Real world risk of discontinuing oral anticoagulation after successful catheter ablation for atrial fibrillation.

Background: Many patients with atrial fibrillation (AF) discontinued oral anticoagulation (OAC) therapy after successful catheter ablation. We aimed to determine the real-world risks and consequences of discontinuing OAC use after catheter ablation for AF. Methods: Patients who underwent successful catheter ablation for AF from January 2004 to December 2020 were divided into continued long-term OAC (On-OAC, n = 1062) and discontinued (Off-OAC, n = 1055) groups. The long-term outcomes including thromboembolic events, major bleeding, all-cause mortality and major adverse cardiovascular events (MACE), were compared between the two groups. Results: The CHA2DS2-VASc score was 3.44 ± 1.12. After a mean follow-up of 37.09 months, thromboembolism risk was higher and major bleeding risk was lower in the Off-OAC than in the On-OAC group (Both log-rank P < 0.001). CHA2DS2-VASc score-stratified subgroup analysis showed similar cumulative event rates between the two groups in men and women with scores of 2 and 3 (intermediate risk for stroke), respectively, (P > 0.05), except for a higher major bleeding rate in the On-OAC group (P = 0.002). Patients at high risk for stroke (men and women with scores ≥3 and ≥ 4) had better non-thromboembolic and non-MACE results (Both log-rank P < 0.05). Conclusion: Men with a CHA2DS2-VASc score of 2 and women with a score of 3 had a relatively low incidence of stroke events after successful catheter ablation for AF and may be safe for anticoagulation cessation. Greater benefits from long-term OAC were observed in men with CHA2DS2-VASc score ≥3 and women with score ≥4.

Radiomics analysis of dual-layer spectral-detector CT-derived iodine maps for predicting tumor deposits in colorectal cancer.

OBJECTIVE: To investigate the value of radiomics analysis of dual-layer spectral-detector computed tomography (DLSCT)-derived iodine maps for predicting tumor deposits (TDs) preoperatively in patients with colorectal cancer (CRC). MATERIALS AND METHODS: A total of 264 pathologically confirmed CRC patients (TDs + (n = 80); TDs - (n = 184)) who underwent preoperative DLSCT from two hospitals were retrospectively enrolled, and divided into training (n = 124), testing (n = 54), and external validation cohort (n = 86). Conventional CT features and iodine concentration (IC) were analyzed and measured. Radiomics features were derived from venous phase iodine maps from DLSCT. The least absolute shrinkage and selection operator (LASSO) was performed for feature selection. Finally, a support vector machine (SVM) algorithm was employed to develop clinical, radiomics, and combined models based on the most valuable clinical parameters and radiomics features. Area under receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis were used to evaluate the model's efficacy. RESULTS: The combined model incorporating the valuable clinical parameters and radiomics features demonstrated excellent performance in predicting TDs in CRC (AUCs of 0.926, 0.881, and 0.887 in the training, testing, and external validation cohorts, respectively), which outperformed the clinical model in the training cohort and external validation cohorts (AUC: 0.839 and 0.695; p: 0.003 and 0.014) and the radiomics model in two cohorts (AUC: 0.922 and 0.792; p: 0.014 and 0.035). CONCLUSION: Radiomics analysis of DLSCT-derived iodine maps showed excellent predictive efficiency for preoperatively diagnosing TDs in CRC, and could guide clinicians in making individualized treatment strategies. CLINICAL RELEVANCE STATEMENT: The radiomics model based on DLSCT iodine maps has the potential to aid in the accurate preoperative prediction of TDs in CRC patients, offering valuable guidance for clinical decision-making. KEY POINTS: Accurately predicting TDs in CRC patients preoperatively based on conventional CT features poses a challenge. The Radiomics model based on DLSCT iodine maps outperformed conventional CT in predicting TDs. The model combing DLSCT iodine maps radiomics features and conventional CT features performed excellently in predicting TDs.

Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

Baicalein alleviates palmitic acid-induced endothelial cell dysfunction via inhibiting endoplasmic reticulum stress.

OBJECTIVE: Endothelial cells play a critical role in maintaining vascular function and kinetic homeostasis, but excessive accumulation of palmitic acid (PA) may lead to endoplasmic reticulum stress and trigger endothelial cell dysfunction. Baicalin (BCL), a natural plant extract, has received widespread attention for its biological activities in anti-inflammation and anti-oxidative stress. However, the mechanism of BCL on PA-induced endothelial cell dysfunction is unclear. Therefore, the aim of this study was to investigate whether BCL could inhibit PA-induced endoplasmic reticulum stress and thus attenuate endothelial cell dysfunction. METHODS: Human umbilical vein endothelial cells (HUVECs) were divided into Control, PA, PA + BCL-10 µM, PA + BCL-20 µM, and PA + BCL-50 µM groups. The PA group was treated with PA (200 µM), while the PA + BCL groups were co-treated with different concentrations of BCL (10 µM, 20 µM, 50 µM) for 24 hours. Cell viability was detected by MTT. Cell migration ability was determined by Transwell assay, apoptosis level by flow cytometry, and tube formation ability by tube formation assay. Finally, the levels of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and angiogenesis-related proteins (VEGFA and FGF2) were detected by western blot, MMP-9, as well as the protein levels of endoplasmic reticulum stress biomarkers (GRP78, CHOP, PERK, and ATF4). RESULTS: The results at the cellular level showed that cell viability, migration ability and tube formation ability of PA-induced HUVECs were significantly reduced, while apoptosis level was significantly increased. However, administration of different concentrations of BCL significantly enhanced PA-induced cell viability, migration ability and tube formation ability of HUVECs while inhibiting apoptosis. The results of protein levels showed that the protein levels of Bax and cleaved caspase-3 were observably up-regulated in the cells of the PA group, while the protein level of Bcl-2 was significantly down-regulated; compared with the PA group, the protein levels of Bax and cleaved caspase-3 were much lower and the Bcl-2 protein level was much higher in the PA + BCL group. Additionally, the protein levels of VEGFA, FGF2 and MMP-9 were raised and those of GRP78, CHOP, PERK and ATF4 were lowered in the PA + BCL group of cells in a concentration-dependent manner. CONCLUSION: BCL significantly attenuates PA-induced endothelial cell dysfunction by inhibiting endoplasmic reticulum stress.

An innovative approach to improving lactic acid production from food waste using iron tailings.

In this study, the feasibility of promoting the lactic acid (LA) fermentation of food waste (FW) with iron tailings (ITs) addition was explored. The best LA yield was 0.91 g LA/g total sugar when 1 % ITs were added into the system. The mechanisms for promoting LA production were acidification alleviation effects and reduction equivalent supply of ITs. Furthermore, the addition of ITs promoted carbohydrate hydrolysis, and the carbohydrates digestibility reached 88.85 % in the 1 % ITs group. The ITs also affected the microbial communities, Lactococcus gradually replaced Streptococcus as the dominant genus, and results suggested that Lactococcus had a positive correlation with LA production and carbohydrate digestibility. Finally, the complex LAB in FW had significant effects on heavy metal removal from ITs, and the removal efficiency Cr, As, Pb, Cd, and Hg can reach 50.84 %, 26.72 %, 59.65 %, 49.75 % and 78.87 % in the 1 % ITs group, respectively.

In vitro studies on the effects of cryopreserved platelet-rich plasma on cells related to wound healing.

Platelet-rich plasma (PRP) holds promise as a therapeutic modality for wound healing; however, immediate utilization encounters challenges related to volume, concentration, and consistency. Cryopreservation emerges as a viable solution, preserving PRP's bioactive components and extending its shelf life. This study explores the practicality and efficacy of cryopreserved platelet-rich plasma (cPRP) in wound healing, scrutinizing both cellular mechanisms and clinical implications. Fresh PRP and cPRP post freeze-thaw underwent assessment in macrophage, fibroblast, and endothelial cell cultures. The impact of cPRP on active component release and cell behavior pertinent to wound healing was evaluated. Varied concentrations of cPRP (1%, 5%, 10%) were examined for their influence on cell polarization, migration, and proliferation. The results showed minimal changes in cPRP's IL-1ß levels, a slight decrease in PDGF-BB, and superior effects on macrophage M2 polarization and fibroblast migration, while no statistical significance was observed in endothelial cell angiogenesis and proliferation. Remarkably, 5% PRP exhibited the most significant stimulation among all cPRP concentrations, notably impacting cell proliferation, angiogenesis, and migration. The discussion underscores that cPRP maintains platelet phenotype and function over extended periods, with 5% cPRP offering the most favorable outcomes, providing a pragmatic approach for cold storage to extend post-thaw viability and amplify therapeutic effects.

What is the context? Platelet-rich plasma (PRP) is a potential bioactive material for wound healing, but using it immediately faces issues like volume, concentration, and consistency.Low-temperature freezing is a method employed to preserve PRP. However, the current understanding of the effects of the freezing-thawing process on the components of PRP and its impact on cells relevant to wound healing remains unclear.What is new? This study explores the feasibility and effectiveness of using cryopreserved PRP at −80°C for promoting wound healing. This research stands out for its focus on cellular responses and practical implications in therapeutic contexts.To understand their distinct impact on different cell types relevant to wound healing, the study meticulously examined various final concentrations of cPRP (1%, 5%, 10%).The study identified the superior effects of 5% cPRP on crucial cellular activities, notably in cell polarization, proliferation, angiogenesis, and migration.What is the impact? Low-temperature freezing can be considered an effective method for PRP preservation.Some bioactive components in cPRP exhibit subtle changes; however, these changes result in better effects on certain cell types related to healing.The study illustrates that all concentrations of cPRP effectively enhance cell proliferation, migration, and differentiation, emphasizing the comparable efficacy of cryopreserved PRP to non-cryopreserved PRP.

Novel lactylation-related signature to predict prognosis for pancreatic adenocarcinoma.

BACKGROUND: Lactate, previously considered a metabolic byproduct, is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment. Further investigations confirmed that lactate is a primary regulator, introducing recently described post-translational modifications of histone and non-histone proteins, termed lysine lactylation. Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation. However, our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited. AIM: To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer. METHODS: RNA-seq and clinical data of pancreatic adenocarcinoma (PDAC) were obtained from the GTEx (Genotype-Tissue Expression) and TCGA (The Cancer Genome Atlas) databases via Xena Explorer, and GSE62452 datasets from GEO. Data on lactylation-related genes were obtained from publicly available sources. Differential expressed genes (DEGs) were acquired by using R package "DESeq2" in R. Univariate COX regression analysis, LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model. Further analyses, including functional enrichment, ESTIMATE, and CIBERSORT, were performed to analyze immune status and treatment responses in patients with pancreatic cancer. PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention; two PDAC cell lines with the most pronounced lactylation were selected. Subsequently, RT-PCR was employed to assess the expression of LRGs genes; SLC16A1, which showed the highest expression, was selected for further investigation. SLC16A1-mediated lactylation was analyzed by immunofluorescence, lactate production analysis, colony formation, transwell, and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells. In vivo validation was performed using an established tumor model. RESULTS: In this study, we successfully identified 10 differentially expressed lactylation-related genes (LRGs) with prognostic value. Subsequently, a lactylation-related signature was developed based on five OS-related lactylation-related genes (SLC16A1, HLA-DRB1, KCNN4, KIF23, and HPDL) using Lasso Cox hazard regression analysis. Subsequently, we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma. A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups. Furthermore, we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport. Both in vivo and in vitro experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression, indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma. CONCLUSION: We constructed a novel lactylation-related prognostic signature to predict OS, immune status, and treatment response of patients with pancreatic adenocarcinoma, providing new strategic directions and antitumor immunotherapies.

Throat microbiota drives alterations in pulmonary alveolar microbiota in patients with septic ARDS.

OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.

Nanoparticle Polymeric Micellar Paclitaxel Versus Paclitaxel for Patients with Advanced Gastric Cancer.

BACKGROUND: Nanoparticle polymeric micellar paclitaxel (NPMP) is a novel Cremophor EL (CrEL)-free nanoparticle micellar formulation of paclitaxel. This study evaluated the efficacy and toxicity of NPMP in the treatment of patients with advanced gastric cancer (AGC). METHODS: Patients with histologically confirmed AGC in Jiangsu Cancer Hospital were retrospectively collected and divided into two groups. Patients in group A received NPMP at a total dose of 360 mg/m2 each cycle, and patients in group B were given paclitaxel at a dose of 210 mg/m2 each cycle. In addition, all patients received 5-fluorouracil at a dose of 0.75 g/m2 on days 1-4 and leucovorin at a dose of 200 mg/m2 on days 1-4 for at least 2 cycles. RESULTS: From January 2021 to May 2023, 63 patients (32 in group A and 31 in group B) could be evaluated for treatment response. A marked disparity in the overall response was observed between groups A and B, indicating statistical significance. The overall response rate was 31% in group A (10/32) and 10% in group B (3/31) (P = 0.034). Disease control rate was 91% in group A (29/32) and 81% in group B (25/31) (P = 0.440). No statistically significant difference in adverse reactions was observed between the two groups. However, the incidence of anemia, leucopenia, nausea, vomiting, diarrhea, liver dysfunction, and allergy in group A was notably lower than that in group B. CONCLUSIONS: NPMP combined chemotherapy offers a new, active, and safe treatment for patients with AGC.

Global trends of acupuncture clinical research on analgesia from 2010 to 2023: a bibliometric and visualization analysis.

Objective: Acupuncture, acknowledged as a potent non-pharmacological therapy, is frequently employed to alleviate pain. Despite its widespread use, there has been a lack of overarching bibliometric analysis of clinical research on acupuncture analgesia. We aimed to summarize current patterns, hotspots, and development trends in this field through bibliometric analysis. Methods: This study evaluates academic publications retrieved from the Web of Science database (2010.01-2023.09) concerning acupuncture analgesia in clinical settings. All primary and secondary studies on humans were included. To track global developmental trends, we employed several software for analyzing annual publication volumes, countries/regions, institutions, authors, cited authors, journals, cited journals, references, and keywords and to draw collaborative networks and reference co-citation network maps. Results: The final search encompassed 7,190 relevant studies, including 1,263 randomized controlled trials (RCTs) and 1,293 systematic reviews and meta-analyses. The results indicated a gradual increase in the number of annual publications on acupuncture analgesia in clinical practice. Among countries and institutions, China (2,139) and Chengdu University of Traditional Chinese Medicine (258) ranked first. Liang FR (89 articles) was the most prolific author, while MacPherson H (604) was the most cited author. MEDICINE (455) was the most productive journal, and Pain (2,473/0.20) ranked first in both the frequency and centrality of cited journals. Notably, the most frequently cited reference was a systematic review of individual patient data on acupuncture carried out for chronic pain that was published by Vickers Andrew J in 2012 (156). Burst analysis identified frontier research areas for 2010-2020, encompassing network meta-analysis, case reports, dry needling, lumbar disc herniation, cancer, post-herpetic neuralgia, insomnia, and bibliometric analysis. Conclusion: This study outlines current trends and potential future research hotspots in clinical acupuncture analgesia over the past decade. Findings emphasize the necessity for enhanced international collaboration to improve research output and translation.

Application of propofol-remifentanil intravenous general anesthesia combined with regional block in pediatric ophthalmic surgery.

OBJECTIVE: The aim of this study is to observe the anesthetic effect and safety of intravenous anesthesia without muscle relaxant with propofol-remifentanil combined with regional block under laryngeal mask airway in pediatric ophthalmologic surgery. METHODS: A total of 90 undergoing ophthalmic surgery were anesthetized with general anesthesia using the laryngeal mask airway without muscle relaxant. They were randomly divided into two groups: 45 children who received propofol-remifentanil intravenous anesthesia combined with regional block (LG group), and 45 children who received total intravenous anesthesia (G group). The peri-operative circulatory indicators, awakening time after general anesthesia, postoperative analgesic effect and the incidence of anesthesia-related adverse events were respectively compared between the two groups. RESULTS: All the children successfully underwent the surgical procedure. The awakening time after general anesthesia and removal time of laryngeal mask were significantly shorter in the LG group than in the G group (P < 0.05). There was no statistically significant difference in the heart rates in the perioperative period between the two groups (P > 0.05). There was no statistically significant difference in the incidence of intraoperative physical response, respiratory depression, postoperative nausea and vomiting (PONV) and emergence agitation (EA) between the two groups (P > 0.05). The pain score at the postoperative hour 2 was lower in the LG group than in the G group (P < 0.05). CONCLUSION: Propofol-remifentanil intravenous anesthesia combined with long-acting local anesthetic regional block anesthesia, combined with laryngeal mask ventilation technology without muscle relaxants, can be safely used in pediatric eye surgery to achieve rapid and smooth recovery from general anesthesia and better postoperative analgesia. This anesthesia scheme can improve the comfort and safety of children in perioperative period, and has a certain clinical popularization value.

Mitochondria-targeting peptide SS-31 attenuates ferroptosis via inhibition of the p38 MAPK signaling pathway in the hippocampus of epileptic rats.

Ferroptosis is a newly identified form of non-apoptotic regulated cell death (RCD) andplaysanimportantrole in epileptogenesis. The p38 mitogen-activated protein kinase (p38 MAPK) pathway has been confirmed to be involved in ferroptosis. The mitochondria-targeting antioxidant Elamipretide (SS-31) can reduce the generation of lipid peroxidation and the buildup of reactive oxygen species (ROS). Collectively, our present study was to decipher whether SS-31 inhibits ferroptosis via the p38 MAPK signaling pathway in the rat epilepsy model induced by pilocarpine (PILO).Adult male Wistar rats were randomly divided into four groups: control group (CON group), epilepsy group (EP group), SS-31 treatment group (SS group), and p38 MAPK inhibitor (SB203580) treatment group (SB group). Our results demonstrated that the rat hippocampal neurons after epilepsy were followed by accumulated iron and malondialdehyde (MDA) content, upregulated phosphorylated p38 MAPK protein (P-p38) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels, reduced glutathione peroxidase 4 (Gpx4) content, and depleted glutathione (GSH) activity. Morphologically, mitochondrial ultrastructural damage under electron microscopy was manifested by a partial increase in outer membrane density, disappearance of mitochondrial cristae, and mitochondrial shrinkage. SS-31 and SB203580 treatment blocked the initiation and progression of ferroptosis in the hippocampus of epileptic rats via reducing the severity of epileptic seizures, reversing the expression of Gpx4, P-p38 , decreasing the levels of iron and MDA, as well as increasing the activity of GSH and Nrf2. To summarize, our findings proved that ferroptosis was coupled with the pathology of epilepsy, and SS-31 can inhibit PILO-induced seizures by preventing ferroptosis, which may be connected to the inhibition of p38 MAPK phosphorylation, highlighting the potential therapeutic value for targeting ferroptosis process in individuals with seizure-related diseases.

[Comparison of Two Methods With a Left-Sided Double-Lumen Tube for Endobronchial Intubation].

Objective To compare the success rates of two methods for endobronchial intubation:the left-sided double-lumen tube(DLT) rotated 90° counter-clockwise with the patient head at the mid positon and the tube rotated 180° counter-clockwise with the patient head turned to the right. Methods Six hundred and forty-eight patients were enrolled in this study,who were to undergo elective thoracic surgery by left-sided DLT intubation in the Peking Union Medical College Hospital from December 2021 to June 2022.They were randomized into a 90° group and a 180° group,with 324 patients in each group.In the 90° group,with the patient head kept at the mid position,the left-sided DLT was advanced until the bronchial cuff passed the vocal cords and then rotated 90° counter-clockwise.In the 180°group,with the left mandible angle of each patient in the straight line with the sternum,the tube was advanced until the bronchial cuff passed the vocal cords and then rotated 180° counter-clockwise.The intubation success rate and the intubation-related complications such as carina mucosal injuries were compared between the two groups. Results The 648 patients included 336 males and 312 females,with the age ranging from 39.0 to 75.0 years old and the average age of(54.6±9.0) years old.The success rate of first intubation was 80.3% in the 90° group and 75.0% in the 180° group,which showed no significant difference(P=0.109).The success rate of second intubation was higher in the 180° group than in the 90° group(P<0.001).The rate of carina mucosal injuries was 23.8% in the 90° group and 25.6% in the 180° group,which showed no significant difference(P=0.585). Conclusions Compared with the conventional method(90°),the intubation of the left-sided DLT rotated 180° counter-clockwise with the patient head turned to the right cannot improve the success rate of the first intubation.However,it could improve the success rate of reintubation as a remedy.

Architecture of symbiotic dinoflagellate photosystem I-light-harvesting supercomplex in Symbiodinium.

Symbiodinium are the photosynthetic endosymbionts for corals and play a vital role in supplying their coral hosts with photosynthetic products, forming the nutritional foundation for high-yield coral reef ecosystems. Here, we determine the cryo-electron microscopy structure of Symbiodinium photosystem I (PSI) supercomplex with a PSI core composed of 13 subunits including 2 previously unidentified subunits, PsaT and PsaU, as well as 13 peridinin-Chl a/c-binding light-harvesting antenna proteins (AcpPCIs). The PSI-AcpPCI supercomplex exhibits distinctive structural features compared to their red lineage counterparts, including extended termini of PsaD/E/I/J/L/M/R and AcpPCI-1/3/5/7/8/11 subunits, conformational changes in the surface loops of PsaA and PsaB subunits, facilitating the association between the PSI core and peripheral antennae. Structural analysis and computational calculation of excitation energy transfer rates unravel specific pigment networks in Symbiodinium PSI-AcpPCI for efficient excitation energy transfer. Overall, this study provides a structural basis for deciphering the mechanisms governing light harvesting and energy transfer in Symbiodinium PSI-AcpPCI supercomplexes adapted to their symbiotic ecosystem, as well as insights into the evolutionary diversity of PSI-LHCI among various photosynthetic organisms.

Ntsr1 contributes to pulmonary hypertension by enhancing endoplasmic reticulum stress via JAK2-STAT3-Thbs1 signaling.

Pulmonary hypertension (PH) is a severe clinical syndrome with pulmonary vascular remodeling and poor long-term prognosis. Neurotensin receptor 1 (Ntsr1), serve as one of the G protein-coupled receptors (GPCRs), implicates in various biological processes, but the potential effects of Ntsr1 in PH development are unclear. The Sugen/Hypoxia (SuHx) or monocrotaline (MCT) induced rat PH model was used in our study and the PH rats showed aggravated pulmonary artery remodeling and increased right ventricular systolic pressure (RVSP). Our results revealed that Ntsr1 induced endoplasmic reticulum (ER) stress response via ATF6 activation contributed to the development of PH. Moreover, RNA-sequencing (RNA-seq) and phosphoproteomics were performed and the Ntsr1-JAK2-STAT3-thrombospondin 1 (Thbs1)-ATF6 signaling was distinguished as the key pathway. In vitro, pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition showed enhanced proliferation and migration properties, which could be inhibited by Ntsr1 knockdown, JAK2 inhibitor (Fedratinib) treatment, STAT3 inhibitior (Stattic) treatment, Thbs1 knockdown or ATF6 knockdown. In addition, adeno-associated virus 1 (AAV1) were used to knockdown the expression of Ntsr1, Thbs1 or ATF6 in rats and reversed the phenotype of PH. In summary, our results reveal that Ntsr1-JAK2-STAT3-Thbs1 pathway can induce enhanced ER stress via ATF6 activation and increased PASMC proliferation and migration capacities, which can be mechanism of the pulmonary artery remodeling and PH. Targeting Ntsr1 might be a novel therapeutic strategy to ameliorate PH.

Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.

Comprehensive consideration of multiple determinants from evidence to recommendations in guidelines for most traditional Chinese medicine was suboptimal: a systematic review.

BACKGROUND: The overall comprehensive consideration of the factors influencing the recommendations in the traditional Chinese medicine (TCM) guidelines remains poorly studied. This study systematically evaluate the factors influencing recommendations formation in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) clinical practice guidelines (CPGs) and TCM CPGs. METHODS: This was a methodological review in which we searched six databases and multiple related websites. The GRADE CPGs were identified as the guidelines developed by the GRADE Working Group or the two Co-Chairs. For the TCM CPGs, we randomly selected guidelines that were published by the TCM or integrative medicine academic societies from China mainland (published by the TCM or integrative medicine academic societies of China mainland). Two reviewers independently screened and extracted data. We included CPGs published in 2018-2022. We extracted information on the influencing factors of evidence to recommendation and conducted the analyses using descriptive statistics and calculated the proportion of relevant items by IBM SPSS Statistics and Microsoft Excel to compare the differences between the GRADE CPGs and the TCM CPGs. RESULTS: Forty-five GRADE CPGs (including 912 recommendations) and 88 TCM CPGs (including 2452 recommendations) were included. TCM recommendations mainly considered the four key determinants of desirable anticipated effects, undesirable anticipated effects, balance between desirable and undesirable effects, certainty of evidence, with less than 20% of other dimensions. And TCM CPGs presented more strong recommendations (for or against) and inappropriate discordant recommendations than GRADE CPGs. GRADE CPGs were more comprehensive considered about the factors affecting the recommendations, and considered more than 70% of all factors in the evidence to recommendation. CONCLUSIONS: The TCM CPGs lack a comprehensive consideration of multiple influencing determinants from evidence to recommendations. In the future, the correct application of the GRADE approaches should be emphasized.

Up-to-date quality survey and evaluation of neonatal screening programs in China.

AIMS: To thoroughly evaluate the quality of the entire process of neonatal screening (NBS) in China. METHODS: We collected survey questionnaires from 54.4% (135/248) of NBS institutions in China and conducted on-site visits to 20 of these facilities to validate the data. The quality performance of the institutions was evaluated, and differences across various factors were analysed. RESULTS: Merely 62.5% of the provinces had acceptable performance in neonatal screening. Institutions with limited staff were more prone to organizational management shortcomings. Institutions in provinces with a per capita GDP below 10,000 USD exhibited lower quality control levels than those with a per capita GDP between 10,000 and 15,000 USD. Obstetrics departments have a lower awareness of quality control compared to other blood collection facilities. CONCLUSIONS: A nationwide, comprehensive quality control system for continuous enhancements in quality management, screening, diagnosis, and treatment is imperative to ensure prompt diagnosis and intervention.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Defining the biogeographical map and potential bacterial translocation of microbiome in human 'surface organs'.

The microbiome in a specific human organ has been well-studied, but few reports have investigated the multi-organ microbiome as a whole. Here, we aim to analyse the intra-individual inter-organ and intra-organ microbiome in deceased humans. We collected 1608 samples from 53 sites of 7 surface organs (oral cavity, esophagus, stomach, small intestine, appendix, large intestine and skin; n = 33 subjects) and performed microbiome profiling, including 16S full-length sequencing. Microbial diversity varied dramatically among organs, and core microbial species co-existed in different intra-individual organs. We deciphered microbial changes across distinct intra-organ sites, and identified signature microbes, their functional traits, and interactions specific to each site. We revealed significant microbial heterogeneity between paired mucosa-lumen samples of stomach, small intestine, and large intestine. Finally, we established the landscape of inter-organ relationships of microbes along the digestive tract. Therefore, we generate a catalogue of bacterial composition, diversity, interaction, functional traits, and bacterial translocation in human at inter-organ and intra-organ levels.