Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials.

STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.

Additional yield of random biopsy in patients with inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND & AIMS: There is limited clinical data regarding the additional yields of random biopsies during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for IBD patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis, and 16.20% in per-lesion analysis. The detection rate were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for PSC proportions of 0-10%, 10-30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0-10%, 10-30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full HD equipment should consider incorporating RB in the standard colonoscopy surveillance for IBD patients, especially in those with PSC.

Massive hemothorax induced by pulmonary arteriovenous malformation rupture: a case report and literature review.

BACKGROUND: Pulmonary arteriovenous malformation (PAVM), also known as pulmonary arteriovenous fistula, is a rare vascular developmental anomaly. Most cases of PAVM are associated with hereditary hemorrhagic telangiectasia (HHT). Hemothorax associated with PAVM is even rarer, and management concerning this complication still challenges. CASE PRESENTATION: A 55-year-old man with sudden onset of dyspnea and chest pain was admitted to our hospital. He had a medical history of epistaxis, intraperitoneal germ cell tumor and PAVM. Chest unenhanced CT revealed the left-sided pleural effusion together with partial passive atelectasis and gradual increase at the interval of six days. Diagnostic thoracocentesis further revealed hemorrhagic effusion. CT angiography (CTA) showed tortuously dilated lumen of the left lower pulmonary artery and PAVM with the formation of aneurysm. Due to his family's refusal of surgery, the patient underwent transcatheter embolization therapy. However, the left pleural effusion did not significantly reduce and there was a slow drop in hemoglobin value even after interventional treatment, indicating the possibility of ongoing active bleeding. Eventually, the patient received lobectomy of the left lower lobe with a satisfactory outcome. CONCLUSIONS: Massive hemothorax resulting from PAVM rupture into the pleural space can lead to fatal outcomes. CTA can accurately diagnose this pathologic condition. Transcatheter embolization is frequently used in the treatment of PAVM, but it may be challenging to achieve the desirable effect in patients with hemothorax. Combined with our case and literature review, direct radical surgery can lead to a successful outcome when PAVM complicated with hemothorax and a large diameter of the draining vein.

Green infrastructure layout based on a dynamic operation feature of drainage systems.

Increasingly frequent urban floods strain the traditional grey infrastructure, overwhelming the capacity of drainage networks and causing challenges in managing stormwater. The heavy precipitation leads to flooding and damage to drainage systems. Consequently, efficient mitigation strategies for flooding have been researched deeply. Green infrastructure (GI) has proved to be effective in responding the increasing risk of flood and alleviate pressure on drainage systems. However, as the primary infrastructure of stormwater management, there is still a lack of attention to the dynamic operation feature of urban sewer systems during precipitation events. To fill this gap, we proposed a novel approach that integrates hydraulic characteristics and the topological structure of a sewer network system. This approach aims to identify influential nodes, which contribute to the connectivity of the sewer network amidst dynamic changes in inflow during precipitation events. Furthermore, we adopted rain barrels to serve as exemplars of GI, and 14 GI layout schemes are produced based on the different ranks of influential nodes. Implementing GI measures on both poorly performing and well-performing nodes can yield distinct benefits in mitigating node flooding. This approach provides a new perspective for stormwater management, establishing effective synergy between GI and the drainage system.

THBru attenuates diabetic cardiomyopathy by inhibiting RAGE-dependent inflammation.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg-1·d-1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 µM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

The burden of cardiovascular disease attributable to high fasting plasma glucose：Findings from the global burden of disease study 2019.

AIM: High fasting plasma glucose (HFPG) is a key risk factor for cardiovascular disease (CVD). Few studies have evaluated the CVD burden attributable to HFPG globally. It is urgent to investigate the current epidemiological pattern and past trends of CVD attributable to HFPG. METHODS: We used the Global Burden of Disease Study (GBD) 2019 to describe the CVD burden attributable to HFPG in 2019 and evaluate temporal trends between 1990 and 2019. RESULTS: Global Disability-Adjusted Life Years (DALYs) cases and death cases of HFPG-related CVD were approximately 72,591,163 and 3,763,298 in 2019, with an increase of 107.4 % and 114.6 % compared with 1990, respectively. Despite the increases, the age-standardized DALYs rate (ASDAR) and age-standardized death rate (ASDR) of HFPG-related CVD contributed to 895.2 per 100,000 people and 48.4 per 100,000 people in 2019, with an estimated annual percentage change (EAPC) of -0.22 and -0.31, respectively, from 1990. The highest ASDAR and ASDR of HFPG-related CVD were in 2019 observed in the low-middle SDI (Socio-demographic Index) and middle-SDI regions. Low SDI and some low-middle SDI regions showed an increase in ASDAR and ASDR of HFPG-related CVD from 1990 to 2019. Males are more affected by HFPG-related CVD than females across all years. The CVD burden attributable to HFPG in the elderly are higher than those in the young in 2019. The main causes of the global CVD burden attributable to HFPG in 2019 were ischemic heart disease, stroke, and peripheral arterial disease. CONCLUSION: The CVD burden attributable to HFPG remains a serious public health challenge threatening human health worldwide. It is necessary to develop more targeted and specific strategies to reduce CVD burden attributable to HFPG, especially in males, elderly, and lower SDI regions.

Gut microbiota alterations in postmenopausal women with osteoporosis and osteopenia from Shanghai, China.

Background: The importance of the gut microbiota in maintaining bone homeostasis has been increasingly emphasized by recent research. This study aimed to identify whether and how the gut microbiome of postmenopausal women with osteoporosis and osteopenia may differ from that of healthy individuals. Methods: Fecal samples were collected from 27 individuals with osteoporosis (OP), 44 individuals with osteopenia (ON), and 23 normal controls (NC). The composition of the gut microbial community was analyzed by 16S rRNA gene sequencing. Results: No significant difference was found in the microbial composition between the three groups according to alpha and beta diversity. At the phylum level, Proteobacteria and Fusobacteriota were significantly higher and Synergistota was significantly lower in the ON group than in the NC group. At the genus level, Roseburia, Clostridia_UCG.014, Agathobacter, Dialister and Lactobacillus differed between the OP and NC groups as well as between the ON and NC groups (p < 0.05). Linear discriminant effect size (LEfSe) analysis results showed that one phylum community and eighteen genus communities were enriched in the NC, ON and OP groups, respectively. Spearman correlation analysis showed that the abundance of the Dialister genus was positively correlated with BMD and T score at the lumbar spine (p < 0.05). Functional predictions revealed that pathways relevant to amino acid biosynthesis, vitamin biosynthesis, and nucleotide metabolism were enriched in the NC group. On the other hand, pathways relevant to metabolites degradation and carbohydrate metabolism were mainly enriched in the ON and OP groups respectively. Conclusions: Our findings provide new epidemiologic evidence regarding the relationship between the gut microbiota and postmenopausal bone loss, laying a foundation for further exploration of therapeutic targets for the prevention and treatment of postmenopausal osteoporosis (PMO).

Is conventional magnetic resonance imaging superior to radiography in the functional integrity evaluation of anterior cruciate ligament in patients with knee osteoarthritis?

BACKGROUND: The functional integrity of the anterior cruciate ligament (ACL) influences surgical decision-making in patients with knee osteoarthritis (KOA). This study aimed to compare the diagnostic value of radiography and magnetic resonance imaging (MRI) in determining the functional status of ACL. METHODS: We analyzed 306 knees retrospectively using preoperative hip-to-ankle anteroposterior standing (APS) radiographs, anteroposterior (AP) and lateral knee radiographs, AP valgus stress (VS) force radiographs, and standard orthogonal MRI. Based on the intraoperative visualization, the knees were grouped into ACL functionally-intact and ACL functionally-deficient (ACLD) groups. The diagnostic validity and reliability were calculated based on the radiograph parameters such as hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA), posterior tibial slope (PTS), sagittal tibiofemoral subluxation (STFS), coronal tibiofemoral subluxation (CTFS), joint line convergence angle (JLCA), the maximum wear point of the proximal tibia plateau (MWPPT%), and MRI parameters including ACL grades and MWPPT%. RESULTS: HKA, MPTA, PTS, STFS, JLCA, and CTFS on APS and AP radiographs, and MWPPT% on radiographs and MRI showed a significant diagnostic value (P < 0.05). There were no statistically significant differences in the single parameters from radiographs and MRI. After constructing the logistic regression models, MRI showed higher sensitivity, specificity, and accuracy, reaching 96.8%, 79.9%, and 83.3%, respectively (P < 0.001). CONCLUSIONS: In patients with KOA, the diagnostic value of single radiographic or MRI parameter in assessing the functional integrity of the ACL are equivalent. However, by constructing predictive models, MRI could significantly improve diagnostic validity compared with radiography.

The Prediction of Recombination Hotspot Based on Automated Machine Learning.

Meiotic recombination plays a pivotal role in genetic evolution. Genetic variation induced by recombination is a crucial factor in generating biodiversity and a driving force for evolution. At present, the development of recombination hotspot prediction methods has encountered challenges related to insufficient feature extraction and limited generalization capabilities. This paper focused on the research of recombination hotspot prediction methods. We explored deep learning-based recombination hotspot prediction and scrutinized the shortcomings of prevalent models in addressing the challenge of recombination hotspot prediction. To addressing these deficiencies, an automated machine learning approach was utilized to construct recombination hotspot prediction model. The model combined sequence information with physicochemical properties by employing TF-IDF-Kmer and DNA composition components to acquire more effective feature data. Experimental results validate the effectiveness of the feature extraction method and automated machine learning technology used in this study. The final model was validated on three distinct datasets and yielded accuracy rates of 97.14%, 79.71%, and 98.73%, surpassing the current leading models by 2%, 2.56%, and 4%, respectively. In addition, we incorporated tools such as SHAP and AutoGluon to analyze the interpretability of black-box models, delved into the impact of individual features on the results, and investigated the reasons behind misclassification of samples. Finally, an application of recombination hotspot prediction was established to facilitate easy access to necessary information and tools for researchers. The research outcomes of this paper underscore the enormous potential of automated machine learning methods in gene sequence prediction.

[Effects of Different Proportions of Ammonium Sulfate Replacing Urea on Soil Nutrients and Rhizosphere Microbial Communities].

In order to investigate the effects of ammonium sulfate, an industrial by-product, on soil nutrients and microbial community when applied in different proportions instead of using urea as nitrogen fertilizer, a pot corn experiment was conducted. A completely randomized block experimental design was used, with a total of five treatments:CK (no fertilization), U10S0 (100 % urea), U8S2 (80 % urea + 20 % ammonium sulfate), U6S4(60 % urea + 40 % ammonium sulfate), and U0S10 (100 % ammonium sulfate). The basic physical and chemical properties of soil and the dry weight of maize plants were determined by conventional methods, and microbial sequencing was performed using the Illumina NovaSeq platform. The experiment results showed that:① In each growth stage of maize, the pH of soil treated with fertilization (7.85-8.15) was decreased compared with that of CK (8.1-8.21), and the pH showed a decreasing trend with the increase in ammonium sulfate content. ② The soil available nitrogen content increased gradually with the increase in the ammonium sulfate ratio at each growth stage of maize. Compared with that in the CK and U10S0 treatments, the ratio in the U0S10 treatment increased 30.56 % to 63.68 % and 13.22 % to 38.43 %, respectively. The variation trend of organic carbon content was opposite to that of available nitrogen (U8S2 > U6S4 > U0S10), and the addition of ammonium sulfate was still higher than that of U10S0 at other growth stages except for the seedling stage. ③ The protease activity of all fertilization treatments was higher than that of the control, and the protease activity was gradually enhanced with the continuous growth of corn and the increase in the ammonium sulfate ratio. The protease activity of the U0S10 treatment was higher than that of the U10S0 treatment at each growth stage of corn, which increased by 10.54 %-100 %. Soil sucrase activity ranged from 0.04 to 0.24 mg·(g·24 h)-1, and those in the U0S10 treatments were significantly higher than those in the U10S0 and CK treatments at all growth stages, increasing by 20.32 % to 99.16 % and 24.31 % to 79.33 %, respectively. ④ The species abundance of bacteria and fungi in maize rhizosphere under all fertilization treatments were lower than those under the CK treatment, followed by those under the U10S0 treatment. The species diversity trend of the bacterial community in the three treatments with ammonium sulfate replacing urea were U8S2 > U0S10 > U6S4, and that of fungi were U6S4 > U8S2 > U0S10. ⑤ The maize dry weight of the U10S0 treatment and U0S10 treatment was the highest, which was 39.47 % and 36.16 % higher than that of the CK treatment, respectively, but the difference was not significant. The Pearson model showed that the species abundance and diversity of soil rhizosphere fungi and bacteria were affected by relevant environmental variables, among which pH value and soil available nitrogen content were the most important factors affecting microbial diversity. In conclusion, when corn planting in calcareous brown soil, replacing urea with a certain proportion of ammonium sulfate can improve soil nutrients more than urea alone, which affects the growth and rhizosphere microbial community of corn to a certain extent and has a greater yield.

The Bioactive Compounds of Epimedium and Their Potential Mechanism of Action in Treating Osteoporosis: A Network Pharmacology and Experimental Validation Study.

Osteoporosis is a global health challenge characterized by bone loss and microstructure deterioration, which urgently requires the development of safer and more effective treatments due to the significant adverse effects and limitations of existing drugs for long-term treatment. Traditional Chinese medicine, like Epimedium, offers fewer side effects and has been used to treat osteoporosis, yet its active compounds and pharmacological mechanisms remain unclear. In this study, 65 potential active compounds, 258 potential target proteins, and 488 pathways of Epimedium were identified through network pharmacology analysis. Further network analysis and review of the literature identified six potential active compounds and HIF-1α for subsequent experimental validation. In vitro experiments confirmed that 2″-O-RhamnosylIcariside II is the most effective compound among the six potential active compounds. It can promote osteoblast differentiation, bind with HIF-1α, and inhibit both HIF-1α gene and protein expression, as well as enhance COL1A1 protein expression under hypoxic conditions. In vivo experiments demonstrated its ability to improve bone microstructures and reduce bone loss by decreasing bone marrow adipose tissue, enhancing bone formation, and suppressing HIF-1α protein expression. This study is the first to describe the therapeutic effects of 2-O-RhamnosylIcariside II on osteoporosis, which was done, specifically, through a mechanism that targets and inhibits HIF-1α. This study provides a scientific basis for the clinical application of Epimedium and offers a new candidate drug for the treatment of osteoporosis. Additionally, it provides new evidence supporting HIF-1α as a therapeutic target for osteoporosis.

Cigarette smoking-related OLC1 overexpression associated with poor prognosis in bladder urothelial carcinoma.

AIMS: To explore the clinical significance of OLC1 and cigarette smoking in bladder urothelial carcinoma (UBC). MATERIALS AND METHODS: OLC1 mRNA expression was detected in 106 UBC samples by mRNA array or reverse real-time PCR. OLC1 protein expression in 114 UBC samples was detected by immunohistochemical staining. Wild-type C57BL/6J mice were injected with cigarette smoke condensate (n = 12) or exposed to cigarette smoke (n = 6) to investigate the correlations between cigarette smoking and OLC1 expression using mRNA array. KEY FINDINGS: The mRNA and protein expression of OLC1 were higher in tumor samples (p < 0.01) and significantly correlated with tumor stage (p < 0.05). OLC1 protein expression and smoking history were correlated with disease-free survival (p < 0.05). OLC1 expression was significantly elevated in smoking patients with higher smoking intensity on both mRNA and protein levels (p < 0.05). Cigarette smoke exposure experiments revealed that OLC1 mRNA overexpressed in bladder uroepithelium of mice. SIGNIFICANCE: OLC1 could serve as a potential prognosis biomarker of UBC, especially for smoking patients.

Elastic films of single-crystal two-dimensional covalent organic frameworks.

The properties of polycrystalline materials are often dominated by defects; two-dimensional (2D) crystals can even be divided and disrupted by a line defect1-3. However, 2D crystals are often required to be processed into films, which are inevitably polycrystalline and contain numerous grain boundaries, and therefore are brittle and fragile, hindering application in flexible electronics, optoelectronics and separation1-4. Moreover, similar to glass, wood and plastics, they suffer from trade-off effects between mechanical strength and toughness5,6. Here we report a method to produce highly strong, tough and elastic films of an emerging class of 2D crystals: 2D covalent organic frameworks (COFs) composed of single-crystal domains connected by an interwoven grain boundary on water surface using an aliphatic bi-amine as a sacrificial go-between. Films of two 2D COFs have been demonstrated, which show Young's moduli and breaking strengths of 56.7 ± 7.4 GPa and 73.4 ± 11.6 GPa, and 82.2 ± 9.1 N m-1 and 29.5 ± 7.2 N m-1, respectively. We predict that the sacrificial go-between guided synthesis method and the interwoven grain boundary will inspire grain boundary engineering of various polycrystalline materials, endowing them with new properties, enhancing their current applications and paving the way for new applications.

Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study.

BACKGROUND: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

A comparative study on the nutritional composition, protein structure and effects on gut microbiota of 5 fermented soybean products (FSPs).

In this study, we conducted an analysis of the differences in nutrient composition and protein structure among various fermented soybean products and their impacts on the gut microbiota of rats. Conventional physicochemical analysis was employed to analyze the fundamental physicochemical composition of the samples. Additionally, we utilized high-performance liquid chromatography and ELISA techniques to quantify the presence of antinutritional compounds. Fourier infrared spectroscopy was applied to delineate the protein structure, while 16 s rRNA gene sequencing was conducted to evaluate alterations in gut microbiota abundance. Subsequently, KEGG was utilized for metabolic pathway analysis. Our findings revealed that fermented soybean products improved the nutritional profile of soybeans. Notably, Douchi exhibited the highest protein content at 52.18 g/100 g, denoting a 26.58 % increase, whereas natto showed a 24.98 % increase. Douchi and natto demonstrated the most substantial relative amino acid content, comprising 50.86 % and 49.04 % of the total samples, respectively. Moreover, the levels of antinutritional factors markedly decreased post-fermentation. Specifically, the α-helix content in doujiang decreased by 13.87 %, while the random coil content in soybean yogurt surged by 132.39 %. Rats that were fed FSP showcased notable enhancements in gut microbiota and associated metabolic pathways. A strong correlation was observed between nutrient composition, protein structure, and gut microbiota abundance. This study furnishes empirical evidence supporting the heightened nutritional attributes of FSPs.

High-intensity ultrasound treatment of Atlantic cod: Impact on nutrients, structure, sensory quality, bioactivity, and in-vitro digestibility.

This study evaluates the impact of high-intensity ultrasound (HIU) on the physicochemical properties and in-vitro digestibility of Atlantic cod (Gadus morhua). Various ultrasound durations (0-60 min) were applied to assess changes in color attributes, total antioxidant capacity (TAC), total flavonoid content (TFC), total phenolic content (TPC), total protein content, and in-vitro protein digestibility (IVPD). Results indicated HIU maximumly increased TAC, TFC, TPC, and peptide content before digestion by 7.28 % (US60), 3.00 % (US30), 32.43 % (US10), and 18.93 % (US60), respectively. While HIU reduced total protein content, it enhanced IVPD by up to 12.24 % (US30). Color attributes electron microscopy reflected structural changes in the cod samples, suggesting the effectiveness of HIU in altering protein structures. These findings highlight HIU's potential as a non-thermal technique for improving the sensory and nutritional quality of Atlantic cod, offering valuable insights for the seafood processing industry and consumers.

Efficacy and safety of ciprofol for sedation in outpatient gynecological procedures: a phase III multicenter randomized trial.

Objective: Ciprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures. Methods: This phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18-65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at -8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain. Results: A total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, -4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p < 0.001), and required more time to reach full awake (MD, 2.3 min; 95% CI, 1.4 to 3.1; p < 0.001) and discharge criteria (MD, 2.3 min; 95% CI, 1.5 to 3.2; p < 0.001). Fewer patients in the ciprofol group were dissatisfied with sedation (relative risk, 0.21; 95% CI, 0.06 to 0.77; p = 0.024). Patients given ciprofol sedation had lower incidences of treat-emergent adverse events (34.4% [31/90] vs. 79.5% [35/44]; p < 0.001) and injection pain (6.7% [6/90] vs. 61.4% [27/44]; p < 0.001). Conclusion: Ciprofol for sedation in ambulatory gynecological procedures was non-inferior to propofol, with less adverse events and injection pain. Clinical trial registration: ClinicalTrials.gov, identifier NCT04958746.

Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial.

OBJECTIVE: To determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression. DESIGN: Randomised, double blind, placebo controlled trial with two parallel arms. SETTING: Five tertiary care hospitals in China, 19 June 2020 to 3 August 2022. PARTICIPANTS: 364 mothers aged ≥18 years who had at least mild prenatal depression as indicated by Edinburgh postnatal depression scale scores of ≥10 (range 0-30, with higher scores indicating worse depression) and who were admitted to hospital for delivery. INTERVENTIONS: Participants were randomly assigned 1:1 to receive either 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth once the umbilical cord had been clamped. MAIN OUTCOME MEASURES: The primary outcome was prevalence of a major depressive episode at 42 days post partum, diagnosed using the mini-international neuropsychiatric interview. Secondary outcomes included the Edinburgh postnatal depression scale score at seven and 42 days post partum and the 17 item Hamilton depression rating scale score at 42 days post partum (range 0-52, with higher scores indicating worse depression). Adverse events were monitored until 24 hours after childbirth. RESULTS: A total of 364 mothers (mean age 31.8 (standard deviation 4.1) years) were enrolled and randomised. At 42 days post partum, a major depressive episode was observed in 6.7% (12/180) of participants in the esketamine group compared with 25.4% (46/181) in the placebo group (relative risk 0.26, 95% confidence interval (CI) 0.14 to 0.48; P<0.001). Edinburgh postnatal depression scale scores were lower in the esketamine group at seven days (median difference -3, 95% CI -4 to -2; P<0.001) and 42 days (-3, -4 to -2; P<0.001). Hamilton depression rating scale scores at 42 days post partum were also lower in the esketamine group (-4, -6 to -3; P<0.001). The overall incidence of neuropsychiatric adverse events was higher in the esketamine group (45.1% (82/182) v 22.0% (40/182); P<0.001); however, symptoms lasted less than a day and none required drug treatment. CONCLUSIONS: For mothers with prenatal depression, a single low dose of esketamine after childbirth decreases major depressive episodes at 42 days post partum by about three quarters. Neuropsychiatric symptoms were more frequent but transient and did not require drug intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04414943.

Deciphering the Transcription Factor Landscape in Neuroendocrine Prostate Cancer Progression: A Novel Approach to Understand NE Transdifferentiation.

Background and Objective: Prostate cancer (PCa) is a leading cause of cancer mortality in men, with neuroendocrine prostate cancer (NEPC) representing a particularly resistant subtype. The role of transcription factors (TFs) in the progression from prostatic adenocarcinoma (PRAD) to NEPC is poorly understood. This study aims to identify and analyze lineage-specific TF profiles in PRAD and NEPC and illustrate their dynamic shifts during NE transdifferentiation. Methods: A novel algorithmic approach was developed to evaluate the weighted expression of TFs within patient samples, enabling a nuanced understanding of TF landscapes in PCa progression and TF dynamic shifts during NE transdifferentiation. Results: unveiled TF profiles for PRAD and NEPC, identifying 126 shared TFs, 46 adenocarcinoma-TFs, and 56 NEPC-TFs. Enrichment analysis across multiple clinical cohorts confirmed the lineage specificity and clinical relevance of these lineage-TFs signatures. Functional analysis revealed that lineage-TFs are implicated in pathways critical to cell development, differentiation, and lineage determination. Novel lineage-TF candidates were identified, offering potential targets for therapeutic intervention. Furthermore, our longitudinal study on NE transdifferentiation highlighted dynamic TF expression shifts and delineated a three-phase hypothesis for the process comprised of de-differentiation, dormancy, and re-differentiation. and proposing novel insights into the mechanisms of PCa progression. Conclusion: The lineage-specific TF profiles in PRAD and NEPC reveal a dynamic shift in the TF landscape during PCa progression, highlighting three distinct phases of NE transdifferentiation.

A time-resolved multi-omics atlas of transcriptional regulation in response to high-altitude hypoxia across whole-body tissues.

High-altitude hypoxia acclimatization requires whole-body physiological regulation in highland immigrants, but the underlying genetic mechanism has not been clarified. Here we use sheep as an animal model for low-to-high altitude translocation. We generate multi-omics data including whole-genome sequences, time-resolved bulk RNA-Seq, ATAC-Seq and single-cell RNA-Seq from multiple tissues as well as phenotypic data from 20 bio-indicators. We characterize transcriptional changes of all genes in each tissue, and examine multi-tissue temporal dynamics and transcriptional interactions among genes. Particularly, we identify critical functional genes regulating the short response to hypoxia in each tissue (e.g., PARG in the cerebellum and HMOX1 in the colon). We further identify TAD-constrained cis-regulatory elements, which suppress the transcriptional activity of most genes under hypoxia. Phenotypic and transcriptional evidence indicate that antenatal hypoxia could improve hypoxia tolerance in offspring. Furthermore, we provide time-series expression data of candidate genes associated with human mountain sickness (e.g., BMPR2) and high-altitude adaptation (e.g., HIF1A). Our study provides valuable resources and insights for future hypoxia-related studies in mammals.