FL% is associated with the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk and total arch replacement.

Objectives: The diameter, area, and volume of the true lumen and false lumen (FL) have been measured in previous studies to evaluate the extent of DeBakey type I aortic dissection. However, these indicators have limitations because of the irregular shapes of the true and false lumens and the constant oscillation of intimal flap during systole and diastole. The ratio of arch lengths seems to be a more reliable indicator. FL% was defined as the ratio of the arch length of FL to the circumference of the aorta at the different levels of the aorta. The purpose of this article was to investigate whether FL% is a predictor of the severity of acute DeBakey type I aortic dissection in patients undergoing frozen elephant trunk (FET) and total arch replacement. Methods: In this retrospective observational study, we analyzed a total of 344 patients with acute DeBakey type I aortic dissection that underwent FET and total arch replacement at our center from October 2015 to October 2019. The patients were divided into two groups by cluster analysis according to the perioperative course. Binary logistic regression analyses were performed to determine whether FL% could predict the severity of acute DeBakey type I aortic dissection. The area under the receiver operating characteristic curve (AUROC) was used to assess the power of the multivariate logistic regression model for the severity of acute DeBakey type I aortic dissection. Results: The patients in the ultra-high-risk group (109 patients) had significantly more severe clinical comorbidities and complications than the patients in the high-risk group (235 patients). The ascending aortic FL% [odds ratio (OR), 11.929 (95% CI: 1.421-100.11); P = 0.022], location of initial tear [OR, 0.68 (95% CI: 0.47-0.98); P = 0.041], the degree of left iliac artery involvement [OR, 1.95 (95% CI: 1.15-3.30); P = 0.013], and the degree of right coronary artery involvement [OR, 1.46 (95% CI: 1.01-2.12); P = 0.045] on preoperative computed tomography angiography were associated with the severity of acute DeBakey type I aortic dissection. The AUROC value of this multivariate logistic regression analysis was 0.940 (95% CI: 0.914-0.967; P < 0.001). The AUROC value of ascending aortic FL% was 0.841 (95% CI: 0.798-0.884; P < 0.001) for the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Conclusions: Ascending aortic FL% was validated as an essential radiologic index for assessing the severity of acute DeBakey type I aortic dissection in patients undergoing FET and total arch replacement. Higher values of ascending aortic FL% were more severe.

Lidocaine pretreatment attenuates inflammatory response and protects against sepsis-induced acute lung injury via inhibiting potassium efflux-dependent NLRP3 activation.

OBJECTIVE: Sepsis may often result in acute lung injury (ALI), with a high mortality and morbidity. Available evidence indicates that activation of NLRP3 inflammasome to induce macrophage inflammation plays a crucial role in the inflammation progression of ALI and lidocaine can attenuate inflammatory responses. We hypothesized that lidocaine may attenuate inflammatory response and sepsis-induced ALI by inhibiting potassium efflux-dependent NLRP3 activation. METHODS: C57BL/6N mice were randomized and divided into six groups (n = 6) receiving different treatments. Lung vascular permeability and histological changes in the lungs were evaluated by Evans blue dye, bronchoalveolar lavage analysis and hematoxylin and eosin staining. J774A.1 macrophages were divided into 12 groups receiving different treatments. The expression of both NLRP3 inflammasome activation-related protein and P2X7 in the macrophages was measured by immunofluorescence staining and Western blots. The whole cell currents were determined by a voltage-patch clamp technique. RESULTS: Challenge with LPS led to ALI in mice with an increased lung injury score (0.54 ± 0.09), which was significantly attenuated by lidocaine pretreatment (0.20 ± 0.08, P < 0.0001). Lidocaine pretreatment significantly decreased the NLRP3 activation and IL-1ß release in the macrophages. Furthermore, lidocaine pretreatment down-regulated the expression of P2X7 receptors, inhibited LPS- and ATP-induced sodium (Na+) inward flow, and maintained the intracellular K+ level in the macrophages. In addition, activation of Na+ influx did not eliminate anti-inflammatory effect of lidocaine. The activation of NLRP3 could be suppressed by extracellular K+ level in a dose-dependent model. However, lidocaine pretreatment eliminated NLRP3 activation and IL-1ß release induced by K+ efflux, and decreased outward K+ current and extracellular K+ level in the macrophages challenged by LPS/ATP. CONCLUSIONS: Lidocaine pretreatment can attenuate the sepsis-induced ALI by an anti-inflammatory mechanism of inhibiting K+ efflux-dependent NLRP3 activation.

Associations between race/ethnicity and SEER-CAHPS patient care experiences among female Medicare beneficiaries with breast cancer.

INTRODUCTION: We aimed to determine if racial/ethnic disparities exist in survivorship care patient experiences among older breast cancer survivors. MATERIALS AND METHODS: Nineteen thousand seventeen female breast cancer survivors aged ≥65 at post-diagnosis survey contributed data via the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) and Centers for Medicare and Medicaid Services Consumer Assessment of Healthcare Providers & Systems (CAHPS) data linkage (2000-2019). Multivariable linear regression models were used to estimate adjusted beta (ß) coefficients and standard error (SE) estimates for associations between race/ethnicity and survivorship care patient experiences. RESULTS: Most women were non-Hispanic (NH)-White (78.1%; NH-Black [8.1%], NH-Asian [6.5%], Hispanic [6.2%]). On average, women reported 76.3 years (standard deviation [SD] = 7.14) at CAHPS survey and 6.10 years since primary diagnosis (SD = 3.51). Compared with NH-White survivors, NH-Black survivors reported lower mean scores for Getting Care Quickly (ß = -5.17, SE = 0.69, p ≤0.001), Getting Needed Care (ß = -1.72, SE = 0.63, p = 0.006), and Overall Care Ratings (ß = -2.72, SE = 0.48, p ≤0.001), mirroring the results for NH-Asian survivors (Getting Care Quickly [ß = -7.06, SE = 0.77, p ≤0.001], Getting Needed Care [ß = -4.43, SE = 0.70, p ≤0.001], Physician Communication [ß = -1.15, SE = 0.54, p = 0.03], Overall Care Rating [ß = -2.32, SE = 0.53, p ≤0.001]). Findings among Hispanic survivors varied, where mean scores were lower for Getting Care Quickly (ß = -2.83, SE = 0.79, p ≤0.001), Getting Needed Care (ß = -2.43, SE = 0.70, p = 0.001), and Getting Needed Prescription Drug(s) (ß = -1.47, SE = 0.64, p = 0.02), but were higher for Health Plan Rating (ß = 2.66, SE = 0.55, p ≤0.001). Education, Medicare plan, and multimorbidity significantly modified various associations among NH-Black survivors, and education was a significant modifier among NH-Asian and Hispanic survivors. DISCUSSION: We observed racial/ethnic disparities in the associations with survivorship care patient experience among NH-Black, Hispanic, and NH-Asian breast cancer survivors. Future research should examine the impact of education, Medicare plans, and multimorbidity on these associations.

[Clinicopathological Features of Primary Small Cell Neuroendocrine Carcinoma of the Bladder].

Objective To investigate the clinicopathological features,immunohistochemical features,diagnosis,and relationship with sporadic prostate cancer in primary small cell neuroendocrine carcinoma of the bladder. Methods We retrospectively analyzed the clinical characteristics of 12 patients with primary small cell neuroendocrine carcinoma of the bladder diagnosed at Beijing Chao-Yang Hospital affiliated to Capital Medical University from January 2013 to September 2022.The histological features of primary small cell neuroendocrine carcinoma of the bladder were re-evaluated by two pathologists according to the 2022 revision of the World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs.Electronic medical records were retrieved,and telephone follow-up was conducted from the time of histopathological diagnosis to the death or the end of the last follow-up until January 31,2023. Results The 12 patients include 7 patients in pT3 stage and 1 patient in pT4 stage.Eight patients were complicated with other types of tumors,such as high-grade urothelial carcinoma of the bladder and squamous cell carcinoma.Five patients had sporadic prostate cancer.Immunohistochemical staining showed that 12 (100.0%),10 (83.3%),and 8 (66.7%) patients were tested positive for CD56,Syn,and CgA,respectively.The Ki67 proliferation index ranged from 80% to 90%.Five patients with urothelial carcinoma were tested positive for CK20,GATA3,and CK7.P504S was positive in all the 5 patients with prostate cancer,while P63 and 34ßE12 were negative.The follow-up of the 12 patients lasted for 3-60 months.Eight of these patients died during follow-up,with the median survival of 15.5 months.Four patients survived. Conclusions Primary small cell neuroendocrine carcinoma of the bladder is a rare urological tumor with high aggressiveness and poor prognosis.In male patients with bladder prostatectomy,all prostate tissue should be sampled.If prostate cancer is detected,the prostate-specific antigen level should be monitored.

Return-to-work self-efficacy questionnaire: Cross-cultural adaptation and validation in China.

AIM: To develop a Chinese version of the return-to-work self-efficacy (RTW-SE-11) and verify its reliability and validity. DESIGN: A validation study. METHODS: The RTW-SE-11 was translated into Chinese according to the Brislin's model, and then the semantic adjustment of questionnaire was carried out through multi-field expert evaluation and preliminary investigation. RESULTS: All 11 items of the original questionnaire were retained. Content validity index (CVI) of the Chinese version of RTW-SE-11 indicated good validity, with Inter-rater Agreement (IR) of 0.97, item CVI of 0.90-1.00 and questionnaire CVI of 0.91. Cronbach's α coefficient of RTW-SE-11 (Chinese version) was 0.923, suggesting high internal consistency, with test-retest reliability of 0.799 and half-fold reliability of 0.926. Patient or public contribution: The Chinese version of the RTW-SE-11 questionnaire confirmed good reliability and validity for the assessment of return to work self-efficacy in Chinese breast cancer patients.

Evaluation of the potential herb-drug interaction between Bojungikki-tang and PD-L1 immunotherapy in a syngeneic mouse model.

Atezolizumab (a PD-L1 inhibitor) has shown remarkable efficacy and tolerability in various cancer types. Despite its efficacy and safety, atezolizumab monotherapy has limitations, such as acquired resistance and adverse events. Bojungikki-tang (BJIKT) is an herbal decoction widely prescribed in Asian countries and used to treat cancer-related symptoms including fatigue, appetite loss, gastrointestinal disorders, and other side effects from cancer therapy. Due to its immunomodulatory effects, Bojungikki-tang has been investigated as a combined treatment with anticancer agents. We evaluated the potential drug-drug interaction (DDI) between Bojungikki-tang and the anti-PD-L1 antibody based on the Food and Drug Administration (FDA) guidelines. In the study, we conducted an in vivo drug-drug interaction study using a syngeneic mouse model of CMT-167 in C57BL/6. We then determined the antibody concentrations to evaluate the pharmacokinetic (PK) drug-drug interaction and measured variable biomarkers related to therapeutic efficacy and immune response. The pharmacodynamic (PD) drug-drug interaction study investigated changes in response between anti-PD-L1 antibody monotherapy and combination therapy. Using the pharmacokinetic and pharmacodynamic data, we conducted a statistical analysis to assess drug-drug interaction potential. In the presence of Bojungikki-tang, the pharmacokinetic characteristics of the anti-PD-L1 antibody were not changed. This study suggested that combination treatment with Bojungikki-tang and atezolizumab is a safe treatment option for non-small cell lung cancer. Clinical studies are warranted to confirm this finding.

The Accurate Interpretation and Clinical Significance of Morphological Features of Fine Needle Aspiration Cells in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid gland; fine needle aspiration cytology is the most basic and reliable diagnostic method before PTC operation. However, it is not clear which cell morphological changes can be used as a reliable standard for the diagnosis of PTC. A retrospective analysis was performed on 337 patients with PTC confirmed by postoperative histology. An additional 197 randomly selected patients with benign thyroid lesions were included in the study and used as a control group. True papillary arrangements, swirl arrangements, and escape arrangements had high specificity, all of which were 100%, but only swirl arrangements had ideal sensitivity (77.61%). The nuclear volume characteristics had a high sensitivity of more than 90%, but the specificities of both nuclear crowding and nuclear overlap were too low, only 16.34% and 23.35%. The sensitivities of five nuclear structural characteristics were more than 90%, but only the specificity of intranuclear cytoplasmic pseudoinclusions (INCIs) reached 100%, nuclear contour irregularity and pale nuclei with powdery chromatin also had ideal interpretation value except for grooves and marginally placed micronucleoli. Although the sensitivity of psammoma bodies (PBs) was low, the specificity was 100%. In terms of preparation methods, the method of liquid-based preparation (LBP) is obviously better than that of conventional smears. The diagnostic efficiency by the combined detection method of parallel tests showed that without reducing the specificity, the sensitivity increased with the increase of the number of morphological characteristics and finally reached 98.81%. The INCIs and swirl arrangements are the most common and important indicators for the diagnosis of PTC, whereas papillary-like arrangements, the crowding and overlap of nuclear, grooves, marginally placed micronucleoli, and multinucleated giant cells are of little significance for the diagnosis of PTC.

Safety and Efficacy of Bojungikki-Tang in Advanced NSCLC Patients Receiving Treatment with Immune Checkpoint Inhibitors: Protocol for a Multicenter, Double-Blind, Randomized, Placebo-Controlled Pilot Trial.

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is a major treatment option for several types of cancer, including non-small cell lung cancer (NSCLC). The proposed study aims to investigate the safety and efficacy of Bojungikki-tang (BJIKT) therapy (an herbal medicine) in patients with advanced NSCLC treated with ICIs. This multicenter, randomized, placebo-controlled pilot study will be performed at three academic hospitals. Thirty patients with advanced NSCLC, undergoing atezolizumab monotherapy as second- and subsequent-line treatment, will be recruited and randomly assigned to either BJIKT treatment (atezolizumab + BJIKT) or placebo (atezolizumab + placebo). The primary and secondary outcomes are the incidence of adverse events (AEs), including immune- related AEs (irAEs) and non-immune-related AEs (non-irAEs); and early termination rate, withdrawal period, symptom improvement of fatigue, and skeletal muscle loss, respectively. The exploratory outcomes are patient objective response rate and immune profile. This is an ongoing trial. Recruitment started on 25 March 2022 and is expected to be completed by 30 June 2023. This study will provide basic evidence for the safety profiles, including irAEs, of herbal medicine in patients with advanced NSCLC treated with ICIs.

Resveratrol Ameliorates Trigeminal Neuralgia-Induced Cognitive Deficits by Regulating Neural Ultrastructural Remodelling and the CREB/BDNF Pathway in Rats.

Chronic pain often leads to cognitive impairment. Resveratrol (Res), a natural polyphenol existing in Polygonum cuspidatum, has been widely investigated for its antinociceptive, anti-inflammatory, and neuroprotective properties. Our aim was to explore the ameliorating effects of resveratrol on pain-related behaviors and learning and memory deficits induced by cobra venom-induced trigeminal neuralgia (TN). The TN model of rats was established by injecting cobra venom solution beneath the epineurium of the infraorbital nerve. Resveratrol was intragastrically administered at a dose of 40 mg/kg twice daily beginning on postoperative day 15. CREB inhibitor 666-15 was intraperitoneally administered at a dose of 10 mg/kg from POD 35-42 after morning resveratrol treatment. Mechanical allodynia was measured via von Frey filaments. Rat free movement was videotaped and analyzed. Spatial learning and memory were evaluated via the Morris water maze test. Ultrastructures of the hippocampal DG region and infraorbital nerve were observed by transmission electron microscopy. We found that resveratrol alleviated TN-induced allodynia, ameliorated learning and memory deficits, restored the ultrastructure of hippocampal neurons and synapses, repaired the damaged myelin sheath of the infraorbital nerve, and activated the CREB/BDNF pathway in the hippocampus of TN rats. CREB inhibitor administration suppressed the resveratrol-rescued abnormal hippocampal ultrastructural changes and aggravated spatial learning and memory impairment by inhibiting CREB/BDNF pathway activation in the hippocampus. Our findings indicated that resveratrol alleviated pain and improved cognitive deficits, probably by regulating neural ultrastructure remodelling and the CREB/BDNF pathway.

Systematic transcriptome analysis reveals molecular mechanisms and indications of bupleuri radix.

Pharmacogenomic analysis based on drug transcriptomic signatures is widely used to identify mechanisms of action and pharmacological indications. Despite accumulating reports on the efficacy of medicinal herbs, related transcriptome-level analyses are lacking. The aim of the present study was to elucidate the underlying molecular mechanisms of action of Bupleuri Radix (BR), a widely used herbal medicine, through a systematic transcriptomic analysis. We analyzed the drug-responsive transcriptome profiling of A549 lung cancer cell line after treating them with multiple doses of BR water (W-BR) and ethanol (E-BR) extracts and their phytochemicals. In vitro validation experiments were performed using both A549 and the immortalized human keratinocyte line HaCaT. Pathway enrichment analysis revealed the anti-cancer effects of BR treatment via inhibition of cell proliferation and induction of apoptosis. Enhanced cell adhesion and migration were observed with the W-BR but not with the E-BR. Comparison with a disease signature database validated an indication of the W-BR for skin disorders. Moreover, W-BR treatment showed the wound-healing effect in skin and lung cells. The main active ingredients of BR showed only the anti-cancer effect of the E-BR and not the wound healing effect of the W-BR, suggesting the need for research on minor ingredients of BR.

Phosphodiesterase 4D contributes to angiotensin II-induced abdominal aortic aneurysm through smooth muscle cell apoptosis.

Abdominal aortic aneurysm (AAA) is a permanent expansion of the abdominal aorta that has a high mortality but limited treatment options. Phosphodiesterase (PDE) 4 family members are cAMP-specific hydrolyzing enzymes and have four isoforms (PDE4A-PDE4D). Several pan-PDE4 inhibitors are used clinically. However, the regulation and function of PDE4 in AAA remain largely unknown. Herein, we showed that PDE4D expression is upregulated in human and angiotensin II-induced mouse AAA tissues using RT-PCR, western blotting, and immunohistochemical staining. Furthermore, smooth muscle cell (SMC)-specific Pde4d knockout mice showed significantly reduced vascular destabilization and AAA development in an experimental AAA model. The PDE4 inhibitor rolipram also suppressed vascular pathogenesis and AAA formation in mice. In addition, PDE4D deficiency inhibited caspase 3 cleavage and SMC apoptosis in vivo and in vitro, as shown by bulk RNA-seq, western blotting, flow cytometry and TUNEL staining. Mechanistic studies revealed that PDE4D promotes apoptosis by suppressing the activation of cAMP-activated protein kinase A (PKA) instead of the exchange protein directly activated by cAMP (Epac). Additionally, the phosphorylation of BCL2-antagonist of cell death (Bad) was reversed by PDE4D siRNA in vitro, which indicates that PDE4D regulates SMC apoptosis via the cAMP-PKA-pBad axis. Overall, these findings indicate that PDE4D upregulation in SMCs plays a causative role in AAA development and suggest that pharmacological inhibition of PDE4 may represent a potential therapeutic strategy.

Bojungikki-Tang Improves Response to PD-L1 Immunotherapy by Regulating the Tumor Microenvironment in MC38 Tumor-Bearing Mice.

Immune checkpoint blockage targeting PD-L1 has led to breakthroughs in cancer treatment. Although anti-PD-L1-based immunotherapy has been approved as standard therapy in various cancer types, its therapeutic efficacy in most colorectal cancers (CRC) is still limited due to the low response to immunotherapy. Therefore, combining treatment with herbal medicines could be an alternative approach for treating CRC to overcome this limitation. Bojungikki-Tang (BJIKT), a herbal formula used in traditional Chinese medicine, clinically improves the quality of life for cancer patients and has been associated with antitumor and immune-modulating activities. However, the regulatory effect of BJIKT on the immune response in the tumor microenvironment remains largely uninvestigated. In this study, we verified the inhibitory effect of BJIKT on tumor growth and investigated the regulatory effect of combination therapy with BJIKT and anti-PD-L1 on antitumor immune responses in an MC38 CRC-bearing C57BL/6 mouse model. Immune profiling analysis by flow cytometry was used to characterize the exact cell types contributing to anticancer activities. Combination treatment with BJIKT and anti-PD-L1 therapy significantly suppressed tumor growth in MC38-bearing mice and increased the proportion of cytotoxic T lymphocytes and natural killer cells in tumor tissues. Furthermore, BJIKT suppressed the population of myeloid-derived suppressor cells, suggesting that this combination treatment effectively regulates the immunological function of T-cells by improving the tumor microenvironment. The herbal formula BJIKT can be a novel therapeutic option for improving anti-PD-L1-based immunotherapy in patients with CRC.

Identification of a novel anticancer mechanism of Paeoniae Radix extracts based on systematic transcriptome analysis.

Paeoniae Radix (PR) has a great therapeutic value in many clinical applications; however, the presence of various bioactive compounds and its complicated effects on human health makes its precise mechanisms of action unclear. This study investigated the effects of PR at the molecular pathway level by profiling genome-wide gene expression changes following dose-dependent treatment of human lung cancer cells (A549) with PR water extract (WPR), PR ethanol extracts (EPR), as well as their individual components. We found that PR exerts anticancer effects in A549 cells by regulating numerous pathways. Specifically, EPR and two compounds, namely, hederagenin (HG) and oleanolic acid (OA), significantly downregulate the Aurora B pathway. Furthermore, we generated an integrated PR extracts-compounds-target genes network in the Aurora B pathway to understand their interactions. Our findings reinforce that inhibiting Aurora kinase activity is a therapeutic target for treating cancers, providing the potential for novel mechanisms of action for PR and its components against lung cancer.

CTA Imaging Features Related to Preoperative Coagulopathy in Patients with Stanford Type A Acute Aortic Dissection.

BACKGROUND: Stanford type A acute aortic dissection (TAAAD) is often accompanied by preoperative disorders of coagulation. The study aimed to evaluate the relationship between computed tomography angiography imaging features and preoperative coagulopathy in TAAAD patients. METHODS: This was a single-center retrospective review of adult patients undergoing TAAAD surgery from January 2015 to January 2019 in the Beijing Anzhen Hospital (Beijing, China). Images were obtained using preoperative enhanced computed tomography in 174 patients with TAAAD. Preoperative coagulopathy was defined as the disseminated intravascular coagulation score greater than 5. The patients were divided into coagulopathy and non-coagulopathy groups. Circumferential arc lengths of the false lumen (Fx) and true lumen (Tx) were measured at four planes (ascending aorta, thoracic-descending aorta, descending aorta and abdominal aorta). We define the value of Fx/(Tx+Fx) × 100% as tear index (TI) and take the four planes' averages to weighed the false lumen's size. By analyzing the two groups of clinical data and computed tomography angiography imaging data, potentially related factors were detected by univariate analysis and multivariate binary logistic regression analysis. RESULTS: The incidence of preoperative coagulopathy for TAAAD patients was 12.07%. In adjusted multivariate binary logistic regression analysis, white blood cell count (odds ratio [OR]: 1.204, 95% confidence interval [CI]: 1.035-1.400, P = 0.016); longitude length of aortic dissection (OR: 1.076, 95% CI: 1.016-1.139, P = 0.012); and Tear index (OR = 1.177, 95% CI: 1.075-1.289, P < 0.001) were significant factors related to the occurrence of preoperative coagulopathy for TAAAD. CONCLUSIONS: The incidence of preoperative coagulopathy in TAAAD patients was 12.07%. The longitude length of AD, TI and white blood cell count were significant factors related to preoperative coagulopathy in patients with TAAAD. The significance of imaging and anatomic changes related to coagulopathy are worth further study in TAAAD patients.

Curcuma longa enhances IFN-γ secretion by natural killer cells through cytokines secreted from macrophages.

Interferon-γ (IFN-γ) regulates the human immune system. To study the interaction between macrophages and natural killer (NK) cells, we established a THP-1 macrophage-conditioned media. Among the 58 natural plant extracts tested, Curcuma longa exerted the strongest IFN-γ-enhancing effect in NK-92 cells through THP-1 macrophages. C. longa extract (CLE) enhanced IFN-γ secretion 2.3- and 4.2-fold at 50 and 100 µg/ml, respectively. Therefore, we evaluated its IFN-γ-enhancing effect in vitro. Although NK-92 cells did not produce IFN-γ following treatment with C. longa, enhanced IFN-γ secretion was observed after treatment with THP-1 macrophage-conditioned media. We hypothesized that the cytokines secreted by the CLE-treated THP-1 macrophages are responsible for stimulating NK-92 cells. Cytokine array results show upregulation of cytokines, including MIP-1α, CXCL-1, IL-1ß, PAI-1, and TNF-α, in CLE-treated THP-1 macrophages. To determine the cytokines responsible for augmenting IFN-γ secretion, NK-92 cells were stimulated with MIP-1α, CXCL-1, IL-1ß, or PAI-1. Enzyme-linked immunosorbent assay results show that all cytokines induced IFN-γ production, although the dose response was somewhat varied. High-performance liquid chromatography analysis of CLE revealed the concentrations of three active curcuminoids, curcumin, demethoxycurcumin, and bisdemethoxycurcumin, as 6.70%, 1.00%, and 0.95%, respectively. Their mixture (with concentrations comparable to their occurrence in CLE) exerted an effect similar to that of the whole CLE. Our findings reveal that CLE indirectly stimulated NK-92 cells to secrete IFN-γ, which is mediated by cytokines produced from THP-1 macrophages. Further, we identified three curcuminoids partly responsible for this IFN-γ-enhancing effect. Therefore, C. longa can be used as a functional food ingredient owing to its immune-boosting ability. PRACTICAL APPLICATION: This study demonstrates that CLE stimulates THP-1 macrophages to secrete cytokines, which can in turn stimulate IFN-γ production by NK-92 cells. A mixture of three curcuminoids present in the extract exerted effects similar to whole CLE, demonstrating that the curcuminoids are partly responsible for the IFN-γ-enhancing effect of C. longa. Since IFN-γ is a key regulator of human immune system, these results suggest the potential use of C. longa as an immune-boosting functional food ingredient.

Adenosine and Cordycepin Accelerate Tissue Remodeling Process through Adenosine Receptor Mediated Wnt/ß-Catenin Pathway Stimulation by Regulating GSK3b Activity.

Adenosine is a cellular metabolite with diverse derivatives that possesses a wide range of physiological roles. We investigated the molecular mechanisms of adenosine and cordycepin for their promoting effects in wound-healing process. The mitochondrial energy metabolism and cell proliferation markers, cAMP responsive element binding protein 1 (CREB1) and Ki67, were enhanced by adenosine and cordycepin in cultured dermal fibroblasts. Adenosine and cordycepin stimulated adenosine receptor signaling via elevated cAMP. The phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 beta (Gsk3b) and Wnt target genes such as bone morphogenetic protein (BMP) 2/4 and lymphoid enhancer binding factor (Lef) 1 were activated. The enhanced gene expression by adenosine and cordycepin was abrogated by adenosine A2A and A2B receptor inhibitors, ZM241385 and PSH603, and protein kinase A (PKA) inhibitor H89, indicating the involvement of adenosine receptor A2A, A2B and PKA. As a result of Wnt/ß-catenin pathway activation, the secretion of growth factors such as insulin-like growth factor (IGF)-1 and transforming growth factor beta (TGFß) 3 was increased, previously reported to facilitate the wound healing process. In addition, in vitro fibroblast migration was also increased, demonstrating their possible roles in facilitating the wound healing process. In conclusion, our data strongly demonstrate that adenosine and cordycepin stimulate the Wnt/ß-catenin signaling through the activation of adenosine receptor, possibly promoting the tissue remodeling process and suggest their therapeutic potential for treating skin wounds.

Combined cesarean delivery and repair of acute aortic dissection at 34 weeks of pregnancy during COVID-19 outbreak: A case report.

BACKGROUND: Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, the exclusion of a patient from COVID-19 should be performed before surgery. However, patients with type A acute aortic dissection (AAD) during pregnancy can seriously endanger the health of either the mother or fetus that requires emergency surgical treatment without the test for COVID-19. CASE SUMMARY: A 38-year-old woman without Marfan syndrome was admitted to the hospital because of chest pain in the 34th week of gestation. She has diagnosed as having a Stanford type-A AAD involving an aortic arch and descending aorta via aortic computed tomographic angiography. The patient was transferred to the isolated negative pressure operating room in one hour and underwent cesarean delivery and ascending aorta replacement. All medical staff adopted third-level medical protection measures throughout the patient transfer and surgical procedure. After surgery, the patient was transferred to the isolated negative pressure intensive care unit ward. The nucleic acid test and anti-COVID-19 immunoglobulin (Ig) G and IgM were performed and were negative. The patient and infant were discharged without complication nine days later and recovered uneventfully. CONCLUSION: The results indicated that the procedure that we used is feasible in patients with a combined cesarean delivery and surgery for Stanford type-A AAD during the COVID-19 outbreak, which was mainly attributed to rapid multidisciplinary consultation, collaboration, and quick decision-making.

[Application and Progress of Convolutional Neural Network-based Pathological Diagnosis of Gastric Cancer].

The incidence of gastric cancer is the highest among all kinds of malignant tumors in China. Because gastric cancer is very hard to identify in its early stage, the early diagnosis rate of gastric cancer in China is relatively low. At present, the pathological diagnosis of gastric cancer mainly depends on the diagnosis of pathologists. However, the gradual improvement of people's living standards and the growing demand for medical and health care have exacerbated the shortage of medical resources, which has become a even more serious problem. Therefore, there is an urgent need for new technologies to help deal with this challenge. In recent years, with the rapid development of artificial intelligence (AI) and digital pathology, AI-aided pathological diagnosis based on convolutional neural network (CNN) as the core technology is showing promises for improving the diagnostic efficiency of gastric cancer. It is also of great significance for the early diagnosis and treatment of the disease and the reduction of its high incidence and mortality. We herein summarize the application and progress of deep-learning CNN in pathological diagnosis of gastric cancer, as well as the existing problems and prospects of future development.

Customized self-expanding bare metal Y stents in the treatment of malignant carinal stenosis: a retrospective analysis.

BACKGROUND: Self-expanding Y metal stent insertion is a safe and effective palliative method for malignant lesions involving the lower trachea, tracheal carina, and the main-stem bronchi. However, the length and degree of airway stenosis in different patients tend to vary, which leads to a call for a customized Y stent that could achieve a better treatment effect. METHODS: This retrospective analysis included patients who received customized self-expanding bare metallic Y stents for malignant carinal stenosis at Beijing Tiantan Hospital, Capital Medical University between January 2007 and June 2020. CT scans and initial bronchoscopy were performed to provide reliable data for stent selection and size customization. Data on technical success, clinical success, and follow-up were analyzed. RESULTS: A total of 36 patients (26 males and 10 females; median age, 61 years; age range, 30-83 years) were enrolled. Technical success was 97.2% (35/36), while clinical success was 97.2% (35/36). There was no procedure-related mortality. Out of 35 patients, 4 (11.4%) had stent-associated complications that did not affect the procedure of stent insertion. Re-stenosis of the stent due to tumor progression was the main mid- and long-term stent-related complication (65% and 57.1%, respectively), followed by stent fractures (5% and 14.3%, respectively). CONCLUSIONS: The current study described the design and insertion of customized self-expanding bare metal Y-stents and demonstrated the feasibility of their use for maintaining tracheal and main-stem bronchus patency in malignant carinal stenosis. This approach could be used as a bridging method before commencing adjuvant therapy and final palliative therapy for the relief of symptoms.