STUDY OBJECTIVE: The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DESIGN: A retrospective cohort study. SETTING: This study was conducted at one tertiary care hospital in China. PATIENTS: We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). INTERVENTIONS: Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MEASUREMENTS: The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. MAIN RESULTS: After matching, hydroxyethyl starch use [8.5 (IQR: 7.5-10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74-1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75-1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41-0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95-1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. CONCLUSIONS: Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.
The cellular-mesenchymal epithelial transition factor (c-Met) is a receptor tyrosine kinase (RTK) located on the 7q31 locus encoding the Met proto-oncogene and plays a critical role in regulating cell proliferation, metastasis, differentiation, and apoptosis through various signaling pathways. However, its aberrant activation and overexpression have been implicated in many human cancers. Therefore, c-Met is a promising target for cancer treatment. However, the anticancer effect of selective single-targeted drugs is limited due to the complexity of the signaling system and the involvement of different proteins and enzymes. After inhibiting one pathway, signal molecules can be transmitted through other pathways, resulting in poor efficacy of single-targeted drug therapy. Dual inhibitors that simultaneously block c-Met and another factor can significantly improve efficacy and overcome some of the shortcomings of single-target inhibitors, including drug resistance. In this review, We introduced c-Met kinase and the synergism between c-Met and other anti-tumor targets, then dual-target inhibitors based on c-Met for the treatment of cancers were summarized and their design concepts and structure-activity relationships (SARs) were discussed elaborately, providing a valuable insight for the further development of novel c-Met-based dual inhibitors.
In this report, we propose a new insight into the interaction between the solvent-polarity-dependent conformational equilibrium and excited state intramolecular proton transfer (ESIPT) behavior of Pz3HC system in four different polar solvents (polarity order: ACN > THF > TOL > CYC). Using quantum chemistry method, we first announce a coexistence mechanism between Pz3HC-1 and Pz3HC-3 in the ground state in four solvents based on the Boltzmann distribution. In particular, Pz3HC-1 is the principal configuration in non-polar solvent, but Pz3HC-3 is the principal configuration in polar solvent. In addition, the simulated fluorescence spectra interprets the negative solvatochromism effect of Pz3HC-1 and Pz3HC-3 in four solvents. The evidence from intramolecular hydrogen bonding (IHB) parameters and electronic perspective collectively confirms the light-induced IHB enhancement and intramolecular charge transfer (ICT) properties in Pz3HC-1 and Pz3HC-3, which raises the likelihood of the ESIPT process. Combining the calculation of potential energy curve (PEC) and intrinsic reaction coordinate (IRC), we demonstrate that the ESIPT ease of Pz3HC-1 in different polar solvents obeys the order of CYC > TOL > THF > ACN, while the order of ESIPT ease in Pz3HC-3 is opposite. Notably, the ESIPT process of Pz3HC-3 in CYC solvent is accompanied by the twisted intramolecular charge transfer (TICT) process. In addition, we also reveal that the enol* and keto* fluorescence peaks of Pz3HC-3 in CYC solvent are quenched by ISC and TICT process, respectively. Our work not only provides a satisfactory explanation of the novel dynamics mechanism for Pz3HC system, but also brings light to the design and application of new sensing molecules in the future.
BACKGROUND: Laying hens undergo intensive metabolism and are vulnerable to cardiac insults. Past research demonstrated overt heart disorders of broiler chickens induced by dietary Se deficiency. OBJECTIVE: This study was to reveal effects and mechanism of dietary Se insufficiency on cardiac injuries of egg-type chicks in their early life. METHODS: White Leghorn chicks (0-day-old, female) were fed a corn-soy, Se-insufficient basal diet (BD, 0.05 mg Se/kg, n = 11) or the BD supplemented with 0.3 mg Se/kg (as sodium selenite, n = 8) for 35 days. Cardiac tissues were collected at the end of study for histology and to determine its relationship with heart Se contents, selenoprotein expression profiles, antioxidant and inflammatory status, and the Toll-like receptor 4/extracellular signal-regulated kinases/p38 map kinase/ C-Jun N-terminal kinase (TLR4/ERK/P38/JNK) pathway. RESULTS: Compared with those fed 0.35 mg Se/kg, chicks fed BD had significantly lower body weights and average daily gain, and 28% lower heart Se than Se-supplemented chicks, and developed cardiac mononuclear inflammatory cell infiltration, along with elevated (P < 0.05) serum levels of creatine kinase, aldolase, and interleukin-1. The BD decreased (P < 0.05) body weight and heart glutathione contents and expression of selenoproteins, but increased (P < 0.05) heart levels of malondialdehyde and reactive oxygen species. These changes were associated with increased (P < 0.05) mRNA and (or) protein levels of cyclooxygenases, lipoxygenase-12, cytokines (IL-1ß), nuclear factor kappa B subunit (NF-κB), chemokines, and receptors (CCL20, CXCR1, CXCLI2), and increased (P < 0.1) TLR4/ERK /P38/JNK in the heart of Se-insufficient chicks. CONCLUSION: Dietary Se insufficiency induced infiltration of mononuclear inflammatory cells in the heart of egg-type chicks. This cardiac injury was mediated by decreased functional expressions of selenoproteins which resulted in apparent elevated oxidative stress and subsequent activations of the TLR4 pathway and NF-κB.
BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most significant causes of mortality due to cancer-related deaths. It has been previously reported that the TGF-ß signaling pathway may be associated with tumor progression. However, the relationship between TGF-ß signaling pathway and HCC remains to be further elucidated. The objective of our research was to investigate the impact of TGF-ß signaling pathway on HCC progression as well as the potential regulatory mechanism involved. METHODS: We conducted a series of bioinformatics analyses to screen and filter the most relevant hub genes associated with HCC. E. coli was utilized to express recombinant protein, and the Ni-NTA column was employed for purification of the target protein. Liquid liquid phase separation (LLPS) of protein in vitro, and fluorescent recovery after photobleaching (FRAP) were utilized to verify whether the target proteins had the ability to drive force LLPS. Western blot and quantitative real-time polymerase chain reaction (qPCR) were utilized to assess gene expression levels. Transcription factor binding sites of DNA were identified by chromatin immunoprecipitation (CHIP) qPCR. Flow cytometry was employed to examine cell apoptosis. Knockdown of target genes was achieved through shRNA. Cell Counting Kit-8 (CCK-8), colony formation assays, and nude mice tumor transplantation were utilized to test cell proliferation ability in vitro and in vivo. RESULTS: We found that Smad2/3/4 complex could regulate tyrosine aminotransferase (TAT) expression, and this regulation could relate to LLPS. CHIP qPCR results showed that the key targeted DNA binding site of Smad2/3/4 complex in TAT promoter region is -1032 to -1182. In addition. CCK-8, colony formation, and nude mice tumor transplantation assays showed that Smad2/3/4 complex could repress cell proliferation through TAT. Flow cytometry assay results showed that Smad2/3/4 complex could increase the apoptosis of hepatoma cells. Western blot results showed that Smad2/3/4 complex would active caspase-9 through TAT, which uncovered the mechanism of Smad2/3/4 complex inducing hepatoma cell apoptosis. CONCLUSION: This study proved that Smad2/3/4 complex could undergo LLPS to active TAT transcription, then active caspase-9 to induce hepatoma cell apoptosis in inhibiting HCC progress. The research further elucidate the relationship between TGF-ß signaling pathway and HCC, which contributes to discover the mechanism of HCC development.
INTRODUCTION: Real-world data on the efficacy of risankizumab (RZB) in clinical moderate-to-severe plaque psoriasis (PsO) are limited. The RAPID study assessed real-world clinical and patient-reported outcomes in RZB-treated PsO patients using data collected from dermatologists in Canada, the Czech Republic, Germany, Japan, and Poland. METHODS: This ongoing, retrospective chart review collected data from medical records of RZB-treated adults with moderate-to-severe PsO (09/2022-06/2023). Eligible patients received RZB, had ≥ 12 months of medical records after RZB initiation (index date), and had Psoriasis Area and Severity Index (PASI), Investigator Global Assessment (IGA), or static Physician's Global Assessment (sPGA) scores ≥ 3 months before and up to 18 months after the index date. The proportion of patients achieving a clear/almost clear PsO (IGA/sPGA = 0/1), PASI ≤ 1, Dermatology Life Quality Index (DLQI) = 0/1, and a 90%/100% improvement from baseline in PASI as well as the mean changes in PASI, DLQI, itch, and skin pain scores at 12 and 18 months were reported for patients with non-missing assessments at baseline and 12 months. RESULTS: Most patients (66.4%) were male, 74.0% were biologic naïve, and 73.0% had scalp PsO. Mean baseline IGA/sPGA was 3.7 ± 0.5, with a mean PASI of 23.3 ± 11.8. After 12 months, 86.1% of patients reported IGA/sPGA ≤ 1, and 75.7% achieved PASI90; these further increased to 91.1% and 80.5% at 18 months. DLQI, itch, and skin pain scores improved over time. CONCLUSIONS: These data demonstrated the durable, real-world effectiveness of RZB in patients with moderate-to-severe PsO through continued improvement in disease and symptom severity over 18 months, with most of the patients reporting clear/almost clear skin.
BACKGROUND: Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition. METHODS: A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test). RESULTS: Patients with BD showed significant cognitive impairment (p < 0.05), which was not affected by medication. Triglycerides (TG), luteinizing hormone (LH), and high-density lipoprotein cholesterol (HDL-c) were altered in stable-medicated BD patients. In addition, regression analysis showed that progesterone (PRGE) and prolactin (PRL) were negatively associated with cognitive performance in stable-medicated BD patients. CONCLUSIONS: Female BD patients may have cognitive deficits and abnormal levels of glycolipids and reproductive hormones. And abnormal levels of glycolipids and reproductive hormones may be associated with cognitive dysfunction in female BD patients.
Bipolar Disorder , Cognitive Dysfunction , Glycolipids , Humans , Female , Bipolar Disorder/blood , Bipolar Disorder/complications , Adult , Glycolipids/blood , Cognitive Dysfunction/blood , Cognitive Dysfunction/physiopathology , Luteinizing Hormone/blood , Prolactin/blood , Progesterone/blood , Triglycerides/blood , Cholesterol, HDL/blood , Middle Aged , Neuropsychological Tests/statistics & numerical data
Background: Aging individuals are vulnerable to various Noncommunicable Diseases (NCDs). Different behaviors are closely related to a decreased risk of suffering from NCDs: sufficient Physical Activity (PA) (e.g., at least 150 mins Moderate-to-vigorous Physical Activity (MVPA) per week) and a healthy daily diet (e.g., at least five portions of Fruit and Vegetable Intake (FVI), 5-6 taels (189.0-226.8 g) Meat, Fish, Egg and Alternatives (MFEA)). Traditional face-to-face interventions were effective in behavior change. However, it was revealed to be resource-intensive and limited transfer due to poor self-regulation skills outside of face-to-face sessions. Thus, eHealth could be a supplement for older adults outside traditional face-to-face settings. The blended approach combining these two interventions might optimize the intervention effects on lifestyle behavior initiation and maintenance, but little research can be found among Hong Kong older adults. Therefore, the study aims to test a blended intervention to promote PA, diet, and health outcomes among Hong Kong community-dwelling older adults. Methods: This study will adopt a 10-week three-arm randomized controlled trial. The blended group will receive weekly (1) two 60-min face-to-face sessions with one for PA and one for diet, and (2) two web-based sessions with one for PA and one for diet. The face-to-face group will receive the same intervention content as the face-to-face sessions in the blended group. The control condition will receive a biweekly telephone call. The outcomes will include MVPA (minutes/week), FVI (portions/day), MFEA consumption (taels/day), social-cognitive factors (self-efficacy, planning, social support, action control), physical health outcomes (clinical indicators, senior physical fitness), mental health outcomes (depression, loneliness) and health-related quality of life. Data collection will be implemented at the pre-test, post-test, and 3-month follow-up test. Discussion: This is the first study evaluating a blended intervention promoting multiple health behaviors among Hong Kong community-dwelling older adults. If the effect of the blended intervention is superior to the traditional face-to-face group and the control group, it will enrich lifestyle intervention approaches and can be applied to older adults, helping them obtain health benefits. Furthermore, a better understanding of mechanisms will also have implications for theory-building. Clinical trial registration: https://www.isrctn.com/ISRCTN32329348, ISRCTN32329348.
Exercise , Independent Living , Telemedicine , Humans , Hong Kong , Aged , Male , Female , Health Promotion/methods , Diet , Life Style , Middle Aged , Randomized Controlled Trials as Topic
OBJECTIVES: This study explores the clinical characteristics associated with the occurrence of acute anterior uveitis (AAU) in patients with axial spondyloarthritis (axSpA) within a large, multicentre database. METHODS: This observational, cross-sectional study of patients with axSpA used data from the Chinese Spondyloarthritis Registry between August 1, 2018, and March 31, 2020. The demographic and clinical features of patients with and without AAU were compared. Univariate and multivariate analyses were performed to determine the association between variables and uveitis. RESULTS: A total of 4304 patients were included in this study. The prevalence of AAU in patients with axSpA was 10.59%. Multivariate logistic regression analysis revealed a positive correlation between AAU and age at diagnosis (odds ratio [OR], 1.026; p<0.001), disease duration (OR, 2.117; p<0.001), current or past Achilles tendinitis (OR, 1.692; p<0.001), current or past dactylitis (OR, 1.687; p=0.002), current or past psoriasis (OR, 3.932; p<0.001), presence of human leukocyte antigen-B27 (HLA-B27) (OR, 2.787; p<0.001), and a good response to non-steroidal anti-inflammatory drugs (NSAIDs) (OR, 1.343; p=0.027). CONCLUSIONS: AAU was the most common extra-articular manifestation in the Chinese Spondyloarthritis Registry. In Chinese patients with axSpA, older age at diagnosis, longer disease duration, presence of HLA-B27, current or past Achilles tendinitis, current or past dactylitis, current or past psoriasis, and a good response to NSAIDs were positively associated with AAU.
AIM: To examine the effects of the thiazolidinedione (TZD) pioglitazone on reducing ketone bodies in non-obese patients with T2DM treated with the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin. METHODS: Crossover trials with two periods, each treatment period lasting 4 weeks, with a 4-week washout period, were conducted. Participants were randomly assigned in a 1:1 ratio to receive pioglitazone combined with canagliflozin (PIOG + CANA group) versus canagliflozin monotherapy (CANA group). The primary outcome was change (Δ) in ß-hydroxybutyric acid (ß-HBA) before and after the CANA or PIOG + CANA treatments. The secondary outcomes were Δchanges in serum acetoacetate and acetone, the rate of conversion into urinary ketones, and Δchanges in factors related to SGLT2 inhibitor-induced ketone body production including non-esterified fatty acids (NEFAs), glucagon, glucagon to insulin ratio, and noradrenaline (NA). Analyses were performed in accordance with the intention-to-treat principle. RESULTS: Twenty-five patients with a mean age of 49 ± 7.97 years and a body mass index of 25.35 ± 2.22 kg/m2 were included. One patient discontinued the study during the washout period. Analyses revealed a significant increase in the levels of serum ketone bodies and an elevation in the rate of conversion into urinary ketones after both interventions. However, differernces in levels of ketone bodies (except for acetoacetate) in the PIOG + CANA group were significantly smaller than in the CANA group (219.84 ± 80.21 µmol/L vs. 317.69 ± 83.07 µmol/L, p < 0.001 in ß-HBA; 8.98 ± 4.17 µmol/L vs. 12.29 ± 5.27 µmol/L, p = 0.018 in acetone). NEFA, glucagon, glucagon to insulin ratio, and NA were also significantly increased after both CANA and PIOG + CANA treatments; while only NEFAs demonstrated a significant difference between the two groups. Correlation analyses revealed a significant association between the difference in Δchanges in serum NEFA levels with the differences in Δchanges in ketones of ß-HBA and acetoacetate. CONCLUSION: Supplementation of pioglitazone could alleviate canagliflozin-induced ketone bodies. This benefit may be closely associated with decreased substrate NEFAs rather than other factors including glucagon, fasting insulin and NA.
Malnutrition persists as one of the most severe symptoms in patients with chronic kidney disease (CKD) globally. It is a critical risk factor for cardiovascular and all-cause mortality in patients with CKD. Readily available objective indicators are used to calculate composite objective nutritional assessment indexes, including the geriatric nutritional risk index, prognostic nutritional index, and controlling nutritional status score. These indexes offer a straightforward and effective method for evaluating nutritional status and predicting clinical outcomes in patients with CKD. This review presents supporting evidence on the significance of composite nutritional indexes.
Objective: Previous research has partially revealed distinct gut microbiota in ankylosing spondylitis (AS). In this study, we performed non-targeted fecal metabolomics in AS in order to discover the microbiome-metabolome interface in AS. Based on prospective cohort studies, we further explored the impact of the tumor necrosis factor inhibitor (TNFi) on the gut microbiota and metabolites in AS. Methods: To further understand the gut microbiota and metabolites in AS, along with the influence of TNFi, we initiated a prospective cohort study. Fecal samples were collected from 29 patients with AS before and after TNFi therapy and 31 healthy controls. Metagenomic and metabolomic experiments were performed on the fecal samples; moreover, validation experiments were conducted based on the association between the microbiota and metabolites. Results: A total of 7,703 species were annotated using the metagenomic sequencing system and by profiling the microbial community taxonomic composition, while 50,046 metabolites were identified using metabolite profiling. Differential microbials and metabolites were discovered between patients with AS and healthy controls. Moreover, TNFi was confirmed to partially restore the gut microbiota and the metabolites. Multi-omics analysis of the microbiota and metabolites was performed to determine the associations between the differential microbes and metabolites, identifying compounds such as oxypurinol and biotin, which were correlated with the inhibition of the pathogenic bacteria Ruminococcus gnavus and the promotion of the probiotic bacteria Bacteroides uniformis. Through experimental studies, the relationship between microbes and metabolites was further confirmed, and the impact of these two types of microbes on the enterocytes and the inflammatory cytokine interleukin-18 (IL-18) was explored. Conclusion: In summary, multi-omics exploration elucidated the impact of TNFi on the gut microbiota and metabolites and proposed a novel therapeutic perspective: supplementation of compounds to inhibit potential pathogenic bacteria and to promote potential probiotics, therefore controlling inflammation in AS.
Feces , Gastrointestinal Microbiome , Metabolome , Probiotics , Spondylitis, Ankylosing , Humans , Spondylitis, Ankylosing/microbiology , Spondylitis, Ankylosing/metabolism , Spondylitis, Ankylosing/immunology , Male , Female , Adult , Feces/microbiology , Metagenomics/methods , Middle Aged , Prospective Studies , Metabolomics , Bacteria/metabolism , Bacteria/classification , Bacteria/isolation & purification , Tumor Necrosis Factor Inhibitors/therapeutic use , Tumor Necrosis Factor Inhibitors/pharmacology
Key Clinical Message: Antipsychotic drug treatment is a commonly used therapeutic strategy in the field of psychiatry. Rational and standardized use of antipsychotics is crucial in clinical practice, and excessive use of antipsychotics may lead to severe toxic reactions. Thus, attention should be given to the monitoring of drug concentration and examination of organ function. Abstract: Excessive use of antipsychotics can cause a variety of adverse effects, including dysfunction of the liver and other organs. Liver cytochrome P450 (CYP450) enzymes play an important role in the metabolism of antipsychotics, and metabolizer types of CYP450 enzymes may influence the therapeutic effects. In this case report, we introduced a 52-year-old woman with a 23-year history of schizophrenia who took excessive doses of multiple antipsychotics and other herbal preparations for nearly 2 years, with poor response to treatment and minor side reactions to the antipsychotics. Pharmacogenomic examination showed that this patient was a CYP1A2 ultra-rapid metabolizer. The examination and treatment of this patient may provide a reference for the management of similar cases with poor response to an alarming tolerance for antipsychotics.
BACKGROUND: Volatile Organic Compounds (VOCs) constitute an omnipresent category of environmental contaminants. Numerous studies have identified associations between various VOCs and human diseases. The anti-aging protein α-Klotho has been shown to exert protective influences across a variety of disease origins and progressions. This study aims to explore the relationship between serum α-Klotho levels and exposure to VOCs in humans. METHODS: This analysis utilized data from 1672 participants aged from 40 to 79â¯years in 2011-2016 NHANES. Exposure to VOCs was assessed through measurements of urinary VOC metabolites (mVOCs), with 16 mVOCs selected for analysis. Multivariate generalized linear models (GLM), restricted cubic splines (RCS), weighted quantile sum (WQS) regression models, and Bayesian kernel machine regression (BKMR) models were employed to examine the connection between serum α-Klotho and individual mVOCs and mVOCs mixtures, as well as to identify the primary monomeric mVOCs responsible for these associations. RESULTS: Our research revealed that 8 mVOCs exhibited inverse associations with serum α-Klotho levels in GLM and RCS models. Particularly noteworthy, N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA), a metabolite of acrylonitrile, emerged as the most influential mVOC in both WQS and BKMR models. Furthermore, the mVOCs mixture was found to be negatively correlated with serum α-Klotho. The detrimental effects of mVOCs on serum α-Klotho were observed to significantly diminish in individuals with elevated serum vitamin D levels. CONCLUSION: Our study highlights a significant inverse relationship between serum α-Klotho and the mixture of mVOCs, indicating that exposure to VOCs may impact the molecular pathways of aging and related diseases by influencing α-Klotho concentrations. Remarkably, the attenuation of this association by high serum vitamin D levels implies potential therapeutic strategies. Our study underscores the importance of minimizing VOCs exposure to mitigate the adverse effects on α-Klotho. Further research is warranted to elucidate the underlying mechanisms of these relationships.
An extensive phytochemical investigation on the rare medicinal plant Semiliquidambar cathayensis (family: Hamamelidaceae) led to the isolation of four new (1-4, named semiliquidacids A-D, respectively) and 25 related known pentacyclic triterpenoids. The new structures with absolute configurations were elucidated by spectroscopic methods, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compound 1 represents the first naturally occurring ursane-type triterpenoid featuring an uncommon C-25 formyl group. Compound 4 and oleanolic acid (13) exhibited remarkable inhibitory effects against the ATP-citrate lyase (ACL, an emerging drug target for hyperlipidemia and related metabolic disorders) with IC50 values of 6.5 and 11.9 µM, respectively. The molecular interaction and binding mode between the bioactive triterpenoids and ACL were elaborated by conducting a molecular docking study. Meanwhile, the chemotaxonomic significance of the isolated triterpenoids has been briefly discussed.
This study investigated the effects of Lactobacillus plantarum fermentation on the structural, physicochemical, and digestive properties of foxtail millet starches. The fermented starch granules formed a structure with honeycomb-like dents, uneven pores, and reduced particle size. As the fermentation time extended, the amylose content of waxy (0.88 %) and non-waxy (33.71 %) foxtail millet starches decreased to the minimum value at 24 h (0.59 % and 29.19 %, respectively), and then increased to 0.85 % and 31.87 % at 72 h, respectively. Both native and fermented foxtail millet starches exhibited an A-type crystal structure. Compared with native samples, the fermented samples performed enhanced proportion of short-branched chain, crystallinity, and short-range ordered degree. After fermentation for 24 h, the solubility, adsorption capacity, and pasting viscosity of foxtail millet starches improved, whereas the swelling power, pasting temperature, breakdown, setback, and degree of retrogradation reduced. Additionally, fermentation increased the transition temperatures, enthalpy, and digestibility. Overall, Lactobacillus plantarum fermentation is considered a competent choice to regulate the characteristics of foxtail millet starch.
BACKGROUND AND AIMS: Propofol, a widely used sedative in gastrointestinal endoscopic procedures, is associated with cardiorespiratory suppression. Remimazolam is a novel ultra-short-acting benzodiazepine sedative with rapid onset and minimal cardiorespiratory depression. This study aimed to compare the safety and efficacy of remimazolam and propofol during endoscopic ultrasound (EUS) procedures. METHODS: A multicenter randomized controlled study was conducted between October 2022 and March 2023 in patients who underwent EUS procedures. Patients were randomly assigned to receive either remimazolam or propofol as a sedative agent. The primary endpoint was cardiorespiratory adverse events during the procedure, including desaturation, respiratory depression, hypotension, and tachycardia. Secondary endpoints included the time to achieve sedation, recovery time, quality of sedation, pain at the injection site, and satisfaction of both the endoscopists and patients. RESULTS: Four hundred patients enrolled in the study: 200 received remimazolam (10.8±7.7 mg) and 200 received propofol (88.0±49.1 mg). For cardiorespiratory adverse events, the remimazolam group experienced fewer occurrences than the propofol group (8.5% vs. 16%, p=0.022). There was a non-significant trend toward less oxygen desaturation (1.0% vs 3.5%, p= 0.09), respiratory depression (0.5% vs 1.5%, p= 0.62), hypotension (2.5% vs 5.5%, p=0.12) and tachycardia (4.5% vs 5.5%, p=0.68) with remimazolam than with propofol. Remimazolam showed a shorter induction time than propofol, while maintaining comparable awakening and recovery times. Injection site pain was significantly lower in the remimazolam group than in the propofol group. The remimazolam group demonstrated a significantly higher quality of sedation and satisfaction scores than the propofol group, as evaluated by both endoscopists and patients. CONCLUSION: Remimazolam was superior to propofol in terms of safety and efficacy during EUS examinations.
BACKGROUND: The diagnostic criteria and phenotypes in polycystic ovary syndrome are heterogeneous. Currently, it is unclear how to assess a patient's prognosis based on the onset time of menstruation disturbance. Evidence on this topic is scarce and has mainly focused on menstrual patterns. OBJECTIVE: This study aimed to assess the association between the onset time of menstrual disturbance and clinical features and in vitro fertilization pregnancy outcomes in patients with polycystic ovary syndrome. STUDY DESIGN: Our study was a secondary analysis of data collected as part of a randomized controlled trial conducted to compare live birth rates between fresh embryo transfer and frozen embryo transfer in 1508 individuals with polycystic ovary syndrome. Here, 1500 participants were classified into 2 groups according to the onset time of menstrual disturbance: immediately after menarche (early group) and after at least 1 year of regular menstruation (late group). We compared the prepregnancy clinical features, variables of ovarian stimulation, pregnancy outcomes after the initial cycle of embryo transfer, and perinatal and neonatal complications in the 2 groups. RESULTS: Compared with the late group, the early group had more antral follicles (32.00 [range, 27.25-39.50] vs 28.00 [range, 24.00-36.00]; P<.001), an elevated level of antimüllerian hormone (7.02 ng/mL [range, 3.60-11.47] vs 5.66 ng/mL [range, 3.65-8.92]; P=.024), a higher level of baseline luteinizing hormone (10.01±5.93 vs 8.51±5.53 IU/l; P<.001) and luteinizing hormone-to-follicle-stimulating hormone ratio (1.51 [range, 1.00-2.32] vs 1.45 [range, 0.92-2.13]; P<.001), lower levels of fasting glucose (5.47 mmol/L [range, 5.11-5.73] vs 5.50 mmol/L [range, 5.17-5.76]; P<.001), and insulin at 2 hours after 75-g oral glucose tolerance test (56.85 µU/mL [range, 34.63-94.54] vs 59.82 µU/mL [range, 33.56-94.67]; P=.027), a higher level of high-density lipoprotein (1.26 mmol/L [range, 1.04-1.37] vs 1.21 mmol/L [range, 1.07-1.45]; P=.006). During in vitro fertilization, the early group had a higher level of peak estradiol (4596.50 pg/mL [range, 2639.25-6321.00] vs 3954.00 pg/mL [range, 2378.75-6113.50]; P=.013), and luteinizing hormone (2.52 IU/L [range, 1.40-4.21] vs 1.93 IU/L [range, 0.91-3.32]; P=.010) on the day of human chorionic gonadotropin trigger. There was no statistically significant difference observed in the number of oocytes and embryos, the rates of pregnancy and live birth, and the risks of obstetrical and neonatal between the 2 groups. CONCLUSION: An early onset of menstrual disturbance in patients with polycystic ovary syndrome may be associated with slightly more severe reproductive features and slightly milder metabolic features. Nonetheless, the outcomes of in vitro fertilization and the initial cycle of embryo transfer were comparable between the 2 groups.
BACKGROUND: Frozen embryo transfer resulted in a higher birthweight and an increased risk of macrosomia than fresh embryo transfer. However, the mechanism was still unclear. When the impact of frozen embryo transfer on fetal growth began was unknown. Crown-rump length at 11-13 weeks had been regarded as a good indicator of fetal growth in the first trimester and had been used for gestational age calculation in women with uncertain last menstrual periods. OBJECTIVE: To evaluate the association between frozen embryo transfer and early fetal growth, particularly the crown-rump length, then fresh embryo transfer. The secondary objective was to investigate the potential correlation between crown-rump length and birthweight. STUDY DESIGN: This was a retrospective cohort study conducted at the Reproductive Medical Center of Shandong University. A total of 4949 patients who obtained singleton pregnancy after frozen embryo transfer and 1793 patients who got singleton pregnancy after fresh embryo transfer between January 1, 2017 and December 31, 2022 were included. The primary outcome was the crown-rump length measured via ultrasound at 11-13 weeks gestation. The secondary outcomes were perinatal outcomes, including birthweight and the risk of large for gestational age, small for gestational age, macrosomia, low birthweight, and premature delivery. Multivariable linear regression models were used to adjust for potential confounders of crown-rump length. RESULTS: A total of 6742 live singleton births after frozen embryo transfer or fresh embryo transfer were included in this study. In the univariable analysis, the frozen embryo transfer group had a larger crown-rump length (5.75±0.53 cm vs 5.57±0.48 cm, P<.001) and an increased risk of larger-than-expected crown-rump length (13.5% vs11.2%, P=.013) than the fresh embryo transfer group. After adjusting for confounders in multivariable linear regression models, frozen embryo transfer was still associated with a larger crown-rump length (regression coefficient, 3.809 [95% confidence intervals, 3.621-3.997], P<.001). When subgrouped by fetal gender, the crown-rump length of the frozen embryo transfer group was larger than the fresh embryo transfer group in both male and female fetuses. In addition, the crown-rump length was consistently larger in the frozen embryo transfer group than the fresh embryo transfer group in subgroups of the peak estradiol levels. The comparisons among different crown-rump length groups showed that smaller-than-expected crown-rump length was associated with increased risks of small for gestational age (6.3% vs 3.0%, P<.001) and preterm delivery (9.6% vs 6.7%, P=.004) than normal crown-rump length. CONCLUSION: Frozen embryo transfer was associated with a larger crown-rump length than fresh embryo transfer, suggesting that the effect of frozen embryo transfer on fetal growth may begin in the early trimester. Suboptimal fetal growth in the first trimester may be associated with low birthweight and premature delivery.
