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Abstract Aims Takotsubo syndrome (TTS) is an acute reversible cardiac dysfunction that may occur during the peri‐operative period and among patients with serious illness. We aimed to evaluate the clinical characteristics, peri‐operative management, and prognosis of peri‐operative TTS (pTTS) and explore the factors associated with pTTS. Methods We conducted a retrospective nested case–control study using the database of patients who underwent in‐hospital non‐cardiac surgeries between January 2017 and December 2020 in Peking University Third hospital. Cases were adult patients diagnosed TTS at discharge who were matched with four controls based on operative types. Multivariable conditional logistic regression was used to identified the factors associated with pTTS. The area under the curve (AUC) was used to evaluate the diagnostic efficacy. Results Among the 128 536 patients underwent non‐cardiac surgery, 20 patients with pTTS and 80 patients without were enrolled in this study. The incidence of pTTS was about 0.016% in our centre. The median age of patients with pTTS was 52.5 (38.25, 76.25) years, although 90% of them were female. Fifty per cent (9 cases) of female patients were pre‐menopausal. Caesarean section has the highest proportion of pTTS (30% of the pTTS cases) with the incidence of caesarean section‐related pTTS of 0.06% in our centre. A high prevalence of non‐apical ballooning pattern of regional wall motion abnormality (seven cases, 35%) and a high mortality (two cases, 10%) were observed. Left ventricular ejection fraction (LVEF) of patients with pTTS was significantly decreased (41.7 ± 8.8%). In the acute phase, supportive treatments aiming to reduce life‐threatening complications were main treatment strategies. After receiving systematic treatment, significant improvements were observed in LVEF (63.1 ± 13.5%), with median recovery time of LVEF of 7.48 days. Leucocyte count [odds ratio (OR): 4.59; 95% confidence interval (CI): 1.10–19.15], haemoglobin (HGB) (OR: 10.52; 95% CI: 1.04–106.36), and the revised cardiac risk index (RCRI) score (OR: 6.30; 95% CI: 1.05–37.88) were the factors significantly associated with pTTS. The RCRI score performed poorly in the prediction of pTTS (AUC: 0.630; 95% CI: 0.525–0.735). After adding leucocyte count and HGB into the RCRI score, the AUC was significantly improved (AUC: 0.768; 95% CI: 0.671–0.865; P = 0.001). Conclusions Patients with pTTS have some differences compared with common TTS, including higher proportion of pre‐menopausal female, higher prevalence during caesarean section, higher prevalence of non‐apical ballooning pattern of regional wall motion abnormality, and higher mortality. The RCRI score performed poorly in the evaluation of pTTS. Adding HGB and leucocyte count into the RCRI score could significantly improve its predictive performance.

AimsIt has been suggested that the triglyceride-glucose (TyG) index is a novel and reliable surrogate marker of insulin resistance (IR). However, its relationship with the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remains uncertain. Accordingly, we sought to examine the relationship between the TyG index and ESRD risk in patients with T2DM and CKD.MethodsFrom January 2013 to December 2021, 1,936 patients with T2DM and CKD hospitalized at Peking University Third Hospital (Beijing, China) were enrolled into the study. The formula for calculating the TyG index was ln[fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. ESRD was defined as an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 or the commencement of dialysis or renal transplantation. The relationship between the TyG index and ESRD risk was analyzed using Cox proportional hazard regression.Results105 (5.42%) participants developed ESRD over a mean follow-up of 41 months. The unadjusted analysis revealed a 1.50-fold (95% confidence interval [CI] 1.17-1.93; P = 0.001) increased risk for ESRD per one unit rise in the TyG index, and the positive association remained stable in the fully adjusted model (hazard ratio, 1.49; 95% CI, 1.12-1.99; P = 0.006). Analysis using restricted cubic spline revealed a significant positive association between the TyG index and ESRD risk. In addition, Kaplan-Meier analysis revealed significant risk stratification with a TyG index cutoff value of 9.5 (P = 0.003).ConclusionIn individuals with T2DM and CKD, a significant and positive association was shown between an elevated TyG index and the risk of ESRD. This conclusion provides evidence for the clinical importance of the TyG index for evaluating renal function decline in individuals with T2DM and CKD.

Non-alcoholic fatty liver disease (NAFLD) is a predominant contributor to end-stage liver disease in the forthcoming decades. Polygonum perfoliatum L. (PPL) is an herbal medicine with anti-lipid peroxidation and anti-inflammatory properties. However, detailed hepatoprotective effects of PPL against NAFLD and its underlying mechanisms are not fully understood. Here, we found that PPL protects against high fat diet (HFD)-induced hepatic steatosis, lipid peroxidation, and glucose-lipid metabolism dysfunction in NAFLD mice. We therefore performed a label-free quantitative proteomic profiling analysis to determine the effect of PPL treatment on liver tissue proteomics and identified that activated PPARs/CPT1A/CPT2-mediated hepatic fatty acid β-oxidation (FAO) process was significantly altered. In vitro treatment of hepatocytes with PPL confirmed this altered process and FAO inhibitor etomoxir (ETO) attenuated the lipid-lowering activity of PPL in hepatocytes. Ultra-high-performance liquid chromatography/Q Exactive-HFX (UPLC/QE-HFX) was used to determine the material basis of anti-NAFLD activity of PPL. Our results have demonstrated the efficacy and potential mechanisms of PPL as an effective pharmacological therapy of NAFLD.

Expression of DNA mismatch repair (MMR) protein (MLH1, PMS2, MSH2, and MSH6) in upper tract urothelial carcinoma (UTUC) has been explored in Western cohorts, but it is rarely reported in Eastern cohorts. We aimed to assess the loss of MMR protein expression among Chinese UTUC patients and study its clinicopathological implications. We enrolled 175 UTUC patients at our center and tested the expression of MMR proteins by immunohistochemistry. Then, we explored these patients’ clinicopathological characteristics. We found loss of MMR proteins in 19 (10.9%) of 175 patients in our cohort (6 MSH2 and MSH6, 2 MSH6 alone, 6 MSH2 alone, 3 MLH1 and PMS2, and 2 PMS2 alone). Loss of MMR proteins was not a significant prognostic factor of relapse-free survival for these patients. In addition, patients with lower T stage or with bladder cancer history were more likely to have loss of MMR protein expression. At last, two metastatic patients (MSH2 and MSH6 loss; MSH2 loss) with loss of MMR protein experienced tumor recession after several cycles of anti-PD-1 immunotherapy. In conclusion, this is the largest Chinese UTUC cohort study to date that explores the loss of MMR protein expression. The rate of MMR loss observed was comparable to that in the Western UTUC cohort, supporting universal UTUC screening in China. Furthermore, a subset of advanced UTUCs with MMR protein loss are probably immunogenic, for whom single or combined immunotherapy may be potential therapeutic options in the future.

Drug-induced liver injury (DILI) is a disease that remains difficult to predict and prevent from a clinical perspective, as its occurrence is hard to fully explain by the traditional mechanisms. In recent years, the risk of the DILI for microbiota dysbiosis has been recognized as a multifactorial process. Amoxicillin-clavulanate is the most commonly implicated drug in DILI worldwide with high causality gradings based on the use of RUCAM in different populations. Antibiotics directly affect the structure and diversity of gut microbiota (GM) and changes in metabolites. The depletion of probiotics after antibiotics interference can reduce the efficacy of hepatoprotective agents, also manifesting as liver injury. Follow-up with liver function examination is essential during the administration of drugs that affect intestinal microorganisms and their metabolic activities, such as antibiotics, especially in patients on a high-fat diet. In the meantime, altering the GM to reconstruct the hepatotoxicity of drugs by exhausting harmful bacteria and supplementing with probiotics/prebiotics are potential therapeutic approaches. This review will provide an overview of the current evidence between gut microbiota and DILI events, and discuss the potential mechanisms of gut microbiota-mediated drug interactions. Finally, this review also provides insights into the “double-edged sword” effect of antibiotics treatment against DILI and the potential prevention and therapeutic strategies.

The study of ultramafic rocks in Western Yunnan is of great significance for an understanding of the tectonic evolution of the Neo-Tethys Ocean. The zircon U–Pb data indicated that the Santaishan serpentinized pyroxene peridotite (SSPP) was formed 186–190 Ma, and the Yingjiang hornblende pyroxenite (YHP) was formed 182–183 Ma. The content of MgO in the SSPP is relatively high, but the SiO2, Al2O3, CaO and TiO2 content and ΣREE are low, while the YHP has opposite characteristics. The samples from the SSPP and YHP have similar distribution patterns of trace elements, both being enriched in large ion lithophile elements (LILEs) such as Rb, Ba and Th and depleted in high field strength elements (HFSEs) such as Ti, P and Nb. These characteristics are consistent with the supra-subduction zone (SSZ) type and mid-ocean ridge basalt (MORB) type of ophiolite in the Bangong–Nujiang suture zone. The SSPP rocks have relatively high (87Sr/86Sr)i ratios (0.7091–0.7131) and positive Hf(t) values (11.2–13.8), with εNd(t) values varying from −1.1 to 9.4. The YHP has relatively low εHf(t) values (3.5 to 6.9), with the Nd–Hf isotopic model ages ranging from 610 to 942 Ma. The signatures of Sr–Nd and Lu–Hf isotopes indicate that the SSPP and YHP were derived from the depleted mantle, and the crustal material in the magma source may have originated from the Neoproterozoic Rodinia supercontinent. In the early Middle Jurassic (190 Ma), the Tengchong Block was in the setting of an active continental margin induced by the subduction of the Bangong–Nujiang Ocean, where the SSZ-type SSPP with ophiolite characteristics was formed. With the continuous subduction of the Bangong–Nujiang Ocean, the slab retreated and induced mantle convection, which resulted in the gradual thinning of the continental crust. Meanwhile, the Yingjiang back-arc basin was formed 183 Ma. Under the influence of the upwelling of the asthenosphere and the mixture of crustal materials, the MORB-type YHP was formed.

BackgroundMajor adverse cardiovascular events (MACEs) represent a significant reason of morbidity and mortality in non-cardiac surgery during perioperative period. The prevention of perioperative MACEs has always been one of the hotspots in the research field. Current existing models have not been validated in Chinese population, and have become increasingly unable to adapt to current clinical needs.ObjectivesTo establish and validate several simple bedside tools for predicting MACEs during perioperative period of non-cardiac surgery in Chinese hospitalized patients.DesignWe used a nested case-control study to establish our prediction models. A nomogram along with a risk score were developed using logistic regression analysis. An internal cohort was used to evaluate the performance of discrimination and calibration of these predictive models including the revised cardiac risk index (RCRI) score recommended by current guidelines.SettingPeking University Third Hospital between January 2010 and December 2020.PatientsTwo hundred and fifty three patients with MACEs and 1,012 patients without were included in the training set from January 2010 to December 2019 while 38,897 patients were included in the validation set from January 2020 and December 2020, of whom 112 patients had MACEs.Main Outcome MeasuresThe MACEs included the composite outcomes of cardiac death, non-fatal myocardial infarction, non-fatal congestive cardiac failure or hemodynamically significant ventricular arrhythmia, and Takotsubo cardiomyopathy.ResultsSeven predictors, including Hemoglobin, CARDIAC diseases, Aspartate aminotransferase (AST), high Blood pressure, Leukocyte count, general Anesthesia, and Diabetes mellitus (HASBLAD), were selected in the final model. The nomogram and HASBLAD score all achieved satisfactory prediction performance in the training set (C statistic, 0.781 vs. 0.768) and the validation set (C statistic, 0.865 vs. 0.843). Good calibration was observed for the probability of MACEs in the training set and the validation set. The two predictive models both had excellent discrimination that performed better than RCRI in the validation set (C statistic, 0.660, P < 0.05 vs. nomogram and HASBLAD score).ConclusionThe nomogram and HASBLAD score could be useful bedside tools for predicting perioperative MACEs of non-cardiac surgery in Chinese hospitalized patients.

Backgroud: Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities in vitro and in vivo. This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK–OCMC Nps), which enhance the aqueous solubility and stability of GK. Methods: The GK–OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK–OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK–OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK–OCMC Nps. Results: The GK–OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. In vitro drug release from GK–OCMC NPs was pH dependent. Moreover, the in vitro cytotoxicity study and cellular uptake assays indicated that the GK–OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK–OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9. Conclusion: GK–OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

Fibre-reinforced polymer (FRP) is a type of composite material used to provide resistance to corrosion when incorporated into piles. However, there is a gap in knowledge in terms of the behaviour of FRP piles under axial or lateral loading in soils. Thus, the aim of this experimental study is to assess the factors that influence the behaviour of FRPs under axial and lateral load in sandy soil. CFRP (carbon-fibre-reinforced polymer) and GFRP (glass-fibre-reinforced polymer) piles were tested in this experiment based on a special pressure chamber. The results show that the surface roughness (Rt), confined pressure (σc), and relative density (Dr) determined the shearing resistance of the soils and subsequently affected the bearing capacity of the FRP piles under an axial load. The flexural stiffness of the FRP piles was determined by the FRP type, pile dimeter, and aging in the environment, which were affected under the lateral load. In addition, an alkaline environment was more aggressive to the FRP piles than those aged in an acidic environment. The numerical modelling results show that the sand types, in terms of the dilation angle and Young’s modulus, also had a great influence on the behaviour. This feature should be considered more carefully in future studies.

The Truong Son orogenic belt (TSOB) is one of the most important orogenic belts in the Indochina block. There are numerous mafic to felsic intrusions in the Early Paleozoic caused by the Tethyan orogeny. However, the tectono-magmatic evolution of the TSOB in the Early Paleozoic is still unclear. In this paper, zircon U-Pb dating, whole-rock geochemistry, and the Sr-Nd isotopic data of the Early Paleozoic magmatic rocks have been systematically investigated to explore the petrogenesis and tectonic significance of these rocks in the TSOB. Based on our new results integrated with previous geological data, four major tectono-magmatic episodes are identified. (1) The Middle Cambrian (~507 Ma) is the early stage of northward subduction of the Tamky-Phuoc Son Ocean. (2) The Early Ordovician to Middle Ordovician (483–461 Ma) is the main subduction stage of the Tamky-Phuoc Son Ocean. The intrusive rock associations imply the closure of the Tamky-Phuoc Son Ocean. (3) The Late Ordovician to Early Silurian (461–438 Ma) is the collision stage of the Kontum massif and Truong Son terrane. (4) The Early Silurian to Late Silurian (438–410 Ma) is the late stage of collision accompanied by slab roll-back.

Heart failure (HF) is a complex clinical syndrome resulting from the impairment of ventricular filling or ejection of blood or both, leading to considerable morbidity and mortality. Based on left ventricular ejection fraction (LVEF), the 2016 European Society of Cardiology (ESC) guideline firstly classified patients with LVEF in the range of 40% to 49% into heart failure with mid-range ejection fraction. Since then, more and more clinical studies targeting HF with mid-range ejection fraction emerged, indicating that they may benefit from similar therapies to those with LVEF ≤40%. So the latest ESC guideline of HF changed the term ‘heart failure with mid-range ejection fraction’ to ‘heart failure with mildly reduced ejection fraction’ (HFmrEF). Simultaneously, burgeoning evidence indicating the emergence of novel technologies (such as speckle tracking echocardiography, cardiac magnetic resonance quantitative imaging), and new biomarkers were conducive to evaluating HF from different perspectives. In this review, we summarized the research progress of HFmrEF in clinical characteristics, prognosis, and treatment, hoping to help cardiologists better evaluate and treat patients of HFmrEF.

The Gejiu Anisian alkaline basalts (GAAB), distributed in the southern part of the Emeishan large igneous province (ELIP), are crucial to understand the tectonomagmatic activity during the Triassic. Geochronological, geochemical, and Sr-Nd-Pb isotopic analyses were systematically applied to explore the origin, petrogenesis, and tectonic setting of the GAAB, and how they relate to the ELIP. Zircon U-Pb dating set the eruption date at 244 Ma. Most of the samples belonged to alkaline basalts and had high TiO2 (2.14–3.23 wt.%) and MgO (4.43–19.58 wt.%) contents. Large ion lithophile elements (LILEs) were enriched relative to high field strength elements (HFSEs). The rare earth elements (REEs) and trace element signatures in the normalized diagrams were similar to oceanic island basalts (OIB) and Emeishan high-Ti basalts. These samples had consistent Sr-Nd isotope compositions: the initial 87Sr/86Sr values ranged from 0.7044 to 0.7048 and εNd(t) = 3.25–4.92. The Pb isotopes were more complex, the (206Pb/204Pb)t, (207Pb/204Pb)t, (208Pb/204Pb)t ratios were 17.493–18.197, 15.530–15.722, and 37.713–38.853, respectively. Our results indicate that the GAAB originated from the deeper enriched mantle with 5% to 15% partial melting of garnet lherzolite and a segregation depth of 2 to 4 GPa (60–120 km). During the formation of the GAAB, clinopyroxene and Ti-Fe oxides were fractionally crystallized with insignificant crustal contamination. The GAAB were formed in a extensional regime that was related to the Gejiu-Napo rift event in the Triassic.

In order to run CFD codes more efficiently on large scales, the parallel computing has to be employed. For example, in industrial scales, it usually uses tens of thousands of mesh cells to capture the details of complex geometries. How to distribute these mesh cells among the multiprocessors for obtaining a good parallel computing performance (HPC) is really a challenge. Due to dealing with the massive mesh cells, it is difficult for the CFD codes without parallel optimizations to handle this kind of large-scale computing. Some of the open source mesh partitioning software packages, such as Metis, ParMetis, Scotch, PT-Scotch, and Zoltan, are able to deal with the distribution of large number of mesh cells. Therefore they were employed as the parallel optimization tools ported into Code_Saturne, an open source CFD code, for testing if they can solve the issue of dealing with massive mesh cells for CFD codes. Through the studies, it was found that the mesh partitioning optimization software packages can help CFD codes not only deal with massive mesh cells but also have a good HPC.

Background: Hepatocellular carcinoma (HCC) poses a significant health burden globally, with high mortality rates despite various treatment options. Immunotherapy, particularly immune-checkpoint inhibitors (ICIs), has shown promise, but resistance and metastasis remain major challenges. Understanding the intricacies of the tumor microenvironment (TME) is imperative for optimizing HCC management strategies and enhancing patient prognosis. Methods: This study employed a comprehensive approach integrating multi-omics approaches, including single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing (Bulk RNA-seq), and validation in clinical samples using spatial transcriptomics (ST) and multiplex immunohistochemistry (mIHC). The analysis aimed to identify key factors influencing the immunosuppressive microenvironment associated with HCC metastasis and immunotherapy resistance. Results: HMGB2 is significantly upregulated in HCCTrans, a transitional subgroup associated with aggressive metastasis. Furthermore, HMGB2 expression positively correlates with an immunosuppressive microenvironment, particularly evident in exhausted T cells. Notably, HMGB2 expression correlated positively with immunosuppressive markers and poor prognosis in HCC patients across multiple cohorts. ST combined with mIHC validated the spatial expression patterns of HMGB2 within the TME, providing additional evidence of its role in HCC progression and immune evasion. Conclusion: HMGB2 emerges as a critical player of HCC progression, metastasis, and immunosuppression. Its elevated expression correlates with aggressive tumor behavior and poor patient outcomes, suggesting its potential as both a therapeutic target and a prognostic indicator in HCC management. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a predominant contributor to endstage liver disease in the forthcoming decades. Polygonum perfoliatum L. (PPL) is an herbal medicine with anti-lipid peroxidation and anti-inflammatory properties. However, detailed hepatoprotective effects of PPL against NAFLD and its underlying mechanisms are not fully understood. Here, we found that PPL protects against high fat diet (HFD)-induced hepatic steatosis, lipid peroxidation, and glucose-lipid metabolism dysfunction in NAFLD mice. We therefore performed a label-free quantitative proteomic profiling analysis to determine the effect of PPL treatment on liver tissue proteomics and identified that activated PPARs/CPT1A/CPT2-mediated hepatic fatty acid β-oxidation (FAO) process was significantly altered. In vitro treatment of hepatocytes with PPL confirmed this altered process and FAO inhibitor etomoxir (ETO) attenuated the lipid-lowering activity of PPL in hepatocytes. Ultra-high-performance liquid chromatography/Q Exactive-HFX (UPLC/QE-HFX) was used to determine the material basis of anti-NAFLD activity of PPL. Our results have demonstrated the efficacy and potential mechanisms of PPL as an effective pharmacological therapy of NAFLD. [ABSTRACT FROM AUTHOR]