Rosin: A comprehensive review on traditional uses, phytochemistry, and pharmacology.

Rosin, a natural resin obtained from conifer trees, has a long history of use in traditional folk medicine for treating abscesses, wounds, carbuncles, and burns, etc. It has been employed in ancient Egypt, China, Nordic countries, and Turkey as a therapeutic remedy. This comprehensive review examines the traditional uses, phytochemistry, and pharmacology of rosin, and it provides a critical update on current knowledge of rosin and identifies potential therapeutic opportunities. The chemical composition of rosin is known to vary depending on factors such as botanical sources, geographical locations, and processing methods. Rosin acids, which account for over 90% of its primary chemical constituents, have been identified as the predominant compounds in rosin. Researchers have isolated approximately 50 compounds from rosin, with terpenoid rosin acids being the most prevalent. Furthermore, the review highlights the potential pharmacological activities of rosin and its constituents. Crude extracts and isolated rosin acids have demonstrated promising properties, including antimicrobial, anti-inflammatory, anti-tumor, insecticidal, wound healing, and anti-obesity effects. However, the review emphasizes that further research is needed, as existing studies are predominantly preliminary. Many of the reported bioactivities require further verification, and the underlying mechanisms of action remain largely unexplored. In conclusion, rosin has been extensively used in traditional medicine across different cultures, and its chemical composition has been confirmed to a significant extent. The pharmacological activities observed in crude extracts and isolated rosin acids support its traditional uses. Nevertheless, additional research is necessary to deepen our understanding of the pharmacological mechanisms underlying its effects.

Controlling the nutritional status score: a new tool for predicting postoperative mortality in patients with infrarenal abdominal aortic aneurysm treated with endovascular aneurysm repair.

Background: AAA is a fatal condition that commonly occurs during vascular surgery. Nutritional status exerts a significant influence on the prognosis of various pathological conditions Scores from the CONUT screening tool have been shown to predict outcomes of certain malignancies and chronic diseases. However, the ramifications of nutritional status on AAA patients undergoing EVAR have not been elucidated in prior studies. In this study, we aimed to elucidate the correlation between CONUT scores and postoperative prognostic outcomes in patients with AAA undergoing EVAR. Methods: This was a retrospective review of 177 AAA patients treated with EVAR from June 2018 to November 2019 in a single center. Patient characteristics, CONUT scores, and postoperative status were collected. These patients were stratified into groups A and B according to CONUT scores. Subsequently, a comparative analysis of the baseline characteristics between the two cohorts was conducted. Cox proportional hazards and logistic regression analyses were employed to identify the autonomous predictors of mid-term mortality and complications, respectively. Results: Compared with group A, patients in group B had higher midterm mortality (p < 0.001). Univariate analysis showed that CONUT scores; respiratory diseases; stent types; preoperative Hb, CRP, PT, and Fb levels were risk factors for death. Multivariate analysis confirmed that CONUT score [HR, 1.276; 95% CI, 1.029-1.584; p = 0.027] was an independent risk factor for mortality. Logistic regression analysis showed that prior arterial disease, smoking, and D-dimer levels were risk factors, although multivariate analysis showed smoking (OR, 3.492; 95% CI, 1.426-8.553; p = 0.006) was an independent risk factor. Kaplan-Meier curves showed that patients in group B had shorter mid-term survival than those in group A (log-rank p < 0.001). Conclusion: Malnutrition was strongly associated with mid-term mortality in patients with infrarenal AAA treated with EVAR.

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery.

BACKGROUND: This study was designed to investigate the clinical outcomes of enhanced recovery after surgery (ERAS) in the perioperative period in elderly patients with non-small cell lung cancer (NSCLC). AIM: To investigate the potential enhancement of video-assisted thoracic surgery (VATS) in postoperative recovery in elderly patients with NSCLC. METHODS: We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS (the ERAS group) and 327 elderly NSCLC patients who received routine care (the control group) after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017. After propensity score matching of baseline data, we analysed the postoperative stay, total hospital expenses, postoperative 48-h pain score, and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection. RESULTS: After propensity score matching, ERAS significantly reduced the postoperative hospital stay (6.96 ± 4.16 vs 8.48 ± 4.18 d, P = 0.001) and total hospital expenses (48875.27 ± 18437.5 vs 55497.64 ± 21168.63 CNY, P = 0.014) and improved the satisfaction score (79.8 ± 7.55 vs 77.35 ± 7.72, P = 0.029) relative to those for routine care. No significant between-group difference was observed in postoperative 48-h pain score (4.68 ± 1.69 vs 5.28 ± 2.1, P = 0.090) or postoperative complication rate (21.2% vs 27.1%, P = 0.371). Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection. CONCLUSION: ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

Clinical Outcomes at 3 Years After Stenting for Thrombotic and Non-thrombotic Iliac Vein Compression Syndrome Patients.

Iliac vein stenting for the treatment of iliac vein compression syndrome (IVCS) has been gradually developed. This article investigated the long-term patency and improvement of clinical symptoms after endovascular stenting for iliac vein obstruction patients. From 2020 to 2022, 83 patients at a single institution with IVCS underwent venous stent implantation and were divided into two groups: non-thrombotic IVCS (n = 55) and thrombotic IVCS (n = 28). The main stent-related outcomes include technical success, long-term patency, and thrombotic events. The technical success rate of all stent implantation was 100%. The mean length of hospital stay and cost were higher in the thrombotic IVCS group than in the non-thrombotic ICVS group, as well as the length of diseased vessel segment and the number of stents implanted were higher than in the control non-thrombotic group. The 1-, 2-, and 3-year patency rates were 85.4%, 80% and 66.7% in the thrombosis group, which were lower than 93.6%, 88.7%, and 87.5% in the control group (P = .0135, hazard ratio = 2.644). In addition, patients in both groups had a foreign body sensation after stent implantation, which resolved spontaneously within 1 year after surgery. Overall, there were statistically significant differences in long-term patency rate outcome between patients with thrombotic and non-thrombotic IVCS, the 1-, 2-, and 3-year patency rates in non-thrombotic IVCS patients were higher than those in thrombotic IVCS patients.

Comparative outcomes of catheter-directed thrombolysis versus AngioJet pharmacomechanical catheter-directed thrombolysis for treatment of acute iliofemoral deep vein thrombosis.

OBJECTIVE: The objective of this study was to compare the outcomes of pharmacomechanical thrombolysis and thrombectomy (PCDT) plus catheter-directed thrombolysis (CDT) vs CDT alone for the treatment of acute iliofemoral deep vein thrombosis (DVT) and summarize the clinical experience, safety outcomes, and short- and long-term efficacy. METHODS: We performed a 4-year retrospective, case-control study. A total of 95 consecutive patients with acute symptomatic iliofemoral deep vein thrombosis (DVT) with a symptom duration of ≤7 days involving the iliac and/or common femoral veins underwent endovascular interventions. The patients were divided into two groups according to their clinical indications: PCDT plus CDT vs CDT alone. Statistical analyses were used to compare the clinical characteristics and outcomes between the two groups. Additionally, the patients were followed up for 3 to 36 months after treatment, and the proportions of post-thrombotic syndrome (PTS) and moderate to severe PTS were analyzed using the Kaplan-Meier survival method. RESULTS: A total of 95 consecutive patients were analyzed in this retrospective study, of whom, 51 underwent CDT alone and 44 underwent PCDT plus CDT. Between the two groups, in terms of immediate-term efficacy and safety, significant differences were found in the catheter retention time (60.64 ± 12.04 hours vs 19.42 ± 4.04 hours; P < .001), dosages of urokinase required (5.82 ± 0.81 million units vs 1.80 ± 0.64 million units; P < .001), the detumescence rate at 24 hours postoperatively (48.46% ± 8.62% vs 76.79% ± 7.98%; P = .026), the descent velocity of D-dimer per day (2266.28 ± 1358.26 µg/L/D vs 3842.34 ± 2048.02 µg/L/D; P = .018), total hospitalization stay (6.2 ± 1.40 days vs 3.8 ± 0.70 days; P = .024), number of postoperative angiograms (2.4 ± 0.80 vs 1.2 ± 0.30; P = .042), and grade III venous patency (>95% lysis: 54.5% vs 68.6%; P = .047). Furthermore, during the follow-up period, significant differences were found in the incidence of PTS (Villalta scale ≥5 or a venous ulcer: 47.0% vs 27.7%; P = .037), and the incidence proportion of moderate to severe PTS at 12 months (15.7% vs 4.5%; P = .024) and 24 months (35.3% vs 11.4%; P = .016). CONCLUSIONS: Compared with CDT alone, in the iliofemoral DVT subgroup with a symptom duration of ≤7 days, PCDT plus CDT could significantly relieve early leg symptoms, shorten the hospitalization stay, reduce bleeding complications, promote long-term venous patency, and decrease the occurrence of PTS and the incidence proportion of moderate to severe PTS. Thus, the short- and long-term outcomes both support the superiority of PCDT plus CDT vs CDT in this subgroup.

Pathological diagnosis and immunohistochemical analysis of minute pulmonary meningothelial-like nodules: A case report.

BACKGROUND: Minute Pulmonary Meningothelial-like Nodules (MPMNs) are rare benign pulmonary nodules, which are more common in elderly women and have a higher detection rate in lung tissues of patients with lung malignant diseases. Its origin is not yet clear. At present, there are few reports on the diagnostic methods such as imaging and pathological manifestations of MPMNs. This article reports a 70-year-old female patient with pulmonary adenocarcinoma combined with MPMNs and reviews of the relevant literature. CASE SUMMARY: A 70-year-old women was admitted to our institution with feeling sour in her back and occasional cough for more than 2 mo. Computerized electronic scanning scan and 3D reconstruction images in our institution showed there were multiple ground-glass nodules in both of her two lungs. The biggest one was in the apicoposterior segment of left upper lobe, about 2.5 mm × 9 mm in size. We performed thoracoscopic resection of the left upper lung apicoposterior segment of the patient, and the final pathological report was minimally invasive adenocarcinoma. Re-examination of high resolution computed tomography 21 mo after surgery showed multiple ground-glass nodules in both lungs, and a new ground-glass nodule was found in the superior segment of the right lower lobe. We took pathological biopsy of the right upper lung and right lower lung nodules for the patient under thoracoscopy. The histomorphology of the right lower lobe nodule showed multiple lesions in the lung tissue, and the small foci in the alveolar septum were distributed in mild form of the aggregation of short spindle cells. The immunohistochemistry showed that the lesion was epithelial membrane antigen (EMA) (+), somatostatin receptor 2a (SSTR2a) (+), S-100 (-), chromogranin A (-), Syn (-), cytokeratin (-) and HMB-45 (-). The final diagnosis was minimally invasive adenocarcinoma, accompanied by MPMNs. We recommend that patients continue to receive treatment after surgery and to do regular follow-up observations. CONCLUSION: The imaging manifestations of MPMNs are atypical, histomorphology and immunohistochemistry can assist in its diagnosis. This article reviews the relevant literature of MPMNs immunohistochemistry and shows that MPMNs are positive for EMA, SSTR2a, and progesterone receptor.

The synthesis and effects of a novel TRPC6 inhibitor, BP3112, on hepatocellular carcinoma.

Aims: Transient receptor potential canonical-6 (TRPC6) is a therapeutic target for hepatocellular carcinoma. The authors aimed to synthesize and determine whether indole-2-carboxamide derivatives have anti-hepatocellular carcinoma activities targeting TRPC6. Materials & methods: Molecular docking was carried out to design these derivatives. The top five compounds were synthesized for activity validation using microscale thermophoresis. Cell cytotoxicity, flow cytometry, western blotting and cell transfection were used to investigate the anti-hepatocellular carcinoma activities and mechanisms in vitro. Xenografts of nude mice were used for in vivo evaluation. Results: The indole-2-carboxamide derivative, BP3112, promoted apoptosis and G1-phase arrest in HCCs via inhibiting TRPC6, and dose-dependently inhibit tumor growth in vivo. Conclusion: BP3112 as a specific inhibitor of TRPC6 is a potential therapeutic agent for hepatocellular carcinoma.

The controlling nutritional status score predicts postoperative mortality in patients with ruptured abdominal aortic aneurysm: a retrospective study.

Background: Ruptured abdominal aortic aneurysms (rAAAs) are challenging for vascular surgeons because they have a high mortality rate. In many diseases, nutritional status is closely associated with prognosis. The Controlling Nutritional Status (CONUT) screening tool score is a prognostic factor in some malignant and chronic diseases; however, the impact of nutritional status on rAAA has not yet been reported. In this study, we explored the relationship between the CONUT score and the postoperative prognosis of patients with rAAA. Methods: This was a retrospective review of 39 patients with rAAA who underwent surgical treatment from March 2018 to September 2021 at one center. Patient characteristics, nutritional status (CONUT score), and postoperative status were recorded. The patients were divided into groups A and B based on the CONUT score. The baseline characteristics of the two groups were compared, and Cox proportional hazards and logistic regression analyses were used to determine independent predictors of mid-term mortality and complications, respectively. Results: The overall mid-term mortality rate was 28.21% (11/39). Compared with group A, group B had higher intraoperative (P = 0.047) and mid-term mortality (P = 0.033) rates. The univariate analysis showed that age [hazard ratio (HR), 1.098; 95% confidence interval (CI), 1.019-1.182; P = 0.014], CONUT score (HR, 1.316; 95% CI, 1.027-1.686; P = 0.03), and surgical procedure (HR, 0.127; 95% CI, 0.016-0.992; P = 0.049) were associated with mid-term mortality, whereas the multivariate analysis showed that the CONUT score (HR, 1.313; 95% CI, 1.009-1.710; P = 0.043) was an independent predictor of mid-term mortality. The multivariate logistic regression analysis did not reveal any associations with complications. The Kaplan-Meier curves showed that group B had a lower mid-term survival rate (log-rank P = 0.024). Conclusion: Malnutrition is closely associated with the prognosis of patients with rAAA, and the CONUT score can be used to predict mid-term mortality.

Three-Dimensional Printing to Guide Fenestrated/Branched TEVAR in Triple Aortic Arch Branch Reconstruction With a Curative Effect Analysis.

PURPOSE: To summarize experience with and the efficacy of fenestrated/branched thoracic endovascular repair (F/B-TEVAR) using physician-modified stent-grafts (PMSGs) under 3D printing guidance in triple aortic arch branch reconstruction. MATERIALS AND METHODS: From February 2018 to April 2022, 14 cases of aortic arch aneurysms and 30 cases of aortic arch dissection (22 acute aortic arch dissection and 8 long-term aortic arch dissection)were treated by F/B-TEVAR in our department, including 34 males and 10 females, with an average age of 59.84 ± 11.72 years. Three aortic arch branches were affected in all patients. A 3D-printed model was made according to computed tomography angiography images and used to guide the fabrication of PMSGs. All patients were followed up. RESULTS: A total of 132 branches were successfully reconstructed with no case of conversion to open surgery. The average operation time was 4.97 ± 1.40 hours, including a mean 44.05 ± 7.72 minutes for stent-graft customization, the mean postoperative hospitalization duration was 9.91 ± 4.47 days, the average intraoperative blood loss was 480.91 mL (100-2810 mL), and the mean postoperative intensive care unit monitoring duration was 1.02 days (0-5 days). No deaths occurred within 30 days of surgery. Postoperative neurological complications occurred in 1 case (2.3%), and retrograde type A dissection occurred in 1 case (2.3%). CONCLUSION: Compared with conventional surgery, triple aortic arch branch reconstruction under the guidance of 3D printing is a minimally invasive treatment method with the advantages of accurate positioning, rapid postoperative recovery, few complications, and reliable short- to mid-term effects. CLINICAL IMPACT: At present the PMSG usually depend on imaging data and software calculation. With the guidance of 3D printing technology, image data could be transformed into 3D model, which has improved the accuracy of the positioning of the fenestrations. The diameter reduction technique and the internal mini cuff technique have made a complement to the slimed-down fenestration selection process and the low rate of endoleak. As reproducible study, our results may provide reference for TEVAR in different cases.

Canonical transient receptor potential channel 1 aggravates myocardial ischemia-and-reperfusion injury by upregulating reactive oxygen species.

The canonical transient receptor potential channel (TRPC) proteins form Ca2+-permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model. Trpc1-/- mice exhibited improved cardiac function, lower serum Troponin T and serum creatine kinase level, smaller infarct volume, less fibrotic scars, and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6-/- mice. Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury. Furthermore, Trpc1 deficiency protected adult mouse ventricular myocytes (AMVMs) and HL-1 cells from death during hypoxia/reoxygenation (H/R) injury. RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species (ROS) generation in Trpc1-/- cardiomyocytes. Among these genes, oxoglutarate dehydrogenase-like (Ogdhl) was markedly downregulated. Moreover, Trpc1 deficiency impaired the calcineurin (CaN)/nuclear factor-kappa B (NF-κB) signaling pathway in AMVMs. Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions. Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter. The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes. In conclusion, our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R, leading to increased Ca2+ influx into associated cardiomyocytes. Subsequently, this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway, ultimately exacerbating ROS production and aggravating myocardial I/R injury.

MAC mediates mammary duct epithelial cell injury in plasma cell mastitis and granulomatous mastitis.

Plasma cell mastitis (PCM) and granulomatous mastitis (GM) are common inflammatory nonbacterial mastitis (NBM). However, the pathogenesis of NBM is still unclear. METHODS: In this study, we statistically analyzed the pathological features of PCM and GM using pathological HE staining and tissue transmission electron microscopy. The levels of MAC (C5b-9n), P-selectin, E-selectin, and ICAM-1 were detected through IHC, WB, ELISA, and qPCR. The expression level and location of MAC were observed by tissue immunological electron microscopy. In addition, exosomes were isolated from tissues, identified using transmission electron microscopy, and the densities were detected by Nano-FCM. Finally, the expression intensity of MAC in exosomes was detected by flow cytometry and immunoelectron microscopy. RESULTS: The damage and apoptosis of mammary duct epithelial cells are the common pathological features of PCM and GM. MAC is primarily located in the cell membrane of mammary ductal epithelial cells and is significantly expressed in PCM and GM. The density of exosomes in PCM and GM tissues was elevated, and MAC was highly expressed in exosomes. In addition, the expression of P-selectin, E-selectin, and ICAM-1 in PCM and GM was significantly higher than in the normal group. CONCLUSION: We found severe damage of the mammary duct epithelial cells in PCM and GM tissues, which was verified by relevant pathological methods. Earlier studies demonstrated that MAC is highly expressed in PCM and GM tissues and exosomes seem to play a very important role in the understanding of MAC. Furthermore, MAC is involved in inflammatory infiltration and lesion of mammary duct epithelial cells upregulated by P-selectin, E-selectin, and ICAM-1. These findings provide new insights into PCM and GM molecular mechanisms.

Case report: Remedial surgical treatment of aorto-duodenal fistula with infected aneurysm after endovascular aortic repair.

Aorto-duodenal fistula (ADF) is a rare cause of upper gastrointestinal bleeding, but it is associated with high mortality. It usually occurs in patients with prior aortic surgery or who have undergone aortic graft placement. Abdominal aortic aneurysm (AAA) might be a cause of primary ADF, which could develop into sudden shock. Because ADF is difficult to diagnose, surgery to correct it has a poor outcome. We here report the successful treatment of an ADF complicated with infected AAA after endovascular repair of a ruptured aneurysm of the iliac artery.

Fabrication of Protonated Two-Dimensional Metal-Organic Framework Nanosheets for Highly Efficient Iodine Capture from Water.

Radioactive iodine (129I and 131I), produced or released from nuclear-related activities, posed severe effects on both human health and environment. The efficient removal of radioiodine from aqueous medium and vapor phase is of paramount importance for the sustainable development of nuclear energy. Herein, a metal-organic framework (MOF) nanosheet with a positive charge was constructed for the capture of iodine for the first time. The as-synthesized ultrathin nanosheets, with a thickness of 4.4 ± 0.1 nm, showed a record-high iodine adsorption capacity (3704.08 mg g-1) from aqueous solution, which is even higher than that from the vapor phase (3510.05 mg g-1). It can be ascribed to the fully interactions between the extensive accessible active sites on the largely exposed surface of 2D MOF nanosheets and the target pollutants, which also gave rise to fast adsorption kinetics with relative high removal efficiencies in the low concentrations, even in seawater. Moreover, a facile recyclability with fast desorption kinetics can also be achieved for the MOF nanosheets. The excellent iodine removal performance in aqueous solution demonstrated that the electrostatic attraction between MOF nanosheets with a positive charge and the negatively charged triiodide (I3-, the dominant form of iodine in aqueous solution) is the driving force in adsorption, which endows the adsorbents with the characteristics of fast adsorption and desorption kinetics. The adsorption mechanism was systematically verified by the studies of ζ potential, Fourier transform infrared, X-ray photoelectron spectroscopy, and Raman spectra.

Inhibition of PTPN21 has antitumor effects in glioma by restraining the EGFR/PI3K/AKT pathway.

Protein tyrosine phosphatase non-receptor type 21 (PTPN21) has been recognised as a new tumour-associated protein that is implicated in diverse tumours. However, the correlation between PTPN21 and glioma remains unaddressed. This investigation focused on the relevance of PTPN21 in glioma. The Cancer Genome Atlas (TCGA) analysis identified PTPN21 as being up-regulated in glioma tissue. The elevation of PTP21 in glioma was validated by evaluating clinical specimen. Kaplan-Meier plot analysis revealed that a high PTPN21 level predicted poor survival rate in glioma patient. Silencing of PTPN21 produced remarkable anticancer effects in glioma cells including proliferation inhibition, cell cycle arrest, metastasis suppression and enhanced chemosensitivity. Mechanistic studies uncovered that PTPN21 contributes to mediation of the phosphatidyl-inositole-3 kinase (PI3K)/AKT pathway via the regulation of epidermal growth factor receptor (EGFR). Restraint of EGFR diminished PTPN21 overexpression-induced promoting effect on PI3K/AKT pathway. Reactivation of AKT reversed PTPN21 silencing-evoked antitumor effect. The tumorigenic potential of PTPN21-silenced glioma cells in vivo was markedly compromised. In summary, this study demonstrates that silencing of PTPN21 produces remarkable anticancer effects in glioma by restraining the EGFR/PI3K/AKT pathway.

Establishing a TNM-like risk classification for metachronous second pulmonary adenocarcinoma in patients with previously resected pulmonary adenocarcinoma.

Background: For metachronous second pulmonary adenocarcinoma (msPAD) in patients with resected PAD, the method to distinguish tumour clonality has not yet been well established, which makes it difficult to determine accurate staging and predict prognosis. Methods: Patients received surgery for the primary and encountered msPAD were recruited into the Surveillance, Epidemiology, and End Results database. We extracted overall survival 1 (OS1) for the primary, overall survival 2 (OS2) for the msPAD, and defined interval survival as the interval time between the first and second PAD. Based on the nomogram and recursive partitioning analysis, a tumor, node, metastasis staging system (TNM)-like risk stratification system was established for OS2 on the premise of suspending the dispute of tumor clonality. Results: A total of 1,045 patients were identified. There is no significant association between interval survival and OS2. A TNM-like risk stratification system was established based on the independent pathological factors for prognosis, including tumor diameter (2nd), node metastasis (2nd), grade (2nd), and extrapulmonary metastasis (2nd). The proposed risk stratification system present well capacity in predicting and stratifying prognosis. Compared with the TNM stage system, the proposed risk stratification system presents a smaller Akaike information criterion (AIC) but larger c-index, and generates higher accuracy to predict prognosis at 160 months of follow-up according to the time-dependent receiver operating curve (ROC) curve. Conclusions: In conclusion, the TNM-like risk stratification appears to be suitable for prognostic prediction and risk stratification for msPAD patients with former PAD resection. This model validates and refines the known classification rules based on the easily collected variables, and highlights potentially clinical implications.

Establishing a prognostic model for metachronous second squamous cell lung cancer in patients with resected squamous cell lung cancer.

BACKGROUND: For metachronous second pulmonary squamous cell carcinoma (msPSC) in patients with resected PSC, the method to distinguish tumour clonality has not yet been well established, which makes it difficult to determine accurate staging and predict prognosis. METHODS: Patients who underwent surgery for first PSC and encountered msPSC were recruited from the Surveillance, Epidemiology, and End Results (SEER) database. We extracted overall survival 1 (OS1) for the first PSC, overall survival 2 (OS2) for msPSC, and interval survival for the time interval between the first and second PSC. The nomogram was calibrated for OS2, and recursive partitioning analysis (RPA) was performed for risk stratification. RESULTS: A total of 617 patients were identified. Several independent prognostic factors were identified and integrated into the nomogram for OS2, including gender, age (2nd), nodal status (1st), node metastasis (2nd), and extrapulmonary metastasis (2nd). The calibration curves showed optimal agreement between the predictions and actual observations, and the c-index was 0.678. Surgery was associated with longer survival for msPSC patients. The prognosis of sublobectomy was comparable and inferior to that of lobectomy in the low- and moderate-risk groups, respectively. Radiotherapy was associated with better outcomes in patients who did not undergo surgery. CONCLUSIONS: The RPA-based clinical nomogram appears to be suitable for the prognostic prediction and risk stratification of OS2 in msPSC. This practical system may help clinicians make decisions and design clinical studies.

Activation of C3 and C5 May Be Involved in the Inflammatory Progression of PCM and GM.

Plasma cell mastitis (PCM) and granulomatous mastitis (GM) are the most common inflammatory diseases constituting nonbacterial mastitis (NBM). However, the pathogenesis of NBM remains unclear. In this study, risk factors for NBM were assessed, as well as the pathological features of PCM and GM. The levels of C3/C3a-C3aR and C5/C5a-C5aR1 of tissues were detected by IHC and WB. Exosomes were isolated from serum and identified by transmission electron microscopy. Then, C3 and C5 levels were detected in peripheral blood, and exosomes were assessed by flow cytometry and immunoelectron microscopy. Obesity and prolonged lactation were risk factors for NBM. The infiltration of plasma cells and lymphocytes around the dilated catheter in PCM and the formation of granulomatous structures in GM were the respective pathological features. C3/C3a-C3aR and C5/C5a-C5aR1 levels were elevated in PCM and GM tissue samples. There were no differences in peripheral blood levels of C3 and C5, while C3a and C5a were highly expressed in exosomes. These results suggest that the complement family is activated in PCM and GM, exosomes enrich C3a and C5a, and mediate the spread of inflammation. These findings provide new insights into the molecular mechanisms of PCM and GM and identify therapeutic targets.

The structures of two polysaccharides from Angelica sinensis and their effects on hepatic insulin resistance through blocking RAGE.

This study found two novel homogeneous polysaccharides from Angelica sinensis, APS-1I and APS-2II, binding to RAGE with a dissociation constant of 2.02 ± 0.2 and 85.92 ± 0.2 µM, respectively. APS-1I is a 17.0 kDa heteropolysaccharide, whose backbone is composed of α-1,6-Glcp, α-1,3,6-Glcp, α-1,2-Glcp, α-1,4-Galp, and α-1,3-Rhap, and whose two branches contain α-1,3,5-Araf, α-1,3-Araf, α-1,4-Galp, ß-1,3-Galp, and ß-1,4-Glcp. APS-2II is a 10.0 kDa linear glucan, that contains α-1,6-Glcp, α-1,3-Glcp, α-1,2-Glcp, and α-T-Glcp. In vitro, APS-1I demonstrated better promotion on glucose absorption and stronger repression on p-IRS-1 (Ser307), p-IRS-2 (Ser731), p-JNK, and p-P38 than APS-2II in insulin resistance (IR)-HepG2 cells. Furthermore, APS-1I treatment couldn't further decrease the inhibition on the phosphorylation of JNK and P38 produced by RAGE siRNA in IR-HepG2 cells. In vivo, APS-1I markedly improved IR and reversed the livers RAGE-JNK/p38-IRS signaling in high-fat-diet and streptozotocin-induced diabetic rats, suggesting that APS-1I could be a potential agent for improving IR in type 2 diabetes.

TRPC1 promotes the genesis and progression of colorectal cancer via activating CaM-mediated PI3K/AKT signaling axis.

Transient receptor potential canonical (TRPC) channels are the most prominent nonselective cation channels involved in various diseases. However, the function, clinical significance, and molecular mechanism of TRPCs in colorectal cancer (CRC) progression remain unclear. In this study, we identified that TRPC1 was the major variant gene of the TRPC family in CRC patients. TRPC1 was upregulated in CRC tissues compared with adjacent normal tissues and high expression of TRPC1 was associated with more aggressive tumor progression and poor overall survival. TRPC1 knockdown inhibited cell proliferation, cell-cycle progression, invasion, and migration in vitro, as well as tumor growth in vivo; whereas TRPC1 overexpression promoted colorectal tumor growth and metastasis in vitro and in vivo. In addition, colorectal tumorigenesis was significantly attenuated in Trpc1-/- mice. Mechanistically, TRPC1 could enhance the interaction between calmodulin (CaM) and the PI3K p85 subunit by directly binding to CaM, which further activated the PI3K/AKT and its downstream signaling molecules implicated in cell cycle progression and epithelial-mesenchymal transition. Silencing of CaM attenuated the oncogenic effects of TRPC1. Taken together, these results provide evidence that TRPC1 plays a pivotal oncogenic role in colorectal tumorigenesis and tumor progression by activating CaM-mediated PI3K/AKT signaling axis. Targeting TRPC1 represents a novel and specific approach for CRC treatment.

A systematic approach to decode the mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC).

Cornus Officinalis (Cornus), the dried pulp of mature Cornus, is used to treat liver diseases. However, the pharmacological mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC) has not been systematically studied. The chemical compounds and the bioactive chemical compounds of Cornus were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Cards database was used to explore the targets in liver cancer pathogenesis. The disease-drug Venn diagram was constructed using the VENN 2.1 and the STRING database was used to analyze protein-protein Interaction Network (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the R package. Molecular docking was performed using Discovery Studio were assessed using Pymol and Discovery Studio 2016. Cell survival of BEL-7404 cells treated by Hydroxygenkwanin (HGK) were valued through CCK-8 assay. Expressions of caspase-3 and cleaved PARP was detected through Western blot. Pharmacological network diagrams of the Cornus compound-target network and HCC-related target network were successfully constructed. A total of 20 active compounds, 1841 predicted biological targets of Cornus, and 7100 HCC-related targets were identified. 37 target genes between Cornus and HCC were screened trough the network pharmacology. Molecular docking studies suggested that HGK has the highest affinity with caspase-3. HGK could induce apoptosis of HCC cells and significantly activate the caspase-3 protease activity in BEL-7404. This study systematically elaborated the mechanism of Cornus in the treatment of HCC and provided a new perspective to exploit Antineoplastic from Cornus.