Baicalein, a component of banxia xiexin decoction, alleviates CPT-11-induced gastrointestinal dysfunction by inhibiting ALOX15-mediated ferroptosis.

Baicalein, one of the active ingredients of banxia xiexin decoction, has good therapeutic efficacy in treating diarrhea and improving gastrointestinal dysfunction. The role and mechanism of Baicalein on irinotecan (CPT-11)-induced gastrointestinal dysfunction are the focus of this study. Concretely, CPT-11 induced delayed diarrhea rat model and intestinal epithelial cell (IEC)-6 cell injury model with Baicalein treatment as needed. Colonic pathological changes were analyzed by hematoxylin-eosin staining, and inflammatory factor expressions in serum were determined by enzyme-linked immunosorbent assay. Immunohistochemistry and western blot were performed to quantify ferroptosis-related protein expressions. Thiobarbituric acid reactive substances (TBARS) kits and colorimetric assay kit were applied to detect lipid peroxidation levels and Fe2+ content, respectively. In vitro experiments also included quantitative real-time polymerase chain reaction, cell counting kit-8, and C11 BODIPY staining. CPT-11 induced aggravation of intestinal tissue damage, inflammatory factor release, Fe2+ accumulation, upregulation of lipid peroxidation and 15-Lipoxygenase (ALOX15) expression, and downregulation of glutathione peroxidase 4 (Gpx4) and SLC7A11 in vivo in rats; however, Baicalein dose-dependently reversed the effects of CPT-11. Baicalein elevated cell viability, reduced lipid peroxidation and Fe2+ accumulation, and elevated Gpx4 and SLC7A11 levels, whereas ALOX15 overexpression reversed the effects of Baicalein on a CPT-11-induced IEC-6 cell injury model. In conclusion, Baicalein plays a mitigating role in CPT-11-induced delayed diarrhea via ALOX15-mediated ferroptosis.

Alterations of gut microbiota biodiversity and relative abundance in women with PCOS: A systematic review and meta-analysis.

BACKGROUND: Numerous studies have implicated that the gut microbiota is associated with polycystic ovary syndrome (PCOS). However, a comprehensive data-based summary shown that the effects of the PCOS on the gut microbiota is minimal. We aim to assess the alterations of gut microbiota in women with PCOS. METHODS: An electronic search of PubMed, Web of Science, Embase, Cochrane Library and Ovid was conducted for eligible studies published from inception to 28 March 2023, without any language or regional restrictions. We used Newcastle-Ottawa Quality Assessment Scale (NOS) to complete the assessment of the risk of bias and Stata 15.1 software to performed meta-analysis. RESULTS: There were 19 human observational studies in total with 617 women with PCOS and 439 healthy individuals were identified. Compared to the control group, the Chao index (WMD -28.88, 95% CI -45.78 to -11.98, I2 = 100%), Shannon index (WMD -0.11, 95% CI -0.18 to 0.00, I2 = 92.2%); and observed operational taxonomic units (OTUs) counts (WMD - 23.48, 95% CI -34.44 to -12. 53, I2 = 99.6%) were significantly lower in women with PCOS. The relative abundance of Bacteroidaceae was significantly higher (WMD 0.12, 95% CI 0.02 to 0.22, I2 = 9.2%), however there were no statistical differences in Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Alcaligenaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Lachnospiraceae, Prevotellaceae, Ruminococcaceae, Veillonellaceae, Bacteroides, Bifidobacterium, Blautia, Dialister, Escherichia-Shigella, Faecalibacterium, Lachnoclostridium, Lachnospira, Megamonas, Phascolarctobacterium, Prevotella, Roseburia, and Subdoligranulum. CONCLUSION: We demonstrated the alpha diversity of gut microbiota and the relative abundance of Bacteroidaceae in women with PCOS are altered. The results indicates that dysbiosis may be a potential pathogenetic factor in PCOS and provided reliable information to investigate the role of gut microbiota in the development and progression of PCOS.

Cognitive-adaptive Functioning Gap and Mediating Factors that Impact Adaptive Functioning in Chinese Preschool-aged Children with Autism Spectrum Disorder.

This study aimed to investigate the gap between adaptive functioning and cognitive functioning, especially verbal and nonverbal intelligence quotient (IQ) in Chinese children with ASD. We systematically explored cognitive functioning, ASD severity, early signs of developmental abnormalities, and socioeconomic factors as mediating factors of adaptive functioning. We enrolled 151 children (age: 2.5?6 years) with ASD and categorized them into one group with IQ ≥ 70 and another with IQ < 70. The two groups were calibrated for age, age at diagnosis, and IQ, and the relationship of adaptive skills with vocabulary acquisition index (VAI) and nonverbal index (NVI) were separately analyzed. Results show that the gap between IQ and adaptive functioning was significant in children with ASD having IQ ≥ 70, with both VAI and NVI showing statistically significant differences (all P < 0.001). VAI correlated positively with scores for overall adaptive skills and specific domains, whereas NVI had no significant correlations with adaptive skill scores. Age of first walking unaided had an independent positive correlation (all P < 0.05) with scores of adaptive skills and specific domains. IQ-adaptive functioning gap is significant in children with ASD having IQ ≥ 70, suggesting that defining "high-functioning autism" merely on the basis of IQ is not appropriate. Verbal IQ and early signs of motor development are specific and possible predictors of adaptive functioning in children with ASD, respectively.

Minimally invasive electrochemical continuous glucose monitoring sensors: Recent progress and perspective.

Diabetes and its complications are seriously threatening the health and well-being of hundreds of millions of people. Glucose levels are essential indicators of the health conditions of diabetics. Over the past decade, concerted efforts in various fields have led to significant advances in glucose monitoring technology. In particular, the rapid development of continuous glucose monitoring (CGM) based on electrochemical sensing principles has great potential to overcome the limitations of self-monitoring blood glucose (SMBG) in continuously tracking glucose trends, evaluating diabetes treatment options, and improving the quality of life of diabetics. However, the applications of minimally invasive electrochemical CGM sensors are still limited owing to the following aspects: i) invasiveness, ii) short lifespan, iii) biocompatibility, and iv) calibration and prediction. In recent years, the performance of minimally invasive electrochemical CGM systems (CGMSs) has been significantly improved owing to breakthrough developments in new materials and key technologies. In this review, we summarize the history of commercial CGMSs, the development of sensing principles, and the research progress of minimally invasive electrochemical CGM sensors in reducing the invasiveness of implanted probes, maintaining enzyme activity, and improving the biocompatibility of the sensor interface. In addition, this review also introduces calibration algorithms and prediction algorithms applied to CGMSs and describes the application of machine learning algorithms for glucose prediction.

Efficacy and moderating factors of the Early Start Denver Model in Chinese toddlers with autism spectrum disorder: a longitudinal study.

BACKGROUND: Several studies have shown the effectiveness of the Early Start Denver Model (ESDM), but few studies have explored the long-term efficacy of ESDM. This study aimed to explore the efficacy and moderating factors of ESDM in Chinese toddlers with autism spectrum disorder (ASD) in a longitudinal way. METHODS: A total of 60 toddlers with ASD were recruited and randomly divided into two groups: ESDM group all received 24 weeks intervention; Control group were waiting for intervention. Baseline assessment (T0) was conducted before intervention, including Gesell Developmental Scale (GDS) and Psycho-educational Profile-3rd Edition (PEP-3). All toddlers with ASD were examined in the first assessment (T1) at 6 months and in the second assessment (T2) at 12 months. RESULTS: In T1 assessment, the increments in speech and personal communication development quotient in GDS were significantly larger in the ESDM group than in the control group (P = 0.010, 0.047). In T2 assessment, the ESDM group had higher elevation in cognitive verbal/preverbal (CVP), social reciprocity and characteristic verbal behaviors assessed by PEP-3 (P = 0.021, 0.046, 0.014). In addition, the severity of stereotyped behavior was negatively associated with improvement in CVP. Family income was positively associated with improvement in speech and CVP (all P < 0.05). CONCLUSIONS: ESDM can effectively improve speech and communication in toddlers with ASD after 24-week intervention. More importantly, ESDM can promote cognition and social interaction and can reduce stereotyped verbal behavior in toddlers with ASD in longitudinal observation. The severity of stereotyped behavior and family ecological factors may be considered as affecting the efficacy of ESDM.

Histone Methyltransferase SETD2 Is Required for Porcine Early Embryonic Development.

SET domain-containing 2 (SETD2) is a methyltransferase that can catalyze the di- and tri-methylation of lysine 36 on histone H3 (H3K36me2/me3). SETD2 frequently mediates H3K36me3 modification to regulate both oocyte maturation and preimplantation embryonic development in mice. However, the specific substrate and function of SETD2 in porcine early embryonic development are still unclear. In this study, SETD2 preferentially catalyzed H3K36me3 to regulate porcine early embryonic development. SETD2 mRNA is dynamically expressed during early embryonic development. Functional studies using an RNA interference (RNAi) approach revealed that the expression levels of SETD2 mRNA were effectively knocked down by siRNA microinjection. Immunofluorescence analysis indicated that SETD2 knockdown (KD) did not affect H3K36me2 modification but significantly reduced H3K36me3 levels, suggesting a preferential H3K36me3 recognition of SETD2 in porcine embryos. Furthermore, SETD2 KD significantly reduced blastocyst rate and disrupted allocation between inner cell mass (ICM) and trophectoderm (TE) lineage. The expression levels of key genes important for specification of the first two lineages apparently decreased in SETD2 KD blastocysts. SETD2 KD markedly increased the apoptotic percentage of cells within embryos and altered the expression of pro- and anti-apoptotic genes. Therefore, our data indicate that SETD2 is essential for porcine early embryonic development.

RNA-seq-based transcriptome analysis of the anti-inflammatory effect of artesunate in the early treatment of the mouse cerebral malaria model.

BACKGROUND: cerebral malaria (CM) is an important complication of malaria with a high mortality rate. Artesunate is recommended as the first-line artemisinin compound treatment for severe malaria. Due to the difficulty of obtaining brain tissue samples clinically, the use of animals to research host responses to CM parasite infections is necessary. Rodent malaria models allow for detailed time series studies of host responses in multiple organs. To date, studies on the transcriptome of severe malaria are only limited to the parasites in the peripheral blood of patients, and there is little data on the transcriptional changes in brain tissue in mice with CM treated with artesunate. METHOD AND RESULT: in this study, fresh tissue samples (three biological replicates per mouse) from the same area of the brain in each animal were collected from the uninfected, Plasmodium berghei ANKA-infected and artesunate-treated C57BL/6 mice, and then transcriptome research was performed by the RNA-seq technique. Differentially expressed genes (DEGs) included Il-21, Tnf, Il-6, Il-1ß, Il-10, Ifng, and Icam-1. Among which, Il-6, Il-10, Tnf-α and Il-1ß were further verified and validated via qRT-PCR and ELISA. This revealed that Il-1ß (p < 0.0001), Il-10 (p < 0.05) and Tnf-α (p < 0.05) were significantly up-regulated in the Pb ANKA-infected versus uninfected group, while Il-1ß (p < 0.0001) and Tnf-α (p < 0.05) were significantly down-regulated after artesunate treatment. All DEGs were closely related to the top 3 artesunate treatment pathways, including the JAK-STAT signaling pathway, apoptosis, and Toll-like receptor signaling pathway. CONCLUSION: the mechanism of improving the prognosis of cerebral malaria by artesunate may not only involve the killing of plasmodium but also the inhibition of a cytokine storm in the host. This study provides new insights into the molecular mechanism by which artesunate improves the prognosis of cerebral malaria.

Posttraumatic growth and rumination among parents of children with autism spectrum disorder: The mediating role of social support.

Although rumination and social support are regarded as essential predictors of posttraumatic growth (PTG), few studies have explored the associations among PTG, rumination, and social support in parents of children with autism spectrum disorder (ASD). This study examined whether social support mediates the relationship between rumination and PTG. Cross-sectional questionnaire data were collected from 385 parents of children with ASD from September 2019 to November 2020 by convenience sampling. Participants completed the Posttraumatic Growth Inventory, Event Related Rumination Inventory, and Social Support Rating Scale. Path analyses showed that subjective support partially mediates the relationship between deliberate rumination and PTG (ß = 0.073, P < 0.001), and indirect effects account for 15.30% of the total effects. In addition, a negative direct path was found between intrusive and PTG because of the suppression effect of subjective support (ß = -0.110, P < 0.01), and indirect effects accounted for 80% of the direct effects. For future studies, it underscores the essential role of subjective support and rumination in promoting PTG in parents of children with ASD.

Event-Triggered Multiagent Consensus Under Relative Output Sensing.

Event-triggered (ET) consensus of linear multiagent systems with relative output sensing on undirected graphs is studied. Two output-feedback protocols with static and time-varying coupling strengths, respectively, are proposed, which, different from the existing results in relative output sensing, integrate effective ET strategies to reduce the communication burdens between agents. To ensure the closed-loop consensus, design conditions about the gain matrices, coupling strengths, and event-triggering functions are derived. Zeno behaviors are also shown to be excluded from the triggering process. In addition, recursive algorithms are devised for computing the continuous-time relative signals required by the event-triggering functions, so that continuous monitoring of neighbors is circumvented. Numerical examples finally demonstrate the effectiveness of the proposed design method.

Emotional Experience and Psychological Intervention of Depression Patients Based on SOM.

Depression is a severe mental illness with an unknown pathogenesis. Clinical diagnosis is based primarily on symptoms and does not include objective biological markers. Finding objective markers for diagnosis and treatment from imaging, on the contrary, is becoming increasingly important. The SOM (self-organizing feature mapping) model was used to identify the depression tendency of users in order to investigate the emotional experience and psychological intervention of patients with depression. On this foundation, the concept of depression index is developed further, and the relationship between depression index and the severity of depression in patients is thoroughly investigated. The system can accurately and quickly identify the depression state by applying it directly to the original EEG signals, without any preprocessing or feature extraction. When combined with traditional classifiers, the analysis and comparison results show that SOM can not only effectively select features but also improve the accuracy of depression classification. This research proposes a new research direction for deep learning in the context of large-scale big data analysis.

Network pharmacology-based predictions of active components and pharmacological mechanisms of Artemisia annua L. for the treatment of the novel Corona virus disease 2019 (COVID-19).

BACKGROUND: Novel Corona Virus Disease 2019 (COVID-19) is closely associated with cytokines storms. The Chinese medicinal herb Artemisia annua L. (A. annua) has been traditionally used to control many inflammatory diseases, such as malaria and rheumatoid arthritis. We performed network analysis and employed molecular docking and network analysis to elucidate active components or targets and the underlying mechanisms of A. annua for the treatment of COVID-19. METHODS: Active components of A. annua were identified through the TCMSP database according to their oral bioavailability (OB) and drug-likeness (DL). Moreover, target genes associated with COVID-19 were mined from GeneCards, OMIM, and TTD. A compound-target (C-T) network was constructed to predict the relationship of active components with the targets. A Compound-disease-target (C-D-T) network has been built to reveal the direct therapeutic target for COVID-19. Molecular docking, molecular dynamics simulation studies (MD), and MM-GBSA binding free energy calculations were used to the closest molecules and targets between A. annua and COVID-19. RESULTS: In our network, GO, and KEGG analysis indicated that A. annua acted in response to COVID-19 by regulating inflammatory response, proliferation, differentiation, and apoptosis. The molecular docking results manifested excellent results to verify the binding capacity between the hub components and hub targets in COVID-19. MD and MM-GBSA data showed quercetin to be the more effective candidate against the virus by target MAPK1, and kaempferol to be the other more effective candidate against the virus by target TP53. We identified A. annua's potentially active compounds and targets associated with them that act against COVID-19. CONCLUSIONS: These findings suggest that A. annua may prevent and inhibit the inflammatory processes related to COVID-19.

CPSF1 mediates retinal vascular dysfunction in diabetes mellitus via the MAPK/ERK pathway.

This study investigated the expression and underlying molecular mechanism of CPSF1 in diabetic retinopathy. Streptozotocin (STZ)-induced Sprague-Dawley (SD) rats were employed as a diabetic model, and high-glucose (HG)-induced human retinal vascular endothelial cells （HRVECs）were used as an in vitro experimental model to explore the effect of CPSF1. The results showed that CPSF1 was downregulated in diabetic retinopathy (DR) tissues and HRVECs under HG conditions. Adeno-associated viral CPSF1 attenuated histological abnormalities of retinas. CPSF1 regulates the apoptosis, migration, and vascularisation of HRVECs under HG conditions in vitro. CPSF1 mediates retinal vascular dysfunction by suppressing the phosphorylation mechanism in the mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway in DR. In conclusion, CPSF1 may be associated with the development of DR, and upregulated CPSF1 alleviates apoptosis and migration via MAPK/ERK pathway.

Finite-Time Consensus for Singularity-Perturbed Multiagent System via Memory Output Sliding-Mode Control.

In some practical systems, it often remains difficult to directly measure all state variables. This article investigates the memory output sliding-mode control (SMC) for the finite-time consensus of singularly perturbed multiagent systems (SPMASs). First, the virtual state-feedback sliding surface (SFSS) is constructed to ensure the consensus of all agent states. Then, the unknown output derivatives in SFSS are approximated by a moving finite difference method with error estimation and refinement, which gives rise to a new delay-dependent sliding surface. On this basis, the memory output switching control law is designed to stabilize the consensus errors in finite time, even in the presence of estimation biases, singular perturbations, and input noises. Different from the observer-based SMC, the proposed memory output SMC is of simple static form without introducing extra dynamical structures for state estimation. The effectiveness and superiority of the design method are verified in an SPMAS with double-integrator dynamics.

Development of a novel necroptosis-associated miRNA risk signature to evaluate the prognosis of colon cancer patients.

BACKGROUND: Necroptosis is a recently discovered caspase-independent form of cell death which plays an important role in the occurrence and development of cancer. As an important regulatory factor in necroptosis, microRNAs (miRNAs) are important for the development of colon cancer. This study established a novel necroptosis-related miRNA risk signature to evaluate the prognosis of patients with colon adenocarcinoma (COAD). METHODS: The necroptosis-related miRNAs were selected by assessing the differential expression of miRNAs in 459 COAD patient samples and 8 control samples from The Cancer Genome Atlas (TCGA). Selection operator Cox analyses and survival analyses were used to establish the risk signature of 7 miRNAs related to necroptosis. Functional enrichment analysis and nomograms were used to explore the potential effects of necroptosis-related miRNAs on prognosis and metastasis. The target genes of the necroptosis-related miRNAs were predicted using online databases and the genes related to overall survival (OS) were screened. RESULTS: The risk signature was based on 7 necroptosis-related miRNAs. Nomograms showed that the risk signature was effective at predicting the prognosis and TNM stage of COAD patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that these miRNAs play an important role in cancer development, metastasis, and prognosis. A total of 38 target genes for these miRNAs were found to be associated with the OS in COAD patients. CONCLUSIONS: This study provided novel evidence that necroptosis-related miRNAs are associated with the prognosis of COAD patients. A risk signature established based on these miRNAs could effectively predict the prognosis and metastasis of COAD in patients.

The Effect of Artemisinin-Based Drugs vs Non-artemisinin-based Drugs on Gametophyte Carrying in the Body After the Treatment of Uncomplicated Falciparum Malaria: A Systematic Review and Meta-analysis.

The WHO recommends Artemisinin-based combination therapy (ACTs) as the first-line treatment for malaria. This meta-analysis aims to analyze the effects of artemisinin and its derivatives as well as non-artemisinin drugs on the gametophytes in the host during the treatment of falciparum malaria. Fourteen studies were included in this analysis, and the artemisinin combination drugs involved were: artemether-lumefantrine (AL), artemisinin (AST), artemether-benflumetol (AB), dihydroartemisinin-piperaquine + trimethoprim + primaquine (CV8), amodiaquine + sulfadoxine-pyrimethamine (ASP), pyronaridine-phosphate + dihydroartemisinin (PP-DHA), dihydroartemisinin (DHA), and mefloquine + artesunate (MA), with 1702 patients. The control intervention measures involved the following: sulfadoxine-pyrimethamine (SP), mefloquine (MQ), atovaquone-proguanil (AT-PG), chloroquine + sulfadoxine-pyrimethamine (C-SP), quinine (Q), pyronaridine-phosphate (PP), pyronaridine (PN), and mefloquine + primaquine (MP), with 833 patients. The effect of ACTs was more obvious (OR = 0.37, 95%CI: 0.22-0.62, p < 0.05). In the control group of second malaria attacks, the difference between the two groups was not statistically significant (RD = 1.16, 95%CI: 0.81-1.66, p < 0.05); there was no significant difference in treatment failure during follow-up (RD = -0.01, 95%CI: 0.04-0.03, p < 0.05). There were also very few serious adverse events in both groups. ACTs showed good therapeutic effects in preventing gametocythemia but did not control the recrudescence rate and overall cure, which indicated the effectiveness of the combination of antimalarial drugs. Further research is required to explore which compatibility method is most conducive to the development of clinical malaria control.

Safety and efficacy of artemisinin-piperaquine for treatment of COVID-19: an open-label, non-randomised and controlled trial.

BACKGROUND: There are no effective therapies for patients with coronavirus disease-2019 (COVID-19). METHODS: Forty-one patients with confirmed COVID-19 were enrolled in the study and divided into two groups: artemisinin-piperaquine (AP) (n = 23) and control (n = 18). The primary outcome were the time taken to reach undetectable levels of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and the percentage of participants with undetectable SARS-CoV-2 on days 7, 10, 14, and 28. The computed tomography (CT) imaging changes within 10 days, corrected QT interval changes, adverse events, and abnormal laboratory parameters were the secondary outcomes. RESULTS: The mean time to reach undetectable viral RNA (mean ± standard deviation) was 10.6 ± 1.1 days (95% confidence interval [CI] 8.4-12.8) for the AP group and 19.3 ± 2.1 days (95% CI 15.1-23.5) for the control group. The percentages of patients with undetectable viral RNA on days 7, 10, 14, 21, and 28 were 26.1%, 43.5%, 78.3%, 100%, and 100%, respectively, in the AP group and 5.6%, 16.7%, 44.4%, 55.6%, and 72.2%, respectively, in the control group. The CT imaging within 10 days post-treatment showed no significant between-group differences (P > 0.05). Both groups had mild adverse events. CONCLUSIONS: In patients with mild-to-moderate COVID-19, the time to reach undetectable SARS-CoV-2 was significantly shorter in the AP group than that in the control group. However, physicians should consider QT interval changes before using AP.

Posttraumatic Growth Among Parents of Children with Autism Spectrum Disorder in China and Its Relationship to Family Function and Mental Resilience: A Cross-Sectional Study.

OBJECTIVE: This study was conducted to examine the posttraumatic growth (PTG) of parents of children with autism spectrum disorder (ASD) and the association among family function, mental resilience and PTG. DESIGN AND METHODS: This descriptive cross-sectional study was conducted with 205 parents of children with ASD in the clinical department of a university-affiliated hospital in Guangzhou from January to October 2019. The Posttraumatic Growth Inventory, Family Assessment Device, and Connor-Davidson Resilience Scale were employed for data collection. RESULTS: The mean PTG score of parents was 59.56±18.46; and 24.63%, 43.84%, and 32.51% of parents exhibited a high level, moderate level and low level, respectively, of PTG. The problem-solving dimension of family function (p = 0.005) and the strength dimension of mental resilience (p ≤0.001) were positively related to PTG. CONCLUSIONS: Parents of children with ASD experienced moderate PTG overall. The problem-solving dimension of family function and the strength dimension of mental resilience were significant predictors of PTG. PRACTICAL IMPLICATIONS: Interventions to improve family function and the mental resilience of parents with ASD children could contribute to improving the PTG of parents.

Safety and Efficacy of Adjunctive Therapy With Artesunate in the Treatment of Severe Malaria: A Systematic Review and Meta-Analysis.

Objective: The purpose of this meta-analysis of longitudinal studies is to determine the safety and efficacy of artesunate combined with other forms of adjunctive therapies for severe malaria. Methods: Following the PRISMA guidelines, we searched multiple databases with the search terms "artesunate" and "adjunctive therapy" and "severe malaria" in July 2020. If the search showed a randomized controlled trial, the study was included in this meta-analysis. The random-effects model was used to calculate the combined incidence rate and relative risk or risk difference. Results: This meta-analysis included nine longitudinal studies with 724 participants. We found that the mortality rates in the artesunate monotherapy group and the artesunate + adjuvant therapy group are similar (RD = -0.02, 95% confidence interval: -0.06-0.02). The incidence of adverse reactions in the artesunate monotherapy group and the artesunate + adjuvant therapy group was also similar. Conclusion: No significant differences in safety and efficacy were observed between the artesunate monotherapy group and the artesunate + adjuvant therapy group. Higher quality and rigorously designed randomized controlled studies are needed to validate our findings.

Efficacy and Safety of Artemisinin-Piperaquine for the Treatment of Uncomplicated Malaria: A Systematic Review.

OBJECTIVE: The World Health Organization recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria to improve the therapeutic efficacy and limit the choice of drug-resistant parasites. This systematic review and meta-analysis aimed to evaluate the comparative efficacy and safety of artemisinin-piperaquine (AP) in the treatment of uncomplicated malaria relative to other commonly used ACTs. METHODS: As per the PRISMA guidelines, the EMBASE, MEDLINE, the Google Scholar Library, and Cochrane library databases were systematically searched from inception until July 2020 with the following terms: "artemisinin-piperaquine" or "AP." Only randomized controlled trials (RCTs) were included. The competing interventions included dihydroartemisinin-piperaquine (DHA-PPQ), artemether-lumefantrine (AL, Coartem), artesunate-melfloquine (ASAM) and artesunate-amodiaquine (ASAQ, Artekin). Single-arm clinical trial on AP was also assessed. The reported outcomes, including the overall response, cure rate, fever and parasite clearance time, hematology, biochemistry, electrocardiogram (ECG), adverse events, recurrence rate, and sensitivity analyses, were systematically investigated. All data were analyzed using the Review Manager 5.3. RESULTS: A total of seven studies were reviewed, including five RCTs and two single-arm studies. A pooled analysis of 5 RCTs (n = 772) revealed a comparable efficacy on polymerase chain reaction (PCR)-confirmed cure rate between AP and competing interventions in treating uncomplicated malaria. As for the fever and parasite clearance time, due to the lack of complete data in some studies, only 3 studies' data could be used. The patients showed good tolerance to all drugs, and some side-effects (such as headache, anoxia, vomiting, nausea, and dizziness) were reported for every group, but they were self-limited and showed no significant difference. CONCLUSIONS: AP appeared to show similar efficacy and safety, with a simpler mode of administration and easier compliance when compared with other ACTs used in the treatment of uncomplicated malaria. Considering that the potential evolution of drug resistance is of a great concern, additional RCTs with high-quality and more rigorous design are warranted to substantiate the efficacy and safety in different populations and epidemiological regions.

Inhibition of NLRP3 Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Apoptosis by NF-κB Signaling.

BACKGROUNDS/AIMS: To explore whether NLRP3 is involved in the development of cataract and to study the effect of NLRP3 on hydrogen peroxide (H2O2)-induced injury in human lens epithelial cells. METHODS: Oxidative stress-induced apoptosis model was constructed by treating HLEB3 cells with 50 µM H2O2 at different times (6 h, 12 h) and was confirmed by flow cytometry and Western blot. HLEB3 were divided into NC, NC+H2O2, shNLRP3, and shNLRP3+H2O2 groups. Quantitative real-time polymerase chain reaction and Western blot were employed to detect mRNA and protein expressions, DCFH-DA to measure reactive oxygen species production, and Annexin V-FITC/PI staining to determine cell apoptosis. RESULTS: NLRP3 expression significantly increased in H2O2-induced HLEB3 cells. shRNA interference of NLRP3 inflammasome protects HLEB3 cells against oxidative stress-induced apoptosis by decreasing the expression levels of caspase-3 and Bax and increasing Bcl-2 expression. shNLRP3 was able to effectively suppress H2O2-induced apoptosis via inhibition of NF-κB signaling. CONCLUSION: NLRP3 might be involved in the apoptosis of lens epithelial cells. The inhibition of NLRP3 obviously attenuated H2O2-induced oxidative stress injury of human lens epithelial cells via NF-κB signaling.