The Effects of Pulmonary Artery Catheter on the Short-Term Outcomes of Patients Undergoing Off-Pump Coronary Artery Bypass Grafting: A Single-Center Retrospective Study.

Background: Pulmonary artery catheters (PAC) are widely used in patients undergoing off-pump coronary artery bypass (OPCAB) grafting surgery. However, primary data suggested that the benefits of PAC in surgical settings were limited. Therefore, the present study sought to estimate the effects of PAC on the short-term outcomes of patients undergoing OPCAB surgery. Methods: The characteristics, intraoperative data, and postoperative outcomes of consecutive patients undergoing primary, isolated OPCAB surgery from November 2020 to December 2021 were retrospectively extracted. Patients were divided into two groups (PAC and no-PAC) based on PAC insertion status. Data were analyzed with a 1:1 nearest-neighbor propensity score matched-pair in PAC and no-PAC groups. Results: Of the 1004 Chinese patients who underwent primary, isolated OPCAB surgery, 506 (50.39%) had PAC. Propensity score matching yielded 397 evenly balanced pairs. Compared with the no-PAC group (only implanted a central venous catheter), PAC utilization was not associated with improved in-hospital mortality in the entire or matched cohort. Still, the matched cohort showed that PAC utilization increased epinephrine usage and hospital costs. Conclusions: The current study demonstrated no apparent benefit or harm for PAC utilization in OPCAB surgical patients. In addition, PAC utilization was more expensive.

Tanshinone IIA induces ER stress and JNK activation to inhibit tumor growth and enhance anti-PD-1 immunotherapy in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains at the forefront of new cancer cases, and there is an urgent need to find new treatments or improve the efficacy of existing therapies. In addition to the application in the field of cerebrovascular diseases, recent studies have revealed that tanshinone IIA (Tan IIA) has anticancer activity in a variety of cancers. PURPOSE: To investigate the potential anticancer mechanism of Tan IIA and its impact on immunotherapy in NSCLC. METHODS: Cytotoxicity and colony formation assays were used to detect the Tan IIA inhibitory effect on NSCLC cells. This research clarified the mechanisms of Tan IIA in anti-tumor and programmed death-ligand 1 (PD-L1) regulation by using flow cytometry, transient transfection, western blotting and immunohistochemistry (IHC) methods. Besides, IHC was also used to analyze the nuclear factor of activated T cells 1 (NFAT2) expression in NSCLC clinical samples. Two animal models including xenograft mouse model and Lewis lung cancer model were used for evaluating tumor suppressive efficacy of Tan IIA. We also tested the efficacy of Tan IIA combined with programmed cell death protein 1 (PD-1) inhibitors in Lewis lung cancer model. RESULTS: Tan IIA exhibited good NSCLC inhibitory effect which was accompanied by endoplasmic reticulum (ER) stress response and increasing Ca2+ levels. Moreover, Tan IIA could suppress the NFAT2/ Myc proto oncogene protein (c-Myc) signaling, and it also was able to control the Jun Proto-Oncogene(c-Jun)/PD-L1 axis in NSCLC cells through the c-Jun N-terminal kinase (JNK) pathway. High NFAT2 levels were potential factors for poor prognosis in NSCLC patients. Finally, animal experiments data showed a stronger immune activation phenotype, when we performed treatment of Tan IIA combined with PD-1 monoclonal antibody. CONCLUSION: The findings of our research suggested a novel mechanism for Tan IIA to inhibit NSCLC, which could exert anti-cancer effects through the JNK/NFAT2/c-Myc pathway. Furthermore, Tan IIA could regulate tumor PD-L1 levels and has the potential to improve the efficacy of PD-1 inhibitors.

Free-Viewpoint Video in Open Surgery: Development of Surgical Arena 360.

OBJECTIVE: We aimed to apply the free-viewpoint video technology developed and introduced mainly for sports spectators to an open surgical video recording system. DESIGN: Prospective feasibility study. SETTING: University of Tsukuba Hospital, Ibaraki, Japan. PARTICIPANTS: Patients who underwent open pancreaticoduodenectomy for pancreatic cancer between December 2022 and March 2023 were included. The gastrojejunal anastomosis was the subject of the recording. RESULTS: Four surgeries were recorded with Surgical Arena 360, which is the free-viewpoint video system that we developed. The feasibility of performing a series of surgical procedures without interrupting the surgeon's line of sight or manipulation was demonstrated in all cases. CONCLUSIONS: Our study revealed that Surgical Arena 360, an open surgical video recording system developed by applying free-viewpoint video technology, can provide new insights into surgical support and clinical knowledge to surgeons by enabling secure capture of the open surgical field from multiple angles.

Microbes mediated immunogenic cell death in cancer immunotherapy.

Immunogenic cell death (ICD) is one of the 12 distinct cell death forms, which can trigger immune system to fight against cancer cells. During ICD, a number of cellular changes occur that can stimulate an immune response, including the release of molecules called damage-associated molecular patterns (DAMPs), signaling to immune cells to recognize and attack cancer cells. By virtue of their pivotal role in immune surveillance, ICD-based drug development has been a new approach to explore novel therapeutic combinations and personalized strategies in cancer therapy. Several small molecules and microbes can induce ICD-relevant signals and cause cancer cell death. In this review, we highlighted the role of microbe-mediate ICD in cancer immunotherapy and described the mechanisms through which microbes might serve as ICD inducers in cancer treatment. We also discussed current attempts to combine microbes with chemotherapy regimens or immune checkpoint inhibitors (ICIs) in the treatment of cancer patients. We surmise that manipulation of microbes may guide personalized therapeutic interventions to facilitate anticancer immune response.

Characteristics of Tongue Pressure Measured by Novel Multisite Flexible Sensors in Nasopharyngeal Carcinoma Patients With Dysphagia.

OBJECTIVE: To explore characteristics of tongue pressure changes in nasopharyngeal carcinoma (NPC) patients with dysphagia after radiotherapy using a novel system with multisite flexible sensors. DESIGN: Prospective observational study. SETTING: Inpatient rehabilitation centers and community dwellings. PARTICIPANTS: Nineteen patients with dysphagia after radiotherapy for NPC and 19 healthy participants were recruited for this study (N=38). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: A new 9-site (3 × 3) flexible tongue pressure sensor was used to measure tongue-to-palate pressure across different parts of the tongue. The oral tongue was divided into 3 parts: anterior tongue region (TAR), central tongue region (TCR), and posterior tongue region (TPR); 3 sensors were placed on each part. The mean tongue pressure and endurance time at the 3 sites in the TAR, TCR, and TPR were analyzed. The ratios of the mean TAR, TCR, and TPR values were calculated. RESULTS: Pressures of TAR, TCR, and TPR in NPC patients with dysphagia were significantly lower than those in healthy participants (P<.05). The pressure in TPR decreased most significantly, followed by that in TCR. The endurance times of TAR and TCR were longer than those of healthy participants (P<.05). The endurance time of TPR was not significantly different between the patients and healthy participants (P>.05). Ratios of pressure between TAR and TCR and TAR and TPR in patients were lower than that in healthy participants (P<.05). There was no significant difference in the TCR to TPR pressure ratio between patients and healthy participants (P>.05). CONCLUSIONS: Tongue pressure significantly decreased in NPC patients with dysphagia, and the drop in pressure was most pronounced in the TPR area. The results of our study indicate that we should pay attention to the pressure training of the TPR during treatments. The endurance time of the TAR and TCR increased significantly, which may be due to bolus transport compensation. Therefore, clinical rehabilitation strategies should aim to increase the endurance time training in NPC patients after radiotherapy to help increase the effectiveness of the swallowing process in patients.

Hepialiamides A-C: Aminated Fusaric Acid Derivatives and Related Metabolites with Anti-Inflammatory Activity from the Deep-Sea-Derived Fungus Samsoniella hepiali W7.

A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A-C (1-3) and one novel hybrid polyketide hepialide (4), together with 18 known miscellaneous compounds (5-22). The structures of the new compounds were elucidated through detailed spectroscopic analysis. as well as TD-DFT-based ECD calculation. All isolates were tested for anti-inflammatory activity in vitro. Under a concentration of 1 µM, compounds 8, 11, 13, 21, and 22 showed potent inhibitory activity against nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells, with inhibition rates of 34.2%, 30.7%, 32.9%, 38.6%, and 58.2%, respectively. Of particularly note is compound 22, which exhibited the most remarkable inhibitory activity, with an IC50 value of 426.2 nM.

Penicopeptide A (PPA) from the deep-sea-derived fungus promotes osteoblast-mediated bone formation and alleviates ovariectomy-induced bone loss by activating the AKT/GSK-3ß/ß-catenin signaling pathway.

The potential of marine natural products as effective drugs for osteoporosis treatment is an understudied area. In this study, we investigated the ability of lead compounds from deep-sea-derived Penicillium solitum MCCC 3A00215 to promote bone formation in vitro and in vivo. We found that penicopeptide A (PPA) promoted osteoblast mineralization among bone marrow mesenchymal stem cells (BMSCs) in a concentration-dependent manner, and thus, we selected this natural peptide for further testing. Our further experiments showed that PPA significantly promoted the osteogenic differentiation of BMSCs while inhibiting their adipogenic differentiation and not affecting their chondrogenic differentiation. Mechanistic studies showed that PPA binds directly to the AKT and GSK-3ß and activates phosphorylation of AKT and GSK-3ß, resulting in the accumulation of ß-catenin. We also evaluated the therapeutic potential of PPA in a female mouse model of ovariectomy-induced systemic bone loss. In this model, PPA treatment prevented decreases in bone volume and trabecular thickness. In conclusion, our in vitro and in vivo results demonstrated that PPA could promote osteoblast-related bone formation via the AKT, GSK-3ß, and ß-catenin signaling pathways, indicating the clinical potential of PPA as a candidate compound for osteoporosis prevention.

Effects of Maternal Dietary Enteromorpha prolifera Polysaccharide Iron Supplement on Mineral Elements and Iron Level of Neonatal Piglets.

Iron plays a key role in maternal health during pregnancy and fetal growth. Enteromorpha polysaccharide-iron (EP-Fe) as an organic iron chelate may improve the iron transmission of mother and offspring, ameliorate the poor pregnancy outcomes of sows, and alleviate the growth restriction of piglets caused by iron deficiency. This study aimed to evaluate the effects of maternal dietary supplementation with EP-Fe on reproductive performance and placental iron transmission of sows, as well as growth performance of piglets. Sixty pregnant sows at the 95th day of gestation were randomly divided into control group and EP-Fe group (EP-Fe, 139 mg kg-1). Blood samples of sows and neonatal piglets, colostrum, and tissue samples were collected on the day of delivery. The animal experiment ended at the 21st day of post-delivery. Results showed that maternal dietary EP-Fe increased colostrum iron (P < 0.05) of sows, as well as final litter weight (P < 0.05) and average daily weight of piglets (P < 0.05) during days 1-21 of lactation, as well as iron and manganese content in umbilical cord blood (P < 0.05) and hepatic iron of neonatal piglets (P < 0.01), and decreased fecal iron (P < 0.001), serum calcium (P < 0.05), phosphorus (P < 0.05), and zinc (P < 0.01) in the parturient sow. RT-qPCR results showed that Fpn1 and Zip14 in placenta, as well as TfR1 and Zip14 in duodenum of neonatal piglets, were activated by maternal EP-Fe supplement. These findings suggest that maternal dietary EP-Fe could increase iron storage of neonatal piglets via improving placental iron transport and iron secretion in colostrum, thus enhancing the growth performance of sucking piglets.

Predictive value of SUVmax in visceral pleural invasive lung adenocarcinoma with different diameters.

OBJECTIVES: This study aimed to investigate predictive visceral pleural invasion (VPI) occurrence value of the maximum standardized uptake value (SUVmax) in patients with lung adenocarcinoma (LA). PATIENTS AND METHODS: A total of 388 LA patients were divided into D1ab, D1c, D1, D2, D2a, D2b, D3, and all patient groups based on their tumor diameter (D). Patients were also classified into negative VPI (VPI-n) and positive VPI (VPI-p) groups according to VPI presence. SUVmax of patients was measured with 18F-fluorodeoxyglucose (FDG) by PET/computed tomography (18F-PET/CT). Receiver operating characteristic (ROC) analysis and the area under curve (AUC) of SUVmax were applied to determine optimal cut-off value for predicting VPI occurrence. RESULTS: There were significant differences in SUVmax between VPI-n and VPI-p groups ( P  < 0.05) at the same tumor diameter. SUVmax cut-off value and sensitivity (Se,%) of VPI occurrence in each group were following: D1ab was 3.79 [AUC = 0.764, P  < 0.001], Se86.11%; D1c was 5.47 (AUC = 0.706, P  < 0.001), Se 93.75%; D1 was 5.49 (AUC = 0.731, P  < 0.001), Se 79.76%; D2 was 7.36 (AUC = 0.726, P  < 0.001), Se81.67%. All patient group was 7.26 (AUC = 0.735, P  < 0.001), Se74.19%. CONCLUSION: In LA patients with the same diameter, SUVmax of the VPI-p group was significantly higher than that of the VPI-n group. The cut-off value of SUVmax for predicting VPI of T1 stage, T1 substages, and T2 stage LA could be determined through ROC curve. SUVmax measurement by PET/CT scan in stratified tumor size is helpful for predicting VPI occurrences of the physician.

Drug-eluting beads versus conventional transarterial chemoembolization for the treatment of unresectable hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Transarterial chemoembolization (TACE) consists of conventional TACE (cTACE) and drug-eluting beads TACE (DEB-TACE). The benefits of the 2 treatments remain controversial. We conduct this meta-analysis to assess the efficacy and safety of the 2 methods for the patients with unresectable hepatocellular carcinoma. METHODS: In order to get a sound conclusion, we did thorough search all relevant studies with clear and stringent keyword criteria on the main databases. Objective tumor response rate, overall survival (OS) rate and adverse events were calculated and analyzed by RevMan 5.3 software. The random-effects or fixed-effects model was applied to pool the estimates according to Cochran Q test and I2 statistics. RESULTS: Twenty-four studies involving 2987 patients were eligible. DEB-TACE significantly improved objective tumor response rate (OR) (risk ratio [RR] = 1.27, 95% confidence interval [CI] [1.08, 1.48]; P = .003). While as for 1-year, 2-year, 3-year, 5-year OS rates, there were no evidences to indicate that DEB-TACE was significantly better than cTACE (RR = 1.05, 95% CI [0.99, 1.11]; P = .08), (RR = 1.02, 95% CI [0.93, 1.11]; P = .68), (RR = 0.92, 95% CI [0.77, 1.10]; P = .37), (RR = 0.92, 95% CI [0.47, 1.80]; P = .81), respectively. Adverse events rate (AE) was also similar in both groups (RR = 1.11, 95% CI [0.99,1.26]; P = .08). CONCLUSION: This meta-analysis demonstrates that DEB-TACE is not superior than cTACE regarding to OS and AE. However, DEB-TACE still be considered to provide a better objective tumor response rate for patients with unresectable hepatocellular carcinoma.

CERS4 predicts positive anti-PD-1 response and promotes immunomodulation through Rhob-mediated suppression of CD8+Tim3+ exhausted T cells in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the main malignant tumors with high mortality and short survival time. Immunotherapy has become the standard treatment for advanced NSCLC, but it has the problems of drug resistance and low response rate. Therefore, obtaining effective biomarkers to predict and enhance immune checkpoint inhibitors (ICIs) efficacy in NSCLC is important. Sphingolipid metabolism is recently found to be closely involved in tumor immunotherapy. CERS4, an important sphingolipid metabolizing enzyme, is positively correlated with the efficacy of anti-PD-1 therapy for NSCLC. Upregulation of CERS4 expression could improve the efficacy of anti-PD-1 therapy for NSCLC. High expression of CERS4 could downregulate the expression of Rhob in tumor. Significantly, the ratio of CD4+/CD8+ T cell increased and the ratio of Tim-3+/CD8+ T cell decreased in spleen and peripheral blood cells. When Rhob was knocked out, the efficacy of PD-1 mAb treatment increased, and the frequency of Tim-3+ CD8+ T cell decreased. This finding further confirmed the role of sphingolipid metabolites in regulating the immunotherapeutic function of NSCLC. These metabolites may improve the efficacy of PD-1 mAb in NSCLC by regulating the CERS4/Rhob/Tim-3 axis. Overall, this study provided a potential and effective target for predicting and improving the efficacy of ICIs for NSCLC. It also provided a new perspective for the study on the mechanisms of ICIs resistance for NSCLC.

Detection of Single Cancer Cell Multidrug Resistance With Single Cell Bioanalyzer.

Objectives: Despite the development of various cancer treatment methods, chemotherapy remains the most common approach for treating cancer. The risk of tumors acquiring resistance to chemotherapy remains a significant hurdle to the successful treatment of various types of cancer. Therefore, overcoming or predicting multidrug resistance in clinical treatment is essential. The detection of circulating tumor cells (CTCs) is an important component of liquid biopsy and the diagnosis of cancer. This study aims to test the feasibility of single-cell bioanalyzer (SCB) and microfluidic chip technology in identifying patients with cancer resistant to chemotherapy and propose new methods to provide clinicians with new choices. Methods: In this study, we used rapidly isolated viable CTCs from the patient blood samples method combined with SCB technology and a novel microfluidic chip, to predict whether patients with cancer are resistant to chemotherapy. SCB and microfluidic chip were used to select single CTCs, and the accumulation of chemotherapy drug was fluorescently measured in real time on these cells in the absence and presence of permeability-glycoprotein inhibitors. Results: Initially, we successfully isolated viable CTCs from the blood samples of patients. Additionally, the present study accurately predicted the response of 4 lung cancer patients to chemotherapeutic drugs. In addition, the CTCs of 17 patients with breast cancer diagnosed at Zhuhai Hospital of Traditional Chinese and Western Medicine were assessed. The results indicated that 9 patients were sensitive to chemotherapeutic drugs, 8 patients were resistant to a certain degree, and only 1 was completely resistant to chemotherapy. Conclusion: The present study indicated that the SCB technology could be used as a prognostic assay to evaluate the CTCs response to available drugs and guide physicians to treatment options that are most likely to be effective.

Fructose-enabled killing of antibiotic-resistant Salmonella enteritidis by gentamicin: Insight from reprogramming metabolomics.

Salmonella enterica is a food-borne pathogen that poses a severe threat to both poultry production and human health. Antibiotics are critical for the initial treatment of bacterial infections. However, the overuse and misuse of antibiotics results in the rapid evolution of antibiotic-resistant bacteria, and the discovery and development of new antibiotics are declining. Therefore, understanding antibiotic resistance mechanisms and developing novel control measures are essential. In the present study, GC-MS-based metabolomics analysis was performed to determine the metabolic profile of gentamicin sensitive (SE-S) and resistant (SE-R) S. enterica. Fructose was identified as a crucial biomarker. Further analysis demonstrated a global depressed central carbon metabolism and energy metabolism in SE-R. The decrease in the pyruvate cycle reduces the production of NADH and ATP, causing a decrease in membrane potential, which contributes to gentamicin resistance. Exogenous fructose potentiated the effectiveness of gentamicin in killing SE-R by promoting the pyruvate cycle, NADH, ATP and membrane potential, thereby increasing gentamicin intake. Further, fructose plus gentamicin improved the survival rate of chicken infected with gentamicin-resistant Salmonella in vivo. Given that metabolite structures are conserved across species, fructose identified from bacteria could be used as a biomarker for breeding disease-resistant phenotypes in chicken. Therefore, a novel strategy is proposed for fighting against antibiotic-resistant S. enterica, including exploring molecules suppressed by antibiotics and providing a new approach to find pathogen targets for disease resistance in chicken breeding.

The miR-34b-5p-negative target Gnai2 aggravates fluorine combined with aluminum-induced apoptosis of rat offspring hippocampal neurons and NG108-15 cells.

It is known that fluorine and aluminum are commonly found in the environment and that long-term overexposure can adversely affect the organism's nervous system, damaging the structure and function of brain tissue. Our previous study showed that fluorine combined with aluminum (FA) could trigger apoptosis in vitro and cause spatial learning and memory impairment and differentially expressed miRNAs (including miR-34b-5p) in the hippocampi in vivo. However, the detailed mechanism is unclear. Learning memory damage is implicated in excessive hippocampal neuron apoptosis, and miR-34b-5p participates in regulating the hippocampal neuron apoptosis. Thus, in the current research, Sprague-Dawley (SD) rats were subjected to FA, and NG108-15 control cells and NG108-15 cells pretransfected with miR-34b-5p agomir or antagomir were exposed to FA. We found that FA triggered apoptosis of rat hippocampal neurons and NG108-15 cells, increased miR-34b-5p expression, and decreased Gnai2, PKA, ERK and CREB expression. Inhibition of miR-34b-5p alleviated FA-induced NG108-15 cell apoptosis and further increased Gnai2, PKA, ERK, and CREB expression, and vice versa. Furthermore, miR-34b-5p modulated the level of Gnai2 by directly targeting its 3'-untranslated region (UTR), as verified through the dual Luciferase reporter assay. These outcomes suggested that miR-34b-5p participated in FA-induced neuronal apoptosis by targeting Gnai2 negatively, thereby inhibiting the PKA/ERK/CREB signaling pathway.

Laser Combined with Radiotherapy for Keloid Treatment: A Novel and Efficient Comprehensive Therapy with a Lower Recurrence Rate.

BACKGROUND: Keloids are a fibroproliferative skin disorder with a high recurrence rate. Combined therapies are often used in clinical treatment, but, in addition to the relatively high risk of relapse and complexity of the treatment process, side effects remain unknown for combination therapies. METHODS: A total of 99 patients with keloids in 131 positions were included in this retrospective study. Fractional CO 2 laser therapy was first applied with energy ranging from 360 to 1008 mJ; then, 6-Mev, 900-cGy electron beam irradiation was applied twice. The first pass was initiated within 24 hours after the laser therapy, and the second pass was performed on the seventh day after laser therapy. The Patient and Observer Scar Scale evaluated the lesions before the treatment and at 6, 12, and 18 months after treatment. At each follow-up visit, the patients filled out a questionnaire on recurrence, side effects, and satisfaction. RESULTS: The authors found a significant decrease in total Patient and Observer Scar Scale score [29 (23, 39) versus 61.2 ± 13.4; P < 0.001] at the 18-month follow-up compared with the baseline value (before the therapy). A total of 12.1% of the patients had recurrences during the 18-month follow-up period (11.1% partial recurrence and 1.0% complete recurrence). The total satisfaction rate was 97.0%. No severe adverse effects were observed during the follow-up period. CONCLUSIONS: Laser combined with radiotherapy is a new comprehensive therapy comprising ablative lasers and radiotherapy for keloids. It had excellent clinical efficacy, low recurrence rate, and no serious adverse effects. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

ß-Elemene enhances erlotinib sensitivity through induction of ferroptosis by upregulating lncRNA H19 in EGFR-mutant non-small cell lung cancer.

Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. ß-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that ß-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that ß-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.

Low-dose phthalates promote breast cancer stem cell properties via the oncogene ΔNp63α and the Sonic hedgehog pathway.

BACKGROUND: The omnipresence of human phthalate (PAE) exposure is linked to various adverse health issues, including breast cancer. However, the effects of low-dose PAE exposure on breast cancer stem cells (BCSCs) and the underlying mechanism remain unexplored. METHODS: BCSCs from breast cancer cell lines (MDA-MB-231 and MCF-7) were enriched using a tumorsphere formation assay. Gene and protein expression was detected by measurement of quantitative real-time reverse transcription PCR, western blot, and immunofluorescence assays. Transient transfection assays were used to evaluate the involvement of Gli1, a signaling pathway molecule and ΔNp63α, an oncogene in influencing the PAE-induced characteristics of BCSCs. RESULTS: PAE (butylbenzyl phthalate, BBP; di-butyl phthalate, DBP; di-2-ethylhexyl phthalate, DEHP) exposure of 10-9 M significantly promoted the tumorsphere formation ability in BCSCs. Breast cancer spheroids with a 10-9 M PAE exposure had higher levels of BCSC marker mRNA and protein expression, activated sonic hedgehog (SHH) pathway, and increased mRNA and protein levels of an oncogene, ΔNp63α. Furthermore, suppression of the SHH pathway attenuated the effects of PAEs on BCSCs. And the overexpression of ΔNp63α enhanced PAE-induced characteristics of BCSCs, while low expression of ΔNp63α inhibited the promotion effects of PAEs on BCSCs and the SHH pathway. CONCLUSION: Low-dose PAE exposure promoted the stem cell properties of BCSCs in a ΔNp63α- and SHH-dependent manner. The influence of low-dose exposure of PAEs and its relevance for the lowest observed effect concentrations requires further investigation, and the precise underlying mechanism needs to be further explored.

Dermoscopy in Mycobacterium marinum infection and its correlation with clinical and histopathological features: a prospective observational study.

BACKGROUND: Mycobacterium marinum is a nontuberculous mycobacterium and a conditional pathogen to humans, which can be inoculated directly and cause chronic skin granulomas. Dermoscopy has been applied to other granulomatous skin diseases, but not to M. marinum infection. AIM: To explore the dermoscopic features of M. marinum infection, and its correlation with clinical and histopathological features. METHODS: In total, 27 lesions from 27 patients (19 women, 8 men, age range 28-71 years) diagnosed with M. marinum infection were identified by clinical examination, histopathological results, PCR sequencing and mycobacterial culture in the dermatology outpatient department of our hospital from March 2020 to February 2022. The dermoscopy images and pathological characteristics were analysed. RESULTS: Lesions were located on the hands, forearms and upper arms. The following dermoscopic features were observed: yellowish-orange structureless areas (85·2%), white striped structures (59·3%), follicular plugs (29·6%), yellowish oval clods (14·8%) and reddish or pinkish areas (14·8%). Vessel structures were visible in all cases: long hairpin vessels (81·5%), corkscrew vessels (25·9%), comma-shaped vessels (22·2%) and linear vessels (22·2%). CONCLUSION: Yellowish-orange structureless areas, white striped structures and long hairpin vessels are the most common dermoscopic features of M. marinum infection. Thus, dermoscopy could be used as a noninvasive auxiliary diagnostic method to provide a diagnostic basis for this disease.

Biphasic alcoholysis coupled with high-speed countercurrent chromatography for high performance on separating phorbol from Croton tiglium Linn extracts.

Phorbol is a tetracyclic diterpenoid found in Euphorbia tirucalli, Croton tiglium, and Rehmannia glutinosa, and is nuclear of various phorbol esters. The rapid obtaining of phorbol with high purity highly contributes to its application, such as synthesizing phorbol esters with designable side chains and particular therapeutic efficacy. This study introduced a biphasic alcoholysis method for obtaining phorbol from croton oil by using polarity imparity organic solvents in both phases and established a high-speed countercurrent chromatography method for simultaneous separation and purification of phorbol. The optimized operation conditions of biphasic alcoholysis were a reaction time of 91 min, a temperature of 14°C, and a croton oil-methanol ratio of 1:30 (g:ml). The phorbol during the biphasic alcoholysis was 3.2-fold higher in content than that obtained in conventional monophasic alcoholysis. The optimized high-speed countercurrent chromatography method was using the ethyl acetate/n-butyl alcohol/water at 4.7:0.3:5 (v:v:v) with Na2 SO4 at 0.36 g/10 ml as the solvent system, using the mobile phase flow rate of 2 ml/min, the revolution of 800 r/min, under which the retention of the stationary phase was achieved at 72.83%. The crystallized phorbol following high-speed countercurrent chromatography was obtained as high purity of 94%.