the carbon substrate, the open structure of ZSO@CNFM and the 3D continuous highly conductive framework for rapid electron/ion transfer.

Efficacy of Eltrombopag with Immunosuppressive Therapy Versus Immunosuppressive Therapy Alone on Severe Aplastic Anaemia: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Severe aplastic anaemia (SAA) is a syndrome of bone marrow failure caused by T cell-mediated destruction of haematopoietic stem cells and progenitor cells. Whether patients with SAA should be treated with eltrombopag (EPAG) and immunosuppressive therapy (IST) or IST alone remains debatable. Therefore, we conducted this meta-analysis to compare the efficacy of eltrombopag + IST with that of IST alone in patients with SAA and to assess the difference in the efficacy of eltrombopag in adults and children. METHODS: We performed this meta-analysis by retrieving studies that met the inclusion and exclusion criteria from PubMed, EMBASE, and the Cochrane Library up to 1 January 2023. We used a random-effects model to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for primary and secondary outcomes. I2 statistics were used to evaluate the heterogeneity of the included studies. RESULTS: Six studies involving a total of 699 patients were included. In terms of the primary outcomes, our pooled results indicated that patients treated with EPAG + IST had a higher 6-month overall response rate (OR = 2.25; 95% CI, 1.60-3.16; p < 0.00001), a higher 6-month complete response rate (OR = 2.61; 95% CI, 1.82-3.74; p < 0.00001), and a lower 6-month nonresponse rate (OR = 0.32; 95% CI, 0.19-0.52; p < 0.00001). However, there was no significant difference in the rate of 6-month partial response (OR = 0.94; 95% CI, 0.49-1.81; p = 0.85). CONCLUSION: This meta-analysis indicated that patients treated with additional eltrombopag for IST may have a higher rate of haematological response.

Using spontaneous eye blink-related brain activity to investigate cognitive load during mobile map-assisted navigation.

The continuous assessment of pedestrians' cognitive load during a naturalistic mobile map-assisted navigation task is challenging because of limited experimental control over stimulus presentation, human-map-interactions, and other participant responses. To overcome this challenge, the present study takes advantage of navigators' spontaneous eye blinks during navigation to serve as event markers in continuously recorded electroencephalography (EEG) data to assess cognitive load in a mobile map-assisted navigation task. We examined if and how displaying different numbers of landmarks (3 vs. 5 vs. 7) on mobile maps along a given route would influence navigators' cognitive load during navigation in virtual urban environments. Cognitive load was assessed by the peak amplitudes of the blink-related fronto-central N2 and parieto-occipital P3. Our results show increased parieto-occipital P3 amplitude indicating higher cognitive load in the 7-landmark condition, compared to showing 3 or 5 landmarks. Our prior research already demonstrated that participants acquire more spatial knowledge in the 5- and 7-landmark conditions compared to the 3-landmark condition. Together with the current study, we find that showing 5 landmarks, compared to 3 or 7 landmarks, improved spatial learning without overtaxing cognitive load during navigation in different urban environments. Our findings also indicate a possible cognitive load spillover effect during map-assisted wayfinding whereby cognitive load during map viewing might have affected cognitive load during goal-directed locomotion in the environment or vice versa. Our research demonstrates that users' cognitive load and spatial learning should be considered together when designing the display of future navigation aids and that navigators' eye blinks can serve as useful event makers to parse continuous human brain dynamics reflecting cognitive load in naturalistic settings.

JMJD3/H3K27me3 epigenetic modification regulates Th17/Treg cell differentiation in ulcerative colitis.

Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized by chronic inflammation and ulceration of the colonic mucosa, frequent relapse, and cancerization that is difficult to cure. In recent years, the incidence of UC has increased. However, its etiology and pathogenesis are still not completely clear. In this study, dextran sodium sulfate (DSS) was used to induce the model, and GSK-J1 and dexamethasone were administered to the mice. A variety of molecular biology and immunological techniques, such as immunofluorescence, PCR and chromatin immunoprecipitation (ChIP), were used to examine JMJD3/H3K27me3-mediated regulation of Th17/Treg cell differentiation in UC by targeting histone modification. This study will provide an important theoretical basis for understanding the pathogenesis and potential therapeutic targets of UC.

Clinical Effects of Acupuncture for Stroke Patients Recovery.

Stroke is assumed as one of the common cerebrovascular diseases that endangers human health and life. Its incidence and mortality rates are high, while survivors (50% to 70%) suffer from different degrees of disability. Hemiplegia is a common disability after stroke, mainly manifested as muscle weakness of the affected side, limb spasm, and limited activity, which severely impacts a patient's daily life. There are various rehabilitation methods for stroke hemiplegia, including modern rehabilitation medicine, motor therapy, acupuncture, and rehabilitation robot. The cost and effect of different rehabilitation methods are not the same. It is the focus to find an economical and effective rehabilitation method. In this paper, 128 stroke patients aged 41 to 73 hospitalized between January 2019 and January 2021 were analyzed. The intervention group used standard physical therapy and traditional acupuncture therapy, and the control group only used standard physical therapy. We used RStudio 1.1.419 (RStudio Corporation) for analysis. Experimental results show that the short-term efficacy of the intervention group is better than that of the control group. The intervention group was better than the control group in recovery from injury during rehabilitation, degree of muscle spasm, self-care ability in daily life, and overall degree of damage. In the long-term efficacy analysis, we can see that with the increase in the number of acupuncture, the efficacy of the intervention group is still better than that of the control group. Compared with physical rehabilitation alone, acupuncture has better short-term, and long-term clinical effects for stroke patients improves motor dysfunction and improves the quality of life and independence of stroke patients. With the increase in the number of acupuncture treatments, the patient's rehabilitation effect will be better.

Efficacy and safety of integrated traditional Chinese medicine and standard Western medicine for patients with acute coronary syndrome: protocol for a systematic review and meta-analysis.

BACKGROUND: Acute coronary syndrome (ACS), which usually results from the buildup of fatty deposits (plaques) in and on the walls of coronary arteries, remains a major cause of morbidity and mortality worldwide. In the present systematic review, we aim to evaluate the efficacy and safety of adding traditional Chinese medicine (TCM) to standard western medicine to treat patients with ACS. METHODS: A systematic search was carried out in the China National Knowledge Infrastructure (CNKI; Chinese), the Chinese Biomedical Literature Disk Database CBMdisc (Chinese), Wanfang Data (Chinese), PubMed, Embase, and Web of Science for relevant papers up to January 20, 2021. All published randomized controlled trials related to the integration of TCM and Western medicine for ACS will be included. The primary outcome is the effective rate and cardiovascular function index (left ventricular ejection fraction, early peak flow velocity, and thrombolysis in myocardial infarction). The secondary outcome is blood lipid level (total cholesterol, triacylglycerol, low/high density lipoprotein) and the incidence of adverse cardiovascular events. Study selection, data collection, and quality evaluation will be conducted by 2 reviewers independently. Comprehensive meta-analyses together with sensitivity and subgroup analyses will be performed with Stata 15.0 software (StataCorp). DISCUSSION: The results will provide a high-quality guidance for the current clinical treatment of ACS, and the patients more options to relieve their symptoms. The findings from this study may provide updated evidence concerning the efficacy and safety of TCM for patients with ACS. TRIAL REGISTRATION: This protocol has been registered in the INPLASY platform (https://inplasy.com/), and the registration number is INPLASY202140145.

Platelets in Acute Coronary Syndrome Patients with High Platelet Reactivity after Dual Antiplatelet Therapy Exhibit Upregulation of miR-204-5p.

Acute coronary syndrome (ACS) patients treated with dual antiplatelet therapy (DAPT) show individual differences in platelet reactivity (PR). Here, we aim to find differences in the platelet microRNA (miRNA) expression profiles of high PR and low PR patients to serve as potential biomarkers. ADP-induced platelet aggregation (PAG) was used to determine PR. High-throughput sequencing technology was used to profile differentially expressed platelet miRNAs in high PR (PAG>50%) and low PR (PAG≤50%) patients. We used real-time quantitative reverse transcription-polymerase chain reactions (RT-qPCR) to validate the sequencing results. Finally, we statistically evaluated the diagnostic value of the miRNAs and explored their molecular function using bioinformatic analysis. The results show that miR-204-5p was confirmed to be significantly upregulated in the high PR group. The area under the ROC curve (AUC) of miR-204-5p was 0.667, and its expression significantly correlated with the Gensini score. Stepwise binary logistic regression analysis suggested that miR-204-5p expression level was an independent predictor of PR. Furthermore, bioinformatic analysis showed that miR-204-5p may be associated with platelet synapse formation and platelet vesicle release. Our data indicates that platelet miR-204-5p may serve as a novel biomarker of PR to guide treatment with antiplatelet drugs.