Single-Cell Sequencing Reveals MYOF-Enriched Monocyte/Macrophage Subcluster as a Favorable Prognostic Factor in Sepsis.

This research utilized single-cell RNA sequencing to map the immune cell landscape in sepsis, revealing 28 distinct cell clusters and categorizing them into nine major types. Delving into the monocyte/macrophage subclusters, 12 unique subclusters are identified and pathway enrichment analyses are conducted using KEGG and GO, discovering enriched pathways such as oxidative phosphorylation and antigen processing. Further GSVA and AUCell assessments show varied activation of interferon pathways, especially in subclusters 4 and 11. The clinical correlation analysis reveals genes significantly linked to survival outcomes. Additionally, cellular differentiation in these subclusters is explored. Building on these insights, the differential gene expression within these subclusters is specifically scrutinized, which reveal MYOF as a key gene with elevated expression levels in the survivor group. This finding is further supported by in-depth pathway enrichment analysis and the examination of cellular differentiation trajectories, where MYOF's role became evident in the context of immune response regulation and sepsis progression. Validating the role of the MYOF gene in sepsis, a dose-dependent response to LPS in THP-1 cells and C57 mice is observed. Finally, inter-cellular communications are analyzed, particularly focusing on the MYOF+Mono/Macro subcluster, which indicates a pivotal role in immune regulation and potential therapeutic targeting.

Circular olefin copolymers made de novo from ethylene and α-olefins.

Ethylene/α-olefin copolymers are produced in huge scale and widely used, but their after-use disposal has caused plastic pollution problems. Their chemical inertness made chemical re/upcycling difficult. Ideally, PE materials should be made de novo to have a circular closed-loop lifecycle. However, synthesis of circular ethylene/α-olefin copolymers, including high-volume, linear low-density PE as well as high-value olefin elastomers and block copolymers, presents a particular challenge due to difficulties in introducing branches while simultaneously installing chemical recyclability and directly using industrial ethylene and α-olefin feedstocks. Here we show that coupling of industrial coordination copolymerization of ethylene and α-olefins with a designed functionalized chain-transfer agent, followed by modular assembly of the resulting AB telechelic polyolefin building blocks by polycondensation, affords a series of ester-linked PE-based copolymers. These new materials not only retain thermomechanical properties of PE-based materials but also exhibit full chemical circularity via simple transesterification and markedly enhanced adhesion to polar surfaces.

Histone lactylation regulates cancer progression by reshaping the tumor microenvironment.

As a major product of glycolysis and a vital signaling molecule, many studies have reported the key role of lactate in tumor progression and cell fate determination. Lactylation is a newly discovered post-translational modification induced by lactate. On the one hand, lactylation introduced a new era of lactate metabolism in the tumor microenvironment (TME), and on the other hand, it provided a key breakthrough point for elucidation of the interaction between tumor metabolic reprogramming and epigenetic modification. Studies have shown that the lactylation of tumor cells, tumor stem cells and tumor-infiltrating immune cells in TME can participate in the development of cancer through downstream transcriptional regulation, and is a potential and promising tumor treatment target. This review summarized the discovery and effects of lactylation, as well as recent research on histone lactylation regulating cancer progression through reshaping TME. We also focused on new strategies to enhance anti-tumor effects via targeting lactylation. Finally, we discussed the limitations of existing studies and proposed new perspectives for future research in order to further explore lactylation targets. It may provide a new way and direction to improve tumor prognosis.

The SMAC mimetic birinapant alleviates lipopolysaccharide-induced acute lung injury by inhibiting MAPK signaling.

The second mitochondria-derived activator of caspases (SMAC) mimetic birinapant attenuated liver injury by inhibited the degradation of tumor necrosis factor receptor-associated factor 3 (TRAF3) and activation of mitogen-activated protein kinase (MAPK) signaling pathway in liver macrophage, but its role in LPS induced acute lung injury (ALI) is not understood. The present study was to investigate the effects of birinapant on ALI and its possible mechanism. A dose of birinapant (30 mg/kg) or a vehicle was administered intravenously 24 hours before LPS (100 µg) stimulation in mice. The levels of TNF-α, IL-6 and IL-1ß in bronchoalveolar lavage fluid (BALF) were measured by ELISA. The infiltrated macrophages and expression of monocyte chemoattractant protein-1 (MCP-1) was determined by immunohistochemistry staining in the lung tissues. The JNK and p38 MAPK activation, protein expression and K48-linked polyubiquitination of TRAF3 were determined in alveolar macrophage cell line (MH-S cells) after 1µg/ml LPS stimulation. The results showed that the birinapant down-regulated the levels of TNF-α, IL-6 and IL-1ß in the BALF. In addition, birinapant markedly inhibited macrophages infiltration and MCP-1 protein expression in lung tissues. At last, birinapant suppressed the MAPKsignaling pathway and K48-linked ubiquitinated degradation of TRAF3 in MH-S cells after LPS administration. In conclusion, the results proved that birinapant protected against LPS-induced ALI through inhibiting MAPK activation and K48-linked ubiquitination of TRAF3 in alveolar macrophages.

Methionine Promotes Milk Protein Synthesis via the PI3K-mTOR Signaling Pathway in Human Mammary Epithelial Cells.

Breast milk is widely considered to be the most natural, safe, and complete food for infants. However, current breastfeeding rates fall short of the recommendations established by the World Health Organization. Despite this, there are few studies that have focused on the promotion of human lactation through nutrient supplementation. Therefore, the aim of this study was to investigate the effect of methionine on milk synthesis in human mammary epithelial cells (MCF-10A cells) and to explore the underlying mechanisms. To achieve this, MCF-10A cells were cultured with varying concentrations of methionine, ranging from 0 to 1.2 mM. Our results indicated that 0.6 mM of methionine significantly promoted the synthesis of milk protein. An RNA-seq analysis revealed that methionine acted through the PI3K pathway. This finding was validated through real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. In addition, PI3K inhibition assays confirmed that methionine upregulated the expression of both mTOR and p-mTOR through activation of PI3K. Taken together, these findings suggest that methionine positively regulates milk protein synthesis in MCF-10A cells through the PI3K-mTOR signaling pathway.

Field-free spin-orbit torque switching in interlayer exchange coupled Co/Ta/CoTb.

This study investigates a T-type field-free spin-orbit torque device with an in-plane magnetic layer coupled to a perpendicular magnetic layer via a non-magnetic spacer. The device utilizes a Co/Ta/CoTb structure, in which the in-plane Co layer and the perpendicular CoTb layer are ferromagnetically (FM) coupled through the Ta spacer. 'T-type' refers to the magnetization arrangement in the FM/spacer/FIM structure, where the magnetization in FM is in-plane, while in FIM, it is out-of-plane. This configuration forms a T-shaped arrangement for the magnetization of the two magnetic layers. Additionally, 'interlayer exchange coupling (IEC)' denotes the interaction between the two magnetic layers, which is achieved by adjusting the material and thickness of the spacer. Our results show that an in-plane effective field from the IEC enables deterministic current-induced magnetization switching of the CoTb layer. The field-driven and the current-driven asymmetric domain wall motion are observed and characterized by magneto-optic Kerr effect measurements. The functionality of multistate synaptic plasticity is demonstrated by understanding the relationship between the anomalous Hall resistance and the applied current pulses, indicating the potential for the device in spintronic memory and neuromorphic computing.

Enhancing Milk Production by Nutrient Supplements: Strategies and Regulatory Pathways.

The enhancement of milk production is essential for dairy animals, and nutrient supplements can enhance milk production. This work summarizes the influence of nutrient supplements-including amino acids, peptides, lipids, carbohydrates, and other chemicals (such as phenolic compounds, prolactin, estrogen and growth factors)-on milk production. We also attempt to provide possible illuminating insights into the subsequent effects of nutrient supplements on milk synthesis. This work may help understand the strategy and the regulatory pathway of milk production promotion. Specifically, we summarize the roles and related pathways of nutrients in promoting milk protein and fat synthesis. We hope this review will help people understand the relationship between nutritional supplementation and milk production.

Cyperus (Cyperus esculentus L.): A Review of Its Compositions, Medical Efficacy, Antibacterial Activity and Allelopathic Potentials.

Cyperus (Cyperus esculentus L.) is an edible perennial grass-like plant, which propagates exclusively with underground tubers. Its tubers are rich in starch (20-30%), fat (25-35%), sugar (10-20%), protein (10-15%) and dietary fiber (8-9%). In addition, the tubers also contain alkaloids, organic acids, vitamins (C and E), steroids, terpenoids and other active components. The contents of oleic acid and linoleic acid in Cyperus oil are very high, which have important medicinal value and health-promoting properties. Most of the extracts from the tubers, stems and leaves of Cyperus have allelopathic potential and antibacterial, antioxidant and insecticidal activities. In recent years, the planting area of Cyperus has increased significantly all over the world, especially in China and some other countries. This paper presents the current status of Cyperus and the recent trend in research in this area. Published reports on its nutritional contents, active ingredients, medicinal efficacy, antibacterial activity and allelopathic potential were also reviewed.

Kupffer cells depletion alters cytokine expression and delays liver regeneration after Radio-frequency-assisted Liver Partition with Portal Vein Ligation.

Radio-frequency-assisted Liver Partition with Portal Vein Ligation (RALPP) induces comparable hypertrophy of the liver remnant compared to Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) in humans. However, whether it is significantly improved compared to ALPPS is unclear, and the underlying mechanisms of liver regeneration after RALPP need to further investigate. The present study was to develop an animal model mimicking RALPP and explore mechanisms of liver regeneration. The mice in RALPP group received liver radiofrequency ablation and 90% portal vein ligation (PVL), followed by resection of the targeted liver within two days after the first surgery. The mice in ALPPS group underwent 90% PVL combined with parenchyma transection. Controls received liver radiofrequency ablation (RAF group) or PVL (PVL group) or small left lateral lobe (LLL group) resection alone. Liver regeneration was assessed by liver weight and proliferation-associated molecules. The role of Kupffer cells (KCs) in liver regeneration was investigated after RALPP. The results showed that RALPP induced comparable liver regeneration compared to ALPPS, but with less liver injury and mortality in mice. RALPP led to over-expression of TNF-α and IL-6 in the circulating plasma compared with PVL. KCs infiltrating in liver tissues was a characteristic of mice in the RALPP group. KCs depletion markedly depressed cytokine expression and delayed liver regeneration after RALPP. These results suggested that RALPP in mice induced accelerated liver regeneration similar to ALPPS, but safer than ALPPS. KCs depletion altered cytokine expression and delayed liver regeneration after RALPP.

NF-κB activation impedes the transdifferentiation of hypertrophic chondrocytes at the growth plate of mouse embryos in diabetic pregnancy.

BACKGROUND: Diabetes mellitus could cause numerous complications and health problems including abnormality of endochondral bone formation during embryogenesis. However, the underlying mechanisms still remain obscure. METHODS: Streptozotoci (STZ) was injected to induce pregestational diabetes mellitus (PGDM) mouse model. The femurs of E18.5 mouse embryos from control and PGDM groups were harvested. Morphological staining was implemented to determine the abnormality of the bone development. The expressions of the key genes participating in osteogenesis (e.g., Sox9, Runx2, and Osterix), the NF-κB signaling molecules (e.g., P50, P65, IκBα), and the corresponding regulatory factors (e.g., Bmp2, phospho-p38) were evaluated by immunofluorescence, quantitative PCR and western blot. Finally, in vitro chondrocyte differentiation model was employed to verify the role of NF-κB on the expressions of chondro-osteogenic markers. RESULTS: Alcian blue/alizarin red double staining and H&E staining demonstrated the restriction of skeletal development and relatively extended hypertrophic zone at growth plate in E18.5 STZ-induced diabetic mouse embryos compared to the control. Immunofluorescent staining and qPCR showed that Sox9 expression increased, while Runx2 and Osterix expressions decreased in the growth plate of the offspring of PGDM mice. Immunofluorescence of P65 manifested the activation of NF-κB signaling in growth plate in PGDM mouse embryos. Furthermore, the relatively extended hypertrophic zone was also observed in the growth plate of the NF-κB-activated transgenic mice, as well as the activated p65 up-regulated the expression of Bmp2 and p-p38. In ATDC5 cells, we could observe the high glucose up-regulated the P50 and P65 expressions and down-regulated IκBα expression, but the high glucose-activated NF-κB signaling could be reversed by addition of Bay (inhibitor of NF-κB signaling). The expression changes of Bmp2, Sox9 and Runx2 in presence of high glucose were resumed too. CONCLUSION: Our data revealed that NF-κB signaling was involved in mediation effects of dysfunctional trans-differentiation of hypertrophic chondrocytes in the embryonic growth plate induced by maternal diabetic mellitus.

Development and validation of a simple and sensitive LC-MS/MS method for quantification of ampicillin and sulbactam in human plasma and its application to a clinical pharmacokinetic study.

Ampicillin-sulbactam is a broad-spectrum combination antibiotic used for a variety of clinical applications, including as a prophylactic agent to reduce the risk of surgical site infection. The pharmacokinetics of ampicillin-sulbactam after redosing during prolonged surgeries remains incompletely understood. In anticipation of further studying the intra-operative pharmacokinetics of this drug, we have developed a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of ampicillin and sulbactam. The plasma samples were prepared using a simple protein precipitation method. Gradient chromatographic elution was used to separate analytes, and MS/MS analysis was performed in negative ionization mode for both analytes via multiple reaction monitoring (MRM). All validation parameters were evaluated under a good laboratory practice (GLP) environment. For both ampicillin and sulbactam, the lower limit of quantitation (LLOQ) was established as 0.25 µg/mL. The calibration curve ranged from 0.25 to 200 µg/mL for ampicillin and 0.25-100 µg/mL for sulbactam. Inter- and intra-day precisions for both analytes were ≤11.5 % for quality controls and ≤17.4 % for LLOQ; accuracies ranged from -11.5 to 12.5% for 3 quality control levels and -18.1-18.7% for LLOQ. In addition to sensitivity, accuracy and precision, 13 other parameters were also validated for both analytes, and the results met the acceptance criteria. Our method was successfully applied to quantify ampicillin and sulbactam concentrations in patients undergoing surgery.

Reversine suppresses osteosarcoma cell growth through targeting BMP-Smad1/5/8-mediated angiogenesis.

Reversine, or 2-(4-morpholinoanilino)-6cyclohexylaminopurine, is a 2,6-disubstituted purine derivative. This small molecule exhibits tumor-suppressive activities through different molecular mechanisms. In this study, in vitro and in vivo angiogenic models were used to elucidate the effect of Reversine on angiogenesis in the tumor suppression. Firstly, we grafted osteosarcoma-derived MNNG/HOS cell aggregates onto chick embryonic chorioallantoic membrane (CAM) to examine the vascularization of these grafts following Reversine treatment. Following culture, it was determined that Reversine inhibited MNNG/HOS grafts growth, and decreased the density of blood vessels in the chick CAM. We then used CAM and chick embryonic yolk-sac membrane (YSM) to investigate the effects of Reversine on angiogenesis. The results revealed Reversine inhibited the proliferation of endothelial cells, where cells were mainly arrested at G1/S phase of the cell cycle. Scratch-wound assay with HUVECs revealed that Reversine suppressed cell migration in vitro. Furthermore, endothelial cells tube formation assay and chick aortic arch sprouting assay demonstrated Reversine inhibited the sprouting, migration of endothelial cells. Lastly, qPCR and western blot analyses showed BMP-associated Smad1/5/8 signaling expressions were up-regulated by Reversine treatment. Our results showed that Reversine could suppress tumor growth by inhibiting angiogenesis through BMP signaling, and suggests a potential use of Reversine as an anti-tumor therapy.

A Systematic Review and Meta-analysis of Isoniazid Pharmacokinetics in Healthy Volunteers and Patients with Tuberculosis.

PURPOSE: This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis (TB), evaluates whether the current INH dose regimen is appropriate in patients with TB, and evaluates the impact of N-acetyl-transferase-2 (NAT2) status on the PK properties of INH. METHODS: A systematic approach was conducted to find studies with relevant INH PK data published in the English language up to February 2018. The PK properties of INH were extracted with their respective INH dosages and were dose normalized to allow a fair comparison between healthy volunteers and patients with TB. Meta-analysis was then performed for the Cmax and AUC estimates for all INH dosages. FINDINGS: Ninety studies were included in this systematic review. TB status significantly affected the INH Cmax and AUC estimates. In healthy volunteers, the dose-normalized INH Cmax and AUC were statistically higher than those of patients with TB. No significant differences were found in dose-normalized Cmax and AUC between adults with TB and adults with TB/HIV; however, the AUC in pediatric patients was significantly different between patients with TB and patients with TB/HIV. In addition, no significance was observed comparing the dose-normalized Cmax and AUC of pediatric patients with TB and TB/HIV with their respective adult counterparts. Dose-normalized INH Cmax and AUC in patients with fast and intermediate NAT2 were significantly lower than in patients with slow NAT2. IMPLICATIONS: The current recommended dosages of INH were found to produce less drug exposure in patients with TB when compared with healthy volunteers. NAT2 polymorphism greatly impacts the PK properties of INH; hence, testing for acetylator status is highly recommended, and therapeutic drug monitoring would help reduce INH toxicity.

STAT5a induces endotoxin tolerance by alleviating pyroptosis in kupffer cells.

Pyroptosis, a newly discovered type of programmed cell death, affects endotoxin tolerance in macrophages. However, the factors acting on the nod-like receptor 3 (Nlrp3) inflammasome and caspase1 activation to impede pyroptosis and resulting in tolerance and survival in sepsis were needed to discovered. Here, we found that signal transducer and activator of transcription 5A (STAT5a) restrains pyroptosis in Kupffer cells (KCs) and induces endotoxin tolerance (ET) in a sepsis model. The lentiviral knockdown of STAT5a led to enhanced pyroptosis in KCs, increased IL-1ß production and decreased IL-10 production via intricate NF-κb signaling regulation. Thus, our findings reveal a novel mechanism of STAT5a-midiated endotoxin tolerance in KCs.

Dysbacteriosis-Derived Lipopolysaccharide Causes Embryonic Osteopenia through Retinoic-Acid-Regulated DLX5 Expression.

Growing evidence suggests an adverse impact of gut microbiota dysbiosis on human health. However, it remains unclear whether embryonic osteogenesis is affected by maternal gut dysbacteriosis. In this study, we observed that elevated lipopolysaccharide (LPS) levels led to skeletal developmental retardation in an established mouse model of gut microbiota dysbiosis. Using chick embryos exposed to dysbacteriosis-derived LPS, we found restriction in the development of long bones as demonstrated by Alcian blue and alizarin red staining. Micro-CT and histological analysis exhibited decreased trabecular volume, bone mineral density, and collagen production, as well as suppressed osteoblastic gene expression (Ocn, Runx2, Osx, and Dlx5) in chick embryonic phalanges following LPS treatment. Atomic force microscopy manifested decreased roughness of MC3T3-E1 cells and poorly developed matrix vesicles (MVs) in presence of LPS. The expression of the aforementioned osteoblastic genes was suppressed in MC3T3-E1 cells as well. High-throughput RNA sequencing indicated that retinoic acid (RA) may play an important role in LPS-induced osteopenia. The addition of RA suppressed Dlx5 expression in MC3T3-E1 cells, as was also seen when exposed to LPS. Quantitative PCR, Western blot, and immunofluorescent staining showed that retinoic acid receptor α (RARα) was upregulated by LPS or RA treatment, while the expression of DLX5 was downregulated. CYP1B1 expression was increased by LPS treatment in MC3T3-E1 cells, which might be attributed to the increased inflammatory factors and subsequently activated NF-κB signaling. Eventually, blocking RA signals with AGN193109 successfully restored LPS-inhibited osteoblastic gene expression. Taken together, our data reveals that maternal gut microbiota dysbiosis can interfere with bone ossification, in which Dlx5 expression regulated by RA signaling plays an important role.

The on-off action of Forkhead protein O3a in endotoxin tolerance of Kupffer cells depends on the PI3K/AKT pathway.

BACKGROUND: The endotoxin tolerance (ET) of Kupffer cells (KCs) is an important protective mechanism for limiting endotoxin shock. As a key anti-inflammatory molecule, the roles and mechanism of Forkhead protein O3a (Foxo3a) in ET of KCs are not yet well understood. METHODS: ET and nonendotoxin tolerance (NET) KCs models were established in vitro and in vivo. The levels of cytokines were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression and phosphorylation levels were detected by western blotting (WB). Changes in the localization of nuclear factor kappa B (NF-κB) and Foxo3a in KCs were detected by immunofluorescence assays. KCs apoptosis and survival rates were detected by flow cytometry and an automatic cell counter, respectively. RESULTS: The activity of NF-κB and the levels of p-Foxo3a and tumor necrosis factor (TNF-α) in the ET group were significantly lower than those in the NET group, while the levels of Foxo3a and interleukin 10 (IL-10) in the ET group were significantly higher than those in the NET group. Overexpression of Foxo3a or the use of a phosphatidylinositol-3-hydroxykinase (PI3K) inhibitor suppressed the activation of NF-κB by decreasing the levels of p-Foxo3a by inhibiting the activity of PI3K/AKT, which improved the tolerance of KCs and mice to endotoxin. In contrast, silencing Foxo3a or the use of a PI3K agonist reduced the tolerance of KCs and mice to endotoxin. The PI3K agonist counteracted the inhibitory effects of Foxo3a overexpression on NF-κB, impairing the tolerance of KCs to endotoxin. CONCLUSIONS: The on-off action of Foxo3a in the ET of KCs depends on the PI3K/AKT pathway.

Understanding the singlet-triplet energy splittings in transition metal-capped carbon chains.

The singlet-triplet energy splittings (STES) of dication carbon chains capped by three 16-electron and two 14-electron configuration transition metal termini have been investigated using density functional theory. All five transition metal-capped carbon chains (MCC) exhibit an odd-even STES alternation, suggesting that it is a general feature of the MCCs. Analysis of the frontier molecular orbitals indicates that the frontier and neighboring molecular orbitals (MOs) are π orbitals delocalized over the entire carbon chain, the transition metal termini, and the ancillary ligands. In even and odd metal-carbon chains the HOMOs and LUMOs are nearly degenerate and non-degenerate, respectively, resulting in the even-odd STES alternation. Further analysis of the MOs in the MCCs and the uncapped carbon chains indicate that the STES of the MCCs are determined substantially by the uncapped carbon chain. Other ancillary ligands also play important roles in tuning the energy splitting through their π donor and acceptor abilities. These observations are helpful for the design of cumulene materials exhibiting tunable electronic and optical properties.

Cholesterol impairs hepatocyte lysosomal function causing M1 polarization of macrophages via exosomal miR-122-5p.

Nonalcoholic steatohepatitis (NASH) is a major threat to health worldwide. Lipotoxicity and macrophage-mediated inflammation play key roles in the pathogenesis of NASH. In this study, we found that individuals with higher serum LDL-C levels have a higher prevalence of nonalcoholic fatty liver disease (NAFLD) and elevated levels of glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase and alkaline phosphatase. A logistic regression analysis revealed that serum LDL-C level is an independent risk factor for the prevalence and prognosis of NAFLD. In vitro, we used ox-LDL and MßCD-cholesterol to treat Huh7 cells and found that cholesterol loading reduced lysosomal quantity and impaired lysosomal acidification, reducing the number of multivesicular bodies (MVBs) colocalizing with lysosomes. The bafilomycin A1 inhibition of lysosomal function also inhibited lysosomal MVBs degradation, promoting the release of exosomes from the Huh7 cells. Next, we found that cholesterol loading promoted exosome release from the Huh7 cells. The exosomes from the cholesterol-loaded cells increased the ratio of the THP-1 cells positive for the M1 marker (iNOS-1) without affecting the ratio of the cells positive for the M2 marker (CD206). Moreover, an elevated level of miR-122-5p was observed in exosomes derived from the Huh7 cells loaded with cholesterol. While the miR-122-5p mimics promoted THP-1 M1 polarization, downregulating miR-122-5p in the Huh7 cells inhibited the exosome-induced activation of macrophages and macrophage-related inflammation. These findings suggest that cholesterol plays an important role in the development and progression of NASH. Cholesterol-induced lysosomal dysfunction increases exosome release from hepatocytes, resulting in M1 polarization and macrophage-induced inflammation in a miR-122-5p-dependent manner.

Behavioural interventions targeting physical activity improve psychocognitive outcomes in COPD.

This study explored the impact of a self-management behaviour modification (SMBM) programme with/without bronchodilators and with/without exercise training (ExT) to improve daily physical activity on psychological and cognitive outcomes in COPD patients as a secondary analysis of the PHYSACTO trial. A 12-week, four-group, randomised, partially double-blind, placebo-controlled, parallel-group trial of SMBM in addition to tiotropium 5 µg, tiotropium/olodaterol 5/5 µg, tiotropium/olodaterol 5/5 µg plus ExT, or placebo was conducted in 304 patients. Outcomes included anxiety (Hospital Anxiety and Depression Scale (HADS)-A), depression (HADS-D and Patient-Health Questionnaire (PHQ)-9) and cognitive function (Montreal Cognitive Assessment (MoCA)). All outcomes showed statistically and clinically significant improvements after 12 weeks independent of treatment group. However, greater improvements in HADS-A and MoCA were seen in patients who exhibited greater increases in physical activity and exercise capacity, respectively, whereas greater improvements in HADS-D and PHQ-9 were seen in patients who exhibited increases in either physical activity or exercise capacity. The results indicate that SMBM with/without bronchodilators or ExT was associated with improved psychological and cognitive functioning. Anxiety reduced with increased physical activity, cognitive function improved with increased exercise capacity, and depression reduced with increases in either physical activity or exercise capacity. Interventions that increase daily physical activity or exercise capacity may improve psychological and cognitive outcomes in COPD.

Risk Assessment of Laparoscopic Cholecystectomy in Liver Cirrhotic Patients with Clinically Significant Portal Hypertension: A Retrospective Cohort Study.

Objective: This study was aimed to evaluate the correlation between clinically significant portal hypertension (CSPH) and postoperative complications and risk predictors of postoperative complications. Methods: The retrospective study was conducted to identify the effect. The cirrhotic patients were divided into two groups, those with or without CSPH. The intraoperative and postoperative conditions were evaluated. Multivariate logistic regression analysis was performed to identify potential risk predictors for postoperative complications in cirrhotic patients with CSPH. Results: The cirrhotic patients with CSPH who underwent laparoscopic cholecystectomy (LC) had postoperative hospitalization than the patients without CSPH. However, the incidence of postoperative complications between two groups showed no significant difference. The results of multivariate analysis showed that male, gallbladder wall >3 mm, size of stones ≥1 cm, scores of Model for end-stage liver disease (MELD) ≥10, and operation time >60 minutes were the potential risk predictors for postoperative complications. Conclusions: CSPH did not increase the incidence of postoperative complications in cirrhotic patients who underwent LC, but increased conversion rate and prolonged postoperative hospitalization. Furthermore, our study showed that gender, sizes of gallbladder wall and stones, scores of MELD, and operation time were the important postoperative risk predictors for cirrhotic patients with CSPH.