Natural products reverse cancer multidrug resistance.

Cancer stands as a prominent global cause of death. One of the key reasons why clinical tumor chemotherapy fails is multidrug resistance (MDR). In recent decades, accumulated studies have shown how Natural Product-Derived Compounds can reverse tumor MDR. Discovering novel potential modulators to reduce tumor MDR by Natural Product-Derived Compounds has become a popular research area across the globe. Numerous studies mainly focus on natural products including flavonoids, alkaloids, terpenoids, polyphenols and coumarins for their MDR modulatory activity. Natural products reverse MDR by regulating signaling pathways or the relevant expressed protein or gene. Here we perform a deep review of the previous achievements, recent advances in the development of natural products as a treatment for MDR. This review aims to provide some insights for the study of multidrug resistance of natural products.

The complete chloroplast genome of Dianella ensifolia (Asphodelaceae).

Dianella ensifolia (L.) Redouté 1802 is a plant known for its significant medicinal values. In this study, we presented its chloroplast genome. The length of the chloroplast genome was found to be 156,571 bp, with a GC content of 37.86%. It consisted of a large single-copy (LSC) of 85,318 bp and a small single-copy (SSC) of 18,307 bp, a pair of inverted repeats (IRs) of 26,473 bp each that separated the LSC and SSC regions. The chloroplast genome of D. ensifolia consisted of 114 unique genes, including 80 protein-coding genes, four rRNA genes, and 30 tRNA genes. Through phylogenetic analysis, we identified a close relationship between D. ensifolia and D. nigra. This newly sequenced chloroplast genome not only enhances our understanding of the genome of Dianella, but also provides valuable insights for the evolutionary study of the family Asphodelaceae.

YOLOv5s-DSD: An Improved Aerial Image Detection Algorithm Based on YOLOv5s.

Due to the challenges of small detection targets, dense target distribution, and complex backgrounds in aerial images, existing object detection algorithms perform poorly in aerial image detection tasks. To address these issues, this paper proposes an improved algorithm called YOLOv5s-DSD based on YOLOv5s. Specifically, the SPDA-C3 structure is proposed and used to reduce information loss while focusing on useful features, effectively tackling the challenges of small detection targets and complex backgrounds. The novel decoupled head structure, Res-DHead, is introduced, along with an additional small object detection head, further improving the network's performance in detecting small objects. The original NMS is replaced by Soft-NMS-CIOU to address the issue of neighboring box suppression caused by dense object distribution. Finally, extensive ablation experiments and comparative tests are conducted on the VisDrone2019 dataset, and the results demonstrate that YOLOv5s-DSD outperforms current state-of-the-art object detection models in aerial image detection tasks. The proposed improved algorithm achieves a significant improvement compared with the original algorithm, with an increase of 17.4% in mAP@0.5 and 16.4% in mAP@0.5:0.95, validating the superiority of the proposed improvements.

GPR84 regulates pulmonary inflammation by modulating neutrophil functions.

Acute lung injury (ALI) is an acute, progressive hypoxic respiratory failure that could develop into acute respiratory distress syndrome (ARDS) with very high mortality rate. ALI is believed to be caused by uncontrolled inflammation, and multiple types of immune cells, especially neutrophils, are critically involved in the development of ALI. The treatment for ALI/ARDS is very limited, a better understanding of the pathogenesis and new therapies are urgently needed. Here we discover that GPR84, a medium chain fatty acid receptor, plays critical roles in ALI development by regulating neutrophil functions. GPR84 is highly upregulated in the cells isolated from the bronchoalveolar lavage fluid of LPS-induced ALI mice. GPR84 deficiency or blockage significantly ameliorated ALI mice lung inflammation by reducing neutrophils infiltration and oxidative stress. Further studies reveal that activation of GPR84 strongly induced reactive oxygen species production from neutrophils by stimulating Lyn, AKT and ERK1/2 activation and the assembly of the NADPH oxidase. These results reveal an important role of GPR84 in neutrophil functions and lung inflammation and strongly suggest that GPR84 is a potential drug target for ALI.

Multidisciplinary treatment of primary intracranial yolk sac tumor: A case report and literature review.

RATIONALE: Intracranial yolk sac tumors (YSTs) are rare malignancies with limited treatment options and a dismal prognosis. They are usually managed with surgical resection and chemoradiotherapy. PATIENT CONCERNS: Here, we report a patient with primary YST in the pineal region who achieved long term survival. Despite undergoing treatment, he experienced several recurrences over a 15-year period. DIAGNOSIS: Brain magnetic resonance imaging (MRI) demonstrated the presence of space-occupying lesions in the pineal region and the medial tail of the left lateral ventricle. The tumors were excised, and the histological diagnosis suggested an intracranial YST. INTERVENTIONS: The patient achieved long term survival after combined modality therapy including surgery, stereotactic radiosurgery (SRS)/intensity modulated radiation therapy (IMRT), chemotherapy, and targeted therapy. OUTCOMES: The disease remained stable. However, the patient gave up treatment and passed away in October 2020, with a total survival of about 15 years. LESSONS: To the best of our knowledge, this patient with intracranial YST had received a longer survival compared with other published reports. We summarize previously published reports of intracranial YST and discuss the importance of multidisciplinary treatment. SRS may have a role, as a focal boost to residual tumor after resection or in case of recurrence after conventional radiotherapy, in the multimodality management of intracranial YSTs.

Opioid-sparing effect of modified intercostal nerve block during single-port thoracoscopic lobectomy: Retraction: A randomised controlled trial.

BACKGROUND: Peripheral local anaesthetic blockade has an important role in multimodal postoperative analgesia after video-assisted thoracic surgery. Intercostal nerve block has an opioid-sparing effect after thoracoscopic surgery, but there is little information about an intra-operative opioid-sparing effect. OBJECTIVE: This prospective randomised trial was designed to evaluate the feasibility of a modified intercostal nerve block and its potential opioid-sparing effect during single-port thoracoscopic lobectomy. DESIGN: This was a randomised controlled study. SETTING: The First Affiliated Hospital of Anhui Medical University, Hefei, China, from January 2020 to April 2020. PATIENTS: Fifty patients scheduled for single-port thoracoscopic lobectomy were enrolled. INTERVENTION: Patients were randomised to receive the intercostal nerve block using 10 ml 0.35% ropivacaine (group MINB) or conventional general anaesthesia (group CGA). Following a bolus of 0.5 to 1.0 µg kg-1 remifentanil, it was then infused at 0.2 to 0.5 µg kg-1 min-1 during surgery to keep mean arterial pressure or heart rate values around 20% below baseline values. MAIN OUTCOME MEASURES: The primary outcome was intra-operative remifentanil consumption. RESULTS: Median [IQR] remifentanil consumption was reduced in the MINB group [0 µg (0 to 0 µg)] compared with the CGA group [1650.0 µg (870.0 to 1892.5 µg)]. The median difference was 1650.0 µg (95%CI 1200.0 to 1770.0 µg; P = 0.00). The total number of analgesic demands during the first 24 and 48 h in the MINB group was significantly less than in the CGA group (difference = 1; 95% CI 1 to 3; P = 0.00 and difference = 4; 95% CI 3 to 5; P = 0.00; respectively). The difference in time to first demand for analgesia was significant [difference = 728 min (95% CI 344 to 1381 min), P = 0.00] and also in the number of patients requiring additional tramadol (P = 0.03). CONCLUSION: We have shown intra-operative opioid-sparing with a modified intercostal nerve block during single-port thoracoscopic lobectomy, with opioid-sparing extending 48 h after surgery. However, the opioid-sparing effect was not associated with a reduction in opioid side effects. TRIAL REGISTRATION: http://www.chictr.org.cn, ChiCTR2000029337.

Zwitterionic Hydrogel-Impregnated Membranes with Polyamide Skin Achieving Superior Water/Salt Separation Properties.

Support-free nonporous membranes have emerged as a new material platform for osmotic pressure-driven processes due to its insusceptibility to internal concentration polarization (ICP). Herein, we demonstrate high-performance membranes of zwitterionic hydrogels impregnated in porous membranes with a skin layer of highly cross-linked polyamides on both sides prepared by gel-liquid interfacial polymerization (GLIP). Such a configuration eliminates the pores and thus ICP, while the thin polyamide layer provides high salt rejection but negligible resistance to the water transport compared with the hydrogels. The polyamide skin layers are characterized using scanning electron microscopy and atomic force microscopy. The effect of the hydrogel compositions and polyamide formation conditions on the water/salt separation properties is thoroughly investigated. Example membranes show water permeance and salt rejection comparable to state-of-the-art commercial forward osmosis membranes and essentially no ICP.

A meta-analysis of treatment effects of imiquimod for basal cell carcinoma.

OBJECTIVE: We conducted this meta-analysis to assess the efficacy and safety of imiquimod in comparison with other treatments in patients with BCC. METHODS: A comprehensive literature search was performed in the database of PubMed, Embase, and Web of Science. Outcomes of interest included histological/composite clearance rate, success rate, complete response rate, tumor free survival, and adverse events. Pooled risk ratio (RR) with 95% confidence intervals (CIs) using a fixed-effects or random-effects model were determined for each outcome. RESULTS: A total of 13 studies involving 4256 patients were identified. Imiquimod was associated with significantly higher histological clearance rate (RR = 9.28, 95%CI: 5.56, 15.49; P < .001) and composite clearance rate (RR = 34.24, 95%CI: 21.29, 55.06; P = .001). Moreover, imiquimod also significantly increased complete response rate (RR = 3.15, 95%CI: 1.55, 6.38; P = .001) but had no effect in the success rate (RR = 0.98, 95%CI: 0.89, 1.08; P = .727) and probability of tumor-free survival (RR = 1.15, 95%CI: 0.98, 1.35; P = .088), as compared with other treatments. There were more patients in imiquimod group who developed adverse events than in other treatment group (RR = 2.00, 95%CI: 1.39, 2.88; P < .001). CONCLUSION: This study indicated the effects of imiquimod in improving the histological/composite clearance rates as compared with other treatments. However, its treatment-related adverse events also should be noticed. Our findings supported that, imiquimod could be used as the first-choice treatment for BCC.

Exenatide Protects Against Cardiac Dysfunction by Attenuating Oxidative Stress in the Diabetic Mouse Heart.

Cardiovascular disease is the major cause of death in patients with diabetes. Current treatment strategies for diabetes rely on lifestyle changes and glucose control to prevent angiopathy and organ failure. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used as an add-on therapy to insulin treatment. Exenatide also has multiple beneficial effects in addition to its hypoglycemic effects, such as preventing hepatic steatosis and protecting against cardiac injury from doxorubicin-induced cardiotoxicity or ischemic reperfusion. However, the mechanisms underlying the cardioprotective effects of exenatide in diabetes have not been fully clarified. To address this issue, we investigated the cardioprotective effects of exenatide in type 1 and type 2 diabetic mice. We found that exenatide simultaneously attenuated reactive oxidative species (ROS) production through increases in the antioxidant enzymes manganese dependent superoxide dismutase (MnSOD) and catalase. Moreover, exenatide decreased tumor protein P53 (p53) expression and prevented cell apoptosis in H9c2 cells. The presence of the catalase inhibitor 3-AT attenuated the effects of exenatide. Overall, the results strongly indicate that exenatide treatment may be protective against the development of diabetic cardiomyopathy.

AMPKα2 Deficiency Does Not Affect the Exercise-Induced Improvements in Glucose Tolerance and Metabolic Disorders in Mice Fed a High-Fat Diet.

Exercise can improve obesity and metabolic disorders in mice fed a high-fat diet (HFD), but the role of AMPKα2 in the process remains unclear. The aim of this study was to investigate the role of AMPKα2 in the exercise-induced improvements in glucose tolerance and metabolic turnover in obesity mice. Male wild-type mice (n=12) and AMPKα2 knockout (AMPKα2 KO) mice (n=12) were fed a HFD for 16 wk and were then randomly divided into four groups: WT HFD group (WT HF), AMPKα2 KO HFD group (AMPKα2 KO HF), WT HFD exercise group (WT HE), and AMPK HFD exercise group (AMPKα2 KO HE). The HF groups continue to be fed a HFD from 16 wk to 24 wk, and the HE groups were fed a HFD and performed exercise training. After 8 wk of exercise, all mice were placed in an energy metabolism chamber to test their metabolic turnover, include locomotor activity, food intake, oxygen consumption (VO2), carbon dioxide production (VCO2), energy expenditure (EE) and respiratory exchange ratio (RER), over a period of 3 d. Exercise improved glucose tolerance, VO2, VCO2 and EE in mice fed a HFD (p<0.05). The VO2, VCO2 and EE in AMPKα2 KO HE group were lower than these in WT HE group (p<0.05). Our findings revealed exercise improved glucose tolerance and metabolic disorders in C57 and AMPKα2 KO mice fed a HFD. AMPKα2 is not essential for exercise-induced improvements in glucose tolerance and metabolic disorders.

Phenolic glycosides from Curculigo orchioides Gaertn.

Five new chlorophenolic glucosides, curculigine E (1), curculigine F (2), curculigine G (3), curculigine H (5), curculigine I (6) and one new phenolic glycoside, orcinoside H (4), together with eight known phenolic glycosides (7-14) were isolated from the Curculigo orchioides Gaertn. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and 2D NMR). The isolated phenolic glycosides were evaluated for antiosteoporotic activity against MC3T3-E1 cell line using MTT assays. Compounds 1, 2, 3, and 5 showed moderate antiosteoporotic activity with the proliferation rate of 10.1-14.1%.

Gracilibacillus kekensis sp. nov., a moderate halophile isolated from Keke Salt Lake.

A novel moderately halophilic bacterium, designated strain K170(T), was isolated from Keke Salt Lake in Qinghai, China. The strain grew with 0-22 % (w/v) NaCl, at 4-50 °C and at pH 6-11, with optimum growth in 3 % (w/v) NaCl, at 40 °C and at pH 8. The predominant respiratory quinone was menaquinone 7 (MK-7). The polar lipids included diphosphatidylglycerol, phosphatidylglycerol, unidentified phospholipids, aminolipids and glycolipids. The major cellular fatty acids were anteiso-C(15 : 0), iso-C(15 : 0) and anteiso-C(17 : 0). The DNA G+C content was 35.8 mol%. Phylogenetic analysis based on the full-length 16S rRNA gene sequence revealed that strain K170(T) was a member of the genus Gracilibacillus. High levels of 16S rRNA gene sequence similarity were found between strain K170(T) and Gracilibacillus boraciitolerans DSM 17256(T) (97.3 %) and Gracilibacillus thailandensis JCM 15569(T) (97.1 %). 16S rRNA gene sequence similarities between strain K170(T) and the type strains of other recognized members of the genus Gracilibacillus were below 97 %. The DNA-DNA hybridization values of strain K170(T) with G. boraciitolerans DSM 17256(T) and G. thailandensis JCM 15569(T) were 21.9 % and 34.3 %, respectively. On the basis of these results, strain K170(T) is considered to represent a novel species of the genus Gracilibacillus, for which the name Gracilibacillus kekensis sp. nov. is proposed; the type strain is K170(T) ( = CGMCC 1.10681(T) = DSM 23178(T)).

Effects of Mycobacterium vaccae vaccine on immunological function in elderly patients with stable chronic obstructive pulmonary disease / 中华老年医学杂志

Objective To investigate the effects of Mycobacterium vaccae vaccine on immunological function and clinical character in elderly patients with stable chronic obstructive pulmonary disease (COPD). MethodsA total of 100 elderly patients with stable COPD were randomly divided into immunotherapy group (group A, n= 50) and non-immunotherapy group (group B, n= 50), and normal control group (group C, n = 50). The levels of peripheral blood T-lymphocyte subsets (CD3+ , CD4+, CD8+ , CD4+/CD8+ ratio), natural killer cells (NK cells), immunoglobulins (IgG, IgA, IgM) and cytokines (IL-6, IL-8, TNF-a) were measured respectively before and after therapy. Group A and B were followed up for 1 year, then the times of acute outbreak and hospitalization of patients in the two groups were also compared. Results The levels of CD4 + ,CD4+/CD8+ ratio and NK cells in group A, B were significantly lower before therapy (P＜0. 05～0. 01＝, and the levels of IL-6, IL -8, TNF-a and IgA were significantly higher than in group C (P＜0. 01＝. After treatment with Mycobacterium vaccae vaccine in group A, the levels of CD4+ , CD4+/CD8+ ratio and NK cells were significantly higher (P＜0. 05-0. 01＝ and IL-6, IL-8, TNF-a and IgA were significantly lower than before treatment (all P＜0. 01＝. These levels showed no significant changes in group B after treatment (P＞0. 05). After 1-year follow-up, the times of acute outbreak and hospitalization on patients were statistically lower in group A than in group B (P＜ 0. 01 ).ConclusionsMycobacterium vaccae vaccine can improve cellular immunity function and reduce the times of acute outbreak and hospitalization in patients with stable COPD, so it has a higher clinical application value.

The expression of the early growth responsive gene-1 in acute pulmonary embolism of rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate the dynamic changes of Egr-1 expression in the lungs of acute pulmonary embolism of rats by infusion of autoblood thrombs.</p><p><b>METHODS</b>The model of pulmonary embolism by infusion of autoblood thrombs in the pulmonary artery of rats was established and the mean pulmonary arterial pressure was continuously monitored by computer, and the results were evaluated by lung perfusion scan and pathological changes. Expression of Egr-1 proteinum and mRNA were measured by immunohistochemistry and reverse transcription polymerase chain reaction.</p><p><b>RESULTS</b>The mPAP of rats was increased significantly after infusion of autoblood thrombs at the half hour, and reached high level at the second hour, then remained the high level to four hours compared with group control at the same time point (P < 0.01). ECT image was showed significantly filling defect after infusion of autoblood thrombs at the first hour. The infused thromb was witnessed by hematoxylin and eosin stain. In the tracheal epithelium cells, alveolar epithelium cells and vascular smooth muscle cells of embolism rats, Egr-1 protein expression was increased significantly after embolization at the second hour compared with group control at the same time point (P<0.01), and was decreased slowly at the fourth hour. Egr-1 mRNA expression was showed the similar changes.</p><p><b>CONCLUSION</b>Expression of Egr-1 was low level in group control, but increased significantly after infusion of autoblood thromb at the second hour in the specificity of cells, suggesting that Egr-1 expression might be an important link of pathological changes in the acute pulmonary embolism.</p>

[Therapeutic effect of L-ornithine-L-aspartate on liver cirrhosis complicated by hepatic encephalopathy].

OBJECTIVE: To observe the therapeutic effects of L-ornithine-L-aspartate on liver cirrhosis complicated by hepatic encephalopathy. METHODS: Eighty-five patient with liver cirrhosis complicated by hepatic encephalopathy were divided into therapy group (n=45) and control group (n=40). Patients in the control group were treated with routine comprehensive therapy, and those in the therapy group received additional intravenous administration with 40 ml L-ornithine-L-aspartate in 250 ml 10% glucose and saline (once daily, 7 days for a treatment course). RESULTS: L-ornithine-L-aspartase significantly decreased blood ammonia and improved hepatic function (P<0.05 or 0.01). The therapeutic effects of therapy group was better than that of the control group (P<0.05), and no significant side effect was observed in L-ornithine-L-aspartate treatment. CONCLUSION: L-ornithine-L-aspartate is effective for hepatic encephalopathy and has not obvious side effect.

[Alteration of Vitamin E levels in patients with pancreatic adenocarcinoma].

OBJECTIVE: To investigate the alterations of Vitamin E (Vit E) levels in patients with pancreatic adenocarcinoma and explore its mechanism of action. METHOD: A comparative analysis of the serum Vit E levels was conducted in patients with various pancreatic diseases. RESULTS: In patients with acute pancreatitis, chronic pancreatitis and pancreatic adenocarcinoma, serum Vit E levels were significantly lower than those in normal subjects (P<0.05), and among the 3 groups of patients with pancreatic diseases, patients with the malignancies had significantly lower Vit E levels than the other 2 groups of patients (P<0.001). CONCLUSION: Significant reduction in Vit E levels occurs in patients with pancreatic adenocarcinoma, indicating that oxidation and anti-oxidation imbalance might be involved in the pathogenesis of the malignancy in the pancreas.

A clinical study on the interventional treatment of acute pulmonary embolism / 介入放射学杂志

Objective To evaluate the effectiveness of interventional procedures in the treatment of acute pulmonary embolism(PE). Methods Pulmonary arterial thrombolytic therapy, suction and fragmentation of thromhi, anti-spasm, and balloon dilation were performed in eighteen cases with clinically highly suspected PE confirmed by emergent pulmonary artery angiography beforehand. Wedged pulmonary arterial pressure, pulmonary recanalization rate, the display ratio of distal pulmonary capillary net, blood gas analysis, blood oxygen saturation, and the improvement of clinical symptoms and signs were used for evaluation of the effectiveness. Seventeen of the alive cases with dislodgement of deep vein thrombi of the lower extremities were confirmed for the formation of PE and then thrombolytic treatment of the thrombotic deep vein was performed after the placement of inferior vena cava filter. Results Pulmanory artery angiographies showed embolism of the pulmonary arterial trunks or more than two of the branches. The post-treatment pulmonary patency reached 80%-90% in three cases, 90%-95% in eleven cases and 100% in five cases. The display ratio of distal pulmonary capillary net was over 90% in all the cases. Wedged pulmonary arterial pressure decreased to below 25 mmHg in thirteen cases, and to 25-30 mmHg in five cases. Blood oxygen saturation rate improved immediately to 90%-95% in ten cases and to 95%-100% in eight cases. Cough, hemoptysis, dyspnea, and chest pain were completely relieved in thirteen cases and significantly relieved in five cases. Digestive track bleeding was complicated in one case. Conclusions Pulmonary artery angiography is the golden standard for the diagnosis of pulmonary embolism. Interventional therapy is very effective for acute pulmonary embolism, which can significantly reduce the mortality rate.