Research on Chinese medicinal materials cultivation: A bibliometric and visual analysis.

Chinese medicinal materials (CMMs) are important strategic resource in China. The cultivation process of medicinal plants is the key link which directly affect the quality and efficacy. The literatures of CMMs cultivation were acquired from China National Knowledge Infrastructure (CNKI) database and State Intellectual Property Office (SIPO) patent database for the years between 2001 and 2021. All the articles found were subjected to bibliometric analysis. The development trends and key topics were analyzed and visualized by VOSviewer and CiteSpace software. The results indicate that ecological planting, under-forest economy, intercropping patterns and industrialization production are the research hotspots in this field; cultivation technology and nutritional fertilization technology are the main areas addressed in recent years. Therefore, the high-quality and sustainable development of CMMs cultivation should be examined in terms of theoretical approaches, technical innovation, multi-cooperation, and intellectual property protection.

Serum Interleukin-1 Levels Are Associated with Intracranial Aneurysm Instability.

Serum interleukin-1 (IL-1) are possibly indicative of the inflammation in the intracranial aneurysm (IA) wall. This study aimed to investigate whether IL-1 could discriminate the unstable IAs (ruptured intracranial aneurysms (RIAs) and symptomatic unruptured intracranial aneurysms (UIAs)) from stable, asymptomatic UIAs. IA tissues and blood samples from 35 RIA patients and 35 UIA patients were collected between January 2017 and June 2020 as the derivation cohort. Blood samples from 211 patients with UIAs were collected between January 2021 and June 2022 as the validation cohort (including 63 symptomatic UIAs). Blood samples from 35 non-cerebral-edema meningioma patients (non-inflammatory control) and 19 patients with unknown-cause subarachnoid hemorrhage (hemorrhagic control) were also collected. IL-1ß and IL-1.ra (IL-1 receptor antagonist) were measured in serum and IA tissues, and the IL-1 ratio was calculated as log10 (IL-1.ra/IL-1ß). Based on the derivation cohort, multivariate logistic analysis showed that IL-1ß (odds ratio, 1.48, P = 0.001) and IL-1.ra (odds ratio, 0.74, P = 0.005) were associated with RIAs. The IL-1 ratio showed an excellent diagnostic accuracy for RIAs (c-statistic, 0.91). Histological analysis confirmed the significant correlation of IL-1 between serum and aneurysm tissues. IL-1 ratio could discriminate UIAs from non-inflammatory controls (c-statistic, 0.84), and RIAs from hemorrhagic controls (c-statistic, 0.95). Based on the validation cohort, the combination of IL-1 ratio and PHASES score had better diagnostic accuracy for symptomatic UIAs than PHASES score alone (c-statistic, 0.88 vs 0.80, P < 0.001). Serum IL-1 levels correlate with aneurysm tissue IL-1 levels and unstable aneurysm status, and could serve as a potential biomarker for IA instability.

A decision tree model to help treatment decision-making for severe spontaneous intracerebral hemorrhage.

BACKGROUND: Surgical treatment demonstrated a reduction in mortality among patients suffering from severe spontaneous intracerebral hemorrhage (SSICH). However, which SSICH patients could benefit from surgical treatment was unclear. This study aimed to establish and validate a decision tree (DT) model to help determine which SSICH patients could benefit from surgical treatment. MATERIALS AND METHODS: SSICH patients from a prospective, multicenter cohort study were analyzed retrospectively. The primary outcome was the incidence of neurological poor outcome (modified Rankin scale as 4-6) on the 180th day posthemorrhage. Then, surgically-treated SSICH patients were set as the derivation cohort (from a referring hospital) and validation cohort (from multiple hospitals). A DT model to evaluate the risk of 180-day poor outcome was developed within the derivation cohort and validated within the validation cohort. The performance of clinicians in identifying patients with poor outcome before and after the help of the DT model was compared using the area under curve (AUC). RESULTS: One thousand two hundred sixty SSICH patients were included in this study (middle age as 56, and 984 male patients). Surgically-treated patients had a lower incidence of 180-day poor outcome compared to conservatively-treated patients (147/794 vs. 128/466, P <0.001). Based on 794 surgically-treated patients, multivariate logistic analysis revealed the ischemic cerebro-cardiovascular disease history, renal dysfunction, dual antiplatelet therapy, hematoma volume, and Glasgow coma score at admission as poor outcome factors. The DT model, incorporating these above factors, was highly predictive of 180-day poor outcome within the derivation cohort (AUC, 0.94) and validation cohort (AUC, 0.92). Within 794 surgically-treated patients, the DT improved junior clinicians' performance to identify patients at risk for poor outcomes (AUC from 0.81 to 0.89, P <0.001). CONCLUSIONS: This study provided a DT model for predicting the poor outcome of SSICH patients postsurgically, which may serve as a useful tool assisting clinicians in treatment decision-making for SSICH.

Association of embolization with long-term outcomes in brain arteriovenous malformations: a propensity score-matched analysis using nationwide multicenter prospective registry data.

BACKGROUND: Brain arteriovenous malformations (AVMs) account for 25% of hemorrhagic strokes in young adults. Although embolization has been widely performed as a stand-alone procedure to cure brain AVM, it is undermined whether patients benefit from this treatment. This study aimed to compare the long-term outcome of hemorrhagic stroke or death in patients with either conservative management or stand-alone embolization for AVM. METHODS: The study population was derived from a nationwide multicenter prospective collaboration registry (the MATCH registry) between August 2011 and August 2021. The propensity score-matched survival analysis was performed in the overall and stratified AVM cases (unruptured and ruptured), respectively, to compare the long-term outcome of hemorrhagic stroke or death, and neurological status. The efficacy of distinct embolization strategies was also evaluated. Hazard ratios (HRs) with 95% CI were calculated using Fine-Gray competing risk models. RESULTS: Of the 3682 consecutive AVMs, 906 underwent either conservative management or embolization as the stand-alone management strategy. After propensity score matching, a total of 622 (311 pairs) patients constituted an overall cohort. The unruptured and ruptured subgroups were composed of 288 cases (144 pairs) and 252 cases (126 pairs), respectively. In the overall cohort, embolization did not prevent long-term hemorrhagic stroke or death compared with conservative management [2.07 vs. 1.57 per 100 patient-years; HR, 1.28 (95% CI, 0.81-2.04)]. Similar results were maintained in both unruptured AVMs [1.97 vs. 0.93 per 100 patient-years; HR, 2.09 (95% CI, 0.99-4.41)] and ruptured AVMs [2.36 vs. 2.57 per 100 patient-years; HR, 0.76 (95% CI, 0.39-1.48)]. Stratified analysis showed that the target embolization might be beneficial for unruptured AVMs [HR, 0.42 (95% CI, 0.08-2.29)], while the curative embolization improved the outcome of ruptured AVMs [HR, 0.29 (95% CI, 0.10-0.87)]. The long-term neurological status was similar between these two strategies. CONCLUSIONS: This prospective cohort study did not support a substantial superiority of embolization over conservative management for AVMs in preventing long-term hemorrhagic stroke or death.

The markers and risk stratification model of intracranial aneurysm instability in a large Chinese cohort.

Intracranial aneurysm is the leading cause of nontraumatic subarachnoid hemorrhage. Evaluating the unstable (rupture and growth) risk of aneurysms is helpful to guild decision-making for unruptured intracranial aneurysms (UIA). This study aimed to develop a model for risk stratification of UIA instability. The UIA patients from two prospective, longitudinal multicenter Chinese cohorts recruited from January 2017 to January 2022 were set as the derivation cohort and validation cohort. The primary endpoint was UIA instability, comprising aneurysm rupture, growth, or morphology change, during a 2-year follow-up. Intracranial aneurysm samples and corresponding serums from 20 patients were also collected. Metabolomics and cytokine profiling analysis were performed on the derivation cohort (758 single-UIA patients harboring 676 stable UIAs and 82 unstable UIAs). Oleic acid (OA), arachidonic acid (AA), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) were significantly dysregulated between stable and unstable UIAs. OA and AA exhibited the same dysregulated trends in serums and aneurysm tissues. The feature selection process demonstrated size ratio, irregular shape, OA, AA, IL-1ß, and TNF-α as features of UIA instability. A machine-learning stratification model (instability classifier) was constructed based on radiological features and biomarkers, with high accuracy to evaluate UIA instability risk (area under curve (AUC), 0.94). Within the validation cohort (492 single-UIA patients harboring 414 stable UIAs and 78 unstable UIAs), the instability classifier performed well to evaluate the risk of UIA instability (AUC, 0.89). Supplementation of OA and pharmacological inhibition of IL-1ß and TNF-α could prevent intracranial aneurysms from rupturing in rat models. This study revealed the markers of UIA instability and provided a risk stratification model, which may guide treatment decision-making for UIAs.

Serum interleukin-1 is a new biomarker to predict the risk of rebleeding of ruptured intracranial aneurysm after admission.

Interleukin-1 (IL-1) could induce inflammation of the aneurysm wall, which might be related to intracranial aneurysm rupture. The aim of this study was to investigate whether IL-1 could serve as a biomarker to predict the risk of rebleeding after admission. Data between January 2018 and September 2020 were collected from patients with ruptured intracranial aneurysms (RIAs) and were retrospectively reviewed. The serum IL-1ß and IL-1ra levels were detected using a panel, and IL-1 ratio was calculated as the log10 (IL-1ra/IL-1ß). The predictive accuracy of IL-1 compared with previous clinical morphology (CM) model and other risk factors were evaluated by the c-statistic. Five hundred thirty-eight patients were finally included in the study, with 86 rebleeding RIAs. The multivariate Cox analysis confirmed aspect ratio (AR) > 1.6 (hazard ratio (HR), 4.89 [95%CI, 2.76-8.64], P < 0.001), size ratio (SR) > 3.0 (HR, 2.40 [95%CI, 1.34-4.29], P = 0.003), higher serum IL-1ß (HR, 1.88 [95%CI, 1.27-2.78], P = 0.002), and lower serum IL-1ra (HR, 0.67 [95%CI, 0.56-0.79], P < 0.001) as the independent risk factors for rebleeding after admission. According to the c-statistics, the IL-1 ratio had the highest predictive accuracy (0.82), followed by IL-1ra and IL-1ß (0.80), AR > 1.6 (0.79), IL-1ra (0.78), IL-1ß (0.74), and SR > 3.0 (0.56), respectively. Subgroup analysis based on AR and SR presented similar results. The model combining IL-1 ratio and CM model showed higher predictive accuracy for the rebleeding after admission (c-statistic, 0.90). Serum IL-1, especially IL-1 ratio, could serve as a biomarker to predict the risk of rebleeding after admission.

Methylprednisolone is related to lower incidence of postoperative bleeding after flow diverter treatment for unruptured intracranial aneurysm.

Background and objectives: Regarding the anti-inflammatory effect, methylprednisolone is a candidate to prevent patients with unruptured intracranial aneurysms (UIAs) from postoperative bleeding (PB) after flow diverter (FD) treatment. This study aimed to investigate whether methylprednisolone is related to a lower incidence of PB after FD treatment for UIAs. Methods: This study retrospectively reviewed UIA patients receiving FD treatment between October 2015 and July 2021. All patients were observed until 72 h after FD treatment. The patients receiving methylprednisolone (80 mg, bid, for at least 24 h) were considered as standard methylprednisolone treatment (SMT) users, otherwise as non-SMT users. The primary endpoint indicated the occurrence of PB, including subarachnoid hemorrhage, intracerebral hemorrhage, and ventricular bleeding, within 72 h after FD treatment. This study compared the incidence of PB between SMT users and non-SMT users and investigated the protective effect of SMT on PB after FD treatment using the Cox regression model. Finally, after controlling the potential factors related to PB, we performed subgroup analysis to further confirm the protective effect of SMT on PB. Results: This study finally included 262 UIA patients receiving FD treatment. PB occurred in 11 patients (4.2%), and 116 patients (44.3%) received SMT postoperatively. The median time from the end of surgery to PB was 12.3 h (range: 0.5-48.0 h). SMT users had a lower incidence of PB comparing with non-SMT users (1/116, 0.9% vs. 10/146, 6.8%, respectively; p = 0.017). The multivariate Cox analysis demonstrated that SMT users (HR, 0.12 [95%CI, 0.02-0.94], p = 0.044) had a lower risk of PB postoperatively. After controlling the potential factors related to PB (i.e., gender, irregular shape, surgical methods [FD and FD + coil] and UIA sizes), the patients receiving SMT still had a lower cumulative incidence of PB, comparing with patients receiving non-SMT (all p < 0.05). Conclusion: SMT was correlated with the lower incidence of PB for patients receiving FD treatment and may be a potential method to prevent PB after the FD treatment.

Association of calcium channel blockers with lower incidence of intracranial aneurysm rupture and growth in hypertensive patients.

OBJECTIVE: Calcium channel blockers (CCBs) are antihypertensive agents with potential vascular protection effects. This study investigated whether CCB usage was associated with a lower incidence of unruptured intracranial aneurysm (UIA) instability (growth and rupture) in patients with hypertension. METHODS: UIA patients were included in two prospective, multicenter cohort studies (IARP-CP and 100-Project cohorts). All patients received conservative treatment and were regularly followed up every 6 months by CT angiography for 2 years. Patients taking CCBs at least 5 days per week were considered CCB users; otherwise, they were considered non-CCB users. The primary endpoint was UIA instability (rupture, growth of > 20% and/or 1 mm in any dimension, or appearance of a new dome irregularity on imaging follow-up). RESULTS: A total of 392 UIA patients with hypertension (191 male, 201 female; median age 57 years) were included with a mean follow-up duration of 21.7 ± 5.2 months. The primary endpoint was met in 81 patients (20.7%) during follow-up, including 68 patients with aneurysms that grew and 13 with aneurysms that ruptured. CCB users had a lower UIA instability rate than non-CCB users (27/237 [11.4%] vs 54/155 [34.8%], p < 0.001). Multivariable Cox analysis demonstrated that CCB use was associated with a lower risk of UIA instability (HR 0.37, 95% CI 0.22-0.61; p < 0.001). The protective effect of CCB use was consistent in patients taking a single antihypertensive agent (HR 0.22, 95% CI 0.12-0.40; p < 0.001) and patients taking > 1 antihypertensive agent (HR 0.42, 95% CI 0.20-0.87; p = 0.021). For patients with controlled hypertension, CCB use was still associated with a lower risk of UIA instability (HR 0.22, 95% CI 0.09-0.52; p = 0.001). CONCLUSIONS: In UIA patients with hypertension, CCB use was associated with a lower incidence of aneurysm instability.

Early-start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage and high risk of ischemic events (E-start): Protocol for a multi-centered, prospective, open-label, blinded endpoint randomized controlled trial.

Background: For severe spontaneous intracerebral hemorrhage (sSICH) patients with high risk of ischemic events, the incidence of postoperative major cardiovascular/cerebrovascular and peripheral vascular events (MACCPE) is notable. Although antiplatelet therapy is a potential way to benefit these patients, the severe hemorrhagic complications, e.g., intracranial re-hemorrhage, is a barrier for early starting antiplatelet therapy. Objectives: This randomized controlled trial aims to identify the benefit and safety of early starting antiplatelet therapy after operation for sSICH patients with high risk of ischemic events. Methods: This study is a multicenter, prospective, randomized, open-label, blinded-endpoint trial. We will enroll 250 sSICH patients with a high risk of ischemic events (including cerebral infarcts, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep venous thrombosis). The participants will be randomized in a 1:1 manner to early-start group (start antiplatelet therapy at 3 days after operation) and normal-start group (start antiplatelet therapy at 30 days after operation). The early-start group will receive aspirin 100 mg daily. The control group will not receive antithrombotic therapy until 30 days after operation. The efficacy endpoint is the incidence of MACCPE, and the safety endpoint is the incidence of intracranial re-hemorrhage. Discussion: The Early-Start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage trial (E-start) is the first randomized trial about early start antiplatelet therapy for operated sSICH patients with a high risk of ischemic events. This study will provide a new strategy and evidence for postoperative management in the future. Clinical trial registration: ClinicalTrials.gov, identifier NCT04820972; Available at: https://clinicaltrials.gov/ct2/show/NCT04820972?term=NCT04820972&draw=2&rank=1.Chinese Clinical Trial Registry, identifier ChiCTR2100044560; Available at: http://www.chictr.org.cn/showproj.aspx?proj=123277.

Berberine inhibited the formation of metastasis by intervening the secondary homing of colorectal cancer cells in the blood circulation to the lung and liver through HEY2.

BACKGROUND: Metastasis is the leading cause of death in patients with colorectal cancer (CRC). The 5-year survival rate of CRC patients in whom the cancer has spread to distant sites is 13.5%. The most common sites of CRC metastasis are liver and lung. The principal therapies for CRC metastatic disease are surgery, but its benefits are limited. PURPOSE: This study aimed to reveal the regulatory mechanism of berberine on secondary homing of CRC cells to form metastatic focus. This was more valuable than the previous direct study of the migration and metastasis characteristics of CRC cells. METHODS: In this study, we used the functional enrichment analysis of differentially expressed genes after berberine treatment and investigated co-expression modules related with CRC metastasis by WGCNA. PPI and survival analyses of significant modules were also conducted. The biological functions of berberine in CRC lung and liver metastasis were investigated by a series of in vitro and in vivo experiments: MTT, colony formation and mouse tail vein injection. And we scanned through the entire extracellular domain of HEY2 protein for autodocking analysis with berberine. RESULTS: We found the differentially expressed genes (DEGs) after berberine treatment were related with cancer progression and metastasis related pathways. Through WGCNA analysis, four cancer progression and metastasis related modules were detected. After PPI and survival analysis, we identified and validated HEY2 as a hub gene, high expression and poor survival at the metastatic stage. Functionally, berberine inhibited the survival, invasion and migration of CRC cells in vitro and in vivo. Mechanistically, berberine treatment down-regulated the expression of HEY2, metastasis related protein E-cadherin, ß-catenin and Cyclin D1 during Mesenchymal epithelial transformation (MET). Berberine and HEY2 showed a significant interaction, and berberine binded to HEY2 protein at the residue HIS-99 interface with a hydrogen-bond distance of 1.9A. CONCLUSIONS: We revealed that berberine could significantly inhibit the expression of hub gene HEY2 and metastasis related proteins E-cadherin and ß-catenin and Cyclin D1 during MET in CRC lung and liver metastases. In total, HEY2 was a promising candidate biomarker for prognosis and molecular characteristics in CRC metastasis.

Glycyrrhiza uralensis promote the metabolism of toxic components of Aconitum carmichaeli by CYP3A and alleviate the development of chronic heart failure.

Aconitum, as "the first drug of choice for invigorating Yang and saving lives", has been widely used for the treatment of heart failure. However, toxic components of Aconitum can easily lead to serious arrhythmia, even death (Y. CT., 2009; Zhang XM., 2018). In this study, a High Performance Liquid Chromatography (HPLC) method for the determination of aconitine (AC), mesaconitine (MA) and hypaconitine (HA) was established; The effect of Glycyrrhiza on CYP3A1 / 2 mRNA expression was detected by RT-PCR; SD rats were given Aconitum and compatibility of Glycyrrhizae and Aconitum by gavage respectively, the blood concentration of toxic components were determined by LC-MS / MS; The CHF rat model was established by intraperitoneal injection of adriamycin (2.5 mg / kg), and were randomly divided into model, Aconitum, the compatibility of Glycyrrhizae and Aconitum and Captopril group, 5 mice/group. After 4 weeks of gavage, the corresponding indexes were detected by ELISA and HPLC. The results showed that Ketoconazole significantly inhibited the metabolites of AC, MA and HA; Glycyrrhiza induced CYP3A gene expression; The level of ALD in the compatibility of Glycyrrhizae and Aconitum group was significantly lower than that in Aconitum group. After intervention with the compatibility of Glycyrrhizae and Aconitum, ATP increased, ADP decreased significantly. In conclusion, we found Glycyrrhiza promoted the metabolism of toxic components of Aconitum by up regulating the expression of CYP3A, and reduced the content of BNP, Ang II and ALD, improved the energy metabolism disorder of myocardium, alleviated the development of CHF.

Adventitial injection of HA/SA hydrogel loaded with PLGA rapamycin nanoparticle inhibits neointimal hyperplasia in a rat aortic wire injury model.

Neointimal hyperplasia is a persistent complication after vascular interventions, and it is also the leading cause of vascular graft restenosis and failure after arterial interventions, so novel treatment methods are needed to treat this complication. We hypothesized that adventitial injection of HA/SA hydrogel loaded with PLGA rapamycin nanoparticle (hydrogel-PLGA-rapamycin) could inhibit neointimal hyperplasia in a rat aortic wire injury model. The HA/SA hydrogel was fabricated by the interaction of hyaluronic acid (HA), sodium alginate (SA), and CaCO3; and loaded with PLGA rapamycin nanoparticle or rhodamine uniformly. A SD rat aortic wire injury induced neointimal hyperplasia model was developed, the control group only received wire injury, the adventitial application group received 10 µL hydrogel-PLGA-rapamycin after wire injury, and the adventitial injection group received 10 µL hydrogel-PLGA-rapamycin injected into the aortic adventitia after wire injury. Tissues were harvested at day 21 and analyzed by histology and immunohistochemical staining. Hydrogel loaded with rhodamine can be successfully injected into the aortic adventitia and was encapsuled by the adventitia. The hydrogel could be seen beneath the adventitia after adventitial injection but was almost degraded at day 21. There was a significantly thinner neointima in the adventitial application group and adventitial injection group compared to the control group (p = 0.0009). There were also significantly fewer CD68+ (macrophages) cells (p = 0.0012), CD3+ (lymphocytes) cells (p = 0.0011), p-mTOR+ cells (p = 0.0019), PCNA+ cells (p = 0.0028) in the adventitial application and adventitial injection groups compared to the control group. The endothelial cells expressed arterial identity markers (Ephrin-B2 and dll-4) in all these three groups. Adventitial injection of hydrogel-PLGA-rapamycin can effectively inhibit neointimal hyperplasia after rat aortic wire injury. This may be a promising drug delivery method and therapeutic choice to inhibit neointimal hyperplasia after vascular interventions.

A Novel Coagulation Classification and Postoperative Bleeding in Severe Spontaneous Intracerebral Hemorrhage Patients on Antiplatelet Therapy.

BACKGROUND AND PURPOSE: For patients with severe spontaneous intracerebral hemorrhage on antiplatelet therapy (patients with APT-SICH), postoperative rebleeding (PR) is an important cause of poor outcomes after surgery. As impacted by coagulation disorder caused by APT, patients with APT-SICH are likely to suffer from PR. This study aimed to assess the risk of PR in patients with APT-SICH receiving emergency surgery using a novel coagulation classification. METHODS: This prospective, multicenter cohort study consecutively selected patients with APT-SICH between September 2019 and March 2021. The preoperative coagulation factor function was recorded, and the platelet function was assessed using thrombelastography. Based on platelet and coagulation factor function, a novel four-type coagulation classification, i.e., Type I (severe coagulation disorder), Type IIa (low platelet reserve capacity), Type IIb (normal coagulation), and Type III (hypercoagulation), was presented. The primary outcome was PR, defined as the rebleeding in the operative region or new intracerebral hemorrhage correlated with the operation. RESULTS: Of the included 197 patients with APT-SICH, PR occurred in 40 patients (20.3%). The novel coagulation classification categorized 28, 32, 122, and 15 patients into Type I, Type IIa, Type IIb, and Type III, respectively. The Type I patients had the highest incident rate of PR (39.3 per 100 persons), followed by the Type IIa patients (31.3 per 100 persons). In the PR-related analysis, the large hematoma volume (hazard ratio (HR): 1.02; 95% CI: 1.02-1.03; p < 0.001), Type I (HR: 9.72; 95% CI: 1.19-79.67; p = 0.034), and Type IIa (HR: 8.70; 95% CI: 1.09-69.61; p = 0.041) were correlated with the highest risk of PR. The coagulation classification could discriminate the PR patients from no PR (NPR) patients (p < 0.001), and it outperformed the conventional coagulation assessment (only considering platelet count and coagulation factor function) (c-statistic, 0.72 vs. 0.55). CONCLUSION: The novel coagulation classification could discriminate the patients with APT-SICH with the highest risk of PR preoperatively. For the Type I and Type IIa patients, emergency surgery should be performed carefully.

Berberine inhibits non-small cell lung cancer cell growth through repressing DNA repair and replication rather than through apoptosis.

At present, there are still many problems in the treatment of lung cancer, such as high cost, side effects and low quality of life. The advantages of traditional Chinese medicine (TCM) in the treatment of lung cancer are reflected. Berberine has been increasingly popular in colorectal cancer treatment, but little is known about its bioactivity against non-small cell lung cancer (NSCLC). Cell proliferation, cell apoptosis, cDNA microarray, gene and protein expression, and NSCLC transplanted tumour growth were performed. Berberine suppressed NSCLC cell proliferation and colony formation in vitro and inhibited NSCLC tumour growth in subcutaneously transplanted tumour lung tumour models, leading to prolonged survival of tumour-bearing mice. However, berberine did not induce the cleavage of Caspase 3 and PARP1, and could not induce apoptosis in all NSCLC cells. Moreover, 646 genes were differentially expressed upon berberine administration, which were involved in seven signal pathways, such as DNA replication. In cDNA microarray, berberine downregulated the expression of RRM1, RRM2, LIG1, POLE2 that involving DNA repair and replication. Our findings demonstrate that berberine inhibits NSCLC cells growth through repressing DNA repair and replication rather than through apoptosis. Berberine could be used as a promising therapeutic candidate for NSCLC patients.

Hydrogel-coated needles prevent puncture site bleeding.

INTRODUCTION: Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm. We hypothesized that a hydrogel-coated needle would effectively and rapidly stop bleeding after vascular cannulation. METHODS: A hydrogel composed of sodium alginate, hyaluronic acid, and calcium carbonate was coated onto the surface of suture needles. Needles were observed using scanning electronic microscopy (SEM) and immunofluorescence. Cannulation was performed in both mouse and rat models; the liver, kidney, jugular vein, inferior vena cava and aorta were punctured using uncoated and hydrogel-coated needles. Needles coated with a hydrogel with and without CD34 antibody were used to puncture the rat jugular vein and aorta. Tissues were examined by histology and immunofluorescence. RESULTS: The hydrogel was successfully coated onto the surface of 22G and 30G needles and confirmed by SEM. Hydrogel-coated needles rapidly stopped bleeding after cannulation of the liver, kidney, jugular vein, inferior vena cava and aorta. Hydrogel-coated needles that contained CD34 antibody attracted vascular progenitor cells near the puncture site; there were fewer M1-type macrophages and more M2-type macrophages. CONCLUSION: Hydrogel-coated needles can effectively and rapidly stop puncture-site bleeding. The hydrogel that contains CD34 antibody attracted vascular progenitor cells, potentially promoting healing of the site after cannulation. STATEMENT OF SIGNIFICANCE: Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm and remains a significant clinical problem. We developed a hydrogel composed of sodium alginate, hyaluronic acid, and calcium carbonate; hydrogel-coated needles effectively and rapidly stopped bleeding after vascular cannulation. Interestingly, the hydrogel can also serve as a carrier for drugs that are delivered to the puncture site during the short time of cannulation that could additionally promote puncture site healing. Hydrogel-coated needles may be a new method for rapid hemostasis with application to patients especially at risk for bleeding.

Berberine Inhibits FOXM1 Dependent Transcriptional Regulation of POLE2 and Interferes With the Survival of Lung Adenocarcinoma.

Background: Berberine is one of the most interesting and promising natural anticancer drugs. POLE2 is involved in many cellular functions such as DNA replication and is highly expressed in a variety of cancers. However, the specific molecular mechanism of berberine interfering with POLE2 expression in lung adenocarcinoma (LUAD) is still unknown to a great extent. Method: The KEGG database (Release 91.0) and Gene Ontology (GO) category database were used for functional annotation of differentially expressed genes after berberine treatment. Reproducibility assessment using TCGA dataset. The biological functions of berberine in LUAD were investigated by a series of in vitro and in vivo experiments: MTT, colony formation, mouse xenograft and plasmid transfection. The molecular mechanisms of berberine were demonstrated by plasmid transfection, quantitative RT-PCR and Western blotting. Result: The elevated expression of FOXM1 and the high enrichment of DNA replication pathway were confirmed in LUAD by microarray and TCGA analysis, and were positively correlated with poor prognosis. Functionally, berberine inhibited the proliferation and survival of LUAD cell lines in vitro and in vivo. Mechanistically, berberine treatment down regulated the expression of FOXM1which closely related to survival, survival related genes in Cell cycle and DNA replication pathway, and significantly down regulated the expression of survival related POLE2. Interestingly, we found that the transcription factor FOXM1 could act as a bridge between berberine and POLE2. Conclusion: Berberine significantly inhibited LUAD progression via the FOXM1/POLE2, and FOXM1/POLE2 may act as a clinical prognostic factor and a therapeutic target for LUAD. Berberine may be used as a promising therapeutic candidate for LUAD patients.

Rosthorin A inhibits non-small cell lung cancer cell growth and metastasis through repressing epithelial-mesenchymal transition via downregulating Slug.

Lung cancer always ranks first in the number of cancer deaths every year, accounting for 18.4% of total cancer deaths in 2018. Metastasis is the main cause of death in lung cancer patients. The identification of bioactive components of traditional Chinese medicine is very important for the development of novel reagents against non-small cell lung cancer (NSCLC). Rosthorin A has originated from Rabdosia rosthornii (Diels) Hara which excerpts from 'Chinese materia medica', and is known to have 'clear heat phlegm' properties in the folk. Little is known about the biological functions and mechanisms of Rosthorin A in cancer cells at present. The role of EMT in metastasis of a tumor cell is self-evident. Slug is an important EMT inducer, which is related to the development of lung cancer. Cell growth, clone assay, cell migration, cell invasion, and protein expression, and NSCLC transplanted tumor growth were performed in A549, H1299, and H1975 cells. Rosthorin A significantly inhibited the growth of NSCLC cells, it could prolong the survival of nude mice. Rosthorin A inhibited the migration and invasion of A549, H1299, and H1975 cells. Rosthorin A up-regulated E-cadherin expression level and down-regulated the expression of ß-catenin, N-cadherin, vimentin, Slug, and Twist. Rosthorin A could promote the expression of E-cadherin and inhibit the development of EMT by downregulating Slug, to inhibit the development and metastasis of NSCLC cells. In summary, Rosthorin A could be used as a promising candidate for the treatment of NSCLC patients with recurrence and metastasis.

Hyaluronic acid-heparin conjugated decellularized human great saphenous vein patches decrease neointimal thickness.

Although the science of implantable materials has advanced therapeutic options in vascular surgery, graft failure is still a problem in need of a durable solution. With the development of coating and decellularization techniques, coated prosthetic grafts have become an option; however, whether decellularized human saphenous vein can be conjugated and implanted is not known. Human great saphenous vein (GSV) was harvested and decellularized and hyaluronic acid (HA)-heparin was conjugated to the GSV; water contact angles (WCA), morphology, and sulfur element change were measured before and after heparin bonding. GSV patches were implanted into the rat inferior vena cava and aorta; patches were harvested (Day 14) and analyzed. HA-heparin was successfully conjugated to the decellularized human GSV with altered morphology and reduced WCA. The HA-heparin coated decellularized GSV patch was anti-thrombotic in vitro, and significantly decreased neointimal thickness both in patch venoplasty and angioplasty in a rat model. Both CD90 and nestin positive cells participated in neointima formation. These data show that HA-heparin coated human GSV patches decrease neointimal thickness when used both in venoplasty and arterioplasty. Tissue engineered decellularized human GSV is a promising vascular prosthesis.

Coptis Chinensis affects the function of glioma cells through the down-regulation of phosphorylation of STAT3 by reducing HDAC3.

BACKGROUND: Glioma remains the most common cause of brain cancer-related mortality. Glioma accounts for 50-60% of brain cancer. Due to their low toxicity and infrequent side effects, traditional herbs have been increasingly popular. Coptis Chinensis is commonly used in cancer treatment in combination with other Chinese Medicine herbs. However, little is known about its biological functions and mechanisms in glioma cells. METHODS: In this study, the anti-glioma cell effect of Coptis Chinensis was determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, plate clone test, scratch tests, flow cytometry, western blotting and a glioma xenograft tumor model. RESULTS: The results showed that Coptis Chinensis significantly suppressed glioma cell proliferation, tumor formation, migration and tumor growth, and prolonged the survival time of glioma cell-bearing mice. The flow cytometry result showed that Coptis Chinensis induced cell cycle arrest and apoptosis in glioma cells. Western blotting showed that Coptis Chinensis down-regulated the Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels and reduced the expression of Histone deacetylase 3 (HDAC3) and caspase 3. CONCLUSIONS: Coptis Chinensis can inhibit various aspects of glioma cell functions. This study provides favorable scientific evidence for the potential use of natural products such as Coptis Chinensis in the clinical treatment of patients with glioma.

Endoscopic expand transnasal approach to the suprasellar region: anatomical study and clinical considerations.

BACKGROUND: The expanded endonasal approach (EEA) is used sparingly by surgeons for resection of lesions in the ventrocranial base. Herein, we examined the anatomy of the ventrocranial base by endoscopy and comment on the use of EEA in clinical practice. METHODS: Twenty artery-injected adult cadaveric heads were studied under surgical conditions using the endoscopic EEA. The extent of the surgical exposure, the endoscopic anatomic view and the maneuverability of surgical instruments about the suprasellar region were studied by the endoscopic EEA. RESULTS: The EEA by endoscope can reach the suprasellar region. In this approach, the optocarotid recess, supra and infra-optic chiasm interspace, the ophthalmic artery and others were important anatomical landmarks for identification of the suprasellar region. CONCLUSIONS: The endoscopic EEA can be used to remove many types of lesions in the ventrocranial base. The microanatomy observed using the endoscope provides important anatomical information on the suprasellar region for neurosurgeons.