ANGPTL8 deficiency attenuates lipopolysaccharide-induced liver injury by improving lipid metabolic dysregulation.

Liver injury is closely related to poor outcomes in sepsis patients. Current studies indicate that sepsis is accompanied by metabolic disorders, especially those related to lipid metabolism. It is highly important to explore the mechanism of abnormal liver lipid metabolism during sepsis. As a key regulator of glucose and lipid metabolism, angiopoietin-like 8 (ANGPTL8) is involved in the regulation of multiple chronic metabolic diseases. In the present study, severe liver lipid deposition and lipid peroxidation were observed in the early stages of lipopolysaccharide (LPS) induced liver injury. LPS promotes the expression of ANGPTL8 both in vivo and in vitro. Knockout of ANGPTL8 reduced hepatic lipid accumulation and lipid peroxidation, improved fatty acid oxidation and liver function, and increased the survival rate of septic mice by activating the PGC1α/PPARα pathway. We also found that the expression of ANGPTL8 induced by LPS depends on TNF-α, and that inhibiting the TNF-α pathway reduces LPS-induced hepatic lipid deposition and lipid peroxidation. However, knocking out ANGPTL8 improved the survival rate of septic mice better than inhibiting the TNF-α pathway. Taken together, the results of our study suggest that ANGPTL8 functions as a novel cytokine in LPS-induced liver injury by suppressing the PGC1α/PPARα signaling pathway. Therefore, targeting ANGPTL8 to improve liver lipid metabolism represents an attractive strategy for the management of sepsis patients.

Seed dormancy types and germination response of 15 plant species in temperate montane peatlands.

Despite their crucial role in determining the fate of seeds, the type and breaking mode of seed dormancy in peatland plants in temperate Asia with a continental monsoon climate are rarely known. Fifteen common peatland plant species were used to test their seed germination response to various dormancy-breaking treatments, including dry storage (D), gibberellin acid soaking (GA), cold stratification (CS), warm followed cold stratification (WCS), GA soaking + cold stratification (GA + CS) and GA soaking + warm followed cold stratification (GA + WCS). Germination experiment, viability and imbibition test, and morphological observation of embryos were conducted. Of the 15 species, nine showed physiological dormancy (PD), with non-deep PD being the dominant type. Four species, Angelica pubescens, Cicuta virosa, Iris laevigata, and Iris setosa exhibited morphophysiological dormancy. Two species, Lycopus uniflorus and Spiraea salicifolia, demonstrated nondormancy. Overall, the effect hierarchy of dormancy-breaking is: CS > GA > WCS > GA + CS > D > GA + WCS. Principal component analysis demonstrated that seed traits, including embryo length: seed length ratio, seed size, and monocot/eudicot divergence, are more likely to influence seed dormancy than environmental factors. Our study suggests that nearly 90% of the tested peatland plant species in the Changbai Mountains demonstrated seed dormancy, and seed traits (e.g. embryo-to-seed ratio and seed size) and abiotic environmental factors (e.g. pH and temperature seasonality) are related to germination behavior, suggesting seed dormancy being a common adaptation strategy for the peatland plants in the temperate montane environment.

Salvage surgery and conversion surgery for patients with non-small cell lung cancer: A narrative review.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.

Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy.

BACKGROUND: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited. AIM: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA. METHODS: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 (n = 66) and HBV-DNA > 2000 (n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables. RESULTS: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group (P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively (P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% (P = 0.09) and DCR of 72.73% vs 74.07% (P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind. CONCLUSION: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

Targeted small molecule therapy and inhibitors for lymphoma.

Lymphoma, a blood tumor, has become the ninth most common cancer in the world in 2020. Targeted inhibition is one of the important treatments for lymphoma. At present, there are many kinds of targeted drugs for the treatment of lymphoma. Studies have shown that Histone deacetylase, Bruton's tyrosine kinase and phosphoinositide 3-kinase all play an important role in the occurrence and development of tumors and become important and promising inhibitory targets. This article mainly expounds the important role of these target protein in tumors, and introduces the mechanism of action, structure-activity relationship and clinical research of listed small molecule inhibitors of these targets, hoping to provide new ideas for the treatment of lymphoma.

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Neurosyphilis Presenting as Psychiatric Symptoms at Younger Age: A Case Report.

Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.

Evolution and health risk of indicator microorganisms in landscape water replenished by reclaimed water.

As an important means to solve water shortage, reclaimed water has been widely used for landscape water supply. However, with the emergence of large-scale epidemic diseases such as SARS, avian influenza and COVID-19 in recent years, people are increasingly concerned about the public health safety of reclaimed water discharged into landscape water, especially the pathogenic microorganisms in it. In this study, the water quality and microorganisms of the Old Summer Palace, a landscape water body with reclaimed water as the only replenishment water source, were tracked through long-term dynamic monitoring. And the health risks of indicator microorganisms were analyzed using Quantitative Microbial Risk Assessment (QMRA). It was found that the concentration of indicator microorganisms Enterococcus (ENT), Escherichia coli (EC) and Fecal coliform (FC) generally showed an upward trend along the direction of water flow and increased by more than 0.6 log at the end of the flow. The concentrations of indicator microorganisms were higher in summer and autumn than those in spring. And there was a positive correlation between the concentration of indicator microorganisms and COD. Further research suggested that increased concentration of indicator microorganisms also led to increased health risks, which were more than 30% higher in other areas of the park than the water inlet area and required special attention. In addition, (water) surface operation exposure pathway had much higher health risks than other pathways and people in related occupations were advised to take precautions to reduce the risks.

A comparison of different intensified upstream processes highlighting the advantage of WuXi Biologics' Ultra-high Productivity platform (WuXiUPTM) in improved product quality and purification yield.

WuXiUPTM, WuXi Biologics' Ultra-high Productivity platform, is an intensified and integrated continuous bioprocess platform developed for production of various biologics including monoclonal antibodies, fusion proteins, and bispecific antibodies. This process technology platform has manifested its remarkable capability in boosting the volumetric productivity of various biologics and has been implemented for large-scale clinical material productions. In this paper, case studies of the production of different pharmaceutical proteins using two high-producing and intensified culture modes of WuXiUPTM and the concentrated fed-batch (CFB), as well as the traditional fed-batch (TFB) are discussed from the perspectives of cell growth, productivity, and protein quality. Both WuXiUPTM and CFB outperformed TFB regarding volumetric productivity. Additionally, distinctive advantages in product quality profiles in the WuXiUPTM process, such as reduced acidic charge variants and fragmentation, are revealed. Therefore, a simplified downstream purification process with only two chromatographic steps can be developed to deliver the target product at a satisfactory purity and an extremely-high yield.

Linearization of wavelength sweeping lasers for the construction of 4-D FMCW LiDAR images of slow-moving objects using baseband beat note signals.

A FMCW LiDAR system of both the distributed feedback laser and external cavity laser is established in baseband beat notes, rather than up-conversion to an intermediate frequency to exclude flicker noise. Meanwhile, utilizing fast-scanning MEMS mirrors, high-quality real-time (1 fps) 4-D images of the slow-moving object (10 mm/s) can be directly constructed at the baseband with a central frequency as low as 100 kHz and a small Doppler shift. The proposed LiDAR architecture based on such a low-frequency baseband significantly improves the optical power budget on the transmitter side and eliminates the costly high-speed sampling circuits on the receiver side.

Nurturing gut health: role of m6A RNA methylation in upholding the intestinal barrier.

The intestinal lumen acts as a critical interface connecting the external environment with the body's internal state. It's essential to prevent the passage of harmful antigens and bacteria while facilitating nutrient and water absorption. The intestinal barriers encompass microbial, mechanical, immunological, and chemical elements, working together to maintain intestinal balance. Numerous studies have associated m6A modification with intestinal homeostasis. This review comprehensively outlines potential mechanisms through which m6A modification could initiate, exacerbate, or sustain barrier damage from an intestinal perspective. The pivotal role of m6A modification in preserving intestinal equilibrium provides new insights, guiding the exploration of m6A modification as a target for optimizing preventive and therapeutic strategies for intestinal homeostasis.

Sorption characteristics of phosphorus on marine sediments in the presence of black carbon derived from fly ash.

The sorption behavior of phosphorus on marine sediments in the presence of black carbon derived from fly ash (FC) was studied. For both the FC and sediment samples, the kinetic curves could be described by a two-compartment first order equation, and the isotherms fit the Freundlich and Langmuir models well. The high specific surface area with abundant acidic functional groups of FC promoted the sorption and make this process more irreversible. The effects were more significant with higher amount of FC added. After sorption, more significant increase in Ex-P, Fe/Al-P and CaP was found in the sediment with FC added, while the organic groups in FC rarely react with phosphorus to form OP. The pH of medium influenced the sorption character, and FC promoted the process significantly at pH < pHPZNPC. The sorption was endothermic with an increase in randomness. The presence of FC had little effects on the thermodynamic parameters.

Construction of a 3-year risk prediction model for developing diabetes in patients with pre-diabetes.

Introduction: To analyze the influencing factors for progression from newly diagnosed prediabetes (PreDM) to diabetes within 3 years and establish a prediction model to assess the 3-year risk of developing diabetes in patients with PreDM. Methods: Subjects who were diagnosed with new-onset PreDM at the Physical Examination Center of the First Affiliated Hospital of Soochow University from October 1, 2015 to May 31, 2023 and completed the 3-year follow-up were selected as the study population. Data on gender, age, body mass index (BMI), waist circumference, etc. were collected. After 3 years of follow-up, subjects were divided into a diabetes group and a non-diabetes group. Baseline data between the two groups were compared. A prediction model based on logistic regression was established with nomogram drawn. The calibration was also depicted. Results: Comparison between diabetes group and non-diabetes group: Differences in 24 indicators including gender, age, history of hypertension, fatty liver, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, HbA1c, etc. were statistically significant between the two groups (P<0.05). Differences in smoking, creatinine and platelet count were not statistically significant between the two groups (P>0.05). Logistic regression analysis showed that ageing, elevated BMI, male gender, high fasting blood glucose, increased LDL-C, fatty liver, liver dysfunction were risk factors for progression from PreDM to diabetes within 3 years (P<0.05), while HDL-C was a protective factor (P<0.05). The derived formula was: In(p/1-p)=0.181×age (40-54 years old)/0.973×age (55-74 years old)/1.868×age (≥75 years old)-0.192×gender (male)+0.151×blood glucose-0.538×BMI (24-28)-0.538×BMI (≥28)-0.109×HDL-C+0.021×LDL-C+0.365×fatty liver (yes)+0.444×liver dysfunction (yes)-10.038. The AUC of the model for predicting progression from PreDM to diabetes within 3 years was 0.787, indicating good predictive ability of the model. Conclusions: The risk prediction model for developing diabetes within 3 years in patients with PreDM constructed based on 8 influencing factors including age, BMI, gender, fasting blood glucose, LDL-C, HDL-C, fatty liver and liver dysfunction showed good discrimination and calibration.

Comprehensive single cell transcriptomics analysis of murine osteosarcoma uncovers Skp2 function in metastasis, genomic instability and immune activation and reveals additional target pathways.

Osteosarcoma (OS) is the most common primary pediatric bone malignancy. One promising new therapeutic target is SKP2, encoding a substrate recognition factor of the SCF E3 ubiquitin ligase responsible for ubiquitination and proteasome degradation of substrate p27, thus driving cellular proliferation. We have shown previously that knockout of Skp2 in an immunocompetent transgenic mouse model of OS improved survival, drove apoptosis, and induced tumor inflammation. Here, we applied single-cell RNA-sequencing (scRNA-seq) to study primary OS tumors derived from Osx-Cre driven conditional knockout of Rb1 and Trp53. We showed that murine OS models recapitulate the tumor heterogeneity and microenvironment complexity observed in patient tumors. We further compared this model with OS models with functional disruption of Skp2: one with Skp2 knockout and the other with the Skp2-p27 interaction disrupted (resulting in p27 overexpression). We found reduction of T cell exhaustion and upregulation of interferon activation, along with evidence of replicative and endoplasmic reticulum-related stress in the Skp2 disruption models, and showed that interferon induction was correlated with improved survival in OS patients. Additionally, our scRNA-seq analysis uncovered decreased activities of metastasis-related gene signatures in the Skp2-disrupted OS, which we validated by observation of a strong reduction in lung metastasis in the Skp2 knockout mice. Finally, we report several potential mechanisms of escape from targeting Skp2 in OS, including upregulation of Myc targets, DNA copy number amplification and overexpression of alternative E3 ligase genes, and potential alternative lineage activation. These mechanistic insights into OS tumor biology and Skp2 function suggest novel targets for new, synergistic therapies, while the data and our comprehensive analysis may serve as a public resource for further big data-driven OS research.

Identification of bladder cancer subtypes and predictive signature for prognosis, immune features, and immunotherapy based on immune checkpoint genes.

Immunotherapy based on immune checkpoint genes (ICGs) has recently made significant progress in the treatment of bladder cancer patients, but many patients still cannot benefit from it. In the present study, we aimed to perform a comprehensive analysis of ICGs in bladder cancer tissues with the aim of evaluating patient responsiveness to immunotherapy and prognosis. We scored ICGs in each BLCA patient from TCGA and GEO databases by using ssGSEA and selected genes that were significantly associated with ICGs scores by using the WCGNA algorithm. NMF clustering analysis was performed to identify different bladder cancer molecular subtypes based on the expression of ICGs-related genes. Based on the immune related genes differentially expressed among subgroups, we further constructed a novel stratified model containing nine genes by uni-COX regression, LASSO regression, SVM algorithm and multi-COX regression. The model and the nomogram constructed based on the model can accurately predict the prognosis of bladder cancer patients. Besides, the patients classified based on this model have large differences in sensitivity to immunotherapy and chemotherapy, which can provide a reference for individualized treatment of bladder cancer.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Dose-response study of propofol combined with two different doses of esketamine for laryngeal mask airway insertion in women undergoing hysteroscopy.

Objective: To prospectively determine the median effective dose (ED50) of propofol for inhibiting a response to laryngeal mask airway (LMA) insertion when combined with different doses of esketamine in female patients. Methods: A total of 58 female patients (aged 20-60 years, ASAⅠ-Ⅱ) scheduled for elective hysteroscopy were enrolled and randomly divided into 2 groups, one of which was administered 0.2 mg/kg of esketamine (K1 group, n = 28) and the other 0.3 mg/kg of esketamine (K2 group, n = 30). The 2 groups received the corresponding doses of esketamine intravenously, followed by an intravenous injection of propofol (injection time was 30 s). The initial dose of propofol was 2 mg/kg, and the dose ratio of propofol in the adjacent patients was 0.9. If a positive reaction occurred due to LMA insertion, the dose ratio in the next patient was increased by 1 gradient; if not, the dose ratio was decreased by 1 gradient. The ED50, 95 % effective dose (ED95) and 95 % confidence interval (CI) of propofol for inhibiting a response to LMA insertion in the 2 esketamine groups were calculated using probit analysis. Results: The ED50 of propofol for inhibiting a response to LMA insertion in female patients was 1.95 mg/kg (95 % CI, 1.82-2.08 mg/kg) in the K1 group and 1.60 mg/kg (95 % CI, 1.18-1.83 mg/kg) in the K2 group. The ED95 of propofol for inhibiting a response to LMA insertion in female patients was 2.22 mg/kg (95 % CI, 2.09-2.86 mg/kg) in the K1 group and 2.15 mg/kg (95 % CI, 1.88-3.09 mg/kg) in the K2 group. Conclusion: Propofol combined with 0.3 mg/kg of esketamine has low ED50 and ED95 effective doses for inhibiting an LMA insertion response in female patients undergoing hysteroscopy and surgery. There were no significant adverse effects, but the additional dose of propofol and airway pressure were significantly higher than those in the group administered 0.2 mg/kg of esketamine. Based on the results, we recommend the combination of propofol with 0.2 mg/kg esketamine for optimal conditions during LMA insertion in women undergoing hysteroscopy.

Clinicopathological characteristics and prognosis of Epstein-Barr virus-associated gastric cancer.

OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.