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.

Blood cell-produced amyloid-ß induces cerebral Alzheimer-type pathologies and behavioral deficits.

It is traditionally believed that cerebral amyloid-beta (Aß) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aß. The role of peripherally produced Aß in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aß to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aß in the blood, and caused AD phenotypes including Aß plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aß levels, and alleviated brain Aß burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aß plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aß can decrease brain Aß deposition and represents a novel therapeutic approach for AD.

UBE2S exerts oncogenic activities in urinary bladder cancer by ubiquitinating TSC1.

Ubiquitin-conjugating enzyme E2S (UBE2S), an important E2 enzyme in the process of ubiquitination, has exhibited oncogenic activities in various malignant tumors. However, it remains unknown whether UBE2S plays a role in urinary bladder cancer (UBC) development. In the current study, our data confirmed UBE2S upregulation in UBC. In vitro and in vivo experiments demonstrated that UBE2S knockdown resulted in attenuated proliferation and enhanced apoptosis, which was inverse to the phenotypes with UBE2S overexpression. Gain and loss of function assays confirmed that UBE2S exerts oncogenic activities in UBC by mediating the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, we discovered that this UBE2S-modulated carcinogenic mechanism was in the consequence of directly targeting tuberous sclerosis 1 (TSC1), which is the upstream inhibitor of mTOR signaling for ubiquitous degradation. Taken together, this study demonstrated that UBE2S is a carcinogen in UBC and promotes UBC progression by ubiquitously degrading TSC1. This consequently mediates the activation of the mTOR pathway, suggesting a potential therapeutic regimen for UBC by targeting the newly identified UBE2S/TSC1/mTOR axis.

Controlling the atomic-orbital-resolved photoionization for neon atoms by counter-rotating circularly polarized attosecond pulses.

We theoretically investigate the atomic-orbital-resolved vortex-shaped photoelectron momentum distributions (PMDs) and ionization probabilities by solving the two-dimensional time-dependent Schrödinger equation (2D-TDSE) of neon in a pair of delayed counter-rotating circularly polarized attosecond pulses. We found that the number of spiral arms in vortex patterns is twice the number of absorbed photons when the initial state is the ψm=±1 state, which satisfy a change from c2n+2 to c2n (n is the number of absorbed photons) rotational symmetry of the vortices if the 2p state is replaced by 2p+ or 2p- states. For two- and three-photon ionization, the magnetic quantum number dependence of ionization probabilities is quite weak. Interestingly, single-photon ionization is preferred when the electron and laser field corotate and ionization probabilities of 2p- is much larger than that of 2p+ if the proper time delay and wavelength are used. The relative ratio of ionization probabilities between 2p- and 2p+ is insensitive to laser peak intensity, which can be controlled by changing the wavelength, time delay, relative phase and amplitude ratio of two attosecond pulses.

Formation and migration of α-dicarbonyl compounds during storage and reheating of a sugary food simulation system.

BACKGROUND: The thermal processing of food results in the formation of α-dicarbonyl compounds (α-DCs) such as glyoxal (GO), methylglyoxal (MGO), 2,3-butanedione (2,3-BD), and 3-deoxyglucosone (3-DG), which are precursors of potentially harmful advanced glycation end products. Some of the α-DCs found in food products might result from chemical deterioration reactions during storage and reheating. A range of sugary food simulation systems were stored at three different temperatures (4, 25, and 37 °C) and reheated using three different processing methods to investigate the formation and migration of α-DCs. RESULTS: During 20 days of storage, the concentration of α-DCs declined, following which the concentration remained approximately constant. Methylglyoxal was the major α-DC affected during storage, its relative content decreasing from 233.71 to 44.12 µg mL-1 in the glucose-lysine system. The concentration of α-DCs decreased with increasing temperature. Microwave reheating increased the formation of α-DC compounds. The largest increases in 3-DG concentrations were observed in the maltose-lysine systems (24.94 to 35.74 µg mL-1 ). The concentration of α-DCs only changed a little in response to reheating at 100 °C, but declined when reheated at 150 °C. CONCLUSION: The concentration of α-DCs following storage and reheating depends on the type of sugar, lysine content, temperature, and method of reheating. © 2020 Society of Chemical Industry.

Cerebellar Fastigial Nucleus Stimulation in a Chronic Unpredictable Mild Stress Rat Model Reduces Post-Stroke Depression by Suppressing Brain Inflammation via the microRNA-29c/TNFRSF1A Signaling Pathway.

BACKGROUND We previously reported that cerebellar fastigial nucleus stimulation reduced post-stroke depression in a rat model by reducing inflammation. This study aimed to investigate the molecular inflammatory signaling pathways associated with cerebellar fastigial nucleus stimulation in an established rat model of post-stroke depression. MATERIAL AND METHODS Twenty-four Sprague-Dawley rats included a sham group (N=6), an untreated stroke group (N=6), an untreated post-stroke depression model group (PSD) (N=6), and the model group treated with cerebellar fastigial nucleus stimulation (FNS) (N=6). The rat stroke model involved occlusion of the middle cerebral artery occlusion (MCAO). Post-stroke depression model was established using chronic unpredictable mild stress treatment and was verified using an open field test. Real-time polymerase chain reaction (PCR) and Western blot compared expression levels of microRNA-29c (miR-29c), miR-676, TNFRSF1A, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-1ß in cerebellar tissue. U251 human glioblastoma cells and SH-SY5Y human neuroblastoma cells were studied in vitro. RESULTS Cerebellar fastigial nucleus stimulation reduced behaviors associated with depression in the rat model, upregulated the expression of miR-29c, and reduced the expression of TNFRSF1A and inflammatory cytokines, and mildly reduced neuronal apoptosis. Bioinformatics data analysis identified a regulatory relationship between miR-29c and TNFRSF1A. SH-SY5Y cells treated with a miR-29c mimic, or TNFRSF1A short interfering RNA (siRNA), identified a negative regulatory relationship between TNFRSF1A and miR-29c. CONCLUSIONS In a rat model, cerebellar fastigial nucleus stimulation reduced the expression of TNFRSF1A by upregulating miR-29c expression, which suppressed the expression of inflammatory cytokines, resulting in reduced severity of post-stroke depression.

Ornithine decarboxylase is involved in methyl jasmonate-regulated postharvest quality retention in button mushrooms (Agaricus bisporus).

BACKGROUND: In the present study, we investigated the role of ornithine decarboxylase (ODC) in the methyl jasmonate (MeJA)-regulated postharvest quality maintenance of Agaricus bisporus (J. E. Kange) Imbach button mushrooms by pretreating mushrooms with a specific irreversible inhibitor called α-difluoromethylornithine (DFMO) before exposure to MeJA vapor. RESULTS: Mushrooms were treated with 0 or 100 µmol L-1 MeJA or a combination of 120 µmol L-1 DFMO and 100 µmol L-1 MeJA, respectively, before storage at 4 °C for 21 days. Treatment with MeJA alone induced the increase in ODC activity whereas this effect was greatly suppressed by pretreatment with DFMO. α-Difluoromethylornithine strongly attenuated the effect of MeJA on decreasing cap opening, slowing the decline rate of soluble protein and total sugar, and accumulating total phenolics and flavonoids. α-Difluoromethylornithine pretreatment also counteracted the ability of MeJA to inhibit polyphenol oxidase and lipoxygenase activities, and malondialdehyde production, and to stimulate superoxide dismutase and catalase activities. It also largely downregulated MeJA-induced accumulation of free putrescine (Put). CONCLUSION: These results reveal that ODC is involved in MeJA-regulated postharvest quality retention of button mushrooms, and this involvement is likely to be associated with Put levels. © 2018 Society of Chemical Industry.

Efficient production of a recombinant Venerupis philippinarum defensin (VpDef) in Pichia pastoris and characterization of its antibacterial activity and stability.

VpDef is a novel defensin isolated from the clam Venerupis philippinarum. Previously it was expressed in Escherichia coli; however, the E. coli-derived recombinant VpDef did not show effective antimicrobial activity against Staphyloccocus aureus or the Gram-negative bacteria tested. As such, the goal of this study was to design, express, and purify a recombinant VpDef (rVpDef) in Pichia pastoris and to determine its antibacterial potency and stability. A 6.9 KDa rVpDef was successfully expressed as a secreted peptide in P. pastoris, and the amount of rVpDef accumulation was shown to reach as high as approximate 60 µg per 1 ml of culture medium only after an initial optimization was performed. The purified rVpDef demonstrated a broad antibacterial spectrum and was active against six typical common bacteria, both Gram-positive and Gram-negative. A minimal inhibition concentration of as low as 50 µg/ml was observed for rVpDef against the growth of E. coli O157 (ATCC 35150). Moreover, rVpDef was tolerant to temperature shock and proteinase digestion and maintained a high stability over a relatively broad pH range. In addition, rVpDef had a low hemolytic activity against rabbit erythrocytes. Taken together, this study demonstrated that rVpDef could be produced in a large-scale manner in P. pastoris and has a good antibacterial activity and suitable stability. This is the first report on heterologous expression of a biologically active VpDef in P. pastoris, supporting its use for both research and application purposes.

Matrix assisted laser desorption/ionization time-of-flight mass spectrometric determination of benzo[a]pyrene using a MIL-101(Fe) matrix.

A method is described for the matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF)-based determination of benzo[a]pyrene (BaP) by using the metal-organic framework MIL-101(Fe) as a matrix. Following optimization of the experimental parameters, the method has a detection limit as low as 0.1 µg·L-1, which makes it more sensitive than previous methods for BaP analysis, and its analysis time is only 1 min. Its applicability was evaluated by analyzing sesame oil, linseed oil, camellia seed oil, and olive oil spiked with BaP at three levels (10, 1, and 0.5 µg·kg-1), and the recovery range was found to range from 80.0 to 114.8% with relative standard deviations (RSDs) between 3.9 and 13.7%. Graphical abstract The metal-organic framework MIL-101(Fe) was applied as a new matrix to the quantitative detection of benzo[a]pyrene (BaP) by matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF).

Three kinds of lateral flow immunochromatographic assays based on the use of nanoparticle labels for fluorometric determination of zearalenone.

Colloidal gold, quantum dots and polystyrene microspheres were used as labels in three kinds of lateral flow immunochromatographic assays (ICAs) for the detection of zearalenone (ZEN) in cereal samples. The assays allow ZEN to be quantified within 20 min. The LODs are 10 µg·L-1 of ZEN for the colloidal gold-based ICA, and 1 µg·L-1 for both the quantum dot and polystyrene microsphere based ICAs. The respective data are 60 µg·kg-1, 6 µg·kg-1 and 6 µg·kg-1, respectively, for spiked samples and cereals. Only minor cross-sensitivity occurred between ZEN and fusarium toxins, and no cross-sensitivity if found for aflatoxin B1, T-2 mycotoxin, ochratoxin A, deoxynivalenol, and fumonisin B1. LODs of the three assays are lower than the maximum limits of ZEN set by most standardization agencies. Graphical abstract Schematic presentation of three lateral flow immunochromatographic assays (ICAs) based on the use of (a) colloidal gold (CG), (b) fluorescent quantum dots (QD), and

Identification and functional characterization of the NAC gene promoter from Populus euphratica.

MAIN CONCLUSION: The PeNAC1 promoter is a non-tissue-specific and stress-inducible promoter containing a GA-responsive element and a MYB recognition sequence that are responsible for induced expression patterns. NAC transcription factors play vital roles in complex signaling networks during plant stress responses. Promoters as crucial molecular switches are involved in the transcriptional regulation of gene activities dynamic network controlling a variety of biological processes, such as developmental processes, responses to hormone and abiotic stress. In this study, a 1217-bp flanking fragment of the stress-responsive NAC gene PeNAC1 was isolated from Populus euphratica. In transgenic Arabidopsis, this promoter fragment was found to have a higher activity than the cauliflower mosaic virus 35S promoter and remained active throughout the plant life cycle, particularly in the spiral vessels and cortical cells of vascular tissues of various organs. We identified a gibberellic acid-responsive element, required for response to gibberellic acid and involved in the salt-stress signaling pathway, and a MYB recognition sequence, which has an important role in promoter response to drought stress, in the PeNAC1 promoter. These results suggest that the PeNAC1 promoter is more effective, non-tissue-specific, and inducible. In addition, the presence of a putative NAC protein-binding motif in the PeNAC1 promoter indicates that PeNAC1 is either regulated by other NAC transcription factors or is self-regulated. Our research will help reveal the regulatory mechanism of the upstream region of the PeNAC1 gene and provide a foundation for the use of the PeNAC1 promoter in molecular breeding.

Comparison of Pressure- and Volume-Controlled Ventilation in Laparoscopic Surgery: A Meta-analysis of Randomized Controlled Trial.

PURPOSE: Volume-controlled ventilation (VCV) has been the traditional mechanical ventilation mode in laparoscopic surgery. Pressure-controlled ventilation (PCV) has been used more frequently in recent years, especially for patients with complicated conditions; however, evidence on whether PCV is superior to VCV is still lacking. A meta-analysis was used to compare the effects of PCV and VCV on respiratory and hemodynamic parameters during laparoscopic surgery. METHODS: PubMed and Embase were each searched from their inception to December 2014 for randomized controlled trials comparing the effects of PCV and VCV on respiratory and hemodynamic parameters during laparoscopic surgery. Standard mean difference (SMD) with 95% confidence interval (CI) was calculated using a random effect model. Outcomes were assessed at three times: preoperative (T1), intraoperative (T2) and postoperative (T3). Respiratory mechanics (including peak airway pressure, plateau pressure, mean airway pressure, compliance, airway resistance, minute volume, end-tidal CO2 tension and tidal volume) and hemodynamic parameters (including heart rate and mean arterial pressure) were calculated. RESULTS: Eight randomized controlled trials with a total of 428 participants, 214 cases using PCV and 214 cases using VCV, were included in the meta-analysis. No significant differences were detected between the groups in terms of hemodynamic parameters. In contrast, with respiratory mechanics, PCV was slightly but significantly associated with lower peak airway pressure, higher compliance, lower airway resistance at T1, lower peak airway pressure, higher compliance, higher mean airway pressure at T2, lower peak airway pressure, lower mean airway pressure and higher end-tidal CO2 tension at T3. For the rest of respiratory parameters, there were no statistical differences between the groups. Subgroup analysis by morbidly obese, type of operations and quality of studies, showed similar results. CONCLUSIONS: Our meta-analysis suggests that hemodynamic parameters are similar in patients who underwent laparoscopic surgery with PCV and VCV, but patients who had PCV exhibited mildly better respiratory data.

Association between miR-146aG>C and miR-196a2C>T polymorphisms and the risk of hepatocellular carcinoma in a Chinese population.

MicroRNAs have been demonstrated to have a role in susceptibility and prognosis of various types of human cancer. We investigated the association between polymorphisms in miR-146aG>C, miR-196a2C>T, and miR-499A>G and hepatocellular carcinoma (HCC) risk and interaction with HCC and hepatitis B virus (HBV) infection. Two hundred sixty-six cases with HCC and 281 health controls were enrolled in the present study. Genotyping of the miR-146aG>C, miR-196a2C>T, and miR-499A>G genotypes was conducted by duplex polymerase chain reaction with the confronting two-pair primer (PCR-RFLP). Subjects with miR-146a GG and G allele had an increased risk of HCC compared with the homozygote CC genotype. Similarly, HCC patients carrying microRNA (miRNA)-196a2 computed tomography, TT, and T allele significantly decreased the risk of HCC relative to the CC genotype. Stratified analysis indicated that miR-196a2C>T polymorphism was associated with reduced risk of HBV-related HCC, but not in hepatitis C virus- and nonviral-related HCC cases. In conclusion, miR-146aG>C and miR-196a2C>T polymorphism are associated with risk of HCC patients in China, especially in patients with HBV infection. SNPs in miRNA sequences can be used as a diagnostic biomarker for HCC.

Effects of cooking with solid fuel on hearing loss in Chinese adults-Based on two cohort studies.

The association between cooking fuel and hearing loss still needs more research to clarify, and two longitudinal cohort studies were explored to find if solid fuel use for cooking affected hearing in Chinese adults. The data from Chinese Health and Retirement Longitudinal Survey (CHARLS) and Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Participants (older than 18) without hearing loss at baseline and follow-up visits were included, which were divided into clean fuel and solid fuel groups. Hearing loss rate was from follow-up visits (both in year 2011) until the recent one (year 2018 in CHARLS and 2019 in CLHLS). Cox regressions were applied to examine the associations with adjustment for potential confounders. Fixed-effect meta-analysis was used to pool the results. A total of 9049 participants (average age 8.34 ± 9.12 [mean ± SD] years; 4247 [46.93%] males) were included in CHARLS cohort study and 2265 participants (average age, 78.75 ± 9.23 [mean ± SD] years; 1148 [49.32%] males) in CLHLS cohort study. There were 1518 (16.78%) participants in CHARLS cohort and 451 (19.91%) participants in CLHLS cohort who developed hearing loss. The group of using solid fuel for cooking had a higher risk of hearing loss (CHARLS: HR, 1.16; 95% CI 1.03-1.30; CLHLS: HR, 1.43; 95% CI 1.11-1.84) compared with the one of using clean fuel. Pooled hazard ratio showed the incidence of hearing loss in the solid fuel users was 1.17 (1.03, 1.29) times higher than that of clean fuel users. Hearing loss was associated with solid fuel use and older people were at higher risk. It is advised to replace solid fuel by clean fuel that may promote health equity.

Automatic detection of small bowel lesions with different bleeding risks based on deep learning models.

BACKGROUND: Deep learning provides an efficient automatic image recognition method for small bowel (SB) capsule endoscopy (CE) that can assist physicians in diagnosis. However, the existing deep learning models present some unresolved challenges. AIM: To propose a novel and effective classification and detection model to automatically identify various SB lesions and their bleeding risks, and label the lesions accurately so as to enhance the diagnostic efficiency of physicians and the ability to identify high-risk bleeding groups. METHODS: The proposed model represents a two-stage method that combined image classification with object detection. First, we utilized the improved ResNet-50 classification model to classify endoscopic images into SB lesion images, normal SB mucosa images, and invalid images. Then, the improved YOLO-V5 detection model was utilized to detect the type of lesion and its risk of bleeding, and the location of the lesion was marked. We constructed training and testing sets and compared model-assisted reading with physician reading. RESULTS: The accuracy of the model constructed in this study reached 98.96%, which was higher than the accuracy of other systems using only a single module. The sensitivity, specificity, and accuracy of the model-assisted reading detection of all images were 99.17%, 99.92%, and 99.86%, which were significantly higher than those of the endoscopists' diagnoses. The image processing time of the model was 48 ms/image, and the image processing time of the physicians was 0.40 ± 0.24 s/image (P < 0.001). CONCLUSION: The deep learning model of image classification combined with object detection exhibits a satisfactory diagnostic effect on a variety of SB lesions and their bleeding risks in CE images, which enhances the diagnostic efficiency of physicians and improves the ability of physicians to identify high-risk bleeding groups.

Short-term efficacy and influencing factors of conventional chemotherapy combined with irinotecan in patients with advanced gastric cancer.

BACKGROUND: Gastric cancer is one of the most common cancers worldwide, with a 5-year survival rate of only 20%. The age of onset of gastric cancer is in line with the general rule of cancer. Most of them occur after middle age, mostly between 40 and 60 years old, with an average age of about 50 years old, and only 5% of patients are under 30 years old. The incidence of male is higher than that of female. AIM: To investigate the short-term efficacy and influencing factors of chemotherapy combined with irinotecan in patients with advanced gastric cancer. METHODS: Eighty patients with advanced gastric cancer who were treated in our hospital from January 2019 to January 2022 were selected. The patients were divided into an observation group (n = 40) and control group (n = 40) by the envelope method. The control group was given preoperative routine chemotherapy. The observation group was treated with irinotecan in addition to the chemotherapy given to the control group. The short-term efficacy of treatment in the two groups, as well as tumor marker levels and quality of life before and after treatment were evaluated. RESULTS: The short-term treatment effect in the observation group was better than that in the control group (P < 0.05), and the total effective rate was 57.50%. The age and proportion of tumor node metastasis (TNM) stage IV patients with ineffective chemotherapy in the observation group were (65.12 ± 5.71) years and 52.94%, respectively, which were notably higher than those of patients with effective chemotherapy (P < 0.05), while the Karnofsky Performance Scale score was (67.70 ± 3.83) points, which was apparently lower than that of patients with effective chemotherapy (P < 0.05). After 3 mo of treatment, the SF-36 scale scores of physiological function, energy, emotional function, and mental health in the observation group were 65.12 ± 8.14, 54.76 ± 6.70, 47.58 ± 7.22, and 66.16 ± 8.11 points, respectively, which were considerably higher than those in the control group (P < 0.05). The incidence rates of grade III-IV diarrhea and grade III-IV thrombocytopenia in the observation group were 32.50% and 25.00%, respectively, which were markedly higher than those in the control group (P < 0.05). CONCLUSION: Chemotherapy combined with irinotecan in patients with advanced gastric cancer has a good short-term efficacy and can significantly reduce serum tumor markers and improve the quality of life of patients. The efficacy may be affected by the age and TNM stage of the patients, and its long-term efficacy needs further study.

Apoptosis-resistant megakaryocytes produce large and hyperreactive platelets in response to radiation injury.

BACKGROUND: The essential roles of platelets in thrombosis have been well recognized. Unexpectedly, thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological, physical and chemical origins, which could be suffered by military personnel and civilians during chemical, biological, radioactive, and nuclear events. Especially, thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia, while the underlying pathogenic mechanism remains elusive. METHODS: A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation (IR). The phenotypic and functional changes of platelets and megakaryocytes (MKs) were determined by a comprehensive set of in vitro and in vivo assays, including flow cytometry, flow chamber, histopathology, Western blotting, and chromatin immunoprecipitation, in combination with transcriptomic analysis. The molecular mechanism was investigated both in vitro and in vivo, and was consolidated using MK-specific knockout mice. The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors. RESULTS: In contrast to primitive MKs, mature MKs (mMKs) are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis. Interestingly, mMKs undergo minority mitochondrial outer membrane permeabilization (MOMP) post IR, resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes (cGAS-STING) pathway via the release of mitochondrial DNA. The subsequent interferon-ß (IFN-ß) response in mMKs upregulates a GTPase guanylate-binding protein 2 (GBP2) to produce large and hyperreactive platelets that favor thrombosis. Further, we unmask that autophagy restrains minority MOMP in mMKs post IR. CONCLUSIONS: Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-ß-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.

Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study.

BACKGROUND: Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS: For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS: Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION: We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING: Science and Technology Commission of Shanghai Municipality.

Effects of SCR-3 on the immunosuppression accompanied with the systemic inflammatory response syndrome.

Steroid receptor coactivator-3 (SRC-3) is a multifunctional protein that plays an important role in mammary gland growth, development, and tumorigenesis. In this study, SCR-3 gene knockout mice were used to study the effects of SCR-3 on the immunosuppression accompanied with systemic inflammatory response syndrome (SIRS). Bacterial clearance assay was performed by blood culture and frozen sections, and the results showed that the absence of SCR-3 protein serious damaged the innate immune system and the body's ability to inactivate or phagocytosis of bacteria was significantly decreased, and the absence of SCR-3 protein also weakened phagocytes' ability to degrade bacteria and their metabolites. Furthermore, animal model of inflammatory reaction was established and the immune function was determined, and the results revealed that SRC-3 protein may play an important role in maintenance of T-cells' immune function, and severe T-cell immune function disorder would be resulted once SRC-3 protein is missing. In addition, the results of our study showed the steady-state of lymphocyte subsets was destroyed after SIRS, leading the suppression of cellular immune function, and the absence of SCR-3 protein may aggravate the suppression of T-lymphocyte function. Therefore, the present study demonstrated that the absence of SCR-3 protein would aggravate immunosuppression. In addition, SRC-3 protein is a significant regulator of infection and inflammation, and SRC-3 protein play an essential role in the development of immunosuppression accompanied with SIRS.