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Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

Oral cancer is a common life-threatening malignancy having high mortality and morbidity rates. During the treatment process, individuals unavoidably experience severe side effects. It is essential to develop safer and more effective strategies. Currently, extracellular vesicles (EVs) and biomimetic nanoparticles are nanomedicines with long-term blood circulation and lower off-target toxicity that orchestrate immune responses and accumulate specifically in tumor sites. EVs create a synergetic effect by encapsulating drugs and collaborating with naturally loaded elements in the EVs. Biomimetic nanoparticles retain the characteristic features of the synthetic nanocarriers and inherit the intrinsic cell membrane functionalities. This review outlines the properties, applications, challenges, pros and cons of EVs and biomimetic nanoparticles, providing novel perspectives on oral cancer.

The prognosis of hepatocellular carcinoma (HCC) remains poor and relapse occurs in more than half of patients within 2 years after hepatectomy. In terms of recent studies, microvascular invasion (MVI) is one of the potential predictors of recurrence. Accurate preoperative prediction of MVI is potentially beneficial to the optimization of treatment planning.To develop a radiomic analysis model based on pre-operative magnetic resonance imaging (MRI) data to predict MVI in HCC.A total of 113 patients recruited to this study have been diagnosed as having HCC with histological confirmation, among whom 73 were found to have MVI and 40 were not. All the patients received preoperative examination by Gd-enhanced MRI and then curative hepatectomy. We manually delineated the tumor lesion on the largest cross-sectional area of the tumor and the adjacent two images on MRI, namely, the regions of interest. Quantitative analyses included most discriminant factors (MDFs) developed using linear discriminant analysis algorithm and histogram analysis with MaZda software. Independent significant variables of clinical and radiological features and MDFs for the prediction of MVI were estimated and a discriminant model was established by univariate and multivariate logistic regression analysis. Prediction ability of the above-mentioned parameters or model was then evaluated by receiver operating characteristic (ROC) curve analysis. Five-fold cross-validation was also appliedThe area under the ROC curve (AUC) of the MDF (0.77-0.85) outperformed that of histogram parameters (0.51-0.74). After multivariate analysis, MDF values of the arterial and portal venous phase, and peritumoral hypointensity in the hepatobiliary phase were identified to be independent predictors of MVI (Noninvasive MRI radiomic model based on MDF values and imaging biomarkers may be useful to make preoperative prediction of MVI in patients with primary HCC.

During recovery from heat stress, plants clear away the heat-stress-induced misfolded proteins through the ubiquitin-proteasome system (UPS). In the UPS, the recognition of substrate proteins by E3 ligase can be regulated by the N-terminal acetyltransferase A (NatA) complex. Here, we determined that Arabidopsis STRESS-RELATED UBIQUITIN-ASSOCIATED-DOMAIN PROTEIN FACTOR 1 (SUF1) interacts with the NatA complex core subunit NAA15 and positively regulates NAA15. The suf1 and naa15 mutants are sensitive to heat stress; the NatA substrate

Mycorrhizae are ubiquitous symbioses established between fungi and plant roots. Orchids, in particular, require compatible mycorrhizal fungi for seed germination and protocorm development. Unlike arbuscular mycorrhizal fungi, which have wide host ranges, orchid mycorrhizal fungi are often highly specific to their host orchids. However, the molecular mechanism of orchid mycorrhizal symbiosis is largely unknown compared to that of arbuscular mycorrhizal and rhizobial symbiosis. Here, we report that an endophytic Sebacinales fungus, Serendipita indica, promotes seed germination and the development of protocorms into plantlets in several epiphytic Epidendroideae orchid species (6 species in 2 genera), including Dendrobium catenatum, a critically endangered orchid with high medicinal value. Although plant–pathogen interaction and high meristematic activity can induce the hypoxic response in plants, it has been unclear whether interactions with beneficial fungi, especially mycorrhizal ones, also involve the hypoxic response. By studying the symbiotic relationship between D. catenatum and S. indica, we determined that hypoxia-responsive genes, such as those encoding alcohol dehydrogenase (ADH), are highly induced in symbiotic D. catenatum protocorms. In situ hybridization assay indicated that the ADH gene is predominantly expressed in the basal mycorrhizal region of symbiotic protocorms. Additionally, the ADH inhibitors puerarin and 4-methylpyrazole both decreased S. indica colonization in D. catenatum protocorms. Thus, our study reveals that S. indica is widely compatible with orchids and that ADH and its related hypoxia-responsive pathway are involved in establishing successful symbiotic relationships in germinating orchids.

Objective: The role of lipid droplets (LDs) and lipid droplet-associated genes (LD-AGs) remains unclear in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate LDs in HNSCC and identify LD-AGs essential for the diagnosis and prognosis of HNSCC patients. background: The role of lipid droplets (LDs) and the lipid droplet-associated genes (LD-AGs) remains unclear in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate LDs in HNSCC and identify LD-AGs essential for the diagnosis and prognosis of HNSCC patients. Methods: The LDs in the HNSCC and normal cell lines were stained with oil red O. Bioinformatic analysis was used to find LD-AGs in HNSCC that had diagnostic and prognostic significance. objective: The role of lipid droplets (LDs) and the lipid droplet-associated genes (LD-AGs) remains unclear in head and neck squamous cell carcinoma (HNSCC). Results: LDs accumulation was increased in HNSCC cell lines compared with normal cell lines (P 0.7, 34 genes demonstrated a high predictive power. Six genes (AUP1, CAV1, CAV2, CAVIN1, HILPDA, and SQLE) out of 34 diagnostic genes were linked to overall survival in patients with HNSCC (P method: The LDs in the HNSCC and normal cell lines were stained with oil red O. Bioinformatic analysis was used to find LD-AGs in HNSCC that had diagnostic and prognostic significance. Conclusions: Increased LDs accumulation was a hallmark of HNSCC, and AUP1, CAV1, CAV2, and SQLE were discovered as differentially expressed LD-AGs with diagnostic and prognostic potential in HNSCC. result: LDs accumulation was increased in HNSCC cell lines compared with normal cell lines (P 0.7, 34 genes demonstrated a high predictive power. Six genes (AUP1, CAV1, CAV2, CAVIN1, HILPDA, and SQLE) out of 34 diagnostic genes were linked to overall survival in patients with HNSCC (P conclusion: Increased LDs accumulation was a hallmark of HNSCC, and AUP1, CAV1, CAV2, and SQLE were discovered as differentially expressed LD-AGs with diagnostic and prognostic potential in HNSCC.

Background: The function of lipid droplets (LDs) has not been clarified in precancerous lesions, and the relationship between LDs, lipid metabolism, and epithelial-mesenchymal transition (EMT) remains unclear in the carcinogenesis processes in the oral cavity.Methods: Tissue frozen sections were collected for oil red O staining of LDs. Forty-eight oral squamous cell carcinomas (OSCC), 78 oral potentially malignant disorders (OPMDs), and 25 normal paraffin-embedded tissue sections were included to explore the LDs surface protein caveolin-2 and perilipin-3, lipid metabolism-related molecule fatty acid binding protein 5 (FABP5), and EMT biomarker E-cadherin expression by immunohistochemical staining. Results: The accumulation of LDs was observed in OPMDs and OSCCs compared to normal tissues (P < 0.05). In general, an increasing trend of caveolin-2, perilipin-3, and FABP5 expression was detected from the normal to OPMDs to OSCC groups (P < 0.05); however, the increased level of perilipin-3 was not significant in OPMDs compared to the normal controls (P > 0.05). In addition, caveolin-2, perilipin-3, and FABP5 expression were positively correlated with epithelial dysplasia in OPMDs, whereas E-cadherin positivity was negatively correlated with epithelial dysplasia and histopathological grade in OPMDs and OSCC, respectively. A negative correlation of caveolin-2 (P < 0.01, r = - 0.1739), and FABP5 (P < 0.01, r = - 0.1880) with E-cadherin expression was detected. The caveolin-2 (P < 0.0001, r = 0.2641) and perilipin-3 (P < 0.05, r = 0.1408) staining was positively correlated with FABP5. OSCC local recurrence was associated with high expression of caveolin-2 (P < 0.05) and FABP5 (P < 0.05), and lymph node metastasis was associated with high FABP5 expression (P < 0.05) but low E-cadherin expression (P < 0.05). The caveolin-2 high expression group had a worse disease-free survival (DFS) (P < 0.05). Conclusion: In the oral epithelial carcinogenesis process, LDs begin to accumulate early in the precancerous stage. LDs may be the regulator of FABP5-associated lipid metabolism and are closely related to the process of EMT; caveolin-2 could be the main functional protein, indicating that caveolin-2 is a potential biomarker for oral carcinogenesis and prognosis.

Background: Icaritin can inhibit cell proliferation and induce apoptosis in Oral Squamous Cell Carcinoma (OSCC). However, low solubility limits its clinical usage. Objectives: To improve the efficacy of icaritin treatment, a micelle system was designed for targeted delivery of drugs to OSCC cells. Methods: In the present study, the micelles loaded with icaritin were self-assembled from the amphipathic polymer via film dispersion. Nanoparticles were characterized with the transmission electron microscope and dynamic light scattering. The cytotoxicity of icaritin nanoparticles was analyzed by CCK-8, and in vitro target-selective intracellular uptake behaviors were observed using a laser confocal microscope. Results: The micelles were spherical with the mean diameter of 121.2 nm. in vitro studies revealed that icaritin was stablely and slowly released from micelles. Cytotoxicity analysis demonstrated that icartin-loaded micelles exhibited better therapeutic efficacy compared with free icaritin. Cellular uptake and intracellular release results revealed that micelles efficiently delivered icaritin into OSCC cells. Conclusion: These results suggest that encapsulated icaritin in polycaprolactone - polyethylene glycol (PCL-PEG) micelles may provide safe and effective drug delivery in OSCC treatments.

Objective This study investigates the mismatch between the National Institutes of Health Stroke Scale (NIHSS) score and the computed tomography (CT) findings measured by the Alberta Stroke Program Early CT Score (ASPECTS) for predicting the functional outcome and safety of intravenous thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS). Methods This prospective observational study includes patients with AIS who underwent CT imaging within 4.5 h of the onset of symptoms. Patients were divided into the NIHSS–ASPECTS mismatch (NAM)-positive and NAM-negative groups (group P and N, respectively). The clinical outcome was assessed using the Modified Rankin Scale (mRS). Safety outcomes included progression, symptomatic intracerebral hemorrhage (sICH), intracerebral hemorrhage (ICH), adverse events, clinical adverse events, and mortality. Results A total of 208 patients were enrolled in the study. In group P, IVT treatment was associated with a good functional outcome at 3 months (p = 0.005) and 1 year (p = 0.001). A higher percentage of patients with favorable mRS (0–2) (p = 0.01) and excellent mRS (0–1) (p = 0.011) functional outcomes was obtained at 1 year in group P with IVT treatment. Group N did not benefit from the same treatment (p = 0.352 and p = 0.480 at 3 months and 1 year, respectively). There were no statistically significant differences in sICH, ICH, mortality rates, or other risks between the IVT and conventional treatment groups. Conclusion IVT treatment is associated with a good functional outcome in patients with NAM, without increasing the risks of sICH, ICH, mortality, or other negative outcomes. NAM promises to be an easily obtained indicator for guiding the treatment decisions of AIS.

Background: Our previous work demonstrated upregulated CD47 in oral squamous cell carcinoma (OSCC). Objective: In the present study,we aimed to investigate the effects of CD47 on tumor cell development and phagocytosis in OSCC and elucidate the underlying mechanisms. Methods: The proliferation, apoptosis, migration, and invasion of oral cancer cells were analyzed after knocking down the expression of CD47. The effects of CD47 on tumor development were also evaluated using a murine model of OSCC. The involvement of CD47 in the phagocytosis of oral cancer cells was identified. Results: Cell proliferation was suppressed by knocking down the expression of CD47 in human OSCC cell line Cal-27 cells but there was no change in theapoptosis rate. Moreover, impaired expression of CD47 inhibited the migration and invasion of Cal-27 cells. Furthermore, we found that nude mice injected with CD47 knocked-down Cal-27 cells displayed decreased tumor volumes at week 9 compared to xenograft transplantations of blank Cal-27 cells. In addition, in vitrophagocytosis of Cal-27 cells by macrophages was significantly enhanced after the knockdown of CD47, which positively correlated with compromised STAT3/JAK2 signaling. Conclusion: In summary, the knockdown of CD47 down regulated the development of OSCC and increased the phagocytosis of Cal-27 cells, indicating that CD47 might be a promising therapeutic target.

δ¹³C and δ¹⁵N are extensively used to understand the biogeochemical mechanisms that moderate ecosystem carbon (C) and nitrogen (N) processes. Little is known about the responses of δ¹³C and δ¹⁵N to alpine grassland degradation on the Qinghai‐Tibetan Plateau (QTP), which prevents a full understanding of degradation‐induced changes in C and N cycling there. We investigated the vegetation δ¹³C and δ¹⁵N, soil δ¹³C and δ¹⁵N, soil properties, and plant community composition of alpine grassland on the QTP that were in different states of degradation. Our results show that the vegetation δ¹³C and δ¹⁵N, and soil δ¹³C and δ¹⁵N, increased with the severity of degradation, whereas soil organic carbon (SOC) and total N content decreased as degradation became more severe. The aboveground biomass percentage of forbs was positively correlated with the soil C/N ratio, vegetation δ¹³C, and soil δ¹³C, and accounted for the largest proportion of the variance for both vegetation δ¹³C and soil δ¹³C (17.25 and 23.65%, respectively). The vegetation δ¹⁵N and soil δ¹⁵N were negatively correlated with the soil C/N ratio, which explained the largest proportion of the variance (18.01 and 25.81%, respectively). Our results suggest that C cycling is strongly moderated by plant community composition, because forbs species and C₄ species, were more prevalent in degraded alpine grassland. Meanwhile, N cycling is indirectly regulated by changes in community composition via its effect on the soil C/N as the degradation became more severe for alpine grassland on the QTP.

Background Exosomes exert considerable influence in mediating regulatory T (Treg) cells differentiation, which attach great importance to attenuating acute cellular rejection after liver transplantation (LT). And, miRNAs are known to play essential roles in cell-cell communication delivered by exosomes. However, the function of exosomal miRNAs in regulating Treg cells after LT remains unknown. Here, we performed an expression profiling analysis of exosome-miRNAs from human plasma after LT and investigated their immunoregulatory effects on Treg cells. Methods Fifty-eight LT patients and nine donors were included in this report. miRNA profiles in plasma exosomes were analyzed using next-generation sequencing. Flow cytometry, HE and multiplex immunofluorescent staining were used to identify Treg cells in the liver and peripheral blood. A mouse LT model was employed to confirm the infiltration of Treg cells in the liver and circulation. A lentiviral vector system was used to overexpress miR-193b-3p in dendritic cells (DCs), and exosomes isolated from these transfected cells were co-cultured with spleen lymphocytes in vitro. A quantitative Real-time PCR and enzyme-linked immunosorbent assay were used to detect the expression of cytokines. Results Treg cell infiltration was increased in the liver along with Th17 and CD8 + T cell, and it was down-regulated in peripheral blood in the acute rejection group, an effect confirmed in the mouse LT model. High-throughput sequencing revealed that miR-193b-3p was markedly up-regulated in plasma exosomes of non-rejection LT patients. The NLRP3 inflammasome was screened as a target for miR-193b-3p based on target prediction and functional enrichment analyses. Exosomal miR-193b-3p derived from DCs increased Treg cells as demonstrated in vitro. miR-193b-3p overexpression down-regulated NLRP3 as well as the inflammatory cytokines IL-1β and IL-17A while increasing levels of the cytokines IL-10 and TGF-β. Conclusion DC deriving exosomal miR-193b-3p promoted Treg cells by inhibiting NLRP3 expression. These findings not only provide a new perspective on the mechanisms, but also hold great promise for the treatment or prevention of liver allograft rejection.

In recent decades, overgrazing and the warming and drying climate have resulted in significant degradation of alpine grasslands in the source region of the Yellow River. However, research into the relationships between vegetation and soil properties has mainly focused on an overall degradation stage, and few studies have investigated which soil properties can impact vegetation change at different stages of degradation. Vegetation and soil properties were observed in the field and measured in the laboratory for different predefined stages of degradation for alpine grassland in Maduo County in the source region of the Yellow River. Results show that: 1) the aboveground and belowground biomass, soil organic carbon, total nitrogen, nitrate, and ammonia content did not decrease significantly from the intact to moderate degradation stage, but decreased significantly at severe and very severe stages of degradation; 2) dominant plant species shifted from gramineaes and sedges to forbs; 3) the species richness and Pielou evenness indices decreased significantly at the very severe degradation stage, the Shannon-Wiener diversity index increased at the slight and moderate degradation, but decreased at the severe and very severe degradation stages; 4) soil bulk density was the strongest soil driver for changes in the plant biomass and community diversity at the intact, slight and moderate degradation stages, whereas soil organic carbon and nitrate nitrogen content were the main driving factors for changes in plant biomass and diversity at the severe and very severe degradation stages. Our results suggest that there may be different interactions between soil properties and plants before and after moderate stages of degradation.

Background Cryoballoon ablation (CBA) and radiofrequency ablation (RFA) are the most common procedures used to treat refractory atrial fibrillation (AF) and are performed through pulmonary vein isolation (PVI). Studies have shown that CBA can approximately match the therapeutic effects of RFA against AF. However, few studies have investigated the difference between CBA and RFA of the effects on left atrial remodeling for paroxysmal AF. Objective Atrial remodeling is considered pivotal to the occurrence and development of AF, therefore we sought to assess the influence of atrial remodeling in patients with paroxysmal AF after CBA and RFA in this study. Methods In this nonrandomized retrospective observational study, we enrolled 328 consecutive patients who underwent CBA or RFA for refractory paroxysmal AF in May 2014 to May 2017 in our hospital. After propensity score matching, 96 patients were included in the CBA group, and 96 were included in the RFA group. Patients were asked to undergo a 12‐lead electrocardiogram, a 24‐h Holter monitor, and an echocardiogram and to provide their clinical history and symptoms at 6 months and 1, 2, and 3 years postprocedurally. Electrical remodeling of the left atrium was assessed by P wave dispersion (Pdis); structural remodeling was assessed by the left atrium diameter (LAD) and left atrial volume index (LAVI) during scheduled visits. Results As of January 2020, compared with baseline, at 1 year, 2 years, and 3 years after ablation, the average changes in Pdis (∆Pdis), LAD (∆LAD), and LAVI (∆LAVI) were significant in both the CBA and RFA groups. Six months after ablation, ∆Pdis, ∆LAD, and ∆LAVI were greater in the CBA group than in the RFA group. There was no significant difference between the two groups in AF/flutter recurrence, but the AF/flutter‐free survival time of CBA group may be longer than RFA group after 2 years after ablation. A higher ∆Pdis, ∆LAD, or ∆LAVI at 1 year after ablation may increase AF/flutter‐free survival. Conclusions Although CBA and RFA are both effective in left atrial electrical and structural reverse‐remodeling in paroxysmal AF, CBA may outperform RFA for both purposes 6 months after ablation. However, during long‐term follow‐up, there was no significant intergroup difference.

Although double positive CD4

Liver transplantation (LT) is an effective strategy for the treatment of end-stage liver disease, but immune rejection remains a significant detriment to the survival and prognosis of these LT patients. While immune rejection is closely related to cytokines, the cytokines investigated within previous studies have been limited and have not included a systematic analysis of proinflammatory cytokines. In the present study, we used a protein chip system and proteomics to detect and analyze serum proinflammatory cytokines and differentially expressed proteins in liver tissue in a mouse model of liver transplantation. In addition, bioinformatics analysis was employed to analyze the proinflammatory cytokines and differential changes in proteins in response to this procedure. With these analyses, we found that serum contents of GC-CSF, CXCL-1, MCP-5, and CXCL-2 were significantly increased after liver transplantation, while IL-5, IL-10, and IL-17 were significantly decreased. Results from Gene Ontology (GO) and KEGG pathway analyses revealed that the cytokine-cytokine receptor, Th1/Th2 cell differentiation, and JAK-STAT signaling pathway were enriched in a network associated with the activation of immune response. Results from our proteomic analysis of liver tissue samples revealed that 470 proteins are increased and 50 decreased, including Anxa1, Anxa2, Acsl4, Sirpa, S100a8, and S100a9. KEGG pathway analysis indicated that the neutrophil extracellular trap formation, NOD-like receptor signaling pathway, and leukocyte transendothelial migration were all associated with liver transplant rejection in these mice. Bioinformatics analysis results demonstrated that CXCL-1/CXCL-2 and S100a8/S100a9 were the genes most closely related to the functions of neutrophils and the mononuclear phagocyte system. These findings provide new insights into some of the critical factors associated with liver transplant rejection and thus offer new targets for the treatment and prevention of this condition.

Most plants in nature establish symbiotic associations with endophytic fungi in soil. Beneficial endophytic fungi induce a systemic response in the aboveground parts of the host plant, thus promoting the growth and fitness of host plants. Meanwhile, temperature elevation from climate change widely affects global plant biodiversity as well as crop quality and yield. Over the past decades, great progresses have been made in the response of plants to high ambient temperature and to symbiosis with endophytic fungi. However, little is known about their synergistic effect on host plants. The endophytic fungus

ROS1-rearranged non-small cell lung cancer (NSCLC) is a subset of NSCLC patients with unique malignant behavior and clinical course. Crizotinib, a multi-targeted ALK/ROS1/MET tyrosine kinase inhibitor (TKI), has promising significant activity in NSCLC with ROS1-rearrangement. The next-generation sequencing (NGS) is commonly used to identify the “druggable” genetic alterations in clinical practice. We identified a novel ROS1 fusion variant (FRK-ROS1) in a de novo stage IV NSCLC patient by NGS testing. This novel ROS1-rearrangement is generated by the fusion FRK to ROS1. The patient was remarkably responsive to crizotinib including the brain metastasis. A 29-year-old male never-smoker with chief complaints of back pain with a lumpy and flaky soft tissue mass in the upper right lobe of the lung and diffuse ground-glass shadow in both lungs e IV (cT4N3M1b). A CT-guided biopsy revealed the predominant adenocarcinoma and partial mucinous adenocarcinoma. By using next-generation sequencing (NGS) assay, we found that the tumor had FRK-ROS1 fusion rather than other actionable mutations. In that case, the patient took the first-line crizotinib and experienced a remarkable tumor response to it and tolerance well until written. FRK-ROS1 is a novel ROS1 fusion variant in NSCLC identified by NGS testing and the first-line crizotinib showed excellent performance in all lesions including the brain metastasis.

BACKGROUND Portopulmonary hypertension (PoPH) is not uncommon in patients waiting for liver transplantation (LT). Severe PoPH has a very high perioperative mortality rate and is still considered a contraindication for LT. Many patients with liver disease require but cannot receive LT due to severe PoPH and eventually died. We report a patient with severe PoPH who underwent successful LT and had near normal pulmonary pressure without drug treatment. CASE SUMMARY A 39-year-old woman was hospitalized with the chief complaint of jaundice and exertional dyspnea and fatigue. Caroli disease and liver cirrhosis was diagnosed 6 years previously. Her liver disease met the criteria for LT. However, right heart catheterization showed that her mean pulmonary artery pressure was increased at 50 mmHg, pulmonary vascular resistance was 460 dyn∙s/cm5 and pulmonary artery wedge pressure was 20 mmHg, which may have been the reasons for her chief complaint. The patient was diagnosed with severe PoPH and was not listed for LT immediately. After 5 mo of pharmacotherapy, her severe PoPH was moderate, and she underwent successful LT. Pulmonary artery pressure steadily decreased according to post-operative echocardiographic monitoring and drugs have been discontinued for a month. CONCLUSION The safety of LT can be greatly improved by reducing mean pulmonary artery pressure to a low level, and LT may cure PoPH.

Various genetic polymorphisms have been linked to lung cancer susceptibility and survival outcomes. Vitamin D (VD) regulates cell proliferation and differentiation, inhibits tumor growth and induces apoptosis. Observations from several previous studies including our own suggest that genetic polymorphisms in the VD pathway may be associated with lung cancer risk. The aim of this study is to assess if genetic polymorphisms in the VD pathway are associated with the prognosis of non-small cell lung cancer (NSCLC). Nine single nucleotide polymorphisms (SNPs) in five genes in the VD pathway were genotyped with the TaqMan assays in 542 patients with primary NSCLC, and the relationships between these SNPs and overall survival were evaluated. We found that SNP rs10741657 in the CYP2R1 gene was associated with the prognosis of NSCLC, especially in elderly patients and not being treated with chemotherapy. Some of the VD pathway-related genetic polymorphisms may influence the prognosis of NSCLC. More research is needed to further confirm the finding and test if VD supplements can be used for NSCLC treatment.

BACKGROUND: There are few detailed consensus and guidelines on perioperative clinical characteristics of liver transplantation (LT) in patients with methylmalonic acidemia (MMA). This retrospective study investigated details of the clinical course and individualized treatment plan of the center with largest experience in China. METHODS: A total of 7 MMA patients undergoing LT in Beijing Friendship Hospital from June 2013 to December 2017 were enrolled in the study, whose clinical data (clinical characteristics, laboratory findings, chronological changes in urine MMA levels, treatment, etc.) during perioperative period were analyzed retrospectively. All the patients received strict postoperative management. RESULTS: All the 7 cases were confirmed to have isolated MMA, among which, 3 cases received living donor liver transplantation (LDLT), 4 cases received deceased donor liver transplantation (DDLT). A wild fluctuate of metabolic condition was observed within the first few days after surgery and two weeks after LT, the mean base excess of blood value (BE-B) restored to normal whereas plasma bicarbonate (HCO(3)(−)) was still below normal value even with intermittent sodium bicarbonate correction. It also showed marked reduction in propionylcarnitine (C3) and C3/C2 level and the mean urine MMA by gas chromatography-mass spectrometry (GC-MS) was reduced by 81.7% (P72× higher than upper limit of normal. The metabolism-correcting medications were administered as before. The renal function of one case with renal insufficiency before LT (serum creatinine rising) maintained stable by adjusting the immunosuppressive regimen during the observation period. All patients survive to date. CONCLUSIONS: LT is an effective treatment to prevent metabolic crisis, but patients with MMA tend to be metabolically fragile even after surgery. During perioperative period, close monitoring should be given for acidosis episodes so as to implement sodium bicarbonate correction. Metabolism-correcting medications are still needed. Special immunosuppressive regimen is an effective way of maintaining renal function for those with kidney dysfunction.

We aimed to combine glycyrrhetinic acid with doxorubicin to prepare, characterize and evaluate a drug delivery nano-system with REDOX sensitivity for the treatment of breast cancer. M-DOX-GA NPs prepared by nano sedimentation were spherical, with a particle size of 181 nm. And the maximum encapsulation efficiency and drug loading in M-DOX-GA NPs were 89.28% and 18.22%, respectively. Cytotoxicity and cellular uptake experiments of nanoparticles to KC cells, Cal-27 cells and 4T1 cells were studied by the CCK-8 method. The result indicated that M-DOX-GA NPs could accurately release the drug into the tumor cells, thus achieving the targeted release of the drug. Comparing the survival rate of the above three cells, it was found that M-DOX-GA NPs had a good tumor selectivity and had a more significant therapeutic effect on breast cancer. A 4T1-bearing mouse model was established, and the tumor inhibition rate was 77.37% after injection of nanoparticle solution for 14 d. Normal tissue H&E stained sections and TUNEL assay were verified M-DOX-GA NPs have excellent tumor suppressive effect, and can efficiently reduce the toxic side effects on normal organisms, and effectively avoided 4T1 cells metastasis. Immunofluorescence detection and Western-blot analysis figured a decline in both CUGBP1 and α-SMA, which verifying the TME remodeling induced by glycyrrhetinic acid. Collectively, the combination of doxorubicin and glycyrrhetinic acid is an effective and safe strategy for remodeling fibrotic TME by improving the therapeutic outcome for breast cancer.

The natural extract glaucocalyxin A (GLA), purified from the aboveground sections of the Chinese traditional medicinal herb Rabdosia japonica (Burm. f.) Hara var. glaucocalyx (Maxim.) Hara, has various pharmacological benefits, such as anti-bacterial, anti-coagulative, anti-neoplastic, and anti-inflammatory activities. Although GLA has shown anti-tumor activity against various cancers, the therapeutic potential and biological mechanisms of GLA remain to be further explored in oral squamous cell carcinoma (OSCC).This study aimed to elucidate the therapeutic potential and regulatory mechanisms of GLA in OSCC.The cell proliferation and apoptosis effects of GLA were analyzed by CCK-8, clone formation, Annexin V/PI staining, and apoptotic protein expression in vitro. An OSCC xenograft model was applied to confirm the anti-neoplastic effect in vivo. Furthermore, the changes of reactive oxygen species (ROS) were determined by DCFH-DA probe and GSH/GSSG assay, and inhibited by the pan-caspase inhibitor Z-VAD(OMe)-FMK and the ROS scavenger N-acetylcysteine (NAC). The modulation of GLA on mitochondria and ER-dependent apoptosis pathways was analyzed by JC-1 probe, quantitative real-time PCR, and Western blot. Finally, public databases, clinical samples, and transfection cells were analyzed to explore the importance of GLA's indirect targeting molecule CHAC1 in OSCC.GLA significantly inhibited cell proliferation and induced apoptosis in vitro and in vivo. GLA perturbed the redox homeostasis, and cell apoptosis was totally rescued by Z-VAD(OMe)-FMK and NAC. Furthermore, GLA activated the mitochondrial apoptosis pathway. Simultaneously, the overexpression and knockdown of CHAC1 dramatically affected GLA-mediated apoptosis. The endoplasmic reticulum stress-associated ATF4/CHOP signal was identified to participate in GLA-upregulated CHAC1 expression. Finally, we found that CHAC1 expression was lower in OSCC compared with normal tissues and positively correlated with 4-Hydroxynonenal (4-HNE) level. High CHAC1 expression also indicated better overall survival. Moreover, CHAC1 selectively regulated the viability of oral cancer cells.GLA is a promising therapeutic agent that activates the ROS-mediated ATF4/CHOP/CHAC1 axis in OSCC patients.

Recent evidences demonstrate that dysregulated expression of microRNA-320d (miR-320d) has been associated with several cancer development and progression. However the effect of miR-320d on gastric cardiac adenocarcinoma (GCA) and the association of miR-320d with its potential gene target FoxM1 remain unclear. Here, we evaluated expression profile of miR-320d and FoxM1 in 60 human GCA tissues and GCA cell lines (OE-19 and SK-GT2). Immunohistochemistry, qualitative PCR and western-blotting were performed in GCA tissues to detect the expression level of miR-320d and FoxM1. CCK-8, transwell, wound-healing assays, and in vivo experiments were conducted using GCA cells that treated with miR-320d mimics or inhibitors to evaluate the biological functions of miR-320d. Luciferase reporter assay was conducted to confirm possible binding sites of FoxM1 for miR-320d. Compared with paired non-cancerous tissues, it showed that miR-320d expression was significantly decreased in GCA specimens (P P

Objective The aim of this study was to investigate the protective effect and mechanism of Ginkgo biloba extract-761 (EGb 761) in the rat with myocardial ischemia-reperfusion injury (MIRI). Materials and methods Forty Sprague Dawley rats were randomly divided into following four groups: sham group, I/R group and EGb 761 groups (20 and 40 mg/kg). MIRI model was established after 14 days of administration. The myocardial infarct size and myocardial histology were measured and compared. Meanwhile, the levels of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), troponin T (TnT), TNF-α, IL-6, IL-1β, superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were evaluated. Western blot was used to detect the expression of Caspase-3, Bax, Bcl-2, HO-1, Nrf2, Akt, p-Akt and nuclear protein Nrf2. Results The levels of infarct size, CK-MB, LDH, TnT, TNF-α, IL-6 and IL-1β in the EGb 761 groups were significantly lower than those in the ischemia/reperfusion (I/R) group. The content of MDA was lower in the myocardium, whereas the activities of SOD and GSH-Px were higher than those in the I/R group. The expressions of Caspase-3 and Bax in the EGb 761 groups were significantly lower than those in the I/R group, whereas the expressions of Bcl-2, p-Akt and HO-1 and nuclear protein Nrf2 in the EGb 761 groups were higher than those in the I/R group. Conclusion EGb 761 might inhibit the apoptosis of myocardial cells and protect the myocardium by activating the Akt/Nrf2 pathway, increasing the expression of HO-1, decreasing oxidative stress and repressing inflammatory reaction.

An iterative hybrid of finite element boundary integral (FEBI) method and physical optics (PO) is presented for scattering problems of complex structures having junctions with electrically large-scale platform. The treatment of basis functions on the junctions between complex structures and platform is discussed in detail. Moreover, the multilevel fast multipole algorithm and the adaptive cross approximation method are employed to accelerate the solution of FEBI and the computation of interaction between FEBI and PO regions, respectively. Compared with FEBI method, the hybrid method can efficiently reduce the number of unknowns and the computational complexity while preserving acceptable accuracy. In addition, the alternative implementation of FEBI and PO can also maintain good independence of the two methods. Some numerical results are discussed to demonstrate the efficiency and accuracy of the approach.

Aim: To develop nanomedicines for immuno-therapy of oral dysplasia and oral squamous cell carcinoma. Materials & methods: All-trans retinoic acid (ATRA)-poly(lactide-co-glycolide acid) (PLGA)-poly(ethylene glycol) (PEG)-programmed death-ligand 1 (PD-L1) nanomedicines were fabricated by loading ATRA into PLGA-PEG nanocarriers and modification using an anti-PD-L1 antibody. Results: ATRA-PLGA-PEG-PD-L1 nanoparticles showed fast cellular uptake, significantly inhibited proliferation and induced apoptosis in DOK and CAL27 cells. Moreover, in C3H tumor-bearing mice, ATRA-PLGA-PEG-PD-L1 nanoparticles more specifically targeted tumor cells, enhanced anticancer activity and reduced side effects when compared with free ATRA. Furthermore, CD8+ T cells were activated around PD-L1 positive cells in the tumor microenvironment after treatment. Conclusion: ATRA-PLGA-PEG-PD-L1 nanoparticles had low toxicity, high biocompatibility and specifically targeted oral dysplasia and squamous carcinoma cells both in vitro and in vivo.

Background and objectives The aim of this study was to analyze risk factors for failure of subclavian vein catheterization. Methods A retrospective analysis of 1562 patients who underwent subclavian vein puncture performed by the same experienced operator at Peking University Cancer Hospital from January 1, 2016 to January 1, 2019 was conducted. The success or failure of subclavian vein catheterization was registered in all cases. Various patient characteristics, including age, gender, body mass index (BMI), preoperative hemoglobin, preoperative hematocrit, preoperative mean corpuscular hemoglobin concentration (MCHC), preoperative albumin, preoperative serum creatinine, puncture needles from different manufacturers and previous history of subclavian vein catheterization were assessed via univariate and multivariate analyses. Results For the included patients, landmark-guided subclavian vein puncture was successful in 1476 cases and unsuccessful in 86 cases (success rate of 94.5%). Successful subclavian vein catheterization was achieved via right and left subclavian vein puncture in 1392 and 84 cases, respectively. In univariate analyses, age and preoperative hemoglobin were associated with failure of subclavian vein catheterization. In a multivariate analysis, aged more than 60 years was a risk factor while the central venous access with Certofix® was associated with an increased rate of success (p-values of 0.001 and 0.015, respectively). Conclusions This study has demonstrated that patient aged more than 60 years was a risk factor for failure of subclavian vein catheterization while the central venous access with Certofix® was associated with an increased rate of success.