GCY-20 signaling controls suppression of Caenorhabditis elegans egg laying by moderate cold.

Organisms sensing environmental cues and internal states and integrating the sensory information to control fecundity are essential for survival and proliferation. The present study finds that a moderate cold temperature of 11°C reduces egg laying in Caenorhabditis elegans. ASEL and AWC neurons sense the cold via GCY-20 signaling and act antagonistically on egg laying through the ASEL and AWC/AIA/HSN circuits. Upon cold stimulation, ASEL and AWC release glutamate to activate and inhibit AIA interneurons by acting on highly and lowly sensitive ionotropic GLR-2 and GLC-3 receptors, respectively. AIA inhibits HSN motor neuron activity via acetylcholinergic ACR-14 receptor signaling and suppresses egg laying. Thus, ASEL and AWC initiate and reduce the cold suppression of egg laying. ASEL's action on AIA and egg laying dominates AWC's action. The biased opposite actions of these neurons on egg laying provide animals with a precise adaptation of reproductive behavior to environmental temperatures.

Dynamic Nomogram for Predicting the Risk of Perioperative Neurocognitive Disorders in Adults.

BACKGROUND: Simple and rapid tools for screening high-risk patients for perioperative neurocognitive disorders (PNDs) are urgently needed to improve patient outcomes. We developed an online tool with machine-learning algorithms using routine variables based on multicenter data. METHODS: The entire dataset was composed of 49,768 surgical patients from 3 representative academic hospitals in China. Surgical patients older than 45 years, those undergoing general anesthesia, and those without a history of PND were enrolled. When the patient's discharge diagnosis was PND, the patient was in the PND group. Patients in the non-PND group were randomly extracted from the big data platform according to the surgical type, age, and source of data in the PND group with a ratio of 3:1. After data preprocessing and feature selection, general linear model (GLM), artificial neural network (ANN), and naive Bayes (NB) were used for model development and evaluation. Model performance was evaluated by the area under the receiver operating characteristic curve (ROCAUC), the area under the precision-recall curve (PRAUC), the Brier score, the index of prediction accuracy (IPA), sensitivity, specificity, etc. The model was also externally validated on the multiparameter intelligent monitoring in intensive care (MIMIC) Ⅳ database. Afterward, we developed an online visualization tool to preoperatively predict patients' risk of developing PND based on the models with the best performance. RESULTS: A total of 1051 patients (242 PND and 809 non-PND) and 2884 patients (6.2% patients with PND) were analyzed on multicenter data (model development, test [internal validation], external validation-1) and MIMIC Ⅳ dataset (external validation-2). The model performance based on GLM was much better than that based on ANN and NB. The best-performing GLM model on validation-1 dataset achieved ROCAUC (0.874; 95% confidence interval [CI], 0.833-0.915), PRAUC (0.685; 95% CI, 0.584-0.786), sensitivity (72.6%; 95% CI, 61.4%-81.5%), specificity (84.4%; 95% CI, 79.3%-88.4%), Brier score (0.131), and IPA (44.7%), and of which the ROCAUC (0.761, 95% CI, 0.712-0.809), the PRAUC (0.475, 95% CI, 0.370-0.581), Brier score (0.053), and IPA (76.8%) on validation-2 dataset. Afterward, we developed an online tool (https://pnd-predictive-model-dynnom.shinyapps.io/ DynNomapp/) with 10 routine variables for preoperatively screening high-risk patients. CONCLUSIONS: We developed a simple and rapid online tool to preoperatively screen patients' risk of PND using GLM based on multicenter data, which may help medical staff's decision-making regarding perioperative management strategies to improve patient outcomes.

Disexcitation in the ASH/RIM/ADL negative feedback circuit fine-tunes hyperosmotic sensation and avoidance in Caenorhabditis elegans.

Sensations, especially nociception, are tightly controlled and regulated by the central and peripheral nervous systems. Osmotic sensation and related physiological and behavioral reactions are essential for animal well-being and survival. In this study, we find that interaction between secondary nociceptive ADL and primary nociceptive ASH neurons upregulates Caenorhabditis elegans avoidance of the mild and medium hyperosmolality of 0.41 and 0.88 Osm but does not affect avoidance of high osmolality of 1.37 and 2.29 Osm. The interaction between ASH and ADL is actualized through a negative feedback circuit consisting of ASH, ADL, and RIM interneurons. In this circuit, hyperosmolality-sensitive ADL augments the ASH hyperosmotic response and animal hyperosmotic avoidance; RIM inhibits ADL and is excited by ASH; thus, ASH exciting RIM reduces ADL augmenting ASH. The neuronal signal integration modality in the circuit is disexcitation. In addition, ASH promotes hyperosmotic avoidance through ASH/RIC/AIY feedforward circuit. Finally, we find that in addition to ASH and ADL, multiple sensory neurons are involved in hyperosmotic sensation and avoidance behavior.

Low mental health literacy and its association with depression, anxiety and poor sleep quality in Chinese elderly.

BACKGROUND: Mental health literacy (MHL) is rarely reported in the Chinese elderly. This study explored the pattern of MHL in the Chinese elderly in relation to depression, anxiety and poor sleep quality. METHODS: A cross-sectional study was conducted among older adults in Guangzhou, south China. Participants were investigated face-to-face using the Chinese National Mental Health Literacy Scale, the Patient Health Questionnaire-9 item (PHQ-9), the 7-item Generalized Anxiety Disorder (GAD-7) and the Pittsburgh Sleep Quality Index (PSQI). Mental Health Literacy Scale contains three dimensions: mental health knowledge, mental health skills (such as social support, cognitive reappraisal and attentional distraction) and mental health awareness. Multivariate logistic regression was used for examining the association between MHL and mental health. RESULTS: A total of 506 older adults were recruited. The percentage of depression, anxiety, and poor sleep quality were 16.6%, 7.9% and 40.9%, respectively. MHL dimensions independently associated with depression included cognitive reappraisal (OR = 1.95, p < .001), attentional distraction (OR = 0.61, p = 0.044) and awareness (OR = 0.56, p = 0.027). MHL dimensions independently associated with anxiety symptoms included cognitive reappraisal (OR = 1.90, p = 0.011) and attentional distraction (OR = 0.44, p = 0.016). MHL dimensions independently associated with poor sleep quality included social support (OR = 0.75, p = 0.022), cognitive reappraisal (OR = 1.55, p = 0.003) and attentional distraction (OR = 0.65, p = 0.016). CONCLUSION: Given the low MHL and its association with poor mental health in the Chinese elderly, policymakers and health professionals should improve the older adults' MHL, which could be conducive to the prevention and control of their mental health problems.

Positive interaction between ASH and ASK sensory neurons accelerates nociception and inhibits behavioral adaptation.

Central and peripheral sensory neurons tightly regulate nociception and avoidance behavior. The peripheral modulation of nociception provides more veridical and instantaneous information for animals to achieve rapid, more fine-tuned and concentrated behavioral responses. In this study, we find that positive interaction between ASH and ASK sensory neurons is essential for the fast-rising phase of ASH Ca2+ responses to noxious copper ions and inhibits the adaption of avoiding Cu2+. We reveal the underlying neuronal circuit mechanism. ASK accelerates the ASH Ca2+ responses by transferring cGMP through gap junctions. ASH excites ASK via a disinhibitory neuronal circuit composed of ASH, AIA, and ASK. Avoidance adaptation depends on the slope rate of the rising phase of ASH Ca2+ responses. Thus, in addition to amplitude, sensory kinetics is significant for sensations and behaviors, especially for sensory and behavioral adaptations.

[Characteristics, Sources, and Risk Assessment of Perlyfluoroalkyl Substances in Surface Water and Sediment of Luoma Lake].

Through the investigation and detection of the surface water and sediments of Luoma Lake, the structure and occurrence characteristics of PFASs (perlyfluoroalkyl substances) in the two types of media were analyzed, and the principal component analysis method was used to analyze the characteristics of such substances in the surface water. The source was analyzed, and the potential health risks of such substances were evaluated using the risk quotient method. The results showed that a total of 13 PFASs were detected in the surface sediments of Luoma Lake, and one more species was detected in the surface water (PFTeA); ρ(ΣPFASs) in the surface water ranged from 46.09 to 120.34 ng·L-1, and ω(ΣPFASs) in sediments ranged from 2.22 to 9.55 ng·g-1. PFPeA was the major component in surface water, and the mass fraction of PFPeA was 38%. PFBA was the major component in sediment, and the mass fraction of PFPeA was 61%. The multi-media PFASs in Luoma Lake were mainly short-chain substances; the high concentration area of PFASs in the surface water of Luoma Lake was concentrated and distributed at the mouth of the northern rivers. Its concentration showed a decreasing trend from north to south, and the content of PFASs in the sediments showed a decreasing trend from southwest to northeast. The distribution of ΣPFASs, PFBA, and PFOS in the sediments of Luoma Lake and the TOC content in the sediment were related; the principal component analysis showed that the PFASs in the surface water of Luoma Lake were mainly from textile flame retardant, rubber product emulsification, food packaging processes and paper surface treatment industries, the metal electroplating industry, and leather and textile manufacturing industries. PFASs in the surface water of Luoma Lake were at a relatively low health risk level.

U-shaped association between sleep duration and subjective cognitive complaints in Chinese elderly: a cross-sectional study.

BACKGROUND: Subjective cognitive decline (SCD) may be the early screening signal to distinguish susceptible population with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Subjective cognitive complaints (SCCs) have been proved strongly associated with SCD. This study aimed to explore the association between sleep duration and SCCs in the Chinese elderly. METHODS: We conducted a cross-sectional study involving 688 participants aged 60 years and older in Guangdong Province, China. SCCs were assessed by the Subjective Cognitive Decline questionnaire 9 (SCD-Q9), which contained 9 items with two dimensions, including the overall memory function and time comparison (OMTC) and daily activity ability (DAA). Restricted cubic splines and generalized additive model (GAM) were used to fit the association between sleep duration and SCD-Q9 score. RESULTS: There were significant U-shaped associations between sleep duration and overall score of SCD-Q9 (EDF = 3.842, P < 0.001), as well as the OMTC dimension (EDF = 4.471, P < 0.001) in the age- and gender-adjusted GAM. The lowest points on the overall score of SCD-Q9 and OMTC score were observed in those sleeping 8 h per night. After further adjusting for other demographic characteristics, lifestyle behaviors, hypertension and diabetes, the U-shaped associations between sleep duration and the overall score of SCD-Q9 (EDF = 3.575, P = 0.004), sleep duration and the OMTC score (EDF = 4.478, P = 0.010) were still found. The daily activity ability (DAA) score was also non-linear associated with sleep duration both in the age- and gender-adjusted GAM (EDF = 2.314, P < 0.001) and further adjusted GAM (EDF = 2.080, P = 0.010). CONCLUSIONS: Both longer sleep duration (> 8 h) and shorter duration (< 8 h) were linked to worse SCCs. Future studies should explore the protective effect of managing sleep duration on SCD and its progression to dementia.

Subjective cognitive decline symptoms and its association with socio-demographic characteristics and common chronic diseases in the southern Chinese older adults.

BACKGROUND: Subjective cognitive decline (SCD) may be the first symptomatic manifestation of Alzheimer's disease, but information on its health correlates is still sparse in Chinese older adults. This study aimed to estimate SCD symptoms and its association with socio-demographic characteristics, common chronic diseases among southern Chinese older adults. METHODS: Participants aged 60 years and older from 7 communities and 2 nursing homes in Guangzhou were recruited and interviewed with standardized assessment tools. Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure poor sleep quality, depression symptoms and anxiety symptoms. The SCD symptoms were measured by SCD questionnaire 9 (SCD-Q9) which ranged from 0 to 9 points, with a higher score indicating increased severity of the SCD. Participants were divided into low score group (SCD-Q9 score ≤ 3) and higher score group (SCD-Q9 score > 3). Chi-square tests and multivariate logistic regression analysis were used for exploring the influences of different characteristics of socio-demographic and lifestyle factors on SCD symptoms. Univariate and multivariate logistic regression analysis were applied to explore the association between SCD symptoms with common chronic diseases. RESULTS: A total of 688 participants were included in our analysis with a mean age of 73.79 (SD = 8.28, range: 60-101), while 62.4% of the participants were females. The mean score of the SCD-Q9 was 3.81 ± 2.42 in the whole sample. A total of 286 participants (41.6%) were defined as the low score group (≤3 points), while 402 participants (58.4%) were the high score group (> 3 points). Multivariate logistic regression analysis revealed that female (OR = 1.99, 95%CI: 1.35-2.93), primary or lower education level (OR = 2.58, 95%CI: 1.38-4.83), nursing home (OR = 1.90, 95%CI: 1.18-3.05), napping habits (OR = 1.59, 95%CI: 1.06-2.40), urolithiasis (OR = 2.72, 95%CI: 1.15-6.40), gout (OR = 2.12, 95%CI: 1.14-3.93), poor sleep quality (OR = 1.93, 95%CI: 1.38-2.71), depression symptoms (OR = 3.01, 95%CI: 1.70-5.34) and anxiety symptoms (OR = 3.11, 95%CI: 1.29-7.46) were independent positive related to high SCD-Q9 score. On the other hand, tea-drinking habits (OR = 0.64, 95%CI: 0.45-0.92), current smoking (OR = 0.46, 95%CI: 0.24-0.90) were independent negative related to high SCD-Q9 score. CONCLUSIONS: Worse SCD symptoms were closely related to common chronic diseases and socio-demographic characteristics. Disease managers should pay more attention to those factors to early intervention and management for SCD symptoms among southern Chinese older adults.

Protective Effects of Total Flavonoids from Lysimachia christinae on Calcium Oxalate-Induced Oxidative Stress in a Renal Cell Line and Renal Tissue.

Oxidative stress (OS) in renal tubular epithelial cells (RTECs) is induced by calcium oxalate (CaOx) stones and plays an important role in the pathology of CaOx nephrolithiasis. The nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important endogenous antioxidant pathway. Flavonoids are compounds with 2-phenylchromone as the basic mother nucleus and are natural antioxidant components of Lysimachia christinae. Our previous studies demonstrated that the total flavonoids from L. christinae (TFL) reduced calcium and oxalic acid concentrations in urine, thus inhibiting CaOx stone formation. We also showed that TFL can reduce OS in renal tissue. However, whether TFL inhibit the formation of CaOx stones through the Nrf2/ARE pathway requires further investigation. Here, we found that TFL protected against injury to a renal cell line and renal tissue, reduced CaOx-induced OS in renal tissue, and reduced CaOx crystal formation. In addition, TFL significantly increased nuclear Nrf2 and the expression of the downstream antioxidant genes heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1). Furthermore, TFL increased superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) content, thereby alleviating OS in RTECs. Silencing Nrf2 expression blocked the protective effect of TFL on CaOx-induced OS. Taken together, our findings indicate that TFL reduce CaOx-induced OS in renal tissue by activating the Nrf2/ARE pathway.

The role of depression and anxiety in the relationship between poor sleep quality and subjective cognitive decline in Chinese elderly: Exploring parallel, serial, and moderated mediation.

BACKGROUND: Poor sleep quality exacerbates subjective cognitive decline (SCD). Mental health may play an important role in the relationship, but the potential underlying mechanisms remain unknown. METHODS: A cross-sectional study was conducted on older adult residents in Guangdong province, south China from November 2020 to March 2021. A total of 717 adults aged 60 years and over were recruited for a face-to-face investigation on a range of socio-demographic factors, lifestyle behaviors, sleep quality, SCD, depressive and anxiety symptoms. Parallel, serial and moderated mediation models were used to examine whether depression and anxiety mediated in the poor sleep quality-SCD linkage. RESULTS: Both direct and indirect effects of poor sleep quality on SCD symptoms were found. Anxiety and depressive symptoms mediated the relationship between poor sleep quality and SCD symptoms(ßAnxiety = 0.123, 95%CI: 0.079 to 0.173; ßDepression=0.274, 95%CI: 0.200 to 0.348), respectively. Serial mediation analyses indicated that depressive and anxiety symptoms co-play a serial mediating role in the association of poor sleep quality and SCD symptoms (ßa=0.052, 95% CI: 0.026 to 0.084; ßb=0.077, 95% CI: 0.033 to 0.128). Moderated mediation model revealed that the mediation of depressive symptoms on the relationship between poor sleep quality and SCD symptoms was moderated by anxiety symptoms(ß=0.318, 95% CI: 0.164 to 0.472). LIMITATIONS: The study is the cross-sectional design, which limits the causal inference ability. CONCLUSIONS: These findings provided new insights into possible avenues for prevention and intervention on SCD through sleep-based treatments with a multi-faceted approach on psychiatric disorders.

Signal Decoding for Glutamate Modulating Egg Laying Oppositely in Caenorhabditis elegans under Varied Environmental Conditions.

Animals' ability to sense environmental cues and to integrate this information to control fecundity is vital for continuing the species lineage. In this study, we observed that the sensory neurons Amphid neuron (ASHs and ADLs) differentially regulate egg-laying behavior in Caenorhabditis elegans under varied environmental conditions via distinct neuronal circuits. Under standard culture conditions, ASHs tonically release a small amount of glutamate and inhibit Hermaphrodite specific motor neuron (HSN) activities and egg laying via a highly sensitive Glutamate receptor (GLR)-5 receptor. In contrast, under Cu2+ stimulation, ASHs and ADLs may release a large amount of glutamate and inhibit Amphid interneuron (AIA) interneurons via low-sensitivity Glutamate-gated chloride channel (GLC)-3 receptor, thus removing the inhibitory roles of AIAs on HSN activity and egg laying. However, directly measuring the amount of glutamate released by sensory neurons under different conditions and assaying the binding kinetics of receptors with the neurotransmitter are still required to support this study directly.

Dual Recombining-out System for Spatiotemporal Gene Expression in C. elegans.

Specific recording, labeling, and spatiotemporal manipulating neurons are essential for neuroscience research. In this study, we developed a tripartite spatiotemporal gene induction system in C. elegans, which is based on the knockout of two transcriptional terminators (stops in short) by two different recombinases FLP and CRE. The recombinase sites (loxP and FRT) flanked stops after a ubiquitous promoter terminate transcription of target genes. FLP and CRE, induced by two promoters of overlapping expression, remove the stops (subsequent FLP/CRE-out). The system provides an "AND" gate strategy for specific gene expression in single types of cell(s). Combined with an inducible promoter or element, the system can control the spatiotemporal expression of genes in defined cell types, especially in cells or tissues lacking a specific promoter. This tripartite FLP/CRE-out gene expression system is a simple, labor- and cost-saving toolbox for cell type-specific and inducible gene expression in C. elegans.

RNase H meets molecular beacons: an ultrasensitive fluorometric assay for nucleic acids.

An innovative signal amplification strategy assisted by RNase H is described here for the detection of DNA targets in a universal fashion. A tailor-made RNA molecular beacon (RMB) conjugated with a fluorescence resonance energy transfer (FRET) pair (fluorophore and quencher) was designed, characterized, and combined with the employment of RNase H. Its performance is compared to that of other nucleases including Exonuclease III and T7 exonuclease. Fluorometry, performed best at excitation/emission wavelengths of 490/520 nm, gives an amazingly low detection limit of 23 fM for target DNA. The method was verified by the determination of human hemochromatosis (HFE) gene. It is perceived that the method represents a versatile tool for the detection of a wide range of targets. Graphical Abstract An RNase H-assisted signal amplification (RASA) method for the fluorometric assay of nucleic acids has been developed by using a unique RNA molecular beacon (RNA MB) conjugated with a fluorophore (F) and quencher (Q) pair for signal generation.

Two novel p38 MAPKs identified from Epinephelus coioides and their expression pattern in response to Cryptocaryon irritans infection.

P38 mitogen-activated protein kinases (MAPKs) are one of the most important central regulatory proteins response to extra environmental stresses. In this study, two novel p38 MAPKs, Ec-P38γ and Ec-P38δ, were identified from Epinephelus coioides, an economically important cultured fish in China and Southeast Asian counties. Both of Ec-p38γ and Ec-p38δ sequences contain a serine/threonine protein kinase (S_TKc) domain and a highly conserved Thr-Gly-Tyr (TGY) motif. Analysis of phylogenetic relationships illustrated that p38 amino acid sequences were conserved between different species indicating that the functions may be similar. The four subtypes of p38 (α, ß, γ, and δ) mRNA can be detected in all thirteen tissues examined, but the expression level is different in these tissues. The expression patterns of the four Ec-p38 subtypes in E. coioides were also detected response to Cryptocaryon irritans infection, one of the most important protozoan pathogens of marine fish. The expression of four p38 subtypes was up-regulated in the tissues examined, with the highest expressions of Ec-p38α (5.2 times) and Ec-p38δ (4.2 times) occurring in the skin, while Ec-p38ß (24.8 times) and γ (16.6 times) occurred in the spleen. There was no significantly correlation between the expression of Ec-p38γ/Ec-p38δ and the expression of nuclear factor kappaB (NF-kB). The results indicated the sequences and the characters of Ec-p38γ and Ec-p38δ were conserved, the p38 subtypes showed tissue-specific expression patterns in healthy grouper, and their expressions were significantly up-regulated post C. irritans infection, suggesting these p38 MAPKs may play important roles in these tissues during pathogen-caused inflammation.

Role of LAP+CD4+ T cells in the tumor microenvironment of colorectal cancer.

AIM: To investigate the abundance and potential functions of LAP+CD4+ T cells in colorectal cancer (CRC). METHODS: Proportions of LAP+CD4+ T cells were examined in peripheral blood and tumor/paratumor tissues of CRC patients and healthy controls using flow cytometry. Expression of phenotypic markers such as forkhead box (Fox)p3, cytotoxic T-lymphocyte-associated protein (CTLA)-4, chemokine CC receptor (CCR)4 and CCR5 was measured using flow cytometry. LAP-CD4+ and LAP+CD4+ T cells were isolated using a magnetic cell-sorting system and cell purity was analyzed by flow cytometry. Real-time quantitative polymerase chain reaction was used to measure expression of cytokines interleukin (IL)-10 and transforming growth factor (TGF)-ß. RESULTS: The proportion of LAP+CD4+ T cells was significantly higher in peripheral blood from patients (9.44% ± 3.18%) than healthy controls (1.49% ± 1.00%, P < 0.001). Among patients, the proportion of LAP+CD4+ T cells was significantly higher in tumor tissues (11.76% ± 3.74%) compared with paratumor tissues (3.87% ± 1.64%, P < 0.001). We also observed positive correlations between the proportion of LAP+CD4+ T cells and TNM stage (P < 0.001), distant metastasis (P < 0.001) and serum level of carcinoembryonic antigen (P < 0.05). Magnetic-activated cell sorting gave an overall enrichment of LAP+CD4+ T cells (95.02% ± 2.87%), which was similar for LAP-CD4+ T cells (94.75% ± 2.76%). In contrast to LAP-CD4+ T cells, LAP+CD4+ T cells showed lower Foxp3 expression but significantly higher levels of CTLA-4, CCR4 and CCR5 (P < 0.01). LAP+CD4+ T cells expressed significantly larger amounts of IL-10 and TGF-ß but lower levels of IL-2, IL-4, IL-17 and interferon-γ, compared with LAP-CD4+ T cells. CONCLUSION: LAP+CD4+ T cells accumulated in the tumor microenvironment of CRC patients and were involved in immune evasion mediated by IL-10 and TGF-ß.

Asymmetric Donor-π-Acceptor-Type Benzo-Fused Aza-BODIPYs: Facile Synthesis and Colorimetric Properties.

Novel aza-diisoindolylmethene and their BF2 -chelating complexes (benzo-fused aza-BODIPYs) were synthesized on a large scale and in a facile manner from phthalonitrile in tBuOK-DMF solution. The unique asymmetric donor-π-acceptor structure facilitates B-N bond detachment in the presence of trifluoroacetic acid (TFA) in dichloromethane, resulting in sharp color change from red to colorless, with over 250 nm hypsochromic shift in the absorption maximum. This colorimetric process can be reversed by adding a very small amount of proton-accepting solvents or compounds. A (1) H and (11) B NMR spectroscopy study and also density functional theory (DFT) calculations suggest that TFA-induced B-N bond cleavage may disrupt the whole π-conjugation of the BODIPY molecule, resulting in significant colorimetric behavior.

High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding: a meta-analysis.

AIM: To evaluate the efficacy of high-dose proton pump inhibitors (PPIs) vs low-dose PPIs for patients with upper gastrointestinal bleeding. METHODS: PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify relevant randomized controlled trials (RCTs). Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis. The primary endpoint was rebleeding; secondary endpoints were patient numbers that needed surgery, and mortality. The meta-analysis was performed with a fixed effects model or random effects model. RESULTS: Nine eligible RCTs including 1342 patients were retrieved. The results showed that high-dose intravenous PPI was not superior to low-dose intravenous PPI in reducing rebleeding [odds ratio (OR) = 1.091, 95% confidential interval (CI): 0.777-1.532], need for surgery (OR = 1.522, 95% CI: 0.643-3.605) and mortality (OR = 1.022, 95% CI: 0.476-2.196). Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients (OR = 0.831, 95% CI, 0.467-1.480) and European patients (OR = 1.263, 95% CI: 0.827-1.929). CONCLUSION: Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.