The effects of food provisioning on the gut microbiota community and antibiotic resistance genes of Yunnan snub-nosed monkey.

Yunnan snub-nosed monkeys (Rhinopithecus bieti) are the highest elevation lived non-human primate, and their survival has been threatened for decades. To promote their population growth, a reserve provides a typical monkey population with supplemental food. However, the influences of this food provisioning on their gut microbiota and antibiotic resistance genes (ARGs) were unknown. Therefore, we investigated the gut microbiota and ARGs of the food-provisioned monkey population compared with another wild foraging population. We found that food provisioning significantly increased the gut microbiota diversity and changed the community composition, particularly increased both the Firmicutes abundance and Firmicutes/Bacteroidetes ratio. Meanwhile, the food provisioning decreased the complex and stable gut microbiota network. KEGG functions were also influenced by food provisioning, with wild foraging monkeys showing higher functions of metabolism and genetic information processing, especially the carbohydrate metabolism, while food-provisioned monkeys exhibited increased environmental information processing, cellular processes, and organismal systems, including valine, leucine, and isoleucine degradation. In addition, food provisioning increased the abundance of ARGs in the gut microbiota, with most increasing the abundance of bacA gene and changing the correlations between specific ARGs and bacterial phyla in each population. Our study highlights that even food provisioning could promote wildlife nutrient intake, and it is necessary to pay attention to the increased ARGs and potential effects on gut microbiota stability and functions for this human conservation measure.

Advances in the study of microparticles in diabetic retinopathy.

Diabetic retinopathy (DR) is one of the common diabetic microangiopathies, which severely impairs vision in diabetic population. The underlying mechanisms regarding the development of DR are not fully understood, and there is a lack of biomarkers to guide clinical, assessment of disease progression. Recently researchers have found that microparticles (MP) and its bioactive molecules are involved in the development of DR. MP is widely distributed in the circulation and can exert autocrine and paracrine benefits in intercellular signalling, provide a catalytic platform for the thrombospondin complex to promote coagulation, and promote the accumulation of reactive oxygen species to cause endothelial damage. MP interacts with advanced glycosylation end products (AGE) and AGE receptor (RAGE) to activate inflammatory pathways. MP carries a variety of miRNAs that regulate the vascular endothelial growth factor generation pathway. MP has also been applied to the exploration of mesenchymal stromal cell replacement therapy to treat DR. In a word, MP provides new ideas for the study of DR. MP has emerged as a marker to assess the progression of DR. As a potential therapeutic target, MP also has considerable research value.

Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease: A meta-analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is commonly utilized as a prognostic indicator in end-stage liver disease (ESLD), encompassing conditions like liver failure and decompensated cirrhosis. Nevertheless, some studies have contested the prognostic value of NLR in ESLD. AIM: To investigate the ability of NLR to predict ESLD. METHODS: Databases, such as Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Weipu, and Wanfang, were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD. Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1. RESULTS: A total of thirty studies involving patients with end-stage liver disease (ESLD) were included in the evaluation. Among the pooled results of eight studies, it was observed that the Neutrophil-to-Lymphocyte Ratio (NLR) was significantly higher in non-survivors compared to survivors (random-effects model: standardized mean difference = 1.02, 95% confidence interval = 0.67-1.37). Additionally, twenty-seven studies examined the associations between NLR and mortality in ESLD patients, reporting either hazard ratios (HR) or odds ratios (OR). The combined findings indicated a link between NLR and ESLD mortality (random-effects model; univariate HR = 1.07, 95%CI = 1.05-1.09; multivariate HR = 1.07, 95%CI = 1.07-1.09; univariate OR = 1.29, 95%CI = 1.18-1.39; multivariate OR = 1.29, 95%CI = 1.09-1.49). Furthermore, subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality, with Asian studies demonstrating a more pronounced effect. CONCLUSION: Increased NLR in patients with ESLD is associated with a higher risk of mortality, particularly in Asian patients. NLR is a useful prognostic biomarker in patients with ESLD.

Effects of dietary selenized glucose on intestinal microbiota and tryptophan metabolism in rats: Assessing skatole reduction potential.

3-Methylindole (Skatole), a degradation product of tryptophan produced by intestinal microbial activity, significantly contributes to odor nuisance. Its adverse effects on animal welfare, human health, and environmental pollution have been noted. However, it is still unclear whether the intestinal microbiota mediates the impact of selenium (Se) on skatole production and what the underlying mechanisms remain elusive. A selenized glucose (SeGlu) derivative is a novel organic selenium compound. In this study, a diverse range of dietary SeGlu-treated levels, including SeGlu-deficient (CK), SeGlu-adequate (0.15 mg Se per L), and SeGlu-supranutritional (0.4 mg Se per L) conditions, were used to investigate the complex interaction of SeGlu on intestinal microbiome and serum metabolome changes in male Sprague-Dawley (SD) rats. The study showed that SeGlu supplementation enhanced the antioxidant ability in rats, significantly manifested in the increases of the activity of catalase (CAT) and glutathione peroxidase (GSH-Px), while no change in the level of malonaldehyde (MDA). Metagenomic sequencing analysis verified that the SeGlu treatment group significantly increased the abundance of beneficial microorganisms such as Clostridium, Ruminococcus, Faecalibacterium, Lactobacillus, and Alloprevotella while reducing the abundance of opportunistic pathogens such as Bacteroides and Alistipes significantly. Further metabolomic analysis revealed phenylalanine, tyrosine, and tryptophan biosynthesis changes in the SeGlu treatment group. Notably, the biosynthesis of indole, a critical pathway, was affected by SeGlu treatment, with several crucial enzymes implicated. Correlation analysis demonstrated strong associations between specific bacterial species - Treponema, Bacteroides, and Ruminococcus, and changes in indole and derivative concentrations. Moreover, the efficacy of SeGlu-treated fecal microbiota was confirmed through fecal microbiota transplantation, leading to a decrease in the concentration of skatole in rats. Collectively, the analysis of microbiota and metabolome response to diverse SeGlu levels suggests that SeGlu is a promising dietary additive in modulating intestinal microbiota and reducing odor nuisance in the livestock and poultry industry.

The relationship between lateral femoral condyle ratio measured by MRI and anterior cruciate ligament injury.

Background: Previous studies have shown that the lateral femoral condyle ratio (LFCR) measured by X-ray has a significant relationship with the anterior cruciate ligament (ACL) injury. However, few relevant studies have been performed on LFCR measured by magnetic resonance imaging (MRI). Purpose: (1) To evaluate the relationship between LFCR measured by MRI and ACL injury or rerupture. (2) To compare the LFCR measured by MRI with existing bony morphological risk factors and screen out the most predictive risk factors for primary ACL injury or rerupture. Study Design: Cohort study; Level of evidence, 3. Methods: Totally 147 patients who underwent knee arthroscopic surgery from 2015 to 2019 with minimum follow-up of 48 months were retrospectively evaluated. Patients were placed into three groups: 1) the control group of patients with simple meniscus tears without ligament injury; 2) the primary noncontact ACL injury group; 3) ACL rerupture group (ACL reconstruction failure). The LFCR measured by MRI and other previous known risk factors associated with MRI (notch width index, medial tibial slope, lateral tibial slope, medial tibial depth, lateral tibial height) were performed to evaluate their predictive value for ACL injury and rerupture. All the risk factors with p < 0.01 according to univariate analysis were included in the logistic regression models. Receiver operating characteristic (ROC) curves were analyzed for sensitivity, specificity, cut-off, and area under the curve (AUC). Z tests were used to compare the AUC values. Results: The LFCR measured by MRI was obviously higher in primary ACL injury group (0.628 ± 0.020) and in ACL rerupture group (0.625 ± 0.021) than that in the control group (0.593 ± 0.030). The best risk factor was the LFCR with a cut-off of 0.602 (AUC, 0.818; 95% CI, 0.748-0.878; sensitivity, 90%; specificity, 66%). When combined with lateral tibial slope (cutoff, 7°) and lateral tibial height (cutoff, 3.6 mm), the diagnostic performance was improved significantly (AUC, 0.896; 95% CI, 0.890-0.950; sensitivity, 87%; specificity, 80%). Conclusion: The increased LFCR measured by MRI was associated with a significantly higher risk for ACL injury or rerupture. The combination of LFCR, lateral tibial slope and lateral tibial height were the most predictive risk factors. This may help clinicians identify susceptible individuals and allow precision approaches for better prevention, treatment and management of this disease.

Perioperative versus adjuvant S-1 plus oxaliplatin chemotherapy for stage II/III resectable gastric cancer (RESONANCE): a randomized, open-label, phase 3 trial.

Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361).

Relationship between lymphocytes and idiopathic macular hole.

BACKGROUND: An idiopathic macular hole (IMH) is a full-thickness anatomic defect extending from the internal limiting membrane to the photoreceptor layer of the macula without any known cause. Recently, clinical laboratory markers of systemic inflammatory status derived from complete blood counts have been evaluated in ocular diseases. This study aimed to explore whether they could predict the development and progression of IMHs. METHODS: A retrospective review of 36 patients with IMH and 36 sex-and-age-matched patients with cataracts was conducted. We collected complete blood counts of all participating individuals and calculated systemic immunoinflammatory indicators. The maximum base diameter of the IMH (BD), minimum diameter of the IMH (MIN), height of the IMH (H), area of the intraretinal cyst (IRC), and curve lengths of the detached photoreceptor arms were measured on optical coherence tomography (OCT) images. We used these values to calculate the macular hole index (MHI), tractional hole index (THI), diameter hole index (DHI), hole form factor (HFF), and macular hole closure index (MHCI). We performed a receiver operating characteristic (ROC) curve analysis of 30 patients with IMH who were followed up 1 month after surgery. RESULTS: Lymphocyte counts were significantly higher in the IMH group. No other significant differences were observed between the IMH and control groups. Lymphocyte counts in the IMH group were significantly negatively correlated with MIN and BD and were significantly positively correlated with MHI, THI, and MHCI. However, lymphocyte counts were not significantly correlated with H, IRC, DHI, and HFF. In the ROC analysis, BD, MIN, MHI, THI, and MHCI were significant predictors of anatomical outcomes. According to the cut-off points of the ROC analysis, lymphocyte counts were compared between the above-cut-off and below-cut-off groups. Lymphocyte counts were significantly higher in the MIN ≤ 499.61 µm, MHI ≥ 0.47, THI ≥ 1.2, and MHCI ≥ 0.81 groups. There were no significant differences between the above-cut-off and below-cut-off BD groups. CONCLUSIONS: Although inflammation may not be an initiating factor, it may be involved in IMH formation. Lymphocytes may play a relatively important role in tissue repair during the developmental and postoperative recovery phases of IMH.

admetSAR3.0: a comprehensive platform for exploration, prediction and optimization of chemical ADMET properties.

Absorption, distribution, metabolism, excretion and toxicity (ADMET) properties play a crucial role in drug discovery and chemical safety assessment. Built on the achievements of admetSAR and its successor, admetSAR2.0, this paper introduced the new version of the series, admetSAR3.0, as a comprehensive platform for chemical ADMET assessment, including search, prediction and optimization modules. In the search module, admetSAR3.0 hosted over 370 000 high-quality experimental ADMET data for 104 652 unique compounds, and supplemented chemical structure similarity search function to facilitate read-across. In the prediction module, we introduced comprehensive ADMET endpoints and two new sections for environmental and cosmetic risk assessments, empowering admetSAR3.0 to provide prediction for 119 endpoints, more than double numbers compared to the previous version. Furthermore, the advanced multi-task graph neural network framework offered robust and reliable support for ADMET prediction. In particular, a module named ADMETopt was added to automatically optimize the ADMET properties of query molecules through transformation rules or scaffold hopping. Finally, admetSAR3.0 provides user-friendly interfaces for multiple types of input data, such as SMILES string, chemical structure and batch molecule file, and supports various output types, including digital, chart displays and file downloads. In summary, admetSAR3.0 is anticipated to be a valuable and powerful tool in drug discovery and chemical safety assessment at http://lmmd.ecust.edu.cn/admetsar3/.

Unraveling the Ligand-Binding Sites of CYP3A4 by Molecular Dynamics Simulations with Solvent Probes.

Cytochrome P450 3A4 (CYP3A4) is one of the most important drug-metabolizing enzymes in the human body and is well known for its complicated, atypical kinetic characteristics. The existence of multiple ligand-binding sites in CYP3A4 has been widely recognized as being capable of interfering with the active pocket through allosteric effects. The identification of ligand-binding sites other than the canonical active site above the heme is especially important for understanding the atypical kinetic characteristics of CYP3A4 and the intriguing association between the ligand and the receptor. In this study, we first employed mixed-solvent molecular dynamics (MixMD) simulations coupled with the online computational predictive tools to explore potential ligand-binding sites in CYP3A4. The MixMD approach demonstrates better performance in dealing with the receptor flexibility compared with other computational tools. From the sites identified by MixMD, we then picked out multiple sites for further exploration using ensemble docking and conventional molecular dynamics (cMD) simulations. Our results indicate that three extra sites are suitable for ligand binding in CYP3A4, including one experimentally confirmed site and two novel sites.

Evaluation of machine learning models for cytochrome P450 3A4, 2D6, and 2C9 inhibition.

Cytochrome P450 (CYP) enzymes are involved in the metabolism of approximately 75% of marketed drugs. Inhibition of the major drug-metabolizing P450s could alter drug metabolism and lead to undesirable drug-drug interactions. Therefore, it is of great significance to explore the inhibition of P450s in drug discovery. Currently, machine learning including deep learning algorithms has been widely used for constructing in silico models for the prediction of P450 inhibition. These models exhibited varying predictive performance depending on the use of machine learning algorithms and molecular representations. This leads to the difficulty in the selection of appropriate models for practical use. In this study, we systematically evaluated the conventional machine learning and deep learning models for three major P450 enzymes, CYP3A4, CYP2D6, and CYP2C9 from several perspectives, such as algorithms, molecular representation, and data partitioning strategies. Our results showed that the XGBoost and CatBoost algorithms coupled with the combined fingerprint/physicochemical descriptor features exhibited the best performance with Area Under Curve (AUC)  of 0.92, while the deep learning models were generally inferior to the conventional machine learning models (average AUC reached 0.89) on the same test sets. We also found that data volume and sampling strategy had a minor effect on model performance. We anticipate that these results are helpful for the selection of molecular representations and machine learning/deep learning algorithms in the P450 model construction and the future model development of P450 inhibition.

Effects of the elongated needling combined with routine acupuncture therapy in the patients with post-stroke hemiplegia and central pain： a randomized controlled trial. / èŠ’é’ˆé€åˆºè”åˆä½“é’ˆæ²»ç–—å¯¹ä¸­é£ŽåŽåç˜«ä¼´ä¸­æž¢æ€§ç–¼ç—›æ‚£è€ çš„ä¸´åºŠç–—æ•ˆè§‚å¯Ÿï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To investigate the effects of the elongated needling at the points of hand and foot yang meridians and the Governor Vessel combined with the routine acupuncture therapy on pain, balance function and muscle strength of the patients with post-stroke hemiplegia and central post-stroke pain (CPSP), and to investigate whether its therapeutic mechanism is related to antioxidant damage. METHODS: Ninety-four patients with post-stroke hemiplegia and CPSP admitted from March 2020 to September 2021 were divided into a trial group (47 cases, 1 cases dropped out) and a control group (47 cases 3 cases dropped out). In the control group, the rehabilitation exercise combined with routine acupuncture therapy was used, and in the trial group, on the base of the treatment as the control group, the elongated needling at the points of hand and foot yang meridians and the Governor Vessel was supplemented. In the two groups, the treatment was given once daily, and 1 course of treatment was composed of 14 days, a total of 6 courses were required in the trial. Separately, before treatment, and 1, 2 and 3 months after treatment, between two groups, the score of visual analogue scale (VAS) and that of Berg balance scale (BBS), as well as muscle strength were compared；the neural function was evaluated using the national institutes of health stroke scale (NIHSS) and the serum contents of nitricoxide synthase (NOS), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by ELISA in the patients. RESULTS: Compared with those before treatment, VAS score and NIHSS score were all decreased (P<0.05) in the trial and the control group after 1 month, 2 months and 3 months of treatment, and BBS score was increased (P<0.05)；and the case proportion of muscle strength grade 4 and 5 was higher (P<0.05) in the trial group. In the control group, the proportion of grade 4 increased after treatment for 2 months (P<0.05), and that of grade 4 and 5 increased after treatment for 3 months (P<0.05). The serum contents of NOS and SOD were increased (P<0.05), and MDA was decreased (P<0.05) after 3 months of treatment in the two groups. In comparison with the control group at the same time point, VAS score and NIHSS score were lower (P<0.05), BBS score higher (P<0.05) and the muscle strength grade was improved (P<0.05, P<0.01) after 1, 2 and 3 months of treatment, respectively；and the serum contents of NOS and SOD increased (P<0.05), and MDA decreased (P<0.05) after 3 months of treatment in the trial group. CONCLUSIONS: The elongated needling at the points of hand and foot yang meridians and the Governor Vessel, combined with the routine acupuncture therapy alleviates CPSP, improves balance and muscle strength and promotes the recovery of neural function in the patients with post-stroke hemiplegia, the mechanism may be related to antioxidant damage.

High-frequency neural activity dysregulation is associated with sleep and psychiatric disorders in BMAL1-deficient animal models.

Sleep disturbance led by BMAL1-deficiency has been recognized both in rodent and non-human primate models. Yet it remained unclear how their diurnal brain oscillations were affected upon BMAL1 ablation and what caused the discrepancy in the quantity of sleep between the two species. Here, we investigated diurnal electroencephalographs of BMAL1-deficient mice and cynomolgus monkeys at young adult age and uncovered a shared defect of dysregulated high-frequency oscillations by Kullback-Leibler divergence analysis. We found beta and gamma oscillations were significantly disturbed in a day versus night manner in BMAL1-deficient monkeys, while in mice the beta band difference was less evident. Notably, the dysregulation of beta oscillations was particularly associated with psychiatric behaviors in BMAL1-deficient monkeys, including the occurrence of self-injuring and delusion-like actions. As such psychiatric phenotypes were challenging to uncover in rodent models, our results offered a unique method to study the correlation between circadian clock dysregulation and psychiatric disorders.

[Endoscopic ultrasonography features of benign esophageal stenosis in children]. / å„¿ç«¥é£Ÿç®¡è‰¯æ€§ç‹­çª„çš„è¶ å£°å† é•œç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the endoscopic ultrasonography (EUS) features of benign esophageal stenosis in children. METHODS: A retrospective analysis was conducted on the medical data of the children who were diagnosed with benign esophageal stenosis from February 2019 to February 2022. The clinical manifestations, EUS findings, and treatment outcome were analyzed to summarize the EUS features of benign esophageal stenosis in children. RESULTS: A total of 42 children with benign esophageal stenosis were included. Among these children, 19 (45%) had anastomotic stenosis after surgery for esophageal atresia, with unclear echogenic boundary of the esophageal walls and uneven thicknesses of the surrounding wall on EUS, and had 0-12 sessions of endoscopic treatment (average 2.1 sessions); 5 children (12%) had corrosive esophageal stenosis and 1 child (2%) had physical esophageal stenosis, with unclear stratification of the esophageal walls on EUS, and they had 2-9 sessions of endoscopic treatment (average 5.3 sessions); 1 child (2%) had patchy irregular hypoechoic areas of the esophageal walls on EUS and was diagnosed with tracheobronchial remnants with reference to pathology; 16 children (38%) had unexplained esophageal stenosis and unclear stratification of the esophageal walls on EUS, among whom 6 received endoscopic treatment. During follow-up, 95% (40/42) of the children had significant alleviation of the symptoms such as vomiting and dysphagia. CONCLUSIONS: For benign esophageal stenosis in children, EUS can help to evaluate the degree of esophageal wall involvement in esophageal stenosis lesions, possible etiologies, and the relationship between the esophagus and the lesion and provide an important basis for selecting treatment modality and avoiding complications, thereby helping to optimize the treatment regimen.

Large Polarization Near 50 µC/cm2 in a Single Unit Cell Layer SrTiO3.

The generally nonpolar SrTiO3 has attracted more attention recently because of its possibly induced novel polar states and related paraelectric-ferroelectric phase transitions. By using controlled pulsed laser deposition, high-quality, ultrathin, and strained SrTiO3 layers were obtained. Here, transmission electron microscopy and theoretical simulations have unveiled highly polar states in SrTiO3 films even down to one unit cell at room temperature, which were stabilized in the PbTiO3/SrTiO3/PbTiO3 sandwich structures by in-plane tensile strain and interfacial coupling, as evidenced by large tetragonality (∼1.05), notable polar ion displacement (0.019 nm), and thus ultrahigh spontaneous polarization (up to ∼50 µC/cm2). These values are nearly comparable to those of the strong ferroelectrics as the PbZrxTi1-xO3 family. Our findings provide an effective and practical approach for integrating large strain states into oxide films and inducing polarization in nonpolar materials, which may broaden the functionality of nonpolar oxides and pave the way for the discovery of new electronic materials.

Fospropofol disodium versus propofol for long-term sedation during invasive mechanical ventilation: A pilot randomized clinical trial.

STUDY OBJECTIVE: Fospropofol disodium is a propofol prodrug that is water-soluble and has a reduced risk of bacterial contamination and hypertriglyceridemia compared with propofol. Prior to implementing a large randomized trial, we investigated the feasibility, initial efficacy, and safety of fospropofol disodium compared with propofol in long-term mild-to-moderate sedation in intensive care units (ICUs). DESIGN: Single-centered, prospective, unblind, randomized, parallel-group clinical trial. SETTING: The general ICU of university-affiliated teaching hospital. PATIENTS: Adult patients (n = 60) expected to have mechanical ventilation for >24 h were enrolled and randomly assigned to the fospropofol or propofol group. INTERVENTIONS: The fospropofol group received continuous fospropofol disodium infusions and the propofol group received continuous propofol infusions. The sedation goal was a score of -3 to 0 on the Richmond Agitation and Sedation Scale (RASS). MEASUREMENTS: The primary outcome was the percentage of time spent in the target sedation range without rescue sedation. Safety outcomes were based on adverse events. Blood samples were collected to measure formate concentration in plasma. MAIN RESULTS: The median dose was 4.33 (IQR, 3.08-4.94) mg/kg/h in the fospropofol group and 1.96 (IQR, 1.44-2.94) mg/kg/h in the propofol group. The median percentage of time spent in the target RASS range without rescue sedation was identical in both groups, with 83.33% (IQR, 74.43%-100.00%) in the fospropofol group and 83.33% (IQR, 77.45%-100.00%) in the propofol group (p = 0.887). At least one adverse event was identifed in 23 (76.7%) fospropofol patients and 27 (90.0%) propofol patients. The most common adverse events were tachycardia and hypotension. No paresthesia, catheter-related bloodstream infection or propofol infusion syndrome in both groups was reported. Three patients in the fospropofol group had mild hypertriglyceridemia, and nine patients in propofol group had hypertriglyceridemia (mild in eight patients and moderate in one patient) (10% versus 30%, p = 0.104). The formate concentration in plasma was very low, and no significant difference was identified at any time point between the two groups. CONCLUSIONS: Fospropofol disodium appears to be a feasible, effective and safe sedative for patients receiving invasive mechanical ventilation with long-term sedation.

Cross-neutralizing antibody against emerging Omicron subvariants of SARS-CoV-2 in infection-naïve individuals with homologous BNT162b2 or BNT162b2(WT + BA.4/5) bivalent booster vaccination.

Since the emergence of SARS-CoV-2, different variants and subvariants successively emerged to dominate global virus circulation as a result of immune evasion, replication fitness or both. COVID-19 vaccines continue to be updated in response to the emergence of antigenically divergent viruses, the first being the bivalent RNA vaccines that encodes for both the Wuhan-like and Omicron BA.5 subvariant spike proteins. Repeated infections and vaccine breakthrough infections have led to complex immune landscapes in populations making it increasingly difficult to assess the intrinsic neutralizing antibody responses elicited by the vaccines. Hong Kong's intensive COVID-19 containment policy through 2020-2021 permitted us to identify sera from a small number of infection-naïve individuals who received 3 doses of the RNA BNT162b2 vaccine encoding the Wuhan-like spike (WT) and were boosted with a fourth dose of the WT vaccine or the bivalent WT and BA.4/5 spike (WT + BA.4/5). While neutralizing antibody to wild-type virus was comparable in both vaccine groups, BNT162b2 (WT + BA.4/BA.5) bivalent vaccine elicited significantly higher plaque neutralizing antibodies to Omicron subvariants BA.5, XBB.1.5, XBB.1.16, XBB.1.9.1, XBB.2.3.2, EG.5.1, HK.3, BA.2.86 and JN.1, compared to BNT162b2 monovalent vaccine. The single amino acid substitution that differentiates the spike of JN.1 from BA.2.86 resulted in a profound antigenic change.

MedChatZH: A tuning LLM for traditional Chinese medicine consultations.

Generative Large Language Models (LLMs) have achieved significant success in various natural language processing tasks, including Question-Answering (QA) and dialogue systems. However, most models are trained on English data and lack strong generalization in providing answers in Chinese. This limitation is especially evident in specialized domains like traditional Chinese medical QA, where performance suffers due to the absence of fine-tuning and high-quality datasets. To address this, we introduce MedChatZH, a dialogue model optimized for Chinese medical QA based on transformer decoder with LLaMA architecture. Continued pre-training on a curated corpus of Chinese medical books is followed by fine-tuning with a carefully selected medical instruction dataset, resulting in MedChatZH outperforming several Chinese dialogue baselines on a real-world medical dialogue dataset. Our model, code, and dataset are publicly available on GitHub (https://github.com/tyang816/MedChatZH) to encourage further research in traditional Chinese medicine and LLMs.

Progression of unfolded protein response and ferroptosis in angiogenesis.

Angiogenesis is the growth of new blood vessels on preexisting ones. It is the outcome of a multifactorial effect involving several cells, which can be brought on by different stress reactions.The accumulation of unfolded proteins in the endoplasmic reticulum occurs when cells are stressed due to environmental changes, where physical or chemical stimuli induce endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR), a homeostasis response designed to re-establish protein balance. Ferroptosis is a planned death of lipid peroxidation and anomalies in metabolism that is dependent on iron. Large concentrations of iron ions accumulate there, along with high concentrations of lipid peroxides and reactive oxygen species, all of which can contribute to the development of several diseases. Through the production of growth factors, adhesion factors, and inflammatory factors that trigger the start of angiogenesis, both UPR and Ferroptosis can be implicated in angiogenesis.To set the stage for further research on angiogenesis, this work concentrated on the effects of Ferroptosis and UPR on angiogenesis, respectively.

Epitaxial Strain Enhanced Ferroelectric Polarization toward a Giant Tunneling Electroresistance.

A substantial ferroelectric polarization is the key for designing high-performance ferroelectric nonvolatile memories. As a promising candidate system, the BaTiO3/La0.67Sr0.33MnO3 (BTO/LSMO) ferroelectric/ferromagnetic heterostructure has attracted a lot of attention thanks to the merits of high Curie temperature, large spin polarization, and low ferroelectric coercivity. Nevertheless, the BTO/LSMO heterostructure suffers from a moderate FE polarization, primarily due to the quick film-thickness-driven strain relaxation. In response to this challenge, we propose an approach for enhancing the FE properties of BTO films by using a Sr3Al2O6 (SAO) buffering layer to mitigate the interfacial strain relaxation. The continuously tunable strain allows us to illustrate the linear dependence of polarization on epitaxial strain with a large strain-sensitive coefficient of ∼27 µC/cm2 per percent strain. This results in a giant polarization of ∼80 µC/cm2 on the BTO/LSMO interface. Leveraging this large polarization, we achieved a giant tunneling electroresistance (TER) of ∼105 in SAO-buffered Pt/BTO/LSMO ferroelectric tunnel junctions (FTJs). Our research uncovers the fundamental interplay between strain, polarization magnitude, and device performance, such as on/off ratio, thereby advancing the potential of FTJs for next-generation information storage applications.

Early enteral nutrition versus early supplemental parenteral nutrition in patients undergoing major abdominal surgery: a secondary analysis of 2 randomized clinical trials.

BACKGROUND: The effect of early isoenergetic feeding routes [early enteral nutrition (E-EN) or early supplemental parenteral nutrition (E-SPN)] on the outcome of patients undergoing major abdominal surgery is controversial. OBJECTIVES: The aim of this study was to investigate the impact of early isoenergetic EN compared with early isoenergetic SPN on nosocomial infections in patients undergoing major abdominal surgery. METHODS: This study is a secondary, post hoc analysis of data from 2 open-label randomized clinical trials. Participants were recruited from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and with Nutritional Risk Screening 2002 score ≥3. All eligible patients were categorized into 2 groups based on their achievement of the 100% energy target on postoperative day (POD) 3: the E-EN group (n = 199) and the E-SPN group (n = 115). The primary outcome was the incidence of nosocomial infections between POD 3 and hospital discharge. RESULTS: In total, 314 patients [mean (SD) age, 59.2 (11.4) y; 113 (36.0%) females] were included. Patients in the E-EN group showed no significant difference in nosocomial infections compared with those in the E-SPN group {17/199 [8.5%] compared with 10/115 [8.7%], risk difference, 0.2% [95% confidence interval (CI): -6.3, 6.6]}. The hematological nutritional status of the E-EN group showed a significant improvement at discharge compared with the E-SPN group (albumin: 38.0 ± 6.0 g/L compared with 35.5 ± 7.6 g/L; mean difference, -2.5 g/L; 95% CI: -4.0, -1.0 g/L; prealbumin: 200.0 ± 8.0 mg/L compared with 158.4 ± 38.1 mg/L; mean difference, -41.6 mg/L; 95% CI: -41.7, -36.1 mg/L). Other indicators were comparable between groups. CONCLUSION: E-EN compared with isoenergetic SPN may not be associated with a reduced rate of nosocomial infection in patients undergoing major abdominal surgery, but may be associated with improved hematological nutritional status. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT03115957 (https://clinicaltrials.gov/ct2/show/NCT03115957) and NCT03117348 (https://clinicaltrials.gov/ct2/show/NCT03117348).