Epigenetic regulation of megakaryopoiesis and platelet formation.

Platelets, produced by megakaryocytes, play unique roles in physiological processes, such as hemostasis, coagulation, and immune regulation, while also contributing to various clinical diseases. During megakaryocyte differentiation, the morphology and function of cells undergo significant changes due to the programmed expression of a series of genes. Epigenetic changes modify gene expression without altering the DNA base sequence, effectively impacting the inner workings of the cell at different stages of growth, proliferation, differentiation, and apoptosis. These modifications also play an important role in megakaryocyte development and platelet biogenesis. However, the specific mechanisms underlying epigenetic processes or the vast epigenetic regulatory network formed by their interactions remain unclear. In this review, we systematically summarize the key roles played by epigenetics in megakaryocyte development and platelet formation, including DNA methylation, histone modification, and non-coding RNA regulation. We expect our review to provide a deeper understanding of the biological processes underlying megakaryocyte development and platelet formation and to inform the development of new clinical interventions aimed at addressing platelet-related diseases and improving patient prognoses.

Megakaryocytic IGF1 coordinates activation and ferroptosis to safeguard hematopoietic stem cell regeneration after radiation injury.

BACKGROUND: Hematopoietic stem cell (HSC) regeneration underlies hematopoietic recovery from myelosuppression, which is a life-threatening side effect of cytotoxicity. HSC niche is profoundly disrupted after myelosuppressive injury, while if and how the niche is reshaped and regulates HSC regeneration are poorly understood. METHODS: A mouse model of radiation injury-induced myelosuppression was built by exposing mice to a sublethal dose of ionizing radiation. The dynamic changes in the number, distribution and functionality of HSCs and megakaryocytes were determined by flow cytometry, immunofluorescence, colony assay and bone marrow transplantation, in combination with transcriptomic analysis. The communication between HSCs and megakaryocytes was determined using a coculture system and adoptive transfer. The signaling mechanism was investigated both in vivo and in vitro, and was consolidated using megakaryocyte-specific knockout mice and transgenic mice. RESULTS: Megakaryocytes become a predominant component of HSC niche and localize closer to HSCs after radiation injury. Meanwhile, transient insulin-like growth factor 1 (IGF1) hypersecretion is predominantly provoked in megakaryocytes after radiation injury, whereas HSCs regenerate paralleling megakaryocytic IGF1 hypersecretion. Mechanistically, HSCs are particularly susceptible to megakaryocytic IGF1 hypersecretion, and mTOR downstream of IGF1 signaling not only promotes activation including proliferation and mitochondrial oxidative metabolism of HSCs, but also inhibits ferritinophagy to restrict HSC ferroptosis. Consequently, the delicate coordination between proliferation, mitochondrial oxidative metabolism and ferroptosis ensures functional HSC expansion after radiation injury. Importantly, punctual IGF1 administration simultaneously promotes HSC regeneration and hematopoietic recovery after radiation injury, representing a superior therapeutic approach for myelosuppression. CONCLUSIONS: Our study identifies megakaryocytes as a last line of defense against myelosuppressive injury and megakaryocytic IGF1 as a novel niche signal safeguarding HSC regeneration.

3D skin bioprinting as promising therapeutic strategy for radiation-associated skin injuries.

Both cutaneous radiation injury and radiation combined injury (RCI) could have serious skin traumas, which are collectively referred to as radiation-associated skin injuries in this paper. These two types of skin injuries require special managements of wounds, and the therapeutic effects still need to be further improved. Cutaneous radiation injuries are common in both radiotherapy patients and victims of radioactive source accidents, which could lead to skin necrosis and ulcers in serious conditions. At present, there are still many challenges in management of cutaneous radiation injuries including early diagnosis, lesion assessment, and treatment prognosis. Radiation combined injuries are special and important issues in severe nuclear accidents, which often accompanied by serious skin traumas. Mass victims of RCI would be the focus of public health concern. Three-dimensional (3D) bioprinting, as a versatile and favourable technique, offers effective approaches to fabricate biomimetic architectures with bioactivity, which provides potentials for resolve the challenges in treating radiation-associated skin injuries. Combining with the cutting-edge advances in 3D skin bioprinting, the authors analyse the damage characteristics of skin wounds in both cutaneous radiation injury and RCI and look forward to the potential value of 3D skin bioprinting for the treatments of radiation-associated skin injuries.

Establishment and validation of a CT-based prediction model for the good dissolution of mild chronic subdural hematoma with atorvastatin treatment.

PURPOSE: To develop and validate a prediction model based on imaging data for the prognosis of mild chronic subdural hematoma undergoing atorvastatin treatment. METHODS: We developed the prediction model utilizing data from patients diagnosed with CSDH between February 2019 and November 2021. Demographic characteristics, medical history, and hematoma characteristics in non-contrast computed tomography (NCCT) were extracted upon admission to the hospital. To reduce data dimensionality, a backward stepwise regression model was implemented to build a prognostic prediction model. We calculated the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model by a tenfold cross-validation procedure. RESULTS: Maximum thickness, volume, mean density, morphology, and kurtosis of the hematoma were identified as the most significant predictors of good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The prediction model exhibited good discrimination, with an area under the curve (AUC) of 0.82 (95% confidence interval [CI], 0.74-0.90) and good calibration (p = 0.613). The validation analysis showed the AUC of the final prognostic prediction model is 0.80 (95% CI 0.71-0.86) and it has good prediction performance. CONCLUSION: The imaging data-based prediction model has demonstrated great prediction accuracy for good hematoma dissolution in mild CSDH patients undergoing atorvastatin treatment. The study results emphasize the importance of imaging data evaluation in the management of CSDH patients.

Oxymatrine boosts hematopoietic regeneration by modulating MAPK/ERK phosphorylation after irradiation-induced hematopoietic injury.

Hematopoietic toxicity due to ionizing radiation (IR) is a leading cause of death in nuclear incidents, occupational hazards, and cancer therapy. Oxymatrine (OM), an extract originating from the root of Sophora flavescens (Kushen), possesses extensive pharmacological properties. In this study, we demonstrate that OM treatment accelerates hematological recovery and increases the survival rate of mice subjected to irradiation. This outcome is accompanied by an increase in functional hematopoietic stem cells (HSCs), resulting in enhanced hematopoietic reconstitution abilities. Mechanistically, we observed significant activation of the MAPK signaling pathway, accelerated cellular proliferation, and decreased cell apoptosis. Notably, we identified marked increases in the cell cycle transcriptional regulator Cyclin D1 (Ccnd1) and the anti-apoptotic protein BCL2 in HSCs after OM treatment. Further investigation revealed that the expression of Ccnd1 transcript and BCL2 levels were reversed upon specific inhibition of ERK1/2 phosphorylation, effectively negating the rescuing effect of OM. Moreover, we determined that targeted inhibition of ERK1/2 activation significantly counteracted the regenerative effect of OM on human HSCs. Taken together, our results suggest a crucial role for OM in hematopoietic reconstitution following IR via MAPK signaling pathway-mediated mechanisms, providing theoretical support for innovative therapeutic applications of OM in addressing IR-induced injuries in humans.

Characterization and quality evaluation of QiXueShuFu Decoction based on fingerprint and ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry.

QiXueShuFu Decoction (QXSFD) modified from the Bazhen Decoction which was originally from the classic Ming Dynasty is a traditional folk formula that boosts the body's immune system. However, its ambiguous chemical components limited its quality control evaluation. In this study, ultra-performance liquid chromatography (UPLC) fingerprint combined with multivariate analysis was used to evaluate the quality of 15 batches of QXSFD, and UPLC quadrupole-orbitrap mass spectrometry was used to further examine the chemical components in QXSFD, after which representative compounds from each disassembled prescription were selected for comparison. Fifteen batches of samples had 33 common peaks in which 11 differential components could be used as a reference for subsequent quality control. One hundred forty-three components were identified from QXSFD. Saponins were mainly derived from the monarch, terpenes from the minister, and polysaccharides and glycosides from the assistant. In addition, quantitative assay revealed that the content of ferulic acid, chlorogenic acid, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside and 3,6'-disinapoyl sucrose in the whole prescription were higher than the contents of each disassembled prescription. This is the first comprehensive quality report on the chemical components of QXSFD, which is important for pharmacodynamic material basis and quality control.

Matrix metalloproteinase-2 inducing COL1A1 synthesis via integrin alpha â ¤ promotes invasion and metastasis of cholangiocarcinoma cells.

INTRODUCTION AND OBJECTIVES: Cholangiocarcinoma (CCA) is characterized by early distant invasion and metastasis, whereas the underlying mechanism is still obscure. Increasing evidence shows that collagen type Ι alpha 1 (COL1A1) is a gene associated with the progression of multiple diseases. Here, we attempted to investigate the role of COL1A1 in CCA. MATERIALS AND METHODS: The expression of COL1A1 between tumor tissues and adjacent normal tissues obtained from CCA patients was detected by Western blot and immunofluorescence, followed by analysis of its clinical significance. Then, the biological effects of COL1A1 overexpression or knockdown on CCA cells were evaluated in vitro and in vivo. Finally, molecular mechanism of COL1A1 in regulating the invasion and metastasis of CCA cells was determined by a series of experiments. RESULTS: COL1A1 expression was significantly higher in CCA pathological tissues than in corresponding adjacent normal tissues. Analysis of 83 CCA patients showed that higher expression of COL1A1 was correlated with poorer patient prognosis. Notably, overexpression or knockdown experiments revealed that COL1A1 contributed to the migration and invasion, as well as epithelial-to-mesenchymal transition (EMT), in CCA cells. Further investigations demonstrated that matrix metalloproteinase-2 (MMP2) promoted COL1A1 upregulation via the integrin alpha Ⅴ pathway, therefore affecting ECM remodelling and inducing EMT in CCA cells. Moreover, COL1A1 expression was positively related to PD-1 and PD-L1 in CCA, and COL1A1 increased PD-L1 expression by activating the NF-κB pathway. CONCLUSIONS: COL1A1 plays an important role in regulating CCA progression and may act as a promising biomarker and therapeutic target for CCA.

A Review of the Role of Caveolin-1 in Acetaminophen-Induced Liver Injury.

BACKGROUND: Acetaminophen (APAP) is commonly used as an antipyretic and analgesic agent. Excessive APAP can induce liver toxicity, known as APAP-induced liver injury (ALI). The metabolism and pathogenesis of APAP have been extensively studied in recent years, and many cellular processes such as autophagy, mitochondrial oxidative stress, mitochondrial dysfunction, and liver regeneration have been identified to be involved in the pathogenesis of ALI. Caveolin-1 (CAV-1) as a scaffold protein has also been shown to be involved in the development of various diseases, especially liver disease and tumorigenesis. The role of CAV-1 in the development of liver disease and the association between them remains a challenging and uncharted territory. SUMMARY: In this review, we briefly explore the potential therapeutic effects of CAV-1 on ALI through autophagy, oxidative stress, and lipid metabolism. Further research to better understand the mechanisms by which CAV-1 regulates liver injury will not only enhance our understanding of this important cellular process, but also help develop new therapies for human disease by targeting CAV-1 targets. KEY MESSAGES: This review briefly summarizes the potential protective mechanisms of CAV-1 against liver injury caused by APAP.

A stromal lineage maintains crypt structure and villus homeostasis in the intestinal stem cell niche.

BACKGROUND: The nutrient-absorbing villi of small intestines are renewed and repaired by intestinal stem cells (ISCs), which reside in a well-organized crypt structure. Genetic studies have shown that Wnt molecules secreted by telocytes, Gli1+ stromal cells, and epithelial cells are required for ISC proliferation and villus homeostasis. Intestinal stromal cells are heterogeneous and single-cell profiling has divided them into telocytes/subepithelial myofibroblasts, myocytes, pericytes, trophocytes, and Pdgfralow stromal cells. Yet, the niche function of these stromal populations remains incompletely understood. RESULTS: We show here that a Twist2 stromal lineage, which constitutes the Pdgfralow stromal cell and trophocyte subpopulations, maintains the crypt structure to provide an inflammation-restricting niche for regenerating ISCs. Ablating Twist2 lineage cells or deletion of one Wntless allele in these cells disturbs the crypt structure and impairs villus homeostasis. Upon radiation, Wntless haplo-deficiency caused decreased production of anti-microbial peptides and increased inflammation, leading to defective ISC proliferation and crypt regeneration, which were partially rescued by eradication of commensal bacteria. In addition, we show that Wnts secreted by Acta2+ subpopulations also play a role in crypt regeneration but not homeostasis. CONCLUSIONS: These findings suggest that ISCs may require different niches for villus homeostasis and regeneration and that the Twist2 lineage cells may help to maintain a microbe-restricted environment to allow ISC-mediated crypt regeneration.

Research on the Soft-Sensing Method of Indicator Diagram of Beam Pumping Unit.

An accurate calculation of the indicator diagram of a pumping unit is the key factor in analyzing the performance of an oilfield production and operation and in preparing and optimizing an oilfield development plan. Aiming at the problems of the poor stability of the conventional load-displacement sensor method and the wave equation method, owing to the influence of an alternating load on the force sensor and the difficulty in measuring the crank angle using the electrical parameter method, a new soft sensing method employing the input electrical parameters of the motor and the beam inclination has been proposed to obtain the indicator diagram. At first, this method is established based on the beam angle of the pumping unit, which is easily measured using the suspension point displacement mathematics calculation model and the torque factor. Subsequently, the electric motor input parameters, the parameters of the four-bar linkage, and the relationship between the polished rod load have been established. Finally, the motor and the beam angle of the measured electrical parameters have been substituted into the calculation of the suspension point displacement and load value and pull in accordance with the guidelines to eliminate the singularity mutation values. After processing the measured data through a Butterworth filter, the indicator diagram is obtained. The results of the engineering experiment and application show that the average relative error of the method is less than 3.95%, and the maximum relative error remains within 2% for 6 months, which verifies the stability of the soft sensing method.

[Genetic analysis of a child with Generalized arterial calcification of infancy due to variant of ABCC6 gene].

OBJECTIVE: To explore the clinical manifestations and genetic basis for a rare case of Generalized arterial calcification of infancy (GACI). METHODS: A 44-day-old female infant who was treated at Baoding Hospital of Beijing Children's Hospital Affiliated to Capital Medical University on August 26, 2022 was selected as the study subject. Clinical data of the child was collected, and Trio-whole exome sequencing (Trio-WES), whole genome copy number variation sequencing (CNV-seq) and minigene splicing assay were carried out to analyze the pathogenicity of the variants. RESULTS: The child had presented with fever and high inflammatory indicators, for which treatment with various antibiotics was ineffective. Ultrasound had revealed extensive arterial calcification and arterial wall thickening. The child was suspected for GACI with arteritis related to the primary disease. Her fever was relieved by treatment with glucocorticoid and biological agents. Trio-WES revealed that she has harbored compound heterozygous variants of the ABCC6 gene, namely c.4404-1G>A and c.4041+5G>T, for which the latter was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variants were classified as likely pathogenic (PVS1+PM2_Supporting) and variant of unknown significance (PM2_Supporting+PM3+PP3), respectively. The result of CNV-seq was negative. And the minigene splicing assay has further verified that both variants can result in alternative splicing. CONCLUSION: For pyrexia with unknown causes and refractory to conventional treatment, it is necessary to recommend early genetic testing to avoid missed diagnosis of GACI.

Imbalanced lipid homeostasis caused by membrane αKlotho deficiency contributes to the acute kidney injury to chronic kidney disease transition.

After acute kidney injury (AKI), renal tubular epithelial cells (RTECs) are pathologically characterized by intracellular lipid droplet (LD) accumulation, which are involved in RTEC injury and kidney fibrosis. However, its pathogenesis remains incompletely understood. The protein, αKlotho, primarily expressed in RTECs, is well known as an anti-aging hormone wielding versatile functions, and its membrane form predominantly acts as a co-receptor for fibroblast growth factor 23. Here, we discovered a connection between membrane αKlotho and intracellular LDs in RTECs. Fluorescent fatty acid (FA) pulse-chase assays showed that membrane αKlotho deficiency in RTECs, as seen in αKlotho homozygous mutated (kl/kl) mice or in mice with ischemia-reperfusion injury (IRI)-induced AKI, inhibited FA mobilization from LDs by impairing adipose triglyceride lipase (ATGL)-mediated lipolysis and lipophagy. This resulted in LD accumulation and FA underutilization. IRI-induced alterations were more striking in αKlotho deficiency. Mechanistically, membrane αKlotho deficiency promoted E3 ligase peroxin2 binding to ubiquitin-conjugating enzyme E2 D2, resulting in ubiquitin-mediated degradation of ATGL which is a common molecular basis for lipolysis and lipophagy. Overexpression of αKlotho rescued FA mobilization by preventing ATGL ubiquitination, thereby lessening LD accumulation and fibrosis after AKI. This suggests that membrane αKlotho is indispensable for the maintenance of lipid homeostasis in RTECs. Thus, our study identified αKlotho as a critical regulator of lipid turnover and homeostasis in AKI, providing a viable strategy for preventing tubular injury and the AKI-to-chronic kidney disease transition.

Clustered Cobalt Nanodots Initiate Ferroptosis by Upregulating Heme Oxygenase 1 for Radiotherapy Sensitization.

High cobalt (Co) levels in tumors are associated with good clinical prognosis. An anticancer regimen that increases intratumoral Co through targeted nanomaterial delivery is proposed in this study. Bovine serum albumin and cobalt dichloride are applied to prepare cobaltous oxide nanodots using a facile biomineralization strategy. After iRGD peptide conjugation, the nanodots are loaded into dendritic mesoporous silica nanoparticles, generating a biocompatible product iCoDMSN. This nanocomposite accumulates in tumors after intravenous injection by deep tissue penetration and can be used for photoacoustic imaging. Proteomics research and molecular biology experiments reveal that iCoDMSN is a potent ferroptosis inducer in cancer cells. Mechanistically, iCoDMSNs upregulate heme oxygenase 1 (HMOX1), which increases transferrin receptors and reduces solute carrier family 40 member 1 (SLC40A1), resulting in Fe2+ accumulation and ferroptosis initiation. Furthermore, upregulated nuclear factor erythroid 2-related factor 2 (NRF2), arising from the reduction in Kelch-like ECH-associated protein 1 (KEAP1) expression, is responsible for HMOX1 enhancement after iCoDMSN treatment. Owing to intensified ferroptosis, iCoDMSN acts as an efficient radiotherapy enhancer to eliminate cancer cells in vitro and in vivo. This study demonstrates a versatile Co-based nanomaterial that primes ferroptosis by expanding the labile iron pool in cancer cells, providing a promising tumor radiotherapy sensitizer.

Irradiation accelerates SARS-CoV-2 infection by enhancing sphingolipid metabolism.

Cancer patients who receive radiotherapy have a high risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS-CoV-2 using S pseudovirions and probed the underlying mechanism via RNA-seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid sphingomyelinase (ASM), which catalyses the hydrolysis of sphingomyelin to ceramide, contributing to lipid raft formation and promoting SARS-CoV-2 invasion. Inhibition of lipid raft formation with methyl-ß-cyclodextrin (MßCD) or the tyrosine kinase inhibitor genistein and ASM suppression through small interfering RNA or amitriptyline (AMT) treatment abolished the enhancing effect of irradiation on viral infection. Animal experiments supported the finding that irradiation promoted SARS-CoV-2 S pseudovirion infection in A549 cell tumour-bearing BALB/c nude mice, whereas AMT treatment dramatically decreased viral infection. This study discloses the role of sphingolipid metabolism in irradiation-induced SARS-CoV-2 infection, thus providing a potential target for clinical intervention to protect patients receiving radiotherapy from COVID-19.

Three-dimensional arterial spin labeling for the evaluation of the cerebral hemodynamics in ischemic and hemorrhagic Moyamoya disease.

INTRODUCTION: Moyamoya disease (MMD) is a vascular disease with significant risk of mortality due to ischemia or hemorrhage in the brain. The goal of the study was to explore three-dimensional arterial spin labeling (3D-ASL) to improve evaluation of cerebral hemodynamics in patients with MMD. METHODS: Our study included 54 cases of ischemic MMD and 42 cases of hemorrhagic MMD. Dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) and 3D-ASL were performed at 3.0 T. Based on these scans, cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) were calculated and compared between patients with different disease subtypes. Receiver operating characteristics (ROC) analysis was used to assess the diagnostic sensitivity and specificity of different imaging procedures and parameters. RESULTS: Our data suggested that CBF in the lesion area was more severely reduced in patients with hemorrhagic MMD than in those with ischemic MMD. The CBF parameter in 3D-ASL diagnosed hemorrhagic and ischemic MMD with a significant sensitivity and specificity of 80.59% and 57.41% respectively, with an area under the curve (AUC) of 0.75. We also found that the relative CBF (rCBF) of 3D-ASL was more pronounced decreased and the relative MTT and TTP of DSC-PWI were significantly increased in patients with hemorrhagic MMD than those with ischemic MMD. Specificity and sensitivity, and AUC of 3D-ASL were better than the comparison of absolute values from DSC-PWI scans. DISCUSSION/CONCLUSION: Our study indicated that 3D-ASL is powerful in differentiating patients with cerebral ischemic or hemorrhagic MMD, providing another diagnostic tool that could potentially improve precision medicine to monitoring MMD patients.

The effect and safety of probiotics on depression: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: With the escalating social pressures, there has been a continuous rise in the prevalence of depression among the population, leading to substantial healthcare burdens. Moreover, conventional pharmacological interventions still exhibit certain limitations. Therefore, the primary objective of this study is to systematically evaluate the clinical efficacy of probiotics in the treatment of depression. METHODS: Randomized controlled trials of probiotics in treating depressive symptoms were retrieved from Pubmed, Cochrane Library, Web of Science, Wan Fang database, and CNKI between the establishment of the database and March 2022. The primary outcome was Beck's depression rating scale (BDI) scores, while the secondary outcomes were depression scores on the DASS-21 scale, biochemical indicators (IL-6, NO, and TNF-α levels), and adverse events. In addition, Revman 5.3 was used for Meta-analysis and quality evaluation, and Stata 17 was used for the Egger test and Begg's test. A total of 776 patients, including 397 and 379 patients in the experimental and control groups, respectively, were included. RESULTS: The total BDI score of the experimental group was lower than that of the control group (MD = - 1.98, 95%CI - 3.14 to - 0.82), and the score of DASS (MD = 0.90, 95%CI - 1.17 to 2.98), the IL-6 level (SMD = - 0.55, 95%CI - 0.88 to - 0.23), the NO level (MD = 5.27, 95% CI 2.51 to 8.03), and the TNF-α level (SMD = 0.19, 95% CI - 0.25 to 0.63). CONCLUSION: The findings substantiate the therapeutic potential of probiotics in mitigating depressive symptoms by significantly reducing Beck's Depression Inventory (BDI) scores and alleviating the overall manifestation of depression.

Comparison of voiding vesicoureteral urosonography with fluoroscopic voiding cystourethrography in children with vesicoureteral reflux.

Objective: To evaluate the value and compliance rate of voiding vesicoureteral urosonography in pediatric vesicoureteral reflux (VUR). Methods: This is a retrospective study. A total of 80 children with high-risk VUR admitted to Children's Hospital affiliated to Capital Medical University from December 2018 to December 2020 were selected. All patients underwent voiding urosonography (VUS) and fluoroscopic voiding cystourethrography (VCUG). The sensitivity and compliance of voiding vesicoureteral urosonography were compared, and its application value was evaluated. Results: A total of 160 PUUs were examined, and all cases were normal. Among them, 56 PUUs had reflux (35.00%, 56/160), 46 PUUs had reflux under both examination methods (28.75%, 46/160), and 10 PUUs were only detected under VUS (6.25%, 10/160). Thirty-four cases of VUR (42.50%, 34/80) were diagnosed by VUS, among which 15 cases were bilateral reflux and 4 cases were unilateral reflux. Twenty-five cases (35.00%, 25/80) were diagnosed by VCUG, among which 10 cases were bilateral regurgitation and five cases were unilateral regurgitation. No significant difference was observed in the detection rate of reflux between the two methods (P=0.432). A total of 146 PUUs were found to be consistent between the two methods (91.25%, 160), including 2 Grade-I reflux, 6 Grade-II reflux, 14 Grade-III reflux, 12 Grade-IV reflux, eight Grade-V reflux, and 104 without reflux, demonstrating SATISFACTORY consistency between the two groups (Kappa=0.885). Conclusion: Voiding vesicoureteral urosonography has a high coincidence rate in the detection of vesicoureteral reflux in children.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Selenium Atom-Polarization Effect Determines TrxR-Specific Recognition of Metallodrugs.

Thioredoxin reductase (TrxR) is highly overexpressed in cancer cells to promote malignant tumor survival. Designing drugs that inhibit TrxR activity is a promising approach to achieve highly effective cancer chemotherapy. However, the selectivity of TrxR inhibitors continue to be a challenge for scientists. In this work, we demonstrate a new strategy to selectively inhibit TrxR through constructing electrophilic center -N-Se(δ+)-N- by using the polarization effect of the selenium atom. The constructed electrophilic center interacts noncovalently with the active motif of TrxR to avoid the interference of other residues in human tissues, thereby selectively inhibiting intracellular TrxR activity. Computational and experimental analysis confirms that the formed electrophilic selenium center preferred to attack the SeC residues in the redox active center of TrxR at the 498 site through strong noncovalent interactions. Both in vitro and in vivo experimental results confirmed that this strategy can significantly improve the anticancer effect. This study may provide a novel route to design highly effective and selective chemotherapeutic drugs.

Controlling the Shrinkage of 3D Hot Spot Droplets as a Microreactor for Quantitative SERS Detection of Anticancer Drugs in Serum Using a Handheld Raman Spectrometer.

Quantitative measurement is one of the ultimate targets for surface-enhanced Raman spectroscopy (SERS), but it suffers from difficulties in controlling the uniformity of hot spots and placing the target molecules in the hot spot space. Here, a convenient approach of three-phase equilibrium controlling the shrinkage of three-dimensional (3D) hot spot droplets has been demonstrated for the quantitative detection of the anticancer drug 5-fluorouracil (5-FU) in serum using a handheld Raman spectrometer. Droplet shrinkage, triggered by the shaking of aqueous nanoparticle (NP) colloids with immiscible oil chloroform (CHCl3) after the addition of negative ions and acetone, not only brings the nanoparticles in close proximity but can also act as a microreactor to enhance the spatial enrichment capability of the analyte in plasmonic sites and thereby realize simultaneously controlling 3D hot spots and placing target molecules in hot spots. Moreover, the shrinking process of Ag colloid droplets has been investigated using a high-speed camera, an in situ transmission electron microscope (in situ TEM), and a dark-field microscope (DFM), demonstrating the high stability and uniformity of nanoparticles in droplets. The shrunk Ag NP droplets exhibit excellent SERS sensitivity and reproducibility for the quantitative analysis of 5-FU over a large range of 50-1000 ppb. Hence, it is promising for quantitative analysis of complex systems and long-term monitoring of bioreactions.