G-CSF + plerixafor versus G-CSF alone mobilized hematopoietic stem cells in patients with multiple myeloma and lymphoma: a systematic review and meta-analysis.

AIM: The combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor is one of the approaches for hematopoietic stem cell mobilization in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). This systematic review and meta-analysis aimed to determine the ability of G-CSF + plerixafor to mobilize peripheral blood (PB) CD34+ cells and examine its safety profile. METHODS: We performed a database search using the terms 'granulocyte colony stimulating factor', 'G-CSF', 'AMD3100', and 'plerixafor', published up to May 1, 2023. The methodology is described in further detail in the PROSPERO database (CRD42023425760). RESULTS: Twenty-three studies were included in this systematic review and meta-analysis. G-CSF + plerixafor resulted in more patients achieving the predetermined apheresis yield of CD34+ cells than G-CSF alone (OR, 5.33; 95%, 4.34-6.55). It was further discovered that G-CSF + plerixafor could mobilize more CD34+ cells into PB, which was beneficial for the next transplantation in both randomized controlled (MD, 18.30; 95%, 8.74-27.85) and single-arm (MD, 20.67; 95%, 14.34-27.00) trials. Furthermore, G-CSF + plerixafor did not cause more treatment emergent adverse events than G-CSF alone (OR, 1.25; 95%, 0.87-1.80). CONCLUSIONS: This study suggests that the combination of G-CSF and plerixafor, resulted in more patients with MM, NHL, and HL, achieving the predetermined apheresis yield of CD34+ cells, which is related to the more effective mobilization of CD34+ cells into PB.

Hierarchical Capability in Distinguishing Severities of Sepsis via Serum Lactate: A Network Meta-Analysis.

Background: Blood lactate is a potentially useful biomarker to predict the mortality and severity of sepsis. The purpose of this study is to systematically review the ability of lactate to predict hierarchical sepsis clinical outcomes and distinguish sepsis, severe sepsis and septic shock. Methods: We conducted an exhaustive search of the PubMed, Embase and Cochrane Library databases for studies published before 1 October 2022. Inclusion criteria mandated the presence of case-control, cohort studies and randomized controlled trials that established the association between before-treatment blood lactate levels and the mortality of individuals with sepsis, severe sepsis or septic shock. Data was analyzed using STATA Version 16.0. Results: A total of 127 studies, encompassing 107,445 patients, were ultimately incorporated into our analysis. Meta-analysis of blood lactate levels at varying thresholds revealed a statistically significant elevation in blood lactate levels predicting mortality (OR = 1.57, 95% CI 1.48-1.65, I2 = 92.8%, p < 0.00001). Blood lactate levels were significantly higher in non-survivors compared to survivors in sepsis patients (SMD = 0.77, 95% CI 0.74-0.79, I2 = 83.7%, p = 0.000). The prognostic utility of blood lactate in sepsis mortality was validated through hierarchical summary receiver operating characteristic curve (HSROC) analysis, yielding an area under the curve (AUC) of 0.72 (95% CI 0.68-0.76), accompanied by a summary sensitivity of 0.65 (95% CI 0.59-0.7) and a summary specificity of 0.7 (95% CI 0.64-0.75). Unfortunately, the network meta-analysis could not identify any significant differences in average blood lactate values' assessments among sepsis, severe sepsis and septic shock patients. Conclusions: This meta-analysis demonstrated that high-level blood lactate was associated with a higher risk of sepsis mortality. Lactate has a relatively accurate predictive ability for the mortality risk of sepsis. However, the network analysis found that the levels of blood lactate were not effective in distinguishing between patients with sepsis, severe sepsis and septic shock.

Construction and evaluation of neonatal respiratory failure risk prediction model for neonatal respiratory distress syndrome.

BACKGROUND: Neonatal respiratory distress syndrome (NRDS) is a common respiratory disease in preterm infants, often accompanied by respiratory failure. The aim of this study was to establish and validate a nomogram model for predicting the probability of respiratory failure in NRDS patients. METHODS: Patients diagnosed with NRDS were extracted from the MIMIC-iv database. The patients were randomly assigned to a training and a validation cohort. Univariate and stepwise Cox regression analyses were used to determine the prognostic factors of NRDS. A nomogram containing these factors was established to predict the incidence of respiratory failure in NRDS patients. The area under the receiver operating characteristic curve (AUC), receiver operating characteristic curve (ROC), calibration curves and decision curve analysis were used to determine the effectiveness of this model. RESULTS: The study included 2,705 patients with NRDS. Univariate and multivariate stepwise Cox regression analysis showed that the independent risk factors for respiratory failure in NRDS patients were gestational age, pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), hemoglobin, blood culture, infection, neonatal intracranial hemorrhage, Pulmonary surfactant (PS), parenteral nutrition and respiratory support. Then, the nomogram was constructed and verified. CONCLUSIONS: This study identified the independent risk factors of respiratory failure in NRDS patients and used them to construct and evaluate respiratory failure risk prediction model for NRDS. The present findings provide clinicians with the judgment of patients with respiratory failure in NRDS and help clinicians to identify and intervene in the early stage.

Polycyclic pyrroloindoline-containing natural products with a unique 3-heptyl-2a,4a-diazapentaleno[1,6-ab]indene core isolated from Alstonia scholaris.

Alscholarine C (1), featuring an unprecedented pyrroloindoline-containing natural product (PiNP) with a 6/5/5/5 tetracyclic carbon skeleton, and four known PiNPs (2-5), namely demethylalstoscholarinine E (2), Nb-demethylechitamine (3), winphylline A (4), and echitamine (5), were isolated from Alstonia scholaris. Compound 1 was characterized by a hexahydropyrrolo[2,3-b] indole (HPI) core fused to a unique 4-heptylimidazolidine motif, forming an unparalleled 3-heptyl-2a,4a-diazapentaleno[1,6-ab]indene ring system. Their structures were established by spectroscopic analysis, quantum-chemical calculated 13C NMR data with DP4+ probability analyses, and ECD calculations and comparison. A plausible biosynthetic pathway of 1 was proposed. Compound 1 exhibited potential anti-inflammatory activity against LPS-stimulated NO production in RAW264.7 cells.

High-resolution spiral real-time cardiac cine imaging with deep learning-based rapid image reconstruction and quantification.

The objective of the current study was to develop and evaluate a DEep learning-based rapid Spiral Image REconstruction (DESIRE) and deep learning (DL)-based segmentation approach to quantify the left ventricular ejection fraction (LVEF) for high-resolution spiral real-time cine imaging, including 2D balanced steady-state free precession imaging at 1.5 T and gradient echo (GRE) imaging at 1.5 and 3 T. A 3D U-Net-based image reconstruction network and 2D U-Net-based image segmentation network were proposed and evaluated. Low-rank plus sparse (L+S) served as the reference for the image reconstruction network and manual contouring of the left ventricle was the reference of the segmentation network. To assess the image reconstruction quality, structural similarity index, peak signal-to-noise ratio, normalized root-mean-square error, and blind grading by two experienced cardiologists (5: excellent; 1: poor) were performed. To assess the segmentation performance, quantification of the LVEF on GRE imaging at 3 T was compared with the quantification from manual contouring. Excellent performance was demonstrated by the proposed technique. In terms of image quality, there was no difference between L+S and the proposed DESIRE technique. For quantification analysis, the proposed DL method was not different to the manual segmentation method (p > 0.05) in terms of quantification of LVEF. The reconstruction time for DESIRE was ~32 s (including nonuniform fast Fourier transform [NUFFT]) per dynamic series (40 frames), while the reconstruction time of L+S with GPU acceleration was approximately 3 min. The DL segmentation takes less than 5 s. In conclusion, the proposed DL-based image reconstruction and quantification techniques enabled 1-min image reconstruction for the whole heart and quantification with automatic reconstruction and quantification of the left ventricle function for high-resolution spiral real-time cine imaging with excellent performance.

Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of Microglia via Wnt/ß-catenin Pathway in Hypoxic-Ischemic Neonatal Rats.

Inflammatory reaction plays a key role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonates. Microglia are resident innate immune cells in the central nervous system and are profoundly involved in neuroinflammation. Studies have revealed that atorvastatin exerts a neuroprotective effect by regulating neuroinflammation in adult animal models of brain stroke and traumatic brain injury, but its role regarding damage to the developing brain remains unclear. This study aimed to clarify the effect and mechanism of atorvastatin on the regulation of microglia function in neonatal hypoxic-ischemic brain damage (HIBD). The oxygen glucose deprivation (OGD) of microglia and neonatal rat HIBD model was established. Atorvastatin, recombinant sclerostin protein (SOST), and XAV939 (degradation of ß-catenin) were administered to OGD microglia and HIBD rats. The pathological changes of brain tissue, cerebral infarction volume, learning and memory ability of rats, pro-inflammatory (CD16+/Iba1+) and anti-inflammatory (CD206+/Iba1+) microglia markers, inflammation-related indicators (Inos, Tnfα, Il6, Arg1, Tgfb, and Mrc1), and Wnt/ß-catenin signaling molecules were examined. Atorvastatin reduced OGD-induced pro-inflammatory microglia and pro-inflammatory factors, while increasing anti-inflammatory microglia and anti-inflammatory factors. In vivo, atorvastatin attenuated hypoxia-ischemia (HI)-induced neuroinflammation and brain damage. Mechanistically, atorvastatin decreased SOST expression and activated the Wnt/ß-catenin signaling pathway, and the administration of recombinant SOST protein or XAV939 inhibited Wnt/ß-catenin signaling and attenuated the anti-inflammatory effect of atorvastatin. Atorvastatin promotes the pro/anti-inflammatory phenotypic transformation of microglia via the Wnt/ß-catenin pathway in HI neonatal rats. Atorvastatin may be developed as a potent agent for the treatment of HIE in neonates.

Alscholarines A and B, two rearranged monoterpene indole alkaloids from Alstonia scholaris.

Alscholarines A and B (1 and 2), two unprecedented rearranged monoterpene indole alkaloids, were isolated from Alstonia scholaris. Alscholarine A (1) features an imidazole ring fused with a rearranged vallesamine-type alkaloid possessing an unparalleled 6/5/6/6 tetracyclic skeleton through an unprecedented C7-C-19 connectivity. Alscholarine B (2), incorporating an unusual 7-oxa-1-azabicyclo[3.2.1]octane moiety, represents a unique rearranged vallesamine-type alkaloid with a 6/5/6/6/5 ring system via an unprecedented C-6-C-20 connectivity. Their structures were established by spectroscopic analysis, X-ray crystallography, and quantum-chemical calculations. Their plausible biosynthetic pathways were proposed. The vasorelaxant and anti-inflammatory activities of them were also evaluated. Compounds 1-3 showed moderate vasorelaxant activities.

Identification of nonfunctional PABPC1L causing oocyte maturation abnormalities and early embryonic arrest in female primary infertility.

Oocyte maturation arrest, fertilization failure, and early embryonic arrest are important causes of female infertility, whereas the genetic events that contribute to these processes are largely unknown. Loss-of-function of PABPC1L in mice has been suggested to cause female infertility involved in the absence of mature oocytes or embryos in vivo or in vitro. However, the role of PABPC1L in human female reproduction remains largely elusive. In this study, we identified a homozygous missense mutation (c.536G>A, p.R179Q) and a compound heterozygous mutation (c.793C>T, p.R265W; c.1201C>T, p.Q401*) in PABPC1L in two unrelated infertile females characterized by recurrent oocyte maturation abnormalities and early embryonic arrest. These variants resulted in nonfunctional PABPC1L protein and were associated with impaired chromatin configuration and transcriptional silencing in GV oocytes. Moreover, the binding capacity of mutant PABPC1L to mRNAs related to oocyte maturation and early embryonic development was decreased significantly. Our findings revealed novel PABPC1L mutations causing oocyte maturation abnormalities and early embryonic arrest, confirming the essential role of PABPC1L in human female fertility.

Cumulative evidence of the genetic association between SP-B C1580T polymorphisms and risk of neonatal respiratory distress syndrome.

Objective: Surfactant protein SP-B, an important protein in pulmonary surfactant, is required for the stabilization of surfactant films in the lung and maintenance of postnatal lung function. Although the association between SP-B polymorphisms and the risk of neonatal respiratory distress syndrome (RDS) has been evaluated, the results have been inconsistent. We investigated the association between SP-B polymorphisms and the risk of neonatal RDS.Methods: Relevant studies were systematically searched in PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) electronic databases until June 2022. Data were collected independently by two reviewers and converted to odds ratios (ORs) with 95% confidence intervals (CIs). Meta-analysis, subgroup analysis, sensitivity analysis, and publication bias assessment were performed using Stata 12.1 software and Review Manager 5.3.Results: Fourteen studies were included. SP-B C1580T polymorphism was significantly associated with neonatal RDS in five genetic models (T vs. C: OR = 0.70, 95% CI 0.57-0.86, I2 = 78%; TT vs. CC: OR = 0.63, 95% CI 0.53-0.86, I2 = 39%; CT vs. CC: OR = 0.65, 95% CI 0.50-0.84, I2 = 54%; TT + CT vs. CC: OR = 0.62, 95% CI 0.49-0.78, I2 = 59%; TT vs. CC + CT: OR = 0.78, 95% CI 0.67-0.91, I2 = 43%). The CT and TT genotypes may decrease the risk of RDS in neonates. Subgroup analyses revealed that the association of SP-B C1580T polymorphism with neonatal RDS was stable, independent of preterm birth and Hardy-Weinberg equilibrium. In addition, the Han Chinese were more likely to be affected by SP-B C1580T polymorphisms than Caucasians and Finnish.Conclusions: Our findings suggest that SP-B C1580T polymorphism may be a protective factor against neonatal RDS.

Pleiotrophin ameliorates white matter injury of neonatal rats by activating the mTOR/YY1/Id4 signaling pathway.

Brain white matter injury (WMI) is a serious disease of the central nervous system. Pleiotrophin (PTN) promotes the differentiation and myelination of oligodendrocytes (OLs) in vitro. However, the role of PTN in WMI remains unknown. Therefore, this study aimed to investigate the neuroprotective role and potential mechanisms of PTN function in neonatal rats with WMI. The PTN and mammalian target of rapamycin (mTOR) inhibitor everolimus was used to treat a WMI model in postnatal day 3 Sprague-Dawley rats, in which the right common carotid arteries of these rats were isolated, ligated, and exposed to a hypoxic environment (6% O2 + 94% N2 ) for 2 h. OL differentiation and myelination, as well as the spatial learning and memory abilities of the rats were evaluated to examine the effects of PTN. Two proteins of the mTOR signaling pathway, YingYang1 (YY1) and inhibitor of DNA binding 4 (Id4), were detected and were used to explore the potential mechanisms of PTN in rat WMI experiment and oxygen glucose deprivation (OGD) model. We found that the differentiation and myelination of OLs were impaired after WMI. PTN administration rescued this injury by activating mTOR/YY1 and inhibiting Id4. Everolimus administration inhibited mTOR/YY1 and activated Id4, which blocked the neuroprotective role of PTN in WMI. PTN plays a neuroprotective role in neonatal rats with WMI, which could be involved in the mTOR/YY1/Id4 signaling pathway.

SIRS, SOFA, qSOFA, and NEWS in the diagnosis of sepsis and prediction of adverse outcomes: a systematic review and meta-analysis.

BACKGROUND: We compared Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), Quick Sepsis-related Organ Failure Assessment (qSOFA), and National Early Warning Score (NEWS) for sepsis diagnosis and adverse outcomes prediction. METHODS: Clinical studies that used SIRS, SOFA, qSOFA, and NEWS for sepsis diagnosis and prognosis assessment were included. Data were extracted, and meta-analysis was performed for outcome measures, including sepsis diagnosis, in-hospital mortality, 7/10/14-day mortality, 28/30-day mortality, and ICU admission. RESULTS: Fifty-seven included studies showed good overall quality. Regarding sepsis prediction, SIRS demonstrated high sensitivity (0.85) but low specificity (0.41), qSOFA showed low sensitivity (0.42) but high specificity (0.98), and NEWS exhibited high sensitivity (0.71) and specificity (0.85). For predicting in-hospital mortality, SOFA demonstrated the highest sensitivity (0.89) and specificity (0.69). In terms of predicting 7/10/14-day mortality, SIRS exhibited high sensitivity (0.87), while qSOFA had high specificity (0.75). For predicting 28/30-day mortality, SOFA showed high sensitivity (0.97) but low specificity (0.14), whereas qSOFA displayed low sensitivity (0.41) but high specificity (0.88). CONCLUSIONS: NEWS independently demonstrates good diagnostic capability for sepsis, especially in high-income countries. SOFA emerges as the optimal choice for predicting in-hospital mortality and can be employed as a screening tool for 28/30-day mortality in low-income countries.

Molecular Networking Accelerated Discovery of Biflavonoid Alkaloids from Cephalotaxus sinensis.

Four undescribed biflavonoid alkaloids, sinenbiflavones A-D, were isolated from Cephalotaxus sinensis using a MS/MS-based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HR-ESI-MS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A-D are the first examples of amentoflavone-type (C-3'-C-8'') biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C-6-methylated amentoflavone-type biflavonoid alkaloids. Sinenbiflavone D showed weak SARS-CoV-2 3CLpro inhibitory activity with 43 % inhibition rate at 40 µM.

Association between low ambient temperature during pregnancy and adverse birth outcomes: A systematic review and meta-analysis.

BACKGROUND: Extreme temperature events, including extreme cold, are becoming more frequent worldwide, which might be harmful to pregnant women and cause adverse birth outcomes. We aimed to investigate the association between exposure to low ambient temperature in pregnant women and adverse birth outcomes, such as preterm birth, low birth weight, and stillbirth, and to summarize the evidence herein. METHODS: Relevant studies were searched in PubMed, Cochrane, and Embase electronic databases until November 2021. Studies involving low ambient temperature, preterm birth, birth weight, and stillbirth were included. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses were followed to conduct this study risk of bias and methods for data synthesis. RESULTS: A total of 34 studies were included. First, pregnant women exposed to low ambient temperature had an increased risk of preterm birth (risk ratio [RR] 1.08; 95% confidence interval [CI] 1.04-1.13). Subgroup analyses revealed that exposure during late pregnancy was more likely to induce preterm birth. In addition, only pregnant women exposed to <1st percentile of the mean temperature suffered increased risk of preterm birth. Moreover, pregnant women living in medium or hot areas were more prone to have preterm births than those in cold areas when exposed to low ambient temperatures. Asians and Blacks were more susceptible to low ambient temperatures than Caucasians. Second, pregnant women exposed to low ambient temperature had an increased risk of low birth weight (RR 1.07; 95% CI 1.03-1.12). Third, pregnant women had an increased risk of stillbirth while exposed to low ambient temperature during the entire pregnancy (RR 4.63; 95% CI 3.99-5.38). CONCLUSIONS: Exposure to low ambient temperature during pregnancy increases the risk of adverse birth outcomes. Pregnant women should avoid exposure to extremely low ambient temperature (<1st percentile of the mean temperature), especially in their late pregnancy. This study could provide clues for preventing adverse outcomes from meteorological factors. REGISTRATION: No. CRD42021259776 at PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ).

Structurally diverse monoterpene indole alkaloids with vasorelaxant activities from the branches of Alstonia scholaris.

Seven undescribed monoterpene indole alkaloids alstoscholarinines A‒G, along with nineteen known alkaloids, were isolated from the branches of Alstonia scholaris (L.) R. Br. The isolated alkaloids were classified into ten framework types. The structures of the undescribed alkaloids were elucidated by extensive spectroscopic analysis, ECD calculation, and single-crystal X-ray diffraction analysis. Alstoscholarinine A is an unreported and unusual monoterpene indole alkaloid incorporating three nitrogen atoms, characterized by a compact 6/5/6/6/6/5 hexacyclic system bearing a piperidine ring and a unique oxazolidine ring. Alstoscholarinine B represents the first naturally C-17 nor-isositsirikine-type alkaloid. Plausible biosynthetic pathways of alstoscholarinines A and B were proposed. All isolates were evaluated for their vasorelaxant activities against phenylephrine-induced contraction of rat mesenteric arteries. Among them, seven alkaloids showed significant vasorelaxant activities with EC50 values less than 10 µM. Importantly, the akuammicine-type alkaloids in this study showed much better vasorelaxant activities than other framework type alkaloids, indicating that this type of alkaloid may be a valuable source for the discovery of vasodilators. A preliminary structure-activity relationship for vasorelaxant activities of the isolated akuammicine-type alkaloids is also discussed.

Irisin prevents hypoxic-ischemic brain damage in rats by inhibiting oxidative stress and protecting the blood-brain barrier.

Hypoxic-ischemic encephalopathy (HIE) is associated with excessive inflammation, blood-brain barrier dysfunction, and oxidative stress. Irisin can reduce inflammation and ameliorate oxidative stress; however, its effects on hypoxic-ischemic brain damage in newborns are unknown. Newborn Sprague-Dawley rats were subjected to hypoxic-ischemic injury and irisin treatment. TUNEL staining assays, the albumin-Evans blue dye extravasation method, an antioxidants detection kit, quantitative reverse-transcriptase PCR, enzyme linked immunosorbent assay, Western blot analysis, immunohistochemistry, and electron microscopy were used to investigate the possible mechanisms underlying the prevention of HIE by irisin. We discovered that rats affected by HIE and administered irisin had lower levels of IL-6 (but not TNF-α or IL-1ß) less oxidative stress, and enhanced blood-brain barrier integrity. Irisin can effectively attenuate brain damage by reducing oxidative stress and protecting the blood-brain barrier.

Research progress on the antitumor effects of astragaloside IV.

One of the most important and effective components of Astragalus membranaceus is astragaloside IV (AS-IV), which can exert anti-tumor effects through various pathways. For instance, AS-IV exerts an anti-tumor effect by acting at the cellular level, regulating the phenotype switch of tumor-associated macrophages, or inhibiting the development of tumor cells. Furthermore, AS-IV inhibits tumor cell progression by enhancing its sensitivity to antitumor drugs or reversing the drug resistance of tumor cells. This article reviews the different mechanisms of AS-IV inhibition of epithelial-mesenchymal transition (EMT), migration, proliferation, and invasion of tumor cells, inducing apoptosis and improving the sensitivity of anti-tumor drugs. This review summarizes recent progress in the current research into AS-IV anti-tumor effect and provides insight on the next anti-tumor research of AS-IV.

Cytotoxic alkaloids from the twigs and leaves of Cephalotaxus sinensis.

Twelve new Cephalotaxus alkaloids (1-12) and nine known analogues (13-21) were isolated and identified from the twigs and leaves of Cephalotaxus sinensis. The structures of the new compounds (1-12) were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Cephalosine H (8) is the third example of an alkaloid containing the cephalolancine skeleton. Cephalosines J and K (10 and 11) are the rare natural Δ(2)1-alkene-6-hydroxyl homoerythrina-type alkaloids isolated from the Cephalotaxus genus. The racemization of cephalotaxine-type alkaloids is discussed. Alkaloids 6, 7, 11, 16, 18 and 19 exhibited broad and potent cytotoxicities against five human cancer cell lines, with IC50 values ranging from 0.053 to 10.720 µM, highlighting these compounds as promising leads for the development of new antitumor agents.

Diagnostic performance of adenosine deaminase for abdominal tuberculosis: A systematic review and meta-analysis.

Background and aim: Abdominal tuberculosis (TB) is a common type of extrapulmonary TB with an insidious onset and non-specific symptoms. Adenosine deaminase (ADA) levels increase rapidly in the early stages of abdominal TB. However, it remains unclear whether ADA serves as a diagnostic marker for abdominal TB. Methods: We performed a systematic literature search for relevant articles published in PubMed, Web of Science, Cochrane Library, and Embase up to April 2022. First, we used the Quality Assessment of Diagnostic Accuracy Studies tool-2 (QUADAS-2), to evaluate the quality of the included articles. Bivariate and hierarchical summary receiver operating characteristic (HSROC) models were then utilized to analyze pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC). In addition, we explored a subgroup analysis for potential heterogeneity and publication bias among the included literature. Results: Twenty-four articles (3,044 participants, 3,044 samples) which met the eligibility criteria were included in this study. The pooled sensitivity and specificity of ADA for abdominal TB detection were 93% [95% confidence interval (CI): 0.89-0.95] and 95% (95% CI: 0.93-0.96), respectively. PLR and NLR were 18.6 (95% CI: 14.0-24.6) and 0.08 (95% CI: 0.05-0.12), respectively. DOR and AUROC were 236 (95% CI: 134-415) and 0.98 (95% CI: 0.96-0.99), respectively. Furthermore, no heterogeneity or publication bias was found. Conclusions: Our meta-analysis found ADA to be of excellent diagnostic value for abdominal TB and could be used as an auxiliary diagnostic tool. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022297931.

Metabolites with antioxidant and α-glucosidase inhibitory activities produced by the endophytic fungi Aspergillus niger from Pachysandra terminalis.

One new compound and 13 known compounds were isolated from Aspergillus niger, a plant endophytic fungus of Pachysandra terminalis collected from Qinling Mountains, Xi'an, China. The structure of new compound 1 was classically determined by extensive spectroscopic analysis. Compounds 5, 6, 8, and 14 were first reported from Aspergillus, while compound 2 was isolated from A. niger for the first time. All isolated compounds were further evaluated for their antioxidant and α-glucosidase inhibitory activities. Compounds 2 and 3 exhibited significant antioxidant activities with IC50 values of 31.64 µm and 24.32 µm, respectively, similar to the positive control ascorbic acid. Additionally, compound 1 displayed remarkable inhibitory activity against α-glucosidase with an IC50 value of 96.25 µm, which was 3.4-fold more potent than that of the positive control acarbose. Compound 1 has great potential for development as a new lead compound owing to its simple structure and remarkable biological activity.

Comparison of the efficacy and safety of caplacizumab versus placebo in thrombotic thrombocytopenic purpura: a meta-analysis and systematic review based on randomized controlled trials.

Background: We conducted this meta-analysis to investigate the efficacy and safety of caplacizumab in patients with thrombotic thrombocytopenic purpura (TTP). TTP is a potentially fatal disorder characterized by systemic microvascular thrombosis. Methods: Randomized controlled trials (RCTs) were conducted from PubMed, Embase, Cochrane Library and Web of Science, China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases. RCTs of caplacizumab treatment for TPP were mainly included. Data from eligible studies were extracted and analyzed using relative effect sizes versus placebo use. The Cochrane bias assessment tool was used to assess the risk of bias of included studies, and the assessment results were presented graphically in Revman5.3. Results: Four RCTs with a total of 416 patients were included, all of which were of high quality. Caplacizumab was associated with improvements in platelet counts normalization time [weighted mean difference (WMD) -1.18, 95% confidence interval (CI): -2.55 to 0.19, I2=69.9%, P=0.036], plasma exchange (PE) time (WMD -2.97, 95% CI: -4.44 to -1.50, I2=8.2%, P=0.163) and hospital stay (WMD -2.88, 95% CI: -4.56 to -1.21, I2=48.7%, P=0.036). In addition, the occurrence of adverse events was also investigated. The difference in mortality between the two groups was not statistically significant [relative risk (RR) 0.56, 95% CI: 0.18 to 1.72, I2=22.7%, P=0.275], relapse (RR 0.68, 95% CI: 0.13 to 3.49, I2=78.3%, P=0.01), or major thrombotic events (RR 1.01, 95% CI: 0.65 to 1.57, I2=43.4%, P=0.151). Conclusions: Caplacizumab shortens the platelet normalization time, PE time, and hospital stay in patients with TTP, and did not significantly increase the risk of adverse events. These results indicate that caplacizumab treatment provides significant benefits to patients with TTP. Even though this is evidence from RCTs, few original studies were included, so more multicenter RCTs are required.