Circ_0008315 promotes tumorigenesis and cisplatin resistance and acts as a nanotherapeutic target in gastric cancer.

INTRODUCTION: Cisplatin-based chemotherapy is one of the fundamental therapeutic modalities for gastric cancer (GC). Chemoresistance to cisplatin is a great clinical challenge, and its underlying mechanisms remain poorly understood. Circular RNAs (circRNAs) are involved in the pathophysiology of multiple human malignancies. METHODS: High-throughput sequencing was performed to determine the differentially expressed profile of circRNA in GC tissues and cisplatin-resistant GC cells. Quantitative real-time polymerase chain reaction and Fluorescence in situ hybridization was utilized to confirm the dysregulation of circ_0008315 in GC tissues. To evaluate the prognostic significance of circ_0008315 in GC, we used Kaplan-Meier plot. The self-renewal ability of drug-resistant GC cell was verified through tumor sphere formation assay. GC organoids were constructed to simulate the tumor microenvironment and verified the function of circ_0008315 in cisplatin resistance of gastric cancer. In vivo evaluation was conducted using patient-derived xenograft models. Dual-luciferase reporter gene, RNA immunoprecipitation and miRNA pull-down assays were employed to investigate the molecular mechanisms of circ_0008315 in GC. RESULTS: We revealed that a novel circRNA hsa_circ_0008315 was upregulated in GC and cisplatin-resistant GC cells. Elevated circ_0008315 was also observed in cisplatin-resistant GC organoid model. High circ_0008315 expression predicted unfavorable survival outcome in GC patients. Downregulation of circ_0008315 expression inhibited proliferation, mobility, and epithelial-mesenchymal transition of GC cells in vitro and in vivo. Reducing circ_0008315 expression in cisplatin-resistant GC organoid model reversed cisplatin resistance. Mechanistically, circ_0008315 modulated the stem cell properties of GC through the miR-3666/CPEB4 signaling pathway, thereby promoting cisplatin resistance and GC malignant progression. Furthermore, we developed PLGA-PEG nanoparticles targeting circ_0008315, and the nanoparticles could effectively inhibit GC proliferation and cisplatin resistance. CONCLUSION: Circ_0008315 exacerbates GC progression and cisplatin resistance, and can be used as a prognostic predictor. Circ_0008315 may function as a promising nanotherapeutic target for GC treatment.

Low-frequency RTMS attenuates social impairment in the VPA-induced mouse model.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and repetitive behaviors. Despite its prevalence, effective treatments remain elusive. Recent studies have highlighted the importance of the balance between GABAergic and glutamatergic neuronal synaptic functions in ASD development. Repetitive transcranial magnetic stimulation (RTMS) is a painless and effective treatment allowed for use in depression and obsessive-compulsive disorder. However, its efficacy in treating autism is still under investigation. Low-frequency RTMS (LF-RTMS), which shows promise in reducing autism-like behaviors, is considered to regulate synaptic function. OBJECTIVE: We observed and recorded the behaviors of mice to assess the impact of RTMS on their social interactions and repetitive activities. Subsequently, we examined GABAergic and glutamatergic neuronal markers along with synaptic marker proteins to understand the underlying changes associated with these behaviors. METHODS: To evaluate behaviors associated with autism spectrum disorder (ASD), several behavioral tests were conducted, focusing on sociability, repetitive behaviors, locomotion, anxiety, and depression. Additionally, Western blot and immunofluorescence staining were employed to investigate the activity of GABAergic and glutamatergic neurons in the hippocampus, aiming to understand the synaptic mechanisms underlying these behaviors. RESULTS: LF-RTMS treatment effectively relieved the social disability and normalized synaptic function in the hippocampus of ASD mice model induced by valproate (VPA). Importantly, this treatment did not lead to any adverse effects on repetitive behavior, locomotion, anxiety, or depression. CONCLUSION: LF-RTMS attenuated social disability without affecting repetitive behavior, locomotion, anxiety, or depression. Changes in the expression of GABAergic and glutamatergic neuronal synaptic proteins in the hippocampus were also observed.

CircRHBDD1 promotes immune escape via IGF2BP2/PD-L1 signaling and acts as a nanotherapeutic target in gastric cancer.

BACKGROUND: Circular RNAs (circRNAs) have been implicated in the development and progression of gastric cancer (GC). However, it remains unclear whether dysregulated circRNA affects immune escape and the efficacy of immunotherapy in GC. Our aim is to investigate the molecular mechanism of circRNA affecting GC immunotherapy and identify effective molecular therapeutic targets. METHODS: The differential expression profile of circRNAs was established through circRNA sequencing, comparing three paired GC tissues with their adjacent non-cancerous gastric tissues. The expression level of circRHBDD1 in GC tissues was then assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological characteristics of circRHBDD1 were verified through a series of experiments, including agarose gel electrophoresis assays, RNase R treatment, and actinomycin D experiments. The prognostic value of circRHBDD1 in GC was evaluated by conducting both univariate and multivariate survival analyses. Furthermore, loss- and gain-of-function approaches were utilized to investigate the impact of circRHBDD1 on GC immune escape. RNA-sequencing, immunoprecipitation, flow cytometry, and methylated RNA immunoprecipitation (meRIP) analysis were performed to elucidate the underlying molecular mechanisms. RESULTS: We discovered that circRHBDD1 exhibited remarkably high expression levels in GC tissues and cell lines. Notably, the high expression of circRHBDD1 was significantly correlated with poor overall survival and disease-free survival among GC patients. Both in vitro and in vivo experiments revealed that circRHBDD1 upregulated the expression of PD-L1 and impeded the infiltration of CD8+ T cells. Further, we found that circRHBDD1 binds to IGF2BP2, disrupting the interaction between E3 ligase TRIM25 and IGF2BP2, and ultimately inhibiting IGF2BP2 ubiquitination and degradation. Intriguingly, IGF2BP2 enhances PD-L1 mRNA stability through m6A modification. Additionally, we developed Poly (lactide-co-glycolic acid) (PLGA)-Polyethylene glycol (PEG)-based nanoparticles loaded with circRHBDD1 siRNA. In vivo experiments validated that the combination of PLGA-PEG(si-circRHBDD1) and anti-PD-1 offers a safe and efficacious nano-drug regimen for cancer immunotherapy. CONCLUSION: Our results demonstrated that circRHBDD1 promoted GC immune escape by upregulating the expression of PD-L1 and reprogramming T cell-mediated immune response. Inhibition of circRHBDD1 expression could potentially enhance the response of GC patients to immunotherapy, thus improving treatment outcomes. Additionally, the development of a nanodrug delivery system provides a feasible approach for future clinical applications.

The cuproptosis-related gene UBE2D2 functions as an immunotherapeutic and prognostic biomarker in pan-cancer.

BACKGROUND: Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown. METHODS: Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis. RESULTS: The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cells、Macrophages M2、CD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers. CONCLUSIONS: We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy.

Mediating role of body mass index on the relationship between physical activity and physical fitness among junior high school students in Shanghai.

Objectives: This study explored the relationship between physical activity (PA), body mass index (BMI), and physical fitness among junior high school students in Shanghai. Methods: A nationwide offline survey was conducted in Shanghai between August and December 2023, using a purposive sampling design. A total of 403 questionnaires were administered to 10 ninth-grade classes in 10 schools in Shanghai and 372 responses were included in the final analysis. Smart-PLS 4.0, structural equation modeling techniques were employed to analyze the collected data. Results: Light physical activity (LPA) had no influence on BMI, 800/1000 m (800/1000 M), sitting forward bend (FB), standing long jump (SLJ), 50 m (50 M), or vital capacity (VC). The results of part hypothesis supported the hypothetical model and explained that BMI had a negatively influence on 50 M, 800/1000 M and SLJ, BMI had a positively influence on VC. Moderate physical activity (MPA) had a negatively influence on BMI, but vigorous physical activity (VPA) had a positively influence on BMI, they both had influence on 50 M and FB, but had no influence on 800/1000 M, SLJ, and VC. Conclusions: BMI, MPA and VPA were found as pivotal factors influencing physical fitness, MPA and VPA were found to have divergent effects on BMI. This study highlighted the multifaceted nature of the relationship between PA, BMI, and physical fitness in junior high school students in Shanghai.

Constructing a Titanium Silicon Molecular Sieve-Based Z-Scheme Heterojunction with Enhanced Photocatalytic Activity.

Titanium silicon molecular sieve (TS-1) is an oxidation catalyst that possesses a long lifetime of charge transfer excited state, high Ti utilization efficiency, large specific surface area, and good adsorption property; therefore, TS-1 acts as a Ti-based photocatalyst candidate. In this work, TS-1 coupled Bi2MoO6 (TS-1/BMO) photocatalysts were fabricated via a facile hydrothermal route. Interestingly, the optimized TS-1/BMO-1.0 catalyst exhibited a decent photodegradation property toward tetracycline hydrochloride (85.49% in 120 min) under the irradiation of full spectrum light, which were 4.38 and 1.76 times compared to TS-1 and BMO, respectively. The enhanced photodegradation property of the TS-1/BMO-1.0 catalyst could be attributed to the reinforced light-harvesting capacity of the photocatalyst, high charge mobility, and suitable band structure for tetracycline hydrochloride degradation. In addition, the mechanism of photocatalytic degradation of tetracycline hydrochloride by the TS-1/BMO-1.0 catalyst was reasonably proposed based on the band structure, trapping, and ESR tests. This research provided feasible ideas for the design and construction of high-efficiency photocatalysts for contaminant degradation.

The 'Other' subfamily of HECT E3 ubiquitin ligases evaluate the tumour immune microenvironment and prognosis in patients with hepatocellular carcinoma.

Primary liver cancer is the sixth most common cancer and the third leading cause of cancer-related death worldwide. The role of the 'Other' subfamily of HECT E3 ligases (E3s) in hepatocellular carcinoma (HCC) remains unknown. The expression of the 'Other' HECT E3s was performed using The Cancer Genome Atlas (TCGA) data, and the authors found that the 'Other' HECT E3s were differentially expressed in HCC. Prognostic values were assessed using the Kaplan-Meier method and indicated that the high expressions of HECTD2, HECTD3, and HACE1 were associated with a worse clinical prognosis of HCC patients. The expression of HECTD2 was significantly correlated with the infiltration of CD4+ T cells and neutrophils. The levels of HECTD3 and HACE1 were notably related to the dendritic cells and memory B cells infiltrated in HCC. In addition, the three previously mentioned genes have shown to be associated with immune checkpoint genes, such as FOXP3, CCR8, STAT5B, TGFB1 and TIM-3. Moreover, HECTD2 could promote the proliferative activity, cell migration and invasive ability of HCC cells. Collectively, the authors' study demonstrated that HECTD2 was a novel immune-related prognostic biomarker for HCC, providing new insight into the treatment and prognosis of HCC.

Impact of solar-driven heating strategies on the phase change thermal storage performance of erythritol.

With escalating energy demands, solar power stands out for its abundance and renewable advantages, presenting a paramount sustainable solution. Herein, we tactically incorporate phase change material (PCM) into solar energy systems, resulting in substantial enhancements in energy storage and utilization. Through numerical simulations, the thermal dynamics and phase change processes associated with various heating methodologies are investigated, aiming to achieve optimal thermal performance and energy efficiency. Detailed analysis of temperature dynamics within the PCM under two distinct heating methods reveals pivotal thermal fluctuations in both the PCM and water during heat release. The results indicate that bottom heating promptly induces rayleigh convection, resulting in a uniform temperature and a stable phase interface, which are desirable for heat transfer. In contrast, central tube heating concentrates heat transfer in the upper PCM layer, leading to an uneven phase interface and thermal stratification. Configurations with two horizontally aligned heating tubes result in a 36% reduction in melting duration compared to the single central tube setup, highlighting enhanced efficiency. Additionally, the bottom heating approach demonstrates improved energy storage efficiency in both the initial and second heating cycles. These findings highlight the potential of PCM-integrated combined heating systems for solar energy capture, confirming their efficiency and practicality in addressing modern household energy demands.

Comparison of dexmedetomidine and a dexmedetomidine-esketamine combination for reducing dental anxiety in preschool children undergoing dental treatment under general anesthesia: A randomized controlled trial.

BACKGROUND: Dental anxiety is a widespread complication occurring in pediatric patients during dental visits and may lead to undesirable complications. Esketamine may be effective in anxiety. OBJECTIVE: The objective of this study was to investigate the effect of premedication with a dexmedetomidine-esketamine combination compared with dexmedetomidine alone on dental anxiety in preschool children undergoing dental treatment under general anesthesia. METHODS: This is a prospective, double-blinded, randomized controlled trial. A total of 84 patients were scheduled for elective outpatient dental caries treatment under general anesthesia. Patients were randomly premedicated with intranasal dexmedetomidine (group D) or intranasal dexmedetomidine-esketamine (group DS). The primary outcome was the level of dental anxiety assessed by the Modified Child Dental Anxiety Scale (MCDAS) at 2 h after surgery. Secondary outcomes included level of dental anxiety at 1 day and 7 days after surgery, the incidence of dental anxiety at 2 h, 1 day, and 7 days after surgery, sedation onset time, overall success of sedation, acceptance of mask induction, postoperative pain intensity, incidence of emergence agitation in PACU, adverse reactions, HR, and SpO2 before premedication (baseline) and at 10, 20, and 30 min after the end of study drug delivery. RESULTS: The dental anxiety in group DS was lower than that in group D at 2 h, 1 day, and 7 days postoperatively (P = 0.04, 0.004, and 0.006, respectively). The incidences of dental anxiety in group DS were lower than those in group D at 2 h (53 % vs 76 %, P = 0.03), 1 day (47 % vs 71 %, P = 0.04), and 7 days (44 % vs 71 %, P = 0.02) after surgery. Group DS had a higher success rate of sedation (P = 0.03) but showed a lower MAS score (P = 0.005) and smoother hemodynamics (P < 0.01) after drug administration than group D. Group DS showed a significantly lower incidence rate of emergence agitation (P = 0.03) and postoperative pain intensity (P = 0.006) than that in group D during the anesthesia recovery time. The occurrence of adverse reactions was similar in both groups (P > 0.05). LIMITATIONS: We did not analyze and correct for the learning effect caused by repeated applications of the MCDAS and MCDAS scores on the 1 day after surgery were obtained by telephone follow-up. CONCLUSIONS: Compared to premedication with dexmedetomidine alone, premedication with intranasal dexmedetomidine combined with esketamine could significantly improve dental anxiety in preschool children undergoing dental treatment under general anesthesia.

What exactly does the PfK13 C580Y mutation in Plasmodium falciparum influence?

BACKGROUND: The emergence and spread of artemisinin resistance threaten global malaria control and elimination goals, and encourage research on the mechanisms of drug resistance in malaria parasites. Mutations in Plasmodium falciparum Kelch 13 (PfK13) protein are associated with artemisinin resistance, but the unique or common mechanism which results in this resistance is unclear. METHODS: We analyzed the effects of the PfK13 mutation on the transcriptome and proteome of P. falciparum at different developmental stages. Additionally, the number of merozoites, hemozoin amount, and growth of P. falciparum 3D7C580Y and P. falciparum 3D7WT were compared. The impact of iron supplementation on the number of merozoites of P. falciparum 3D7C580Y was also examined. RESULTS: We found that the PfK13 mutation did not significantly change glycolysis, TCA, pentose phosphate pathway, or oxidative phosphorylation, but did reduce the expression of reproduction- and DNA synthesis-related genes. The reduced number of merozoites, decreased level of hemozoin, and slowed growth of P. falciparum 3D7C580Y were consistent with these changes. Furthermore, adding iron supply could increase the number of the merozoites of P. falciparum 3D7C580Y. CONCLUSIONS: These results revealed that the PfK13 mutation reduced hemoglobin ingestion, leading to artemisinin resistance, likely by decreasing the parasites' requirement for haem and iron. This study helps elucidate the mechanism of artemisinin resistance due to PfK13 mutations.

TH-302-loaded nanodrug reshapes the hypoxic tumour microenvironment and enhances PD-1 blockade efficacy in gastric cancer.

BACKGROUND: Hypoxia, a common characteristic of the tumour microenvironment, is involved in tumour progression and immune evasion. Targeting the hypoxic microenvironment has been implicated as a promising antitumour therapeutic strategy. TH-302 can be selectively activated under hypoxic conditions. However, the effectiveness of TH-302 in gastric cancer combined immunotherapy remains unclear. METHODS: We designed mPEG-PLGA-encapsulated TH-302 (TH-302 NPs) to target the hypoxic area of tumour tissues. A particle size analyzer was used to measure the average size and zeta potential of TH-302 NPs. The morphology was observed by transmission electron microscopy and scanning electron microscopy. The hypoxic area of tumour tissues was examined by immunofluorescence assays using pimonidazole. Flow cytometry analysis was performed to measure the levels of TNF-α, IFN-γ, and granzyme B. The synergistic antitumour activity of the combination of TH-302 NPs with anti-PD-1 (α-PD-1) therapy was assessed in vitro and in vivo. Haematoxylin and eosin staining of major organs and biochemical indicator detection were performed to investigate the biological safety of TH-302 NPs in vivo. RESULTS: TH-302 NPs inhibited the proliferation and promoted the apoptosis of gastric cancer cells under hypoxic conditions. In vitro and in vivo experiments confirmed that TH-302 NPs could effectively alleviate tumour hypoxia. TH-302 NPs exhibited high bioavailability, effective tumour-targeting ability and satisfactory biosafety. Moreover, the combination of TH-302 NPs with α-PD-1 significantly improved immunotherapeutic efficacy in vivo. Mechanistically, TH-302 NPs reduced the expression of HIF-1α and PD-L1, facilitated the infiltration of CD8+ T cells and increased the levels of TNF-α, IFN-γ, and granzyme B in tumours, thereby enhancing the efficacy of α-PD-1 therapy. CONCLUSION: TH-302 NPs alleviated the hypoxic tumour microenvironment and enhanced the efficacy of PD-1 blockade. Our results provide evidence that TH-302 NPs can be used as a safe and effective nanodrug for combined immunotherapy in gastric cancer treatment.

Outcomes of pregnancy in women with different types of pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is considered to increase maternal and fetal risk, and we attempt to explore pregnancy outcomes in women with different types of PH. METHODS: We retrospectively analyzed the clinical data of pregnant women with PH who were admitted to Anzhen Hospital from January 2010 to December 2019, and followed up on these parturients and their offspring. RESULTS: Three hundred and sixty-six pregnant women with PH were collected, including 265 pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD), 65 PH caused by left heart disease, 12 idiopathic PH, and 24 PH associated with other diseases. Maternal mean age was 28.4 ± 4.4 years and 72.1% were nulliparous. The estimated systolic pulmonary artery pressure was < 50 mmHg in 40.2% of patients, 50-70 mmHg in 23.2%, and > 70 mmHg in 36.6%. In more than 94% of women, a diagnosis of PH was made before pregnancy. During pregnancy, heart failure occurred in 15% of patients. Cesarean section was performed in 90.5% (20.4% emergency). Complications included fetal mortality (0.5%), preterm delivery (40.4%), and low birth weight (37.7%). A total of 20 mothers died (5.5%). The highest mortality rate was found in patients with idiopathic PH (4/12, 33.3%). A total of 12 children died (3.3%), 5 (1.4%) of them after discharge from the hospital, and 7 (1.9%) were in hospital. CONCLUSIONS: Although most of these women are fertile, PH does increase maternal and fetal risk. Women with idiopathic PH and Eisenmenger syndrome are not recommended to have children.

Rational design of three-in-one Pt/MnO2/GO hybrid nanozyme with enhanced catalytic performance for colorimetric detection of ascorbic acid and cysteine.

In this work, a novel three-in-one Pt/MnO2/GO hybrid nanozyme with wide pH and temperature working range was rational prepared using simple hydrothermal and reduction strategy. The prepared Pt/MnO2/GO displayed enhanced catalytic activity than single active component due to the excellent conductivity of GO, the increased active sites, the increased electron transfer capacity, the synergistic effect between each component and the decreased binding energy for adsorbed intermediates. Combing chemical characterization and theoretical simulation calculations, the O2 reduction process on the Pt/MnO2/GO nanozymes and the generated reactive oxygen species in the nanozyme-TMB system were thoroughly illustrated. Based on the excellent catalytic activity of Pt/MnO2/GO nanozymes, a colorimetric strategy was proposed to detect the ascorbic acid (AA) and cysteine (Cys), and the experimental results indicated that detection range of AA was 0.35-56 µM with a LOD of 0.075 µM and detection range of Cys was 0.5-32 µM with a LOD of 0.12 µM. Good recoveries were achieved in the human serum and fresh fruit juice detection procedures, demonstrating the potential applications of Pt/MnO2/GO-based colorimetric strategy in complex biological and food samples.

Microchip gas chromatography column using magnetic beads coated with polydimethylsiloxane and metal organic frameworks.

Micro gas chromatography (µGC) using microfabricated silicon columns has been developed in response to the requirement for portable on-site gas analysis. Although different stationary phases have been developed, repeatable and reliable surface coatings in these rather small microcolumns remains a challenge. Herein, a new stationary phase coating strategy using magnetic beads (MBs) as carriers for micro column is presented. MBs modified with organopolysiloxane (MBs@OV-1) and a metal organic framework (MBs@HKUST-1) are deposited in on-chip microcolumns assisted with a magnetic field with an optimized modification process. MBs@OV-1 column showed a minimum HETP of 0.074 cm (1351 plates/m) of 62 cm/s. Mixtures of volatile organic compounds are successfully separated using MBs carried stationary phase which demonstrates that this technique has good chromatographic column efficiency. This method not only provides a novel coating process, washing and characterization of the stationary phases but also establishes a straightforward strategy for testing new absorbent materials for µGC systems.

Gait characteristics related to fall risk in patients with cerebral small vessel disease.

Background: Falls and gait disturbance are significant clinical manifestations of cerebral small vessel disease (CSVD). However, few relevant studies are reported at present. We aimed to investigate gait characteristics and fall risk in patients with CSVD. Methods: A total of 119 patients with CSVD admitted to the Department of Neurology at Tianjin Huanhu Hospital between 17 August 2018 and 7 November 2018 were enrolled in this study. All patients underwent cerebral magnetic resonance imaging scanning and a 2-min walking test using an OPAL wearable sensor and Mobility Lab software. Relevant data were collected using the gait analyzer test system to further analyze the time-space and kinematic parameters of gait. All patients were followed up, and univariate and multivariate logistic regression analyses were conducted to analyze the gait characteristics and relevant risk factors in patients with CSVD at an increased risk of falling. Results: All patients were grouped according to the presence or absence of falling and fear of falling and were divided into a high-fall risk group (n = 35) and a low-fall risk group (n = 72). Logistic multivariate regression analysis showed that the toe-off angle [odds ratio (OR) = 0.742, 95% confidence interval (CI) 0.584-0.942, p < 0.05], toe-off angle coefficient of variation (CV) (OR = 0.717, 95% CI: 0.535-0.962, p < 0.05), stride length CV (OR = 1.256, 95% CI: 1.017-1.552, p < 0.05), and terminal double support CV (OR = 1.735, 95% CI: 1.271-2.369, p < 0.05) were statistically significant (p < 0.05) and were independent risk factors for high-fall risk in patients with CSVD. Conclusion: CSVD patients with seemingly normal gait and ambulation independently still have a high risk of falling, and gait spatiotemporal-kinematic parameters, gait symmetry, and gait variability are important indicators to assess the high-fall risk. The decrease in toe-off angle, in particular, and an increase in related parameters of CV, can increase the fall risk of CSVD patients.

Why is Babesia not killed by artemisinin like Plasmodium?

Babesia spp. are intraerythrocytic apicomplexans that digest and utilize red blood cells in a similar way to intraerythrocytic Plasmodium spp., but unlike the latter, are not sensitive to artemisinin. A comparison of Babesia and Plasmodium genomes revealed that Babesia genomes, which are smaller than those of Plasmodium, lack numerous genes, and especially haem synthesis-related genes, that are found in the latter. Single-cell sequencing analysis showed that the different treatment groups of Babesia microti with expressed pentose phosphate pathway-related, DNA replication-related, antioxidation-related, glycolysis-related, and glutathione-related genes were not as sensitive to artemether as Plasmodium yoelii 17XNL. In particular, pentose phosphate pathway-related, DNA replication-related, and glutathione-related genes, which were actively expressed in P. yoelii 17XNL, were not actively expressed in B. microti. Supplying iron in vivo can promote the reproduction of B. microti. These results suggest that Babesia spp. lack a similar mechanism to that of malaria parasites through which the haem or iron in hemoglobin is utilized, and that this likely leads to their insensitivity to artemisinin.

Antibacterial actions of Ag nanoparticles synthesized from Cimicifuga dahurica (Turcz.) Maxim. and their application in constructing a hydrogel spray for healing skin wounds.

Cimicifuga dahurica (Turcz.) Maxim. is an edible natural food and a type of traditional herbal medicine with antipyretic and analgesic properties. In this study, we found that Cimicifuga dahurica (Turcz.) Maxim. extract (CME) has good skin wound healing qualities due to its antibacterial effects on both wound inflammation-related Gram positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram negative (Escherichia coli and Klebsiella pneumoniae) strains. Using CME as a reducing agent, CME-based Ag nanoparticles (CME-AgNPs) with an average particle size of 7 nm were synthesized. The minimum bactericidal concentration (MBC) of CME-AgNPs against the investigated bacterial species varied from 0.08 to 1.25 mg/mL, indicating much higher antibacterial activity than the pure CME. Additionally, a novel network-like thermosensitive hydrogel spray (CME-AgNPs-F127/F68) was developed and shown a skin wound healing rate of 98.40% in 14 days, demonstrating the spray's potential as a novel wound dressing that accelerates wound healing.

Surgery Before Pregnancy in Women with Congenital Heart Disease: A Retrospective Study.

BACKGROUND: This study aimed to investigate if surgery before pregnancy would result in better maternal and fetal outcomes in patients with congenital heart disease. METHODS: A retrospective study was conducted using data collected from the medical records of pregnant patients with congenital heart disease, who were seen at Beijing Anzhen Hospital between 2010 and 2019. The patients were divided into surgical and non-surgical groups, and the differences in outcomes were compared. RESULTS: A total of 999 patients with congenital heart disease (mean age, 28.7±4.3 years) were enrolled, with 403 (40.0%) and 596 (60.0%) in the surgical and non-surgical groups, respectively. The percentages of almost all adverse events were higher in the non-surgical group than in the surgical group. The adverse events included preterm delivery (9.9 vs. 17.1%), low birth weight (6.5 vs. 11.6%), heart failure (2.7 vs. 6.7%), cesarean section (75.7 vs. 85.9%), pulmonary hypertension (13.6 vs. 36.2%), and death (0.5 vs. 2.3%) (all P < 0.05). A total of 16 (1.6%) patients died, including 14 and two in the non-surgical and surgical groups, respectively. Regardless of the type of congenital heart disease, preterm delivery and low birth weight were more common in the non-surgical group compared with the surgical group, and there were no statistical between group differences in the other remaining events. CONCLUSIONS: In the non-surgical group, the results were similar regardless of the type of congenital heart disease, except for preterm delivery and low birth weight. The overall outcome of the surgical group was better than that of the non-surgical group, and surgery before pregnancy reduced maternal and infant risk.

Maternal Outcomes Among Pregnant Women With Congenital Heart Disease-Associated Pulmonary Hypertension.

BACKGROUND: Studies focused on pregnant women with congenital heart disease (CHD)-associated pulmonary hypertension (PH) are scarce and limited by small sample sizes and single-center design. This study sought to describe the pregnancy outcomes in women with CHD with and without PH. METHODS: Outcomes for pregnant women with CHD were evaluated retrospectively from 1993 to 2016 and prospectively from 2017 to 2019 from 7 tertiary hospitals. PH was diagnosed on the basis of echocardiogram or catheterization. The incidence of maternal death, cardiac complications, and obstetric and offspring complications was compared for women with CHD and no PH, mild, and moderate-to-severe PH. RESULTS: A total of 2220 pregnant women with CHD had completed pregnancies. PH associated with CHD was identified in 729 women, including 398 with mild PH (right ventricle to right atrium gradient 30-50 mm Hg) and 331 with moderate-to-severe PH (right ventricle to right atrium gradient >50 mm Hg). Maternal mortality occurred in 1 (0.1%), 0, and 19 (5.7%) women with CHD and no, mild, or moderate-to-severe PH, respectively. Of the 729 patients with PH, 619 (85%) had CHD-associated pulmonary arterial hypertension, and 110 (15%) had other forms of PH. Overall, patients with mild PH had better maternal outcomes than those with moderate-to-severe PH, including the incidence of maternal mortality or heart failure (7.8% versus 39.6%; P<0.001), other cardiac complications (9.0% versus 32.3%; P<0.001), and obstetric complications (5.3% versus 15.7%; P<0.001). Brain natriuretic peptide >100 ng/L (odds ratio, 1.9 [95% CI, 1.0-3.4], P=0.04) and New York Heart Association class III to IV (odds ratio, 2.9 [95% CI, 1.6-5.3], P<0.001) were independently associated with adverse maternal cardiac events in pregnancy with PH, whereas follow-up with a multidisciplinary team (odds ratio, 0.4 [95% CI, 0.2-0.6], P<0.001) and strict antenatal supervision (odds ratio, 0.5 [95% CI, 0.3-0.7], P=0.001) were protective. CONCLUSIONS: Women with CHD-associated mild PH appear to have better outcomes compared with women with CHD-associated moderate-to-severe PH, and with event rates similar for most outcomes with women with CHD and no PH. Multimodality risk assessment, including PH severity, brain natriuretic peptide level, and New York Heart Association class, may be useful in risk stratification in pregnancy with PH. Follow-up with a multidisciplinary team and strict antenatal supervision during pregnancy may also help to mitigate the risk of adverse maternal cardiac events.

Pregnancy outcomes of women with Eisenmenger syndrome: A single-center study.

BACKGROUND: To explore the outcomes of mothers with Eisenmenger syndrome (ES) and their offspring. METHODS: Pregnant women with ES admitted to the Beijing Anzhen Hospital between 2010 and 2019 were retrospectively analyzed and followed up. RESULTS: Forty-two parturient women with ES were recruited, with an average age of 26.7 years (standard deviation [SD], ±4.0 years). The average gestational age was 33.7 weeks (SD, ±2.5 weeks). The average percutaneous oxygen saturation was 84.1 (±9.2), and 40 (95.2%) had caesarean delivery. The average pulmonary artery systolic pressure was 107.5 mmHg (SD, ±20.3 mmHg). Twelve (28.6%) women experienced pulmonary hypertensive crisis; 11 (26.2%) of these women died. Regarding the offspring, the average fetal weight was 1778.1 g (SD, ±555.3 g), six (14.3%) died, and congenital heart disease was diagnosed in three (7.1%). There were significant differences in age, gestational age, percutaneous oxygen saturation, Apgar score, and heart failure between the maternal death and non-death groups (P < 0.05). Death was mainly related to pulmonary hypertensive crisis and heart failure. CONCLUSIONS: We recommend pregnancy termination if ES occurs during early pregnancy; however, patients should be informed of the risks if it occurs during late pregnancy. Multidisciplinary cooperation should be strengthened to improve the prognosis of the mothers and their offspring.