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AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology. METHODS: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed. RESULTS: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253]). CONCLUSIONS/INTERPRETATION: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients.
Subject(s)
Blood Glucose , Critical Illness , Hospital Mortality , Hyperglycemia , Humans , Critical Illness/mortality , Hyperglycemia/mortality , Hyperglycemia/blood , Male , Prospective Studies , Female , Blood Glucose/analysis , Blood Glucose/metabolism , Middle Aged , Aged , Intensive Care Units , Monitoring, Physiologic/methods , Continuous Glucose MonitoringABSTRACT
Real-time monitoring of the structural evolution of battery materials is crucial for understanding their underlying reaction mechanisms, which cannot be satisfied by the typically used post-mortem analysis. While more and more operando techniques were constructed and employed, they are all based on ambient working conditions that are not generally the case for real-world applications. Indeed, batteries work in an environment where self-heat dissipation increases the surrounding temperature, and extreme temperature applications (<-20 °C or >60 °C) are also frequently proposed. Operando characterization techniques under variable temperatures are therefore highly desired for tracking battery reactions under real-working conditions. Here, we develop a methodology to operando monitor the electronic and geometrical structures of battery materials over a wide range of temperatures based on X-ray spectroscopies. It is substantiated with data collected on a model LiNi0.90Co0.05Mn0.05O2/Si@C pouch cell under operando quick X-ray absorption fine structure spectroscopy, by which we found a temperature-dependent structure evolution behavior that is highly correlated with the electrochemical performance. Our work establishes an exemplary protocol for analyzing battery materials under temperature-variable environments that can be widely used in other related fields.
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BACKGROUND: Oxyntic gland neoplasm (OGN) is a rare subtype of gastric cancer. The aim of this study is to evaluate the prevalence, clinicopathological features, effectiveness and safety of endoscopic treatment, as well as the prognosis of OGN. METHODS: We retrospectively analyzed the data of patients pathologically diagnosed with OGN at our hospital from November 1, 2019 to May 1, 2023. RESULTS: A total of 36 patients with 45 lesions were identified, resulting in a disease frequency of 0.047% (36/76,832). The mean age was 55.0 ± 7.5 years, with a male-to-female ratio of about 1:1.12. Most lesions were ≤10 mm in size (84.4%), located in the upper third of the stomach (73.3%), exhibited slight elevation (75.5%), appeared whitish (55%), had dilated blood vessels on the surface (75.5%). 16 and 21 lesions were treated by precutting endoscopic mucosal resection (EMR-P) and endoscopic submucosal dissection (ESD), respectively. No significant differences were found between EMR-P and ESD in terms of en bloc resection rate (100% vs 100%, p = 1.000), complete resection rate (100% vs 90.5%, p = 0.495), and curative resection rate (93.8% vs 90.5%, p = 1.000). No complications such as bleeding and perforation were observed. No recurrence or metastasis was observed during the follow-up period. CONCLUSIONS: OGN is a rare tumor with unique clinical, endoscopic, and pathological characteristics. EMR-P and ESD are deemed safe and effective for treating OGNs. The relatively faster and easier EMR-P seems at least non-inferior to ESD, especially for removal of smaller OGNs. The overall prognosis is favorable.
Subject(s)
Endoscopic Mucosal Resection , Stomach Neoplasms , Humans , Male , Female , Middle Aged , Retrospective Studies , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/therapy , Stomach Neoplasms/epidemiology , Prevalence , Aged , Treatment Outcome , Adult , Prognosis , Gastroscopy , Gastric Mucosa/pathology , Gastric Mucosa/surgery , China/epidemiologyABSTRACT
Fragment-based drug discovery (FBDD) is widely used in drug design. One useful strategy in FBDD is designing linkers for linking fragments to optimize their molecular properties. In the current study, we present a novel generative fragment linking model, GRELinker, which utilizes a gated-graph neural network combined with reinforcement and curriculum learning to generate molecules with desirable attributes. The model has been shown to be efficient in multiple tasks, including controlling logâ¯P, optimizing synthesizability or predicted bioactivity of compounds, and generating molecules with high 3D similarity but low 2D similarity to the lead compound. Specifically, our model outperforms the previously reported reinforcement learning (RL) built-in method DRlinker on these benchmark tasks. Moreover, GRELinker has been successfully used in an actual FBDD case to generate optimized molecules with enhanced affinities by employing the docking score as the scoring function in RL. Besides, the implementation of curriculum learning in our framework enables the generation of structurally complex linkers more efficiently. These results demonstrate the benefits and feasibility of GRELinker in linker design for molecular optimization and drug discovery.
Subject(s)
Drug Design , Drug Discovery , Neural Networks, Computer , Learning , CurriculumABSTRACT
BACKGROUND: The diagnostic assay leveraging multiple reverse transcription loop-mediated isothermal amplification (RT-LAMP) could meet the requirements for rapid nucleic acid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The devised assay merged the lateral flow assay with the RT-LAMP technology and designed specific primers for the simultaneous detection of the target and human-derived internal reference genes within a single reaction. An inquiry into the assay's limit of detection (LOD), sensitivity, and specificity was carried out. The effectiveness of this assay was validated using 498 clinical specimens. RESULTS: This LOD of the assay was determined to be 500 copies/mL, and there was no observed cross-reaction with other respiratory pathogens. The detection results derived from clinical specimens showed substantial concordance with those from real-time reverse transcription-polymerase chain reaction (RT-qPCR) (Cohen's kappa, 0.876; 95% CI: 0.833-0.919; p<0.005). The diagnostic sensitivity and specificity were 87.1% and 100%, respectively. CONCLUSION: The RT-LAMP assay, paired with a straightforward and disposable lateral immunochromatographic strip, achieves visual detection of dual targets for SARS-CoV-2 immediatly. Moreover, the entire procedure abstains from nucleic acids extraction. The samples are lysed at room temperature and subsequently proceed directly to the RT-LAMP reaction, which can be executed within 30 minutes at a constant temperature of 60-65°C. Then, the RT-LAMP amplification products are visualized using colloidal gold test strips. TRIAL REGISTRATION: This study was registered at the Chinese Clinical Trial Registry (Registration number: ChiCTR2200060495, Date of registration 2022-06-03).
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19 Testing , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Sensitivity and Specificity , RNA, Viral/geneticsABSTRACT
BACKGROUND: The role of endoscopic resection (ER) in gastric gastrointestinal stromal tumors (GISTs) has not been fully elucidated. AIMS: The purpose of this work was to evaluate the clinical effectiveness and safety of ER in patients with GISTs originating from the muscularis propria (MP). METHODS: A total of 233 consecutive patients with gastric GISTs originating from the MP layer, who underwent ER between February 2012 and May 2023, were included in this study. Clinical characteristics, tumor features, and outcomes were recorded and compared between patients who underwent en bloc resection and piecemeal resection. RESULTS: Among the 233 patients, the median size of GISTs was 12 mm (range 5-60 mm). Risk assessment categorized 190 patients as very low risk, 26 as low risk, 10 as moderate risk, and 7 as high risk. The procedures performed included endoscopic submucosal excavation (127 cases), endoscopic full-thickness resection (103 cases), and submucosal tunneling endoscopic resection (3 cases). The complete and R0 resection rate was 93.1%. Complications occurred in 4.7% of cases (perioperative perforations 1.7%, perioperative bleeding 1.3%, both 0.9%), resulting in conversion to surgery in 1.3% of cases. Risk factors associated with piecemeal resection were tumor size [odds ratio (OR) 0.402, 95% confidence interval (CI) 0.207-0.783; P = 0.007] and shape (OR 0.045, 95% CI 0.009-0.235; P < 0.001). CONCLUSIONS: ER is proven to be an effective and reasonably safe approach for gastric GISTs originating from the MP. Notably, larger tumor size and irregular shape are identified as risk factors for piecemeal resection during ER procedures.
Subject(s)
Gastrointestinal Stromal Tumors , Stomach Neoplasms , Humans , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Male , Female , Middle Aged , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Aged , Adult , Aged, 80 and over , Endoscopic Mucosal Resection/methods , Endoscopic Mucosal Resection/adverse effects , Gastric Mucosa/surgery , Gastric Mucosa/pathology , Treatment Outcome , Retrospective Studies , Gastroscopy/methods , Gastroscopy/adverse effects , Risk Factors , Postoperative Complications/epidemiology , Postoperative Complications/etiologyABSTRACT
BACKGROUND AND AIM: The incidence of rectal neuroendocrine tumors (R-NETs) has increased in recent years. However, the predictors of lymph node (LN) metastasis and clinical outcomes, particularly following endoscopic treatment, remain unclear. Our study aims to elucidate the potential risk factors for LN metastasis and the clinical outcomes of patients undergoing endoscopic resection in R-NETs. METHODS: A total of 128 patients with R-NETs were retrospectively identified from a single center between June 2012 and December 2021. Risk factors for LN metastasis in R-NETs were analyzed using multivariate analysis. Additionally, the clinical outcomes of endoscopic resections in patients with R-NETs were assessed. RESULTS: In our study, 128 patients with R-NETs were retrospectively analyzed. The risk factors for LN metastasis determined by multivariate analysis were tumor size and patient age at diagnosis. Among the 111 patients treated with endoscopic resection and with tumor margin records available, 92 underwent endoscopic submucosal dissection (ESD) and 19 underwent conventional endoscopic mucosal resection (EMR). There was no significant difference between the two groups regarding the positive rates of basal tumor margin and lateral tumor margin. Furthermore, 64 patients who underwent endoscopic resection for R-NETs were successfully followed up (range, 1.64-76.71 months), during which only one patient developed local recurrence. CONCLUSION: Tumor size and age at diagnosis were predictors for LN metastasis of R-NETs. Both ESD and EMR are alternative techniques with a favorable prognosis for R-NETs, even in cases with positive resection margins. However, due to the relatively small number of patients undergoing EMR and missing data in follow-up protocols, definitive conclusions require further large-scale studies.
Subject(s)
Endoscopic Mucosal Resection , Lymphatic Metastasis , Neuroendocrine Tumors , Rectal Neoplasms , Humans , Male , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Retrospective Studies , Female , Neuroendocrine Tumors/surgery , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/secondary , Middle Aged , Endoscopic Mucosal Resection/methods , Aged , Adult , Risk Factors , Treatment Outcome , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/pathology , Margins of ExcisionABSTRACT
Listeria monocytogenes is a foodborne pathogen. In 2022, we collected 15 strains of L. monocytogenes isolated from patients in some foodborne disease sentinel monitoring hospitals in Sichuan Province. Through whole genome sequencing (WGS), we obtained the virulence genes carried by the strains, multi-locus sequence typing (MLST), core genome MLST (cgMLST), clonal complex (CC), and serum groups and constructed a phylogenetic tree and minimum spanning tree with nonhuman strains. An analysis shows that all 15 strains of L. monocytogenes carry virulence genes LIPI-1 and LIPI-2, whereas the carrying rates of LIPI-3 and LIPI-4 virulence genes are relatively low. The MLST typing results showed a total of 10 sequence types (ST), including 10 CCs, with ST7 being the dominant type. The cgMLST clearly distinguishes strains of different lineages and CC types. The serum group is divided into three types: IIa, IIb, and IVb, with IIa being the dominant serum group. An analysis of antibiotic genes showed that all 15 strains carried FosX, lin, mprF, and norB with high carrying rates. The minimum inhibitory concentration results indicated that all were susceptible to eight antibiotics (ampicillin, penicillin, tetracycline, meropenem, erythromycin, vancomycin, ciprofloxacin, and trimethoprim-sulfamethoxazole). The analysis of strains isolated from different sources of Listeria revealed varying degrees of diversity, and the contamination of meat and environment within the province is closely related to clinical cases. L. monocytogenes isolated from clinical cases in Sichuan Province carry multiple virulence and antibiotic genes, with high potential pathogenicity. It is necessary to further strengthen the monitoring and control of food and environment by L. monocytogenes within Sichuan Province.
Subject(s)
Anti-Bacterial Agents , Listeria monocytogenes , Listeriosis , Microbial Sensitivity Tests , Multilocus Sequence Typing , Phylogeny , Virulence Factors , Whole Genome Sequencing , Listeria monocytogenes/genetics , Listeria monocytogenes/isolation & purification , Listeria monocytogenes/classification , China , Humans , Anti-Bacterial Agents/pharmacology , Listeriosis/microbiology , Listeriosis/epidemiology , Virulence Factors/genetics , Foodborne Diseases/microbiology , Virulence/genetics , Genome, Bacterial , Food MicrobiologyABSTRACT
Staphylococcal food poisoning (SFP) is one of the most common foodborne diseases in the world. This study aimed to investigate the molecular epidemiological characteristics of Staphylococcus aureus isolated from SFP. A total of 103 S. aureus isolates were obtained during 2011-2022 in Sichuan, southwest China. All isolates were tested for the genomic characteristics and phylogenetic analysis by performing whole-genome sequencing. Multilocus sequence typing analysis showed 17 multilocus sequence types (STs), ST7 (23.30%), ST5 (22.33%), and ST6 (16.50%) being the most common. A total of 45 virulence genes were detected, 22 of which were staphylococcal enterotoxin (SE) genes. Among the identified SE genes, selX exhibited the highest prevalence (86.4%). All isolates carried at least one SE gene. The results of the antimicrobial resistance (AMR) gene detection revealed 41 AMR genes of 12 classes. ß-lactam resistance genes (blal, blaR1, blaZ) and tetracycline resistance gene (tet(38)) exhibited a higher prevalence rate. Core genome single nucleotide polymorphism showed phylogenetic clustering of the isolates with the same region, year, and ST. The results indicated that the SFP isolates in southwest of China harbored multiple toxin and resistance genes, with a high prevalence of new SEs. Therefore, it is important to monitor the antimicrobial susceptibility and SE of S. aureus to reduce the potential risks to public health.
Subject(s)
Disease Outbreaks , Enterotoxins , Multilocus Sequence Typing , Phylogeny , Staphylococcal Food Poisoning , Staphylococcus aureus , China/epidemiology , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/drug effects , Staphylococcal Food Poisoning/epidemiology , Staphylococcal Food Poisoning/microbiology , Humans , Enterotoxins/genetics , Whole Genome Sequencing , Polymorphism, Single Nucleotide , Virulence Factors/genetics , Anti-Bacterial Agents/pharmacology , Microbial Sensitivity Tests , Foodborne Diseases/epidemiology , Foodborne Diseases/microbiology , Molecular Epidemiology , Drug Resistance, Bacterial/genetics , Genome, BacterialABSTRACT
The ongoing COVID-19 pandemic still threatens human health around the world. The methyltransferases (MTases) of SARS-CoV-2, specifically nsp14 and nsp16, play crucial roles in the methylation of the N7 and 2'-O positions of viral RNA, making them promising targets for the development of antiviral drugs. In this work, we performed structure-based virtual screening for nsp14 and nsp16 using the screening workflow (HTVS, SP, XP) of Schrödinger 2019 software, and we carried out biochemical assays and molecular dynamics simulation for the identification of potential MTase inhibitors. For nsp14, we screened 239,000 molecules, leading to the identification of three hits A1-A3 showing N7-MTase inhibition rates greater than 60% under a concentration of 50 µM. For the SAM binding and nsp10-16 interface sites of nsp16, the screening of 210,000 and 237,000 molecules, respectively, from ZINC15 led to the discovery of three hit compounds B1-B3 exhibiting more than 45% of 2'-O-MTase inhibition under 50 µM. These six compounds with moderate MTase inhibitory activities could be used as novel candidates for the further development of anti-SARS-CoV-2 drugs.
Subject(s)
Antiviral Agents , Enzyme Inhibitors , Methyltransferases , Molecular Dynamics Simulation , SARS-CoV-2 , Viral Nonstructural Proteins , Viral Nonstructural Proteins/antagonists & inhibitors , Viral Nonstructural Proteins/metabolism , Viral Nonstructural Proteins/chemistry , Methyltransferases/antagonists & inhibitors , Methyltransferases/metabolism , Methyltransferases/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Humans , Molecular Docking Simulation , Drug Evaluation, Preclinical , COVID-19 Drug Treatment , COVID-19/virology , Binding Sites , ExoribonucleasesABSTRACT
Tandem nitrate electroreduction reaction (NO3 -RR) is a promising method for green ammonia (NH3) synthesis. However, the mismatched kinetics processes between NO3 --to-NO2 - and NO2 --to-NH3 results in poor selectivity for NH3 and excess NO2 - evolution in electrolyte solution. Herein, a Ni2+ substitution strategy for developing oxide heterostructure in Co/Fe layered double oxides (LDOs) was designed and employed as tandem electrocataltysts for NO3 -RR. (Co0.83Ni0.16)2Fe exhibited a high NH3 yield rate of 50.4â mg â cm-2 â h-1 with a Faradaic efficiency of 97.8 % at -0.42â V vs. reversible hydrogen electrode (RHE) in a pulsed electrolysis test. By combining with in situ/operando characterization technologies and theoretical calculations, we observed the strong selectivity of NH3 evolution over (Co0.83Ni0.16)2Fe, with Ni playing a dual role in NO3 -RR by i) modifying the electronic behavior of Co, and ii) serving as complementary site for active hydrogen (*H) supply. Therefore, the adsorption capacity of *NO2 and its subsequent hydrogenation on the Co sites became more thermodynamically feasible. This study shows that Ni substitution promotes the kinetics of the NO3 -RR and provides insights into the design of tandem electrocatalysts for NH3 evolution.
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BACKGROUND: Underwater endoscopic mucosal resection (UEMR) is increasingly applied in the treatment of superficial non-ampullary duodenal epithelial tumors (SNADETs). This meta-analysis aimed to assess the efficacy and safety of UEMR for SNADETs ≤20 mm in comparison with conventional endoscopic mucosal resection (CEMR). METHODS: The following electronic databases were searched from 2012 until November 20, 2021: PubMed, Embase, Scopus, Web of Science databases, and Cochrane Library. The primary outcomes were the rates of en bloc resection and complete (R0) resection, and the secondary outcomes were procedure time, adverse events (delayed bleeding and delayed perforation), and recurrence rate. RESULTS: A total of 6 studies with 679 lesions (331 underwent UEMR and 348 CEMR) were included in this study. The pooled analysis showed that UMER achieves a similar en bloc resection rate (87.6 vs. 89.9%; odds ratio [OR], 1.29; 95% confidence interval [CI], 0.45 to 3.73; P =0.64; I2 =74%), a similar R0 resection rate (67.3 vs. 73.6%; OR, 1.11; 95% CI, 0.55 to 2.23; P =0.78; I2 =59%), a shorter procedure time (min) (mean difference [MD], -4.05, 95% CI: -6.40 to -1.71; P =0.0007; I2 =70%) compared with CEMR. There were no significant differences in the rates of delayed bleeding, delayed perforation, and recurrence (2.4 vs. 1.7%, 0 vs. 0.6%, 2.2 vs. 4.4%, respectively). CONCLUSION: This meta-analysis demonstrated that UEMR appears to be an effective and safe alternative to CEMR for SNADETs ≤20 mm.
Subject(s)
Duodenal Neoplasms , Endoscopic Mucosal Resection , Neoplasms, Glandular and Epithelial , Pancreatic Neoplasms , Humans , Endoscopic Mucosal Resection/adverse effects , Endoscopic Mucosal Resection/methods , Intestinal Mucosa/surgery , Intestinal Mucosa/pathology , Treatment Outcome , Duodenum/pathology , Duodenal Neoplasms/surgery , Duodenal Neoplasms/pathology , Pancreatic Neoplasms/pathology , Neoplasms, Glandular and Epithelial/etiology , Neoplasms, Glandular and Epithelial/pathology , Retrospective StudiesABSTRACT
BACKGROUND: Chlamydia psittaci (C. psittaci) causes parrot fever in humans. Development of metagenomic next-generation sequencing (mNGS) enables the identification of C. psittaci. METHODS: This study aimed to determine the epidemiological and clinical characteristics of parrot fever cases in China. A multi-center observational study was conducted in 44 tertiary and secondary hospitals across 14 provinces and municipalities between April 2019 and October 2021. RESULTS: A total of 4545 patients with complicated or atypical pulmonary infection were included in the study, among which the prevalence of C. psittaci was determined to be 2.1% using mNGS. The prevalence of C. psittaci was further determined across demographic groups and types of specimens. It was significantly higher in patients with senior age (2.6% in those > 50 years), winter-spring (3.6%; particularly in December, January, and February), and southwestern (3.4%) and central and southern China (2.7%) (each P < 0.001). Moreover, the prevalence was the highest in bronchoalveolar lavage fluid (BALF) (2.9%), compared with sputum (1.1%) and peripheral blood specimens (0.9%). Additionally, co-infection of principal microorganisms was compared. Certain microorganisms were more likely to co-infect in parrot fever cases, such as Candida albicans in BALF (26.7%) and peripheral blood (6.3%), compared with non-parrot fever cases (19.7% and 1.3%); however, they did not significantly differ (each P > 0.05). CONCLUSION: Parrot fever remains low in patients with complicated or atypical pulmonary infection. It is likely to occur in winter-spring and southwestern region in China. BALF may be the optimal specimen in the application of mNGS. Co-infection of multiple microorganisms should be further considered.
Subject(s)
Coinfection , Pneumonia , Psittacosis , Humans , Middle Aged , Psittacosis/diagnosis , Psittacosis/epidemiology , High-Throughput Nucleotide Sequencing , Candida albicans , China/epidemiology , Pneumonia/epidemiologyABSTRACT
This study aimed to explore the role of lncRNA RPPH1 in hepatocellular carcinoma. The expression of RPPH1 and miR-122 was determined by Real-time PCR. Cell proliferation and colony formation assays were employed to monitor cell growth in vitro. Wound healing and Transwell assays were applied to detect cell migration and invasion. A dual-luciferase reporter assay was used to verify the interaction between RPPH1 and miR-122. The in vivo function of RPPH1 was illustrated by xenograft tumor models. The results showed that the expression of RPPH1 was markedly upregulated in human HCC specimens and cell lines compared to normal controls. However, the trend of miR-122 was the opposite. RPPH1 facilitates the proliferation, migration, and invasion of HCC cells and synchronously suppresses cell apoptosis. The dual-luciferase assay confirmed the relationship between RPPH1 and miR-122. Rescue experiments showed that RPPH1 acted as a competing endogenous RNA (ceRNA) by sponging miR-122 in HCC cells. Moreover, RPPH1 positively regulated the expression of Wnt1 and its downstream targets through miR-122. Our study demonstrates for the first time that RPPH1 promotes HCC progression via the miR-122/Wnt1/ß-catenin axis, which may represent a valuable therapeutic target for patients with HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , beta Catenin/genetics , beta Catenin/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Wnt Signaling Pathway/geneticsABSTRACT
The objective of this study was to evaluate the efficacy and safety of super pulse CO2 laser-assisted punctoplasty with canalicular curettage in primary canaliculitis. In this retrospective serial case study, the clinical data of 26 patients who underwent super pulse CO2 laser-assisted punctoplasty for the treatment of canaliculitis were collected from January 2020 to May 2022. The clinical presentation, intraoperative and microbiologic findings, surgical pain severity, postoperative outcome, and complications were studied. Of the 26 patients, most were females (female:male 20:6), with a mean age of 60.1 ± 16.1 years (range, 19-93). Mucopurulent discharge (96.2%), eyelid redness and swelling (53.8%), and epiphora (38.5%) were the most common presentations. During the surgery, concretions were present in 73.1% (19/26) of the patients. The surgical pain severity scores ranged from 1 to 5, according to the visual analog scale, with a mean score of 3.2 ± 0.8. This procedure resulted in complete resolution in 22 (84.6%) patients and significant improvement in 2 (7.7%) patients, and 2 (7.7%) patients required additional lacrimal surgery with a mean follow-up time of 10.9 ± 3.7 months. The surgical procedure of super pulse CO2 laser-assisted punctoplasty followed by curettage appears to be a safe, effective, minimally invasive, and well-tolerated treatment for primary canaliculitis.
Subject(s)
Canaliculitis , Lasers, Gas , Humans , Male , Female , Adult , Middle Aged , Aged , Canaliculitis/drug therapy , Canaliculitis/surgery , Retrospective Studies , Carbon Dioxide/therapeutic use , Curettage/methods , Treatment OutcomeABSTRACT
Good syndrome (GS) is a rare entity that associates the existence of thymoma with immunodeficiency. Gastrointestinal symptoms is one of the most common clinical manifestations. However, colorectal ulcers in GS were extremely rare. Herein, we present a case of GS presenting with diarrhea and colorectal ulcers to inform readers.
Subject(s)
Colorectal Neoplasms , Thymoma , Thymus Neoplasms , Humans , Ulcer/complications , Thymus Neoplasms/complications , Thymus Neoplasms/diagnosis , Thymoma/complications , Thymoma/diagnosis , Diarrhea/complications , Colorectal Neoplasms/complicationsABSTRACT
Droplet manipulation has found broad applications in various engineering fields, such as microfluidic systems. This work reports a droplet-manipulation method based on particle-stabilized emulsions, where the magnetic particles adsorbed to the droplet surface serve as the actuator. The movement and the release of the droplet can be controlled by applying an external magnetic field. A lattice Boltzmann model for a three-phase system containing liquids and solid particles is adopted, which could provide a full coupling between fluids and particles. The effectiveness of the present droplet-manipulation method is validated through experiments and numerical simulations. Furthermore, the numerical simulation can provide insight into the interactions between the magnetic particles and the droplet during the droplet-driven process. To drive the droplet successfully, the magnetic particle needs to adhere to its surface and act as an "engine" to provide the driving force. As it is a surface-tension-dominant problem, the capillary effect can be considered as an "energy transfer station". The magnetic driving force on the particle is transmitted primarily to the droplet through interfacial capillary forces at the three-phase contact line, which assists the droplet in overcoming the viscous resistance and moving forward. A dimensionless number is proposed as a predictor of droplet transport and particle detachment.
ABSTRACT
Fragment-based drug discovery is a widely used strategy for drug design in both academic and pharmaceutical industries. Although fragments can be linked to generate candidate compounds by the latest deep generative models, generating linkers with specified attributes remains underdeveloped. In this study, we presented a novel framework, DRlinker, to control fragment linking toward compounds with given attributes through reinforcement learning. The method has been shown to be effective for many tasks from controlling the linker length and log P, optimizing predicted bioactivity of compounds, to various multiobjective tasks. Specifically, our model successfully generated 91.0% and 93.9% of compounds complying with the desired linker length and log P and improved the 7.5 pChEMBL value in bioactivity optimization. Finally, a quasi-scaffold-hopping study revealed that DRlinker could generate nearly 30% molecules with high 3D similarity but low 2D similarity to the lead inhibitor, demonstrating the benefits and applicability of DRlinker in actual fragment-based drug design.
Subject(s)
Drug Design , Drug DiscoveryABSTRACT
BACKGROUND: The mortality rate is high in critically ill patients due to the difficulty of diagnosis and treatment. Thus, it is very important to explore the predictive value of different indicators related to prognosis in critically ill patients. METHODS: This was a retrospective cohort study of patients in the intensive care unit (ICU) of the Sixth People's Hospital in Shanghai, China. A total of 1465 ICU patients had lactate values > 2.1 mmol/L at least once within 24 h of ICU admission, and arterial blood gas was monitored more than twice during the ICU stay. RESULTS: The predictive value of lactate clearance at 24 h was not high, and the sensitivity and specificity were lower. The predictive value of the lactate level at baseline and the APACHE II score was higher than that of lactate clearance at 24 h in critically ill patients. The predictive value of the lactate level at baseline combined with the APACHE II score was higher than that of the lactate level at baseline or the APACHE II score alone. In addition, the predictive value of lactate clearance at 24 h combined with the APACHE II score was also significantly higher than that of lactate clearance at 24 h or the APACHE II score alone. In particular, the area under the ROC curve reached 0.900, the predictive value was markedly higher than that of the ROC alone, and the sensitivity and specificity were better when these three indicators were combined. CONCLUSIONS: The combination of lactate level, lactate clearance and APACHE II score better predicts short-term outcomes in critically ill patients.
Subject(s)
Lactic Acid , Humans , APACHE , Retrospective Studies , ChinaABSTRACT
BACKGROUND: Payment methods for human papillomavirus (HPV) vaccine could substantially influence vaccination behavior. In China, HPV vaccination uptake remains currently low. This study aims to determine willingness to pay (WTP) for HPV vaccines among Chinese female health care workers under different payment scenarios. METHODS: This is a nationwide online survey recruiting female health care workers aged 18-45 years from 31 provinces throughout China. We collected the respondents' vaccination status of HPV vaccines and their sociodemographics. Two WTPs were defined and estimated in the study. A general WTP for HPV vaccination was determined using the contingent valuation method with double dichotomous choice bidding. A WTP out-of-pocket was estimated for each HPV vaccine under two scenarios, including partial coverage by governmental subsidy or partial incorporation in basic medical insurance. Accordingly, a multivariable linear regression model was employed to determine the association between sociodemographis and general WTP. Then the maximum WTP out-of-pocket was compared among the respondents' attitude shift towards HPV vaccination, payment scenarios, and levels of vaccine attributes, using non-parametric Kruskal-Wallis test. RESULTS: A total of 15,969 respondents were included in the study. The median general WTP was 2000 CNY (interquartile range, 1000-3200 CNY), positively associated with younger age, unmarried status, higher monthly income, fewer children, more positive vaccination behavior, working in tertiary hospital, higher local GDP and HDI (each P < 0.05). Moreover, the median WTP out-of-pocket was 1250 CNY (540-2000 CNY). It was significantly higher for vaccines partly covered by governmental subsidy (median, 1250 CNY; interquartile range, 560-2000 CNY), imported vaccines (1260 CNY; 630-1960 CNY), and 9-valent vaccines (1400 CNY; 750-2240 CNY) (each P < 0.001). Additionally, majority of respondents did not change their attitude towards HPV vaccination between two payment scenarios; those remaining with more expensive HPV vaccines (51.1%) had higher WTP out-of-pocket (1400 CNY; 560-2250 CNY) than those with cheaper vaccines (39.0%) (1120 CNY; 490-1960 CNY) (P < 0.001). CONCLUSION: Chinese female health care workers have high WTP for HPV vaccines. A direct public funding for HPV vaccination is more preferable. Our findings may facilitate the adjustment of HPV vaccination strategy and payment mechanism in China.