Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

Prognostic Significance of Tumor Necrosis in Patients with Gallbladder Carcinoma Undergoing Curative-Intent Resection.

BACKGROUND: Tumor necrosis has been indicated to correlate with dismal survival outcomes of a variety of solid tumors. However, the significance and prognostic value of tumor necrosis remain unclear in gallbladder carcinoma. The aim of this research is to explore the relationships between necrosis with long-term survival and tumor-related biological characteristics of patients with gallbladder carcinoma. PATIENTS AND METHODS: Patients with gallbladder carcinoma who accepted curative-intent resection in West China Hospital of Sichuan University (China) between January 2010 and December 2021 were retrospectively analyzed. Tumor necrosis was determined by staining the patient's original tissue sections with hematoxylin and eosin. Based on the presence of tumor necrosis, the pathologic features and survival outcomes were compared. RESULTS: This study enrolled 213 patients with gallbladder carcinoma who underwent curative-intent surgery, of whom 89 had tumor necrosis. Comparative analyses indicated that patients with tumor necrosis had more aggressive clinicopathological features, such as larger tumor size (p = 0.002), poorer tumor differentiation (p = 0.029), more frequent vascular invasion (p < 0.001), presence of lymph node metastasis (p = 0.014), and higher tumor status (p = 0.01), and experienced poorer survival. Univariate and multivariate analyses revealed that tumor necrosis was an independent prognostic factor for overall survival (multivariate: HR 1.651, p = 0.026) and disease-free survival (multivariate: HR 1.589, p = 0.040). CONCLUSIONS: Tumor necrosis can be considered as an independent predictive factor for overall survival and disease-free survival among individuals with gallbladder carcinoma, which was a valuable pathologic parameter.

[Effects of 4-hydroxy-2(3H)-benzoxazolone on proliferation and apoptosis of pancreatic cancer L3.6 cells].

This study explored the effects of 4-hydroxy-2(3H)-benzoxazolone(HBOA) on the proliferation and apoptosis of pancreatic cancer cells and its molecular mechanism. The L3.6 cells cultured in vitro were treated with HBOA of 0-1.0 mmol·L~(-1). The cell viability was detected by the cell counting kit-8(CCK-8) method, and the half inhibitory concentration(IC_(50)) was analyzed to determine the drug concentration and time. The cell morphology was observed under an inverted microscope and by acridine orange(AO) staining. The ability of proliferation and self-renewal were evaluated through live cell counting and colony formation experiments. The cell cycle progression and cell apoptosis rate were detected by flow cytometry. The morphology of cell apoptosis was observed by scanning electron microscopy. The mRNA expression of proliferating cell nuclear antigen(PCNA), cyclinA1, cyclinA2, cyclin dependent kinase 2(CDK2), and cyclin dependent kinase inhibitor 1A(P21) were determined by qPCR. The level of reactive oxygen species(ROS), lipid peroxide, and mitochondrial membrane potential were measured by flow cytometry. The activity of protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway was detected by Western blot. Compared with the control group, the cells treated with HBOA exhibited a significant decrease in viability. Then the optimal concentration and intervention time of HBOA were determined to be 0.4 mmol·L~(-1), 0.6 mmol·L~(-1), and 48 h. Compared with the control group, groups with HBOA of 0.4 mmol·L~(-1 )and 0.6 mmol·L~(-1) showed a significant suppression in cell proliferation and colony formation ability, down-regulated mRNA of PCNA, cyclinA1, cyclinA2, and CDK2, up-regulated P21 mRNA, S-phase cell cycle arrest, and increased cell apoptosis rate. There was an appearance of apoptotic bodies, increased ROS and lipid peroxide, decreased mitochondrial membrane potential(with a significant decrease in 0.6 mmol·L~(-1) group), and down-regulated p-Akt and p-mTOR proteins. The results show that HBOA inhibits the proliferation of pancreatic cancer L3.6 cells and induces cell apoptosis, which may be related to the increase in reactive oxygen species and the inhibition of the Akt/mTOR pathway.

Clinical use of real-time remote programming in pacemakers during the COVID-19 pandemic: A case report.

We report a case in which real-time remote interrogation and reprogramming of the parameters of a dual-chamber pacemaker was performed during the COVID-19 pandemic. The described case demonstrated the safety and effectiveness of CIED remote programming based on the 5G cloud technology support platform (5G-CTP), and showed that the application of real-time remote programming would help in reducing the risk of cross-infection between doctors and patients.

Purification and Biological Activities of Enzymatically Degraded Sargassum fusiforme Polysaccharides.

Enzymatic hydrolysate of the crude polysaccharide (SFP) extracted from Sargassum fusiforme was purified by column DEAE-52 and Sephadex G-100 to yield four components, namely, ESFP1, ESFP2, ESFP3 and ESFP4. These components were characterized by chemical composition assay, GC/MS, HPGPC, UV and FT-IR techniques. The in vitro antioxidant activities of the four purified fractions were investigated by measuring their radical scavenging activity and reducing power. The results suggested that all the four components possess good antioxidant activities. Among them, ESFP1 was found to possess the strongest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and hydroxyl radical-scavenging activity, and the greatest ferric reducing power. The immunomodulatory effect of these four polysaccharides was demonstrated by their ability to promote proliferation, and to enhance both phagocytic activity and NO release in a macrophage RAW264.7 model. The results revealed that the bioactivities of the polysaccharides are related to their molecular weight, and the uronic acid and sulfate contents.

Long noncoding RNA LINC00483/microRNA-144 regulates radiosensitivity and epithelial-mesenchymal transition in lung adenocarcinoma by interacting with HOXA10.

Lung adenocarcinoma (LAD) is the leading cause of cancer death worldwide. Long noncoding RNAs (lncRNAs) have been shown to play an important regulatory role in cancer biology, including that of LAD. The aim of this experiment was to explore the interaction of LINC00483, microRNA-144 (miR-144), and homeobox A10 (HOXA10), and their effects on radio sensitivity and epithelial-mesenchymal transition (EMT) of LAD. Initially, microarray analysis was used to screen out miRNAs and lncRNAs, as well as the differentially expressed genes related to LAD. Following the screening process, the targeting relationship of LINC00483, miR-144, and that of miR-144 and HOXA10 was determined. Following that, the expression of LINC00483, miR-144, messenger RNA (mRNA), as well as protein expression of HOXA10, MMP-2, MMP-9, E-cadherin, vimentin, and N-cadherin that followed in cells was determined. Also, the effect of LINC00483 on cell migration and invasion ability, and cell tumorigenic ability was detected. LINC00483 and HOXA10 were found to be upregulated whereas miR-144 was downregulated in LAD. Silencing of LINC00483 could competitively bind to miR-144, thereby upregulating HOXA10. LINC00483 or HOXA10 silencing led to decreased HOXA10, MMP-2, MMP-9, vimentin, and N-cadherin but elevated miR-144 and E-cadherin. Moreover, after being transfected with silenced LINC00483, the cell proliferation, migration, and invasion were inhibited with enhanced radiosensitivity. Consequently, the data of the study indicates that interference of LINC00483 weakens its competitive binding ability to miR-144, thus reducing HOXA10 expression, and enhancing radiosensitivity in LAD.

[Protective effect of Wuzi Yanzong recipe on testicular germ cell apoptosis in natural ageing rats through endoplasmic reticulum stress].

To study the protective effects of Wuzi Yanzong recipe on testis germ cell apoptosis in natural ageing rats through endoplasmic reticulum stress (ERS), 16-month-old male SPF grade SD rats were randomly divided into three groups: ageing model group, and low and high-dose Wuzi Yanzong recipe groups (WZ, 1 and 4 g·kg⁻¹), with 10 rats in each group. In addition, 2-month-old SD male rats were used as adult control group. The ageing model group and the adult control group were fed with normal diet for 4 months. WZ groups were given the medicated feed for 4 months. After fasting for 12 hours, the rats were put to death. Then, the testes were immediately collected. The change of testicular tissue morphology was observed by HE staining. The expression levels of ER stress-related proteins GRP78, p-PERK, p-eif2α, ATF4, p-IRE1, XBP1, ATF6 and apoptosis-related proteins CHOP, caspase12 and p-JNK in testes were detected by Western blot. Compared with the ageing model group, Wuzi Yanzong recipe alleviated the morphological changes of testicular tissue. Western blot results showed that Wuzi Yanzong recipe significantly increased the expression levels of endoplasmic reticulum stress-related proteins GRP78, p-PERK, p-eif2α, ATF4, p-IRE1, XBP1, ATF6 and significantly decreased the expression levels of endoplasmic reticulum-induced apoptosis-related proteins CHOP, caspase 12 and p-JNK. In conclusion, Wuzi Yanzong recipe can alleviate the ageing-related apoptosis of testicular germ cells in natural ageing rats by regulating endoplasmic reticulum stress.

[Protective effect of Wuzi Yanzong recipe on testicular DNA oxidative damage in natural ageing rats].

To study the protective effects of Wuzi Yanzong recipe on DNA oxidative damage of testis germ cells in natural ageing rats based on Nrf2/HO-1 signaling pathway and base excision repair (BER). In the study, 16-month-old SPF grade male SD rats were randomly divided into three groups, namely ageing model group, and low and high-dose Wuzi Yanzong recipe groups (WZ, 1, 4 g·kg⁻¹). In addition, 2-month-old SD rats were used as adult control group (10 rats in each group). The ageing model group and the adult control group were fed with normal diet for 4 months. WZ groups were given medicated feed for 4 months. After fasting for 12 hours, the rats were put to death. Then, the testes were immediately removed. The vitality of superoxide dismutase (SOD) and malondialdehyde (MDA) content in testis were detected by xanthine oxidase method and thiobarbituric acid (TBA) method. The levels of Nrf2 and 8-OHdG were detected by immunofluorescence. The protein expression levels of Nrf2, HO-1, NQO1, APE1, OGG1 and XRCC1 were detected by Western blot. Compared with the ageing model group, WZ significantly increased the SOD vitality and decreased MDA content of testis. In addition, immunofluorescence results showed that WZ significantly attenuated testicular DNA oxidative damage and improved antioxidant capacity. Such changes were accompanied by the down-regulation of DNA oxidative damage response protein 8-OHdG levels and the up-regulation of Nrf2 levels. Moreover, Western blot results showed that WZ significantly increased the protein expression levels of Nrf2, HO-1 and NQO1 of the testis germ cells, when compared with ageing model group. In parallel, the protein expression levels of APE1, OGG1 and XRCC1 were significantly decreased. In conclusion, WZ improves ageing-related DNA oxidative damage via Nrf2/HO-1 and BER pathways.

Comparison of the upfront surgery and neoadjuvant therapy in resectable and borderline resectable pancreatic cancer: an updated systematic review and meta-analysis.

Pancreatic cancer is a malignant disease with a dismal prognosis. While neoadjuvant therapy has shown promise in the treatment of pancreatic cancer, its role remains a subject of controversy among physicians. We aimed to evaluate the benefits of neoadjuvant therapy in patients with resectable and borderline resectable pancreatic cancer. Eligible studies were identified from MEDLINE, Embase, Cochrane Library, and Web of Science. Studies comparing neoadjuvant therapy with upfront surgery (with or without adjuvant therapy) in resectable and borderline resectable pancreatic cancer were included. The primary endpoint assessed was overall survival. A total of 10,022 studies were identified, and the meta-analysis finally enrolled 50 revealed studies. The meta-analysis suggested that neoadjuvant therapy significantly improved the overall survival (HR 0.74, p < 0.001) and recurrence-free survival (HR 0.75, p = 0.006) compared to the upfront surgery approach. Furthermore, neoadjuvant therapy leads to favorable postoperative outcomes, with an enhanced R0 resection rate (OR 1.90, p < 0.001) and reduced lymph node metastasis (OR 0.36, p < 0.001) and perineural invasion (OR 0.42, p < 0.001), although it is associated with a reduced resection rate (OR 0.42, p < 0.001). In addition, patients treated with neoadjuvant therapy experience superior survival benefits compared to those undergoing adjuvant therapy (HR 0.87, p = 0.019). These results are further corroborated by the subgroup analysis of randomized controlled trials. Neoadjuvant therapy has the potential to provide survival benefits and improve postoperative long-term outcomes for patients with resectable and borderline resectable pancreatic cancer. However, to validate and reinforce these findings, further well-designed and large trials are required.

Comparative efficacy and safety of SGLT2is and ns-MRAs in patients with diabetic kidney disease: a systematic review and network meta-analysis.

Objectives: To evaluate the efficacy and safety of non-steroid mineralocorticoid receptor antagonists (ns-MRAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) in patients with diabetic kidney disease (DKD). Methods: Systematic literature searches were performed using PubMed, Embase and Web of Science encompassing inception until January 20, 2024. Randomized control trials (RCTs) comparing ns-MRAs and SGLT2is in DKD were selected. The efficacy outcomes of interest included kidney-specific composite outcome, cardiovascular (CV)-specific composite outcome, end-stage kidney disease (ESKD), and overall mortality. We also investigated safety outcomes, including acute kidney injury (AKI) and hyperkalemia. Results: A total of 10 randomized clinical trials with 35,786 patients applying various treatments were included. SGLT2is (SUCRA 99.84%) have potential superiority in kidney protection. SGLT2is (RR 1.41, 95%CI 1.26 to 1.57) and ns-MRAs (RR 1.17, 95% CI 1.08 to 1.27) were associated with significantly lower kidney-specific composite outcome than the placebo. Regarding the reduction in CV-specific composite outcome and ESKD, SGLT2is (SUCRA 91.61%; 91.38%) have potential superiority in playing cardiorenal protection. Concerning the CV-specific composite outcome (RR 1.27, 95%CI 1.09 to 1.43) and ESKD (RR 1.43, 95%CI 1.20 to 1.72), SGLT2is significantly reduced the risks compared to placebo. Regarding the reduction in overall mortality, SGLT2is (SUCRA 83.03%) have potential superiority in postponing mortality. Concerning the overall mortality, SGLT2is have comparable effects (RR 1.27, 95%CI 1.09 to 1.43) with placebo to reduce the risk of overall mortality compared to placebo. For AKI reduction, ns-MRAs (SUCRA 63.58%) have potential superiority. SGLT2is have comparable effects (RR 1.24, 95%CI 1.05 to 1.46) with placebo to reduce the risk of AKI. For hyperkalemia reduction, SGLT2is (SUCRA 93.12%) have potential superiority. SGLT2is have comparable effects (RR 1.24, 95%CI 1.05 to 1.46) with placebo to reduce the risk of AKI. Concerning hyperkalemia reduction, nsMRAs (RR 1.24 95%CI 0.39 to 3.72) and SGLT2is (RR 1.01 95%CI 0.40 to 3.02) did not show significant benefit compared to placebo. Conclusion: Concerning the efficacy and safety outcomes, SGLT2is may be recommended as a treatment regimen for maximizing kidney and cardiovascular protection, with a minimal risk of hyperkalemia in DKD. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023458613.

Prognostic evaluation in gallbladder carcinoma: Introducing a composite risk model integrating nutritional and immune markers.

The importance of evaluating the nutritional status and immune condition prior to surgery has gained significant attention in predicting the prognosis of cancer patients in recent years. The objective of this study is to establish a risk model for predicting the prognosis of gallbladder carcinoma (GBC) patients. Data from GBC patients who underwent radical resection at West China Hospital of Sichuan University (China) from 2014 to 2021 were retrospectively collected. A novel risk model was created by incorporating the prognostic nutritional index and glucose-to-lymphocyte ratio, and each patient was assigned a risk score. The patients were then divided into low- and high-risk cohorts, and comparisons were made between the two groups in terms of clinicopathological features and prognosis. Propensity score matching was conducted to reduce potential bias. A total of 300 GBC patients receiving radical surgery were identified and included in this study. Patients in the high-risk group were older, had higher levels of serum carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), and cancer antigen 19-9 (CA19-9), were more likely to experience postoperative complications, and had more aggressive tumor characteristics, such as poor differentiation, lymph node metastasis, and advanced tumor stage. They also had lower overall survival (OS) rates (5-year OS rate: 11.2% vs. 37.4%) and disease-free survival (DFS) rates (5-year DFS rate: 5.1% vs. 18.2%). After propensity score matching, the high-risk population still experienced poorer prognosis (5-year OS rate: 12.7% vs 20.5%; 5-year DFS rate: 3.2% vs 8.2%). The risk model combining prognostic nutritional index and glucose-to-lymphocyte ratio can serve as a standalone predictor for the prognosis and assist in optimizing the treatment approach for GBC patients.

Ferroptosis in renal fibrosis: a mini-review.

Ferroptosis is a novel form of programmed cell death that is iron-dependent and distinct from autophagy, apoptosis, and necroptosis. It is primarily characterised by a decrease in glutathione peroxidase 4 (GPX4) activity, or by the accumulation of lipid peroxidation and reactive oxygen species (ROS). Renal fibrosis is a common pathological change in the progression of various primary and secondary renal diseases to end-stage renal disease and poses a serious threat to human health with high morbidity and mortality. Multiple pathways contribute to the development of renal fibrosis, with ferroptosis playing a crucial role in renal fibrosis pathogenesis due to its involvement in the production of ROS. Ferroptosis is related to several signalling pathways, including System Xc-/GPX4, abnormal iron metabolism and lipid peroxidation. A number of studies have indicated that ferroptosis is closely involved in the process of renal fibrosis caused by various kidney diseases such as glomerulonephritis, renal ischaemia-reperfusion injury, diabetic nephropathy and renal calculus. Identifying the underlying molecular mechanisms that determine cell death would open up new insights to address a therapeutic strategy to renal fibrosis. The review aimed to browse and summarise the known mechanisms of ferroptosis that may be associated with biological reactions of renal fibrosis.

Unraveling early recurrence of risk factors in Gallbladder cancer: A systematic review and meta-analysis.

BACKGROUND: Gallbladder cancer (GBC) is the most prevalent biliary tract tumor characterized by a high incidence of recurrence, even after curative-intent surgery. The object of this systematic review and meta-analysis was to investigate the risk factors related to early recurrence (ER). METHODS: A systematic literature review was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify published articles up to February 2024. Data on risk factors associated with ER reported by two or more studies were collected. Selection of different effect models based on data heterogeneity. RESULTS: Out of 6497 initially identified articles based on our search strategies, only 5 were eligible and included in this meta-analysis and 12 ER-related factors were collected. The overall recurrence rate was reported between 32.3% and 61.0 %, and the ER rate ranged from 19.6% to 26.5 %. Concentrations of CA19-9 (OR 3.03 95 % CI 2.20-4.17) and CEA (OR 1.85 95 % CI 1.24-2.77), tumor differentiation (OR 2.79, 95 % CI 1.86-4.20), AJCC T stage (OR 7.64, 95%CI 3.40-17.18), lymphovascular invasion (OR 2.71, 95 % CI 1.83-4.03), perineural invasion (OR 2.71, 95 % CI 1.79-4.12), liver involvement (OR 5.69, 95%CI 3.78-8.56) and adjuvant therapy (OR 2.19, 95 % CI 1.06-4.55) were identified as the risk factors of ER. CONCLUSION: This study may provide valuable insights for early identification of increased ER risk and making informed decisions regarding the comprehensive diagnosis and treatment of patients with GBC. To draw more definitive conclusions, there is a need for high-quality prospective studies involving multiple centers and diverse racial populations.

Glycosides constituents from Codonopsis pilosula.

A new glycoside (1) along with six known analogues (1-7) were isolated from Codonopsis pilosula collected at Shanxi in China. The structure of 1 was established based on comprehensive spectroscopic data and literature comparison. The anti-inflammatory effects of isolated compounds were further investigated in LPS-induced RAW264.7 macrophage.

Five new secondary metabolites from Aster tataricus.

Aster tataricus L.f. is highly valued for its rich reserves of bioactive compounds. Our research focused on the identification of previously unreported compounds found within the ethanol extract of A. tataricus. Through meticulous spectroscopic analyses and computational methods like NMR calculations and ECD, we successfully elucidated the structures of five novel compounds termed tatarisides A-E (1-5), alongside two known compounds (6, 7). The anti-inflammatory assays conducted yielded noteworthy results, particularly in relation to compounds 1 and 5. These compounds exhibited significant potential in inhibiting the release of NO in LPS-induced RAW 264.7 cells, as evidenced by their respective IC50 values of 17.81 ± 1.25 µM and 13.32 ± 0.84 µM. The discovery of these new compounds adds to the existing knowledge of A. tataricus's chemical composition and potential applications.

Effects of Species Invasion and Inundation on the Collembola Community in Coastal Mudflat Wetland from the Perspective of Functional Traits.

The group of soil arthropods known as Collembola is characterized by its abundance and sensitivity to environmental changes. They are ideal an species for soil indicators. In order to clarify the effects of species invasion and inundation on the Collembola community in coastal mudflat wetlands, the correlation between the collembolan functional traits and environmental factors was studied in Shanghai Jiuduansha Wetland National Nature Reserve for the first time. Five sample plots, including three vegetations-Spartina alterniflora (an invasive species), Phragmites australis, and Zizania latifolia-were set up following the differences in vegetation types and between high and low tidal flats. Data on the diversity of the Collembolan species and their functional traits were collected and combined with the soil physicochemical properties and vegetation environment factors in different tidal flats. The key findings and conclusions of the study are as follows: a total of 18 species, four families, and three orders make up the obtained Collembola, two species of Proisotoma are dominant species that account for 49.59% and 24.91% of the total, respectively. The maintenance of the species diversity of Collembola is disturbed by the higher conversion efficiency of Spartina alterniflora rather than Phragmites australis with lower organic carbon (C) content and higher total nitrogen (N) content. The primary environmental variables influencing species distribution were the C/N ratio, total N, and bulk soil density. The bulk density of the soil impacts the movement and dispersal of the functional traits. The depth of the soil layer is related to the functional traits of the sensory ability. The analysis of the functional traits and environment is fairly helpful in exploring how species respond to their environment and offers a better explanation for the habitat selection of Collembola.

Effects of different doses of esketamine intervention on postpartum depressive symptoms in cesarean section women: A randomized, double-blind, controlled clinical study.

BACKGROUND: The optimal dosage and method of esketamine for postpartum depressive symptoms (PDS) are unclear. We conducted a randomized controlled trial (RCT) to investigate the effect of different doses of esketamine on PDS in women undergoing cesarean section, with evidence of prenatal depression. METHODS: The three groups were high- (2 mg kg-1) and low-dose (1 mg kg-1) esketamine via patient controlled intravenous analgesia (PCIA), following an initial intravenous infusion of 0.25 mg kg-1 esketamine, compared to placebo (0.9 % saline infusion). All groups also received the sufentanil (2.2 µg kg-1). The primary outcome was the incidence of PDS at 7 and 42 days postpartum. The secondary outcomes were: the remission from depression and total EPDS scores at 7 days and 42 days postpartum; mean change from baseline in the EPDS score; postoperative analgesia. RESULTS: i). 0.25 mg kg-1 of esketamine intravenous infusion combined with 1 mg kg-1 (n = 99) or 2 mg kg-1 (n = 99) esketamine PCIA reduces PDS incidence at 7 days postpartum (p < 0.05), with high-dose esketamine PCIA also reduces PDS incidence 42 days postpartum (p < 0.05), compared to placebo (n = 97). ii). Low- and high-dose esketamine PCIA lowers NRS scores at rest within 48 h postoperatively (p < 0.01), with high-dose esketamine also reducing the NRS score during movement at 48 h postoperatively (p = 0.018). iii). Neither high- nor low-dose esketamine PCIA increased postoperative adverse reactions (p > 0.05). CONCLUSIONS: Esketamine (0.25 mg kg-1) intravenous infusion combined with 1 mg kg-1 or 2 mg kg-1 esketamine PCIA seems safe and with few adverse effects in the management of PDS and pain in women undergoing cesarean section. LIMITATIONS: The tolerability and safety of esketamine requires further investigation based on more specific scales; the transient side effects of esketamine could have biased the staff and patients. TRIAL REGISTRATION: ChiCTR-ROC-2000039069.

Prognostic Value of the Leuko-Glycemic Index in Acute Myocardial Infarction Patients with or without Diabetes.

Purpose: The leuko-glycaemic index (LGI) is an index that combines white blood cell count and blood glucose and could be a marker of systemic inflammatory response syndrome. The prognostic value of the LGI in acute myocardial infarction (AMI) is still unclear. We aimed to investigate the prognostic value of the LGI for short- and long-term prognosis in AMI patients with different diabetic status. Patients and Methods: This was an observational, multicenter study involving 1256 AMI patients admitted in 11 hospitals between March 2014 and June 2019 in Chengdu. White blood cell count and blood glucose were measured on admission. The LGI was calculated by multiplying both values and dividing them by a thousand. Logistic regression was used to explore the predictive value of LGI in in-hospital mortality. Receiver operating characteristic curve was used to determine the optimal cut-off values of the LGI to predict in-hospital mortality. The patients were classified into diabetic and non-diabetic groups and further divided into higher and lower LGI subgroups according to the optimal cut-off values. The endpoints were all-cause mortality during the hospitalization and major adverse cardiovascular and cerebrovascular events (MACCE) during follow-up, including all-cause mortality, non-fatal myocardial infarction, vessel revascularization and non-fatal stroke. Results: LGI was an independent predictor of all-cause mortality during the hospitalization in non-diabetics, but not in diabetics. The optimal cut-off values of diabetics and non-diabetics were 3593 mg/dl. mm3 and 1402 mg/dl. mm3, respectively. Whether diabetics or not, in-hospital mortality was higher in the higher LGI subgroup (p-value < 0.001). And in the follow-up of 15 months (9 months, 22 months), we observed 99 (8.6%), 6 (0.5%), 54 (4.7%) and 29 (2.5%) cases of death, non-fatal MI, revascularization and non-fatal stroke, respectively. The cumulative incidence of MACCE during follow-up was higher in the higher LGI subgroup, both in the diabetics and non-diabetics (p-value < 0.05). In non-diabetics, higher LGI was an independent predictor of MACCE. Conclusion: LGI was an independent predictor for short- and long-term prognosis in AMI patients without diabetes, but had no prognostic value for short- and long-term prognosis of AMI patients with diabetes.

Elevated lipoprotein(a) levels as an independent predictor of long-term recurrent events in patients with acute coronary syndrome: an observational, retrospective cohort study.

BACKGROUND: Whether lipoprotein(a) [Lp(a)] is associated with recurrent cardiovascular events (RCVEs) still remains controversial. The present study aimed to investigate the prognostic value of Lp(a) for long-term RCVEs and each component of it in people with acute coronary syndrome (ACS). METHODS: This multicenter, observational and retrospective study enrolled 765 ACS patients at 11 hospitals in Chengdu from January 2014 to June 2019. Patients were assigned to low-Lp(a) group [Lp(a) < 30 mg/dl] and high-Lp(a) group [Lp(a) ≥ 30 mg/dl]. The primary and secondary endpoints were defined as RCVEs and their elements, including all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke and unplanned revascularization. RESULTS: Over a median 17-month follow-up, 113 (14.8%) patients presented with RCVEs were reported, among which we observed 57 (7.5%) all-cause deaths, 22 (2.9%) cases of nonfatal stroke, 13 (1.7%) cases of nonfatal MI and 33 (4.3%) cases of unplanned revascularization. The incidences of RCVEs and revascularization in the high-Lp(a) group were significantly higher than those in the low-Lp(a) group ( P < 0.05), whereas rates of all-cause death, nonfatal stroke and nonfatal MI were not statistically different ( P > 0.05). Kaplan-Meier analysis also revealed the same trend. Multivariate Cox proportional hazards analysis showed that 1-SD increase of Lp(a) was independently associated with both the primary endpoint event [hazard ratio (HR), 1.285 per 1-SD; 95% confidence interval (CI), 1.112-1.484; P < 0.001] and revascularization (HR, 1.588 per 1-SD; 95% CI, 1.305-1.932; P < 0.001), but not with the other secondary events. CONCLUSION: Increased Lp(a) is an independent predictor of RCVEs and unplanned revascularization in patients with ACS.