The synergistic effect of Huangqi Gegen decoction on thrombosis relates to the astragalus polysaccharide-improved oral delivery of puerarin.

ETHNO-PHARMACOLOGICAL RELEVANCE: Huangqi Gegen decoction (HGD), which comprises Astragali Radix (AR) and Puerariae Radix (PR), is widely used to treat thrombosis in China. However, the mechanism underlying its synergistic effect in thrombosis treatment remains unclear. AIM OF THE STUDY: Following PR administration, low plasma exposure was reported for its primary ingredients. In this regard, this study examined the effect of AR on PR's antithrombotic efficacy with respect to the impact of Astragalus Polysaccharide (APS) on the oral delivery of Puerarin (PUE). MATERIALS AND METHODS: To evaluate the synergistic effect of HGD, a thrombus mice model was established via intraperitoneal injection of carrageenan. After treatment, histopathological observations were made, and the proportion of thrombus length in the tail, as well as the plasma APTT, PT, INR, and FIB levels, were detected. Molecular docking was employed to assess the PR ingredients that could inhibit the HMGB1/NF-κB/NLRP3 pathway. The Pharmacokinetics of PR ingredients in rats were also compared between the PR and HGD groups. Moreover, the effect of APS on the solubility, intestinal absorption, and pharmacokinetics of PUE was evaluated. Furthermore, the impact of APS on the antithrombotic efficacy of PUE was assessed. RESULTS: In mice, AR enhanced the antithrombotic effect of PR. This improved PR effect was associated with isoflavones-induced downregulation of the HMGB1/NF-κB/NLRP3 pathway. The synergistic effect resulting from the compatibility of HGD components was primarily achieved by improving the plasma exposure of PR isoflavones. Specifically, APS enhanced PUE's water solubility through the formation of self-assembly Nanoparticles, increasing its intestinal absorption and oral bioavailability, which, in turn, suppressed the HMGB1/NF-κB/NLRP3 pathway, thus improving its antithrombotic effect. CONCLUSIONS: Our findings revealed that APS improved PUE's plasma exposure, enhancing its inhibitory effect on the HMGB1/NF-κB/NLRP3 pathway. This mechanism presents a key aspect of the synergistic effect of HGD compatibility in thrombosis treatment.

Analysis of three-dimensional visualization imaging of severe portal vein stenosis after liver transplantation and clinical efficacy of portal vein stent implantation / 器官移植

Objective To analyze three-dimensional imaging characteristics and advantages for severe portal vein stenosis after liver transplantation, and to evaluate clinical efficacy of portal vein stent implantation. Methods Clinical data of 10 patients who received portal vein stent implantation for severe portal vein stenosis after liver transplantation were retrospectively analyzed. Imaging characteristics of severe portal vein stenosis, and advantages of three-dimensional reconstruction imaging and interventional treatment efficacy for severe portal vein stenosis were analyzed. Results Among 10 patients, 3 cases were diagnosed with centripetal stenosis, tortuosity angulation-induced stenosis in 2 cases, compression-induced stenosis in 2 cases, long-segment stenosis and/or vascular occlusion in 3 cases. Three-dimensional reconstruction images possessed advantages in accurate identification of stenosis, identification of stenosis types and measurement of stenosis length. All patients were successfully implanted with portal vein stents. After stent implantation, the diameter of the minimum diameter of portal vein was increased [(6.2±0.9) mm vs. (2.6±1.7) mm, P<0.05], the flow velocity at anastomotic site was decreased [(57±19) cm/s vs. (128±27) cm/s, P<0.05], and the flow velocity at the portal vein adjacent to the liver was increased [(41±6) cm/s vs. (18±6) cm/s, P<0.05]. One patient suffered from intrahepatic hematoma caused by interventional puncture, which was mitigated after conservative observation and treatment. The remaining patients did not experience relevant complications. Conclusions Three-dimensional visualization technique may visually display the location, characteristics and severity of stenosis, which is beneficial for clinicians to make treatment decisions and assist interventional procedures. Timely implantation of portal vein stent may effectively reverse pathological process and improve portal vein blood flow.

Phytochelatin-Mediated Cultivar-Dependent Cd Accumulations of Lactuca sativa and Implication for Cd Pollution-Safe Cultivars Screening.

Cd pollution-safe cultivar (Cd-PSC) is a feasible strategy to minimize Cd contamination in leafy vegetables. The shoot Cd concentrations of 23 Lactuca sativa cultivars under Cd stress ranged from 0.124 to 2.155 mg·kg-1 with a maximum cultivar difference of 8 folds. Typical Cd-PSC C16 (L) and high-Cd-accumulating cultivar C13 (H) were screened to investigate the mechanisms of Cd accumulations in L. sativa through determining Cd concentrations, Cd subcellular distributions, phytochelatin profiles, and phytochelatin biosynthesis-related genes' expressions. Higher Cd distribution in a heat stable fraction in C13 (H) indicated that the high Cd accumulation trait of C13 (H) mainly depended on the Cd-phytochelatin complexes. Root phytochelatin concentrations were significantly elevated in C13 (H) (5.83 folds) than in C16 (L) (2.69 folds) (p < 0.05) under Cd stress. Significantly downregulated expressions of glutathione S-transferase rather than the regulation of phytochelatin synthesis genes in the root of C13 (H) might be responsible for sufficient glutathione supply for phytochelatins synthesis. These findings suggested that phytochelatin elevation in C13 (H) would favor the Cd root to shoot transportation, which provides new insights into the phytochelatin-related cultivar-dependent Cd accumulating characteristic in L. sativa.

Advances in Extraction, Purification, and Analysis Techniques of the Main Components of Kudzu Root: A Comprehensive Review.

Kudzu root (Pueraria lobate (Willd.) Ohwi, KR) is an edible plant with rich nutritional and medicinal values. Over the past few decades, an ample variety of biological effects of Pueraria isoflavone have been evaluated. Evidence has shown that Pueraria isoflavone can play an active role in antioxidant, anti-inflammatory, anti-cancer, neuroprotection, and cardiovascular protection. Over 50 isoflavones in kudzu root have been identified, including puerarin, daidzein, daidzin, 3'-hydroxy puerarin, and genistein, each with unambiguous structures. However, the application of these isoflavones in the development of functional food and health food still depends on the extraction, purification and identification technology of Pueraria isoflavone. In recent years, many green and novel extraction, purification, and identification techniques have been developed for the preparation of Pueraria isoflavone. This review provides an updated overview of these techniques, specifically for isoflavones in KR since 2018, and also discusses and compares the advantages and disadvantages of these techniques in depth. The intention is to provide a research basis for the green and efficient extraction, purification, and identification of Pueraria isoflavone and offers investigators a valuable reference for future studies on the KR.

Assessment of knowledge, cultural beliefs, and behavior regarding medication safety among residents in Harbin, China.

BACKGROUND: Medication misuse or overuse is significantly associated with poor health outcomes. Information regarding the knowledge, cultural beliefs, and behavior about medication safety in the general population is important. AIM: To conduct a survey on medication habits and explored the potential factors impacting medication safety. METHODS: The current survey included adults from 18 districts and counties in Harbin, China. A questionnaire on medication safety was designed based on knowledge, cultural beliefs, and behavior. Both univariate and multivariate analyses were used to explore the factors that impacted medication safety. RESULTS: A total of 394 respondents completed the questionnaires on medication safety. The mean scores for knowledge, cultural beliefs, and behavior about medication safety were 59.41 ± 19.33, 40.66 ± 9.24, and 60.97 ± 13.69, respectively. The medication knowledge score was affected by age (P = 0.044), education (P < 0.001), and working status (P = 0.015). Moreover, the cultural beliefs score was significantly affected by education (P < 0.001). Finally, education (P = 0.003) and working status (P = 0.011) significantly affected the behavior score. CONCLUSION: The knowledge, cultural beliefs, and behavior about medication safety among the general population was moderate. Health education should be provisioned for the elderly, individuals with a low education level, and the unemployed to improve medication safety in Harbin, China.

Xinfuli granule alleviates metabolic remodeling through inhibition of endoplasmic reticulum stress and mitochondrial injury in heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: "Qi deficiency-blood stasis-water retention syndrome" was the most frequent syndrome among heart failure(HF) patients according to Traditional Chinese Medicine (TCM) theory. Xinfuli Granule (XG) was constructed on the basis of classical formula "Baoyuan decoction" to enhance the function of nourishing Qi, activating blood and removing water retention. XG treatment has obtained clinical effect on HF patients. AIM OF THE STUDY: The regulation of XG on energy metabolism of HF was investigated with special focus on endoplasmic reticulum stress (ERS) and mitochondrial function. MATERIALS AND METHODS: Components of XG was acquired by UPLC/Q-TOF-MS Analysis, left anterior descending ligation(LAD)-induced HF rats model and hypoxia-ischemia(H-I)-induced H9c2 cells model were constructed to evaluate the effect of XG treatment. Cardiac function was evaluated by echocardiographic parameters, energy metabolism was evaluated by metabolites and ATP/ADP/AMP levels in blood samples, cardiomyocyte morphology and myocardial fibrosis were assessed by HE staining and Masson staining, mitochondrial ultrastructure was observed under Transmission Electron Microscope, viability and apoptosis rate of H9c2 cells was detected by cell counting kit-8 reaction and flow cytometry analysis, respectively. Mitochondrial membrane potential (MMP) of H9c2 cells was observed by JC-1 kit under fluorescent microscope, expression of peroxisome-proliferator-activated receptor (PPAR)-coactivator (PGC1α), ERS-related genes and RHOA/ROCK pathway were analysed by Quantitative Real-time PCR (RT-qPCR) and Western Blot. RESULTS: Here, we showed that XG alleviated cardiac metabolic remodeling and stimulated ATP production through elevated expression of PGC1α in HF rats. XG also helped recover mitochondrial deformation and decrease apoptosis rate accompanied by an increase of the Bcl2/Bax ratio and the mitochondrial membrane potential in hypoxia-ischemia (H-I) H9c2 cells. In addition, we found that XG downregulated ERS-related proteins ATF4, CHOP, Phospho-eIF2α, and Phospho-PERK, and suppressed the RHOA/ROCK pathway, which served as a potential mediator of ERS. CONCLUSIONS: we found that XG improved energy production by alleviating mitochondrial injury and inhibiting ERS in heart failures mediated by the RHOA/ROCK pathway.

Portal vein aneurysm after liver transplantation: report of two cases and literature review / 器官移植

Objective To summarize the diagnosis and treatment experience of portal vein aneurysm after liver transplantation. Methods Clinical data of two recipients with portal vein aneurysm after liver transplantation were retrospectively analyzed. Clinical features, diagnosis, treatment and prognosis were summarized based on literature review. Results Both two cases were diagnosed with intrahepatic portal vein aneurysm complicated with portal vein thrombosis and portal hypertension after liver transplantation. Case 1 was given with targeted conservative treatment and he refused to undergo liver retransplantation. Physical condition was worsened after discharge, and the patient eventually died from liver graft failure, kidney failure, lung infection, and septic shock. Case 2 received high-dose glucocorticoid pulse therapy, whereas liver function was not improved, and the patient was recovered successfully after secondary liver transplantation. Conclusions Long-term complication of portal vein aneurysm (especially intrahepatic type) after liver transplantation probably indicates poor prognosis. Correct understanding, intimate follow-up and active treatment should be conducted. Liver retransplantation may be a potential treatment regimen.

Research advances in immune checkpoint inhibitor-related cholangitis / 临床肝胆病杂志

Immune checkpoint inhibitors (ICIs) have ushered in a new era of tumor treatment; however, immunotherapy-related adverse events are critical issues that restrict the clinical application of ICIs and have attracted wide attention. The liver is one of the target organs that is easily affected. With the progress in research, scholars have found that besides hepatocytes, intrahepatic and extrahepatic bile ducts can also be attacked by the immune system, leading to the disease known as immune-related cholangitis. This article reviews the research advances in ICI-related cholangitis by summarizing related articles, in order to preliminarily reveal its clinical, pathological, and imaging features and provide clues for early identification, standard treatment, and subsequent research.

Complement use of Chinese herbal medicine after percutaneous coronary intervention: a prospective observational study.

BACKGROUND: Chinese herbal medicine is widely used as a complement or alternative treatment in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) in China. We compared the incidence of the major adverse cardiovascular event (MACE) of CAD patients with or without the complement use of Chinese herbal medicine after PCI. METHODS: In this prospective, observational study that was conducted from September 2016 to August 2019 in Fuwai Hospital (China), we followed up consecutive patients who received PCI treatment for two years. MACE was defined as the composite all-cause mortality, revascularization, and myocardial infarction (MI) and was compared between those using (integrative medicine group) or those not using Chinese herbal medicine as an additional treatment to standard Western medicine, with unadjusted (Kaplan-Meier curves) and risk-adjusted (multivariable Cox regression) analyses. RESULTS: A total of 5942 patients after PCI were enrolled in this study, and 5453 patients were included in the final analysis (4189 [76.8%] male; mean age: 61.9 ± 9.9% years). During the follow-ups, 2932 (53.8%) patients used only Western medicine while 2521(46.2%) patients had used Chinese herbal medicine as an additional treatment to standard Western medicine. Patients in the integrative medicine group (IM group) were older than the Western medicine group (WM group), had more females and less previous MI. The incidence of MACE was 15.3% (449/2932) in WM group and 11.54% (291/2521) in IM group. Cox regression analysis showed that cumulative incidence of MACE was 27% lower in patients of the IM group than those in WM group (hazard ratio = 0.73; 95% CI: 0.63-0.85; P < 0.0001). CONCLUSIONS: For CAD patients after PCI treatment, complement use of Chinese herbal medicine is associated with a lower 2-year MACE incidence. Randomized prospective studies are warranted to provide higher levels of benefit evidence in these patients.

Pore-Structure Control in Metal-Organic Frameworks (MOFs) for Capture of the Greenhouse Gas SF6 with Record Separation.

In the electronics industry, the efficient recovery and capture of sulfur hexafluoride (SF6 ) from SF6 /N2 mixtures is of great importance. Herein, three metal-organic frameworks with fine-tuning pore structures, Cu(peba)2 , Ni(pba)2 , and Ni(ina)2 , were designed for SF6 capture. Among them, Ni(ina)2 has perfect pore sizes (6 Å) that are comparable to the kinetic diameter of sulfur hexafluoride (5.2 Å), affording the benchmark binding affinity for SF6 gas. Ni(ina)2 exhibits the highest SF6 /N2 selectivity (375.1 at 298 K and 1 bar) and ultra-high SF6 uptake capacity (53.5 cm3 g-1 at 298 K and 0.1 bar) at ambient conditions. The remarkable separation performance of Ni(ina)2 was verified by dynamic breakthrough experiments. Theoretical calculations and the SF6 -loaded single-crystal structure provided critical insight into the adsorption/separation mechanism. This porous coordination network has the potential to be used in industrial applications.

The Dislocation- and Cracking-Mediated Deformation of Single Asperity GaAs during Plowing Using Molecular Dynamics Simulation.

This work simulates the plowing process of a single asperity GaAs by diamond indenter using molecular dynamics simulations. The deformation mechanism of asperity GaAs is revealed by examining the topography evolution and stress state during the plowing. This work also investigates the origin of the influence of asperity size, indenter radius and plow depth on the deformation of the asperity GaAs. We observed the initiation and propagation of cracks up to the onset of fracture and the plastic activity near the indenter, obtaining more information usually not available from planar GaAs in normal velocity plowing compared to just plastic activity. The simulations demonstrated the direct evidence of cracking in GaAs induced by plowing at an atomic level and probed the origin and extension of cracking in asperity GaAs. This finding suggests that cracking appears to be a new deformation pattern of GaAs in plowing, together with dislocation-dominated plasticity modes dominating the plowing deformation process. This work offers new insights into understanding the deformation mechanism of an asperity GaAs. It aims to find scientific clues for understanding plastic removal performed in the presence of cracking.

Contrast-enhanced ultrasound imaging for intestinal lymphoma.

BACKGROUND: Intestinal lymphoma is a rare tumor. Contrast-enhanced ultrasound (CEUS) findings of intestinal lymphoma have not been reported previously, and the relationship between CEUS and clinicopathological features and prognostic factors is still unknown. AIM: To describe the B-mode US and CEUS features of intestinal lymphoma and investigate the correlation of CEUS and histopathological features. METHODS: This was a single-center retrospective study. Eighteen patients with histologically confirmed intestinal lymphoma underwent B-mode US and CEUS examinations between October 2016 and November 2019. We summarized the features of B-mode US and CUES imaging of intestinal lymphoma and compared the frequency of tumor necrosis in intestinal lymphomas with reference to different pathological subtypes (aggressive or indolent) and clinical stage (early or advanced). The time-intensity curve parameters of CEUS were also compared between patients with normal and elevated serum lactate dehydrogenase. RESULTS: In B-mode imaging, four patterns were observed in intestinal lymphoma: Mass type (12/18, 66.7%), infiltration type (1/18, 5.6%), mesentery type (4/18, 22.2%) and mixed type (1/18, 5.6%). All cases were hypoechoic and no cystic areas were detected. On CEUS, most cases (17/18, 94.4%) showed arterial hyperechoic enhancement. All cases showed arterial enhancement followed by venous wash out. A relatively high rate of tumor necrosis (11/18, 61.1%) was observed in this study. Tumor necrosis on CEUS was more frequent in aggressive subtypes (10/13, 76.9%) than in indolent subtypes (1/5, 20.0%) (P = 0.047). There were no correlations between tumor necrosis and lesion size and Ann Arbor stage. There was no significant difference in time-intensity curve parameters between normal and elevated lactate dehydrogenase groups. CONCLUSION: B-mode US and CEUS findings of intestinal lymphoma are characteristic. We observed a high rate of tumor necrosis, which appeared more frequently in aggressive pathological subtypes of intestinal lymphoma.

Inhibitory effects of aloperine on voltage-gated Na+ channels in rat ventricular myocytes.

Aloperine (ALO), a quinolizidine alkaloid extracted from Sophora alopecuroides L., modulates hypertension, ventricular remodeling, and myocardial ischemia. However, few studies have evaluated the effects of ALO on other cardiovascular parameters. Accordingly, in this study, we used a rat model of aconitine-induced ventricular arrhythmia to assess the effects of ALO. Notably, ALO pretreatment delayed the onset of ventricular premature and ventricular tachycardia and reduced the incidence of fatal ventricular fibrillation. Moreover, whole-cell patch-clamp assays in rats' ventricular myocyte showed that ALO (3, 10, and 30 µM) significantly reduced the peak sodium current density of voltage-gated Na+ channel currents (INa) in a concentration-dependent manner. The gating kinetics characteristics showed that the steady-state activation and recovery curve were shifted in positive direction along the voltage axis, respectively, and the steady-state inactivation curve was shifted in negative direction along the voltage axis, i.e., which was similar to the inhibitory effects of amiodarone. These results indicated that ALO had anti-arrhythmic effects, partly attributed to INa inhibition. ALO may act as a class I sodium channel anti-arrhythmia agent.

Advances in conversion therapy strategies for liver transplantation for liver cancer / 临床肝胆病杂志

Liver transplantation can completely remove the tumor and the diseased liver at the same time and is the best choice for patients with liver cancer and liver cirrhosis. With the advances in multimodality therapy for liver cancer in recent years, the concept of conversion therapy has been introduced into the fields of surgical treatment of liver cancer and liver transplantation, and successful conversion therapy is expected to help ineligible liver cancer patients to meet the criteria for liver transplantation and thus improve their prognosis. This article briefly introduces the advances in conversion therapy for liver transplantation for liver cancer.

Cyclocarioside O-Q, three novel seco-dammarane triterpenoid glycosides from the leaves of Cyclocarya paliurus.

Three previously undescribed seco-dammarane triterpenoid glycosides O-Q (1-3) along with two known compounds (4 and 5) were isolated and characterized from the leaves of Cyclocarya paliurus. Their structures were determined by comprehensive analysis of 1 D, 2 D NMR and HRESIMS data. Compounds 1-5 were evaluated for their inhibitory effects against human pancreatic tumor (ASPC-1), human gastric carcinoma (SNU5), liver hepatocellular carcinoma (HEPG-2) and human colon tumor (HCT116) cell lines. Among them cyclocarioside P (2) showed somewhat inhibitory activity towards those tumor cells.

Notch and breast cancer metastasis: Current knowledge, new sights and targeted therapy.

Breast cancer is the most common type of invasive cancer in females and metastasis is one of the major causes of breast cancer-associated mortality. Following detachment from the primary site, disseminated tumor cells (DTCs) enter the bloodstream and establish secondary colonies during the metastatic process. An increasing amount of studies have elucidated the importance of Notch signaling in breast cancer metastasis; therefore, the present review focuses on the mechanisms by which Notch contributes to the occurrence of breast cancer DTCs, increases their motility, establishes interactions with the tumor microenvironment, protects DTCs from host surveillance and finally facilitates secondary colonization. Identification of the underlying mechanisms of Notch-associated breast cancer metastasis will provide additional insights that may contribute towards the development of novel Notch-targeted therapeutic strategies, which may aid in reducing metastasis, culminating in an improved patient prognosis.

New concept of surgical treatment for biliary dilatation / 中华消化外科杂志

At present,it is not uncommon for patients with biliary dilatation who have failed to undergo multiple operations in clinic.Dong's classification has a definite guiding significance for choosing appropriate surgical methods.Active hepatectomy with "tailor-made" treatment can cure refractory biliary dilatation involving intrahepatic bile ducts.At present,there are still some controversies about the range of hepatectomy and the management of type D lesions in children.At the same time,we should pay close attention to the long-term complications after dilated bile duct resection.

Indoleamine 2,3-dioxygenase suppresses the cytotoxicity of 1 NK cells in response to ectopic endometrial stromal cells in endometriosis.

It has been reported that the impaired cytotoxicity of natural killer (NK) cells and abnormal cytokines that are changed by the interaction between ectopic endometrial cells and immune cells is indispensable for the initiation and development of endometriosis (EMS). However, the mechanism of NK cells dysfunction in EMS remains largely unclear. Here, we found that NK cells in peritoneal fluid from women with EMS highly expressed indoleamine 2,3-dioxygenase (IDO). Furthermore, IDO+NK cells possessed lower NKp46 and NKG2D but higher IL-10 than that of IDO-NK. Co-culture with endometrial stromal cells (nESCs) from healthy control or ectopic ESCs (eESCs) from women with EMS led to a significant increase in the IDO level in NK cells from peripheral blood, particularly eESCs, and an anti-TGF-ß neutralizing antibody suppressed these effects in vitro. NK cells co-cultured with ESC more preferentially inhibited the viability of nESCs than eESCs did, and pretreating with 1-methyl-tryptophan (1-MT), an IDO inhibitor, reversed the inhibitory effect of NK cells on eESC viability. These data suggest that ESCs induce IDO+NK cells differentiation partly by TGF-ß, and that IDO further restricts the cytotoxicity of NK cells in response to eESCs, which provides a potential therapeutic strategy for EMS patients, particularly those with a high number of impaired cytotoxic IDO+NK cells.

Cs4PbBr6/CsPbBr3 Perovskite Composites with Near-Unity Luminescence Quantum Yield: Large-Scale Synthesis, Luminescence and Formation Mechanism, and White Light-Emitting Diode Application.

All-inorganic perovskites have emerged as a new class of phosphor materials owing to their outstanding optical properties. Zero-dimensional inorganic perovskites, in particular the Cs4PbBr6-related systems, are inspiring intensive research owing to the high photoluminescence quantum yield (PLQY) and good stability. However, synthesizing such perovskites with high PLQYs through an environment-friendly, cost-effective, scalable, and high-yield approach remains challenging, and their luminescence mechanisms has been elusive. Here, we report a simple, scalable, room-temperature self-assembly strategy for the synthesis of Cs4PbBr6/CsPbBr3 perovskite composites with near-unity PLQY (95%), high product yield (71%), and good stability using low-cost, low-toxicity chemicals as precursors. A broad range of experimental and theoretical characterizations suggest that the high-efficiency PL originates from CsPbBr3 nanocrystals well passivated by the zero-dimensional Cs4PbBr6 matrix that forms based on a dissolution-crystallization process. These findings underscore the importance in accurately identifying the phase purity of zero-dimensional perovskites by synchrotron X-ray technique to gain deep insights into the structure-property relationship. Additionally, we demonstrate that green-emitting Cs4PbBr6/CsPbBr3, combined with red-emitting K2SiF6:Mn4+, can be used for the construction of WLEDs. Our work may pave the way for the use of such composite perovskites as highly luminescent emitters in various applications such as lighting, displays, and other optoelectronic and photonic devices.