The anesthesia management of totally thoracoscopic cardiac surgery: A single-center retrospective study.

Anesthesia management of Totally thoracoscopic cardiac surgery (TTCS) has been the subject of much debate and discussion. In this single center retrospective study, we summarize the experience of clinical anesthesia management for TTCS by review the medical records of our medical center and look forward to its future development. In this retrospective study, 103 patients (49 male and 54 female) were enrolled, the mean age was 56.7 ± 14.4 years old. The participants underwent Mitral Valve Replacement (MVR) + Tricuspid Valve Annuloplasty (TVA) (42, 40.8%), Mitral Valve Annuloplasty (MVA) + TVA (38, 36.9%), MVA (21, 20.4%), and MVR (2, 1.9%)，respectively. Intraoperative hypoxemia, radiographic pulmonary infiltrates, and pneumonia were observed in 19 (18.4%), 84 (81.6%), and 13 (12.6%) patients, respectively. The LOS of ICU and POD were as follows: MVR + TVA (55.1 ± 25h, 9.9 ± 3.5 d), MVA + TVA (56.5 ± 28.4h, 9.4 ± 4.2d), MVA (37.9 ± 21.9h, 8.1 ± 2.3d) and MVR (48 ± 4.2h, 7.5 ± 2.1d). No reintubation, reoperations, postoperative cognitive dysfunction, 30-day mortality were observed in the present study. The present study demonstrated that applying this anesthesia management for TTCS associated with acceptable morbidity, intensive care unit and postoperative hospital lengths of stay. The finding from the present study might provide some new approach for Anesthesia management of TTCS.

A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids.

The broad research use of organoids from high-grade serous ovarian cancer (HGSC) has been hampered by low culture success rates and limited availability of fresh tumor material. Here, we describe a method for generation and long-term expansion of HGSC organoids with efficacy markedly improved over previous reports (53% vs. 23%-38%). We established organoids from cryopreserved material, demonstrating the feasibility of using viably biobanked tissue for HGSC organoid derivation. Genomic, histologic, and single-cell transcriptomic analyses revealed that organoids recapitulated genetic and phenotypic features of original tumors. Organoid drug responses correlated with clinical treatment outcomes, although in a culture conditions-dependent manner and only in organoids maintained in human plasma-like medium (HPLM). Organoids from consenting patients are available to the research community through a public biobank and organoid genomic data are explorable through an interactive online tool. Taken together, this resource facilitates the application of HGSC organoids in basic and translational ovarian cancer research.

Effects of Endocrine Metabolic Factors on Hemocyte Parameters, Tumor Markers, and Blood Electrolytes in Patients with Hyperglycemia.

Objective: This study was designed to investigate the effect of endocrine metabolic factors on hemocyte parameters, tumor markers, and blood electrolytes in patients with hyperglycemia. Methods: In this study, 1791 patients with hyperglycemia were recruited and grouped according to different testing indexes, and their medical records and laboratory indexes were recorded and analyzed. Results: In adult patients with hyperglycemia, we found that high-density lipoprotein cholesterol (HDL-C) was negatively correlated with white blood cell (WBC) and could exert an effect on WBC; triglyceride (TG) level was positively associated with lymphocyte (LYM#); age, TG, and P affected the level of LYM#; and uric acid (UA) level was positively related to eosinophil (EO#). Besides, age was positively correlated with red blood cell distribution width-coefficient of variation (RDW-CV) level; fasting blood glucose (FBG) and serum phosphorus (P) were negatively correlated with RDW-CV level; and age, creatinine (Cre), FBG, HDL-C, and P were influencing factors of RDW-CV level in adult hyperglycemic patients. HDL-C was negatively correlated with fibrinogen (Fib) level, and age, HDL-C, serum kalium (K), serum sodium (Na), and body mass index (BMI) were the influencing factors of Fib levels. TG was positively associated with neuron-specific enolase (NSE) level and affected the NSE level. Serum magnesium (Mg) was negatively related to carcinoembryonic antigen (CEA) level, and sex, age, FBG, Mg, and BMI could have an effect on CEA level. As well, age and FBG were positively associated with carbohydrate antigen 50 (CA50) levels, UA was negatively correlated with CA50 levels, and age, aspartate aminotransferase (AST), UA, and FBG were the influencing factors of CA50 levels. FBG was negatively related to Mg levels; K, serum zinc (Zn), and fasting C-peptide (C-P) were positively correlated with Mg levels; and FBG, K, Zn, and C-P had an effect on Mg levels. Conclusion: Endocrine metabolic factors are closely related to hemocyte parameters, tumor markers, and blood electrolytes in patients with hyperglycemia.

Lycium barbarum glycopeptide targets PER2 to inhibit lipogenesis in glioblastoma by downregulating SREBP1c.

Lycium barbarum polysaccharide (LBP) is a substance with various biological activities extracted from Lycium barbarum. LbGPs are peptidoglycans with a short peptide backbone and a complex, branched glycan moiety, which is further extracted and isolated from LBPs. Previous studies have shown that LbGP can inhibit cancer cell growth, but its specific mechanism is not completely clear. In this study, we found that LbGP could inhibit the proliferation of glioma cells and promote the expression of period 2 (PER2) through the PKA-CREB pathway. In addition, LbGP could inhibit the de novo synthesis of lipids by downregulating SREBP1c and its target genes, which depended on the expression of PER2. Moreover, PER2 negatively regulated the expression of SREBP1c via suppressing PI3K/AKT/mTOR pathway. In summary, LbGP may upregulate the expression of PER2 to reduce the expression of SREBP1c, inhibit lipid synthesis in glioblastoma, and inhibit glioblastoma cell proliferation. This study provides an alternative drug for the treatment of glioma and elucidates its potential mechanism.

Analgesic Effects and Adverse Reactions of Lidocaine for Patient-Controlled Intravenous Analgesia on Patients Undergoing Open Hepatectomy: A Retrospective Analysis.

PURPOSE: The aim of this study was to investigate the effect of lidocaine for patient controlled intravenous analgesia (PCIA) in patients who underwent open hepatectomy. DESIGN: A retrospective analysis. METHODS: A total of 281 patients who underwent open hepatectomy from July 2018 to December 2018 were included. All patients were assigned into two groups: the lidocaine group (PCIA consisted of lidocaine, sufentanil, tramadol and granisetron) and the control group (PCIA consisted of sufentanil, tramadol and granisetron). The postoperative visual analogue scale (VAS) and complications (including respiratory depression, hypotension, nausea and vomiting, pruritus, numbness of the corners of the mouth, dizziness) between the groups were compared. FINDINGS: There were no significant differences between the characteristics, duration of surgery and anesthesia, and recovery of postoperative activity between the two groups. In the first 3 days after the operation, the postoperative VAS score of the lidocaine group was lower than that of the control group at resting state, while after activity, the postoperative VAS contrast results were completely opposite. In particularly, the resting state at 48 hours (h) (1.05 ± 1.25 vs 1.57 ± 1.54) after surgery and the activity state at 72 h (3.02 ± 1.51 vs 2.2 ± 1.66) after surgery (P < 0.05). The incidence of mouth numbness and dizziness were significantly increased in the lidocaine group (P < 0.05). CONCLUSION: The addition of lidocaine in PCIA was not beneficial to improve the pain during activities and increased the incidence of perioral numbness and dizziness.

Patients with gastroenteric tumor after upper abdominal surgery were more likely to require rescue analgesia than lower abdominal surgery.

OBJECTIVES: To find out the reasons why patients still need to use rescue analgesics frequently after gastrointestinal tumor surgery under the patient-controlled intravenous analgesia (IV-PCA), and the different abdominal surgery patients using the difference of analgesics. METHODS: A total of 970 patients underwent abdominal operation for gastrointestinal tumors were included. According whether patients used dezocine frequently for rescue analgesics within 2 days after surgery, they assigned into two groups: RAN group (Patients who did not frequently use rescue analgesia, 406 cases) and RAY group (Patients who frequently used rescue analgesia, 564 cases). The data collected included patient's characteristics, postoperative visual analogue scale (VAS), nausea and vomiting (PONV), and postoperative activity recovery time. RESULTS: No differences were observed in the baseline characteristics. Compared with the RAN group, patients in the RAY group had a higher proportion of open surgery, upper abdominal surgery, VAS score at rest on the first 2 days after surgery and PONV, and a slower recovery of most postoperative activities. Under the current use of IV-PCA background, the proportion of rescue analgesics used by patients undergoing laparotomy and upper abdominal surgery was as high as 64.33% and 72.8%, respectively. Regression analysis showed that open surgery (vs laparoscopic surgery: OR: 2.288, 95% CI: 1.650-3.172) and the location of the tumor in the upper abdomen (vs lower abdominal tumor: OR: 2.738, 95% CI: 2.034-3.686) were influential factors for frequent salvage administration. CONCLUSIONS: In our patient population, with our IV-PCA prescription for postoperative pain control, patient who underwent open upper abdominal surgery required more rescue postoperative analgesia.

Analgesic effects of sufentanil in combination with flurbiprofen axetil and dexmedetomidine after open gastrointestinal tumor surgery: a retrospective study.

BACKGROUND: To investigated the effects of sufentanil in combination with flurbiprofen axetil and dexmedetomidine for patient-controlled intravenous analgesia (PCIA) on patients after open gastrointestinal tumor surgery, and compared this combination with traditional PCIA with pure opioids or epidural analgesia (PCEA). METHODS: Patients (n = 640) who underwent open gastrointestinal tumor surgery and received patient-controlled analgesia (PCA) were included. According to the type of PCA, patients were assigned to three groups: MPCIA (PCIA with sufentanil, flurbiprofen axetil, dexmedetomidine and metoclopramide), OPCIA (PCIA with sufentanil, tramadol and metoclopramide) and PCEA group (PCEA with sufentanil and ropivacaine). The characteristics of patients, intraoperative use of analgesics, postoperative visual analogue scale (VAS), postoperative adverse reactions and postoperative recovery were collected. The primary outcome was postoperative VAS score. One-way ANOVA, Kruskal-Wallis H test, Fisher exact probability method, and binary logistic regression analysis were used for analysis. RESULTS: There were no significant differences in the characteristics of patients, operation time, tumor site and the use of postoperative rescue analgesics among the groups. In the first two days after open gastrointestinal tumor surgery, the VAS (expressed by median and interquartile range) of MPCIA (24th h, resting: 1,1; movement: 3,2. 48th h, resting: 0,1; movement: 2,1.) and PCEA (24th h, resting: 0,1; movement: 2,1. 48th h, resting: 0,1; movement: 2,2.) groups were significantly lower than those of OPCIA group (24th h, resting: 2.5,2; movement: 4,2. 48th h, resting: 1.5,1.75; movement: 3,1.) (all p <  0.01). The incidence of postoperative nausea and vomiting in MPCIA group was 13.6% on the first day after surgery, which was significantly higher than that in PCEA group. There was no significant difference in the incidence of other postoperative adverse events. Higher intraoperative sufentanil dosage (OR (95%CI) = 1.017 (1.002-1.031), p = 0.021), lower body mass index (OR (95%CI) = 2.081 (1.059-4.089), p = 0.033), and tumor location above duodenum (OR (95%CI) = 2.280 (1.445-3.596), p <  0.001) were associated with poor postoperative analgesia. CONCLUSIONS: The analgesic effects of PCIA with sufentanil in combination with flurbiprofen axetil and dexmedetomidine on postoperative analgesia was better than that of traditional pure opioids PCIA, and similar with that of PCEA.

[A mini-review on anti-tumor effect of cannabidiol].

Cannabidiol is the main non-psychoactive component of Cannabis sativa, which has multiple medicinal activities, such as antiepileptic, immunomodulation, analgesic, antioxidant, anticonvulsant, anti-anxiety and other functions. In recent years, it has been found that cannabidiol can inhibit the proliferation of various tumor cells, induce apoptosis and autophagy of tumor cells, arrest cell cycle, interrupt invasion and metastasis of tumor cells, regulate tumor microenvironment, exert synergistic therapy with other chemotherapeutic drugs, and reduce the toxicity of chemotherapeutic drugs. However, its anti-tumor effect remains controversial and its application is limited. The study of microspheres, nano liposomes and other new drug delivery systems can improve the anti-tumor effect of cannabidiol. In this study, the anti-tumor mechanism and application of cannabidiol were summarized and discussed in order to provide inspirations for its further investigation and application.

Irreversible Electroporation Treatment With Intraoperative Biliary Stenting for Unresectable Perihilar Cholangiocarcinoma: A Pilot Study.

BACKGROUND: Treating perihilar cholangiocarcinoma (PHCC) is particularly difficult due to the fact that it is usually in an advanced stage at the time of diagnosis. Irreversible electroporation treatment (IRE) involves the local administration of a high-voltage electric current to target lesions without causing damage to surrounding structures. This study investigated the safety and efficacy of using IRE in conjunction with intraoperative biliary stent placement in cases of unresectable PHCC. METHODS: This study enrolled 17 patients with unresectable Bismuth type III/IV PHCC who underwent IRE in conjunction with intraoperative biliary stent placement (laparotomic) in two medical centers in Asia between June 2015 and July 2018. Analysis focused on the perioperative clinical course, the efficacy of biliary decompression, and outcomes (survival). RESULTS: Mean total serum bilirubin levels (mg/dL) on postoperative day (POD) 7, POD30, and POD90 were significantly lower than before IRE (respectively 3.46 vs 4.54, p=0.007; 1.21 vs 4.54, p<0.001; 1.99 vs 4.54, p<0.001). Mean serum carbohydrate antigen 19-9 (CA19-9, U/ml) levels were significantly higher on POD3 than before the operation (518.8 vs 372.4, p=0.001) and significantly lower on POD30 and POD90 (respectively 113.7 vs 372.4, p<0.001; 63.9 vs 372.4, p<0.001). No cases of Clavien-Dindo grade III/IV adverse events or mortality occurred within 90 days post-op. The median progression-free survival was 21.5 months, and the median overall survival was 27.9 months. All individuals who survived for at least one year did so without the need to carry percutaneous biliary drainage (PTBD) tubes. CONCLUSIONS: It appears that IRE treatment in conjunction with intraoperative biliary stent placement is a safe and effective approach to treating unresectable PHCC. The decompression of biliary obstruction without the need for PTBD tubes is also expected to improve the quality of life of patients.

Monitored Anesthetic Care Combined with Scalp Nerve Block in Awake Craniotomy: An Effective Attempt at Enhanced Recovery After Neurosurgery.

BACKGROUND: Enhanced recovery after surgery has been attempted in neurosurgery at a greater rate. However, concern exists regarding the feasibility of using enhanced recovery after neurosurgery (ERANS). How to manage available resources to safely perform ERANS and improve clinical outcomes has been the subject of much debate and discussion. METHODS: Owing to the paucity of data available on the use of ERANS protocols, we performed the present feasibility study. We studied the outcomes of the protocols used within a tertiary referral neurosurgery center. Data from patients who had undergone awake craniotomy within an ERANS protocol were prospectively recorded in our institution from September 2017 to December 2018. We also evaluated the safety and effectiveness of the novel ERANS protocol. RESULTS: A total of 20 patients (mean age, 49.5 ± 17.8 years) were included in the present study. Intraoperative hypertension, hypotension, and bradycardia were present in 4 (20%), 1 (5%), and 1 (5%) patient, respectively. The postoperative morbidities included epilepsy in 1 (5%), pain in 3 (15%), and nausea or vomiting in 2 (10%). No significant changes had occurred in the mean arterial pressure, heart rate, blood glucose, or lactic acid level throughout the procedure. The median length of intensive care unit stay and postoperative hospital stay were 1 and 9.5 days, respectively. No 30-day readmissions or reoperations occurred during the present study. CONCLUSIONS: Applying an ERANS protocol was feasible, associated with a low incidence of complications, and acceptable intensive care unit and postoperative hospital lengths of stay. The findings from the present study might provide a new approach for the further research of ERANS.

Integrin α2ß1-targeting ferritin nanocarrier traverses the blood-brain barrier for effective glioma chemotherapy.

BACKGROUND: Ferritin, the natural iron storage protein complex, self-assembles into a uniform cage-like structure. Human H-ferritin (HFn) has been shown to transverse the blood-brain barrier (BBB) by binding to transferrin receptor 1 (TfR1), which is abundant in endothelial cells and overexpressed in tumors, and enters cells via endocytosis. Ferritin is easily genetically modified with various functional molecules, justifying that it possesses great potential for development into a nanocarrier drug delivery system. RESULTS: In this study, a unique integrin α2ß1-targeting H-ferritin (2D-HFn)-based drug delivery system was developed that highlights the feasibility of receptor-mediated transcytosis (RMT) for glioma tumor treatment. The integrin targeting α2ß1 specificity was validated by biolayer interferometry in real time monitoring and followed by cell binding, chemo-drug encapsulation stability studies. Compared with naïve HFn, 2D-HFn dramatically elevated not only doxorubicin (DOX) drug loading capacity (up to 458 drug molecules/protein cage) but also tumor targeting capability after crossing BBB in an in vitro transcytosis assay (twofold) and an in vivo orthotopic glioma model. Most importantly, DOX-loaded 2D-HFn significantly suppressed subcutaneous and orthotopic U-87MG tumor progression; in particular, orthotopic glioma mice survived for more than 80 days. CONCLUSIONS: We believe that this versatile nanoparticle has established a proof-of-concept platform to enable more accurate brain tumor targeting and precision treatment arrangements. Additionally, this unique RMT based ferritin drug delivery technique would accelerate the clinical development of an innovative drug delivery strategy for central nervous system diseases with limited side effects in translational medicine.

The Effects of Body Mass Index on the Use of Patient-Controlled Intravenous Analgesia After Open Gastrointestinal Tumor Surgery: A Retrospective Analysis.

PURPOSE: To investigate the impact of body mass index (BMI) on the analgesic effects and adverse reactions of patient-controlled intravenous analgesia (PCIA). METHODS: From 2017 to 2018, 390 patients undergoing open gastrointestinal surgery were reviewed at West China Hospital, Sichuan University. All used PCIA of sufentanil combined with dexmedetomidine and flurbiprofen axetil. According to their BMIs, they were placed into six groups: group A (BMI < 18.5kg/m2, 29), group B (18.5kg/m2 ≤ BMI< 22kg/m2, 124), group C (22kg/m2 ≤ BMI < 24kg/m2, 99), group D (24kg/m2 ≤ BMI < 26kg/m2, 69), group E (26kg/m2 ≤ BMI < 28kg/m2, 46) and group F (BMI ≥28kg/m2, 23). Main data of the perioperative use of analgesics, postoperative visual analogue score (VAS), and adverse reactions were collected. RESULTS: Twenty-four hours (h) after surgery, patients in group A had a higher resting VAS than the other groups, especially B (pA-B = 0.011). VAS of patients during activity in group B was lower than those in group C 48 h after surgery (p = 0.013). Compared with groups B to F, group A had a significantly lower incidence of hypertension (p = 0.012) and a significantly higher incidence of vomiting 24 h after surgery (p = 0.009). Binary logistic analysis found that higher age was a risk factor for vomiting 24 h after surgery (OR 1.158, p = 0.045). CONCLUSION: Using the same PCIA, patients with BMIs of less than 18.5 kg/m2 had worse analgesia on the first day after surgery and were more likely to vomit. Postoperative analgesia and related experiences in patients with BMIs of less than 18.5 kg/m2 need to be improved.

pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer.

PURPOSE: In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(ß-amino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model. METHODS: The as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core. RESULTS: The pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37°C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%±1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor. CONCLUSION: The pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.

Mechanics and Biology Interact in Intervertebral Disc Degeneration: A Novel Composite Mouse Model.

The aim of this study was to distinguish the characteristics of intervertebral disc degeneration (IVDD) originating from mechanics imbalance, biology disruption, and their communion, and to develop a composite IVDD model by ovariectomy combined with lumbar facetectomy for mimicking elderly IVDD with osteoporosis and lumbar spinal instability. Mice were randomly divided into four groups and subjected to sham surgery (CON), ovariectomy (OVX), facetectomy (mechanical instability, INS) or their combination (COM), respectively. Radiographical (n = 4) and histological changes (n = 8) of L4/5 spinal segments were analyzed. Tartrate-resistant acid phosphatase (TRAP) staining was conducted to detect osteoclasts, and expression of osterix (OSX), type I collagen (Col I), type II collagen (Col II) and vascular endothelial growth factor (VEGF) were evaluated by immunochemistry. OVX affected the body's metabolism but INS did not, as the body weight increased and uterus weight decreased in OVX and COM mice compared to CON and INS mice. OVX, INS, and COM caused IVDD in various degrees at 12 weeks after surgery. However, the major pathogeneses of OVX- and INS-induced IVDD were different, which focused on endplate (EP) remodeling and annulus fibrosus (AF) collapse, respectively. OVX induced osteopenia of vertebra. In contrast, INS promoted the stress-adaptive increase of subchondral bone trabeculae. The COM produced a reproducible severe IVDD model with characteristics of sparse vertebral trabeculae, cartilaginous EP ossification, subchondral bone sclerosis, fibrous matrix disorder, angiogenesis, disc stiffness, as well as space fusion. Additionally, all groups had elevated bone and cartilage turnover compared with CON group, as the quantity of trap + osteoclasts and the osteogenic OSX expression increased in these groups. Likewise, the VEGF expression levels were similar, accompanied by the altered matrix expression of disc, including the changed distribution and contents of Col II and Col I. The findings suggested that the composite mouse model to some extent could effectively mimic the interactions of biology and mechanics engaged in the onset and natural course of IVDD, which would be more compatible with the IVDD of elderly with vertebral osteoporosis and spinal instability and benefit to further clarify the complicated mechanobiological environment of elderly IVDD progression.

[Preparation of docetaxel-loaded nanomicelles and their anti-Lewis lung cancer effect in vitro].

Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-ß-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.

Expression patterns of members of the ethylene signaling-related gene families in response to dehydration stresses in cassava.

Drought is the one of the most important environment stresses that restricts crop yield worldwide. Cassava (Manihot esculenta Crantz) is an important food and energy crop that has many desirable traits such as drought, heat and low nutrients tolerance. However, the mechanisms underlying drought tolerance in cassava are unclear. Ethylene signaling pathway, from the upstream receptors to the downstream transcription factors, plays important roles in environmental stress responses during plant growth and development. In this study, we used bioinformatics approaches to identify and characterize candidate Manihot esculenta ethylene receptor genes and transcription factor genes. Using computational methods, we localized these genes on cassava chromosomes, constructed phylogenetic trees and identified stress-responsive cis-elements within their 5' upstream regions. Additionally, we measured the trehalose and proline contents in cassava fresh leaves after drought, osmotic, and salt stress treatments, and then it was found that the regulation patterns of contents of proline and trehalose in response to various dehydration stresses were differential, or even the opposite, which shows that plant may take different coping strategies to deal with different stresses, when stresses come. Furthermore, expression profiles of these genes in different organs and tissues under non-stress and abiotic stress were investigated through quantitative real-time PCR (qRT-PCR) analyses in cassava. Expression profiles exhibited clear differences among different tissues under non-stress and various dehydration stress conditions. We found that the leaf and tuberous root tissues had the greatest and least responses, respectively, to drought stress through the ethylene signaling pathway in cassava. Moreover, tuber and root tissues had the greatest and least reponses to osmotic and salt stresses through ethylene signaling in cassava, respectively. These results show that these plant tissues had differential expression levels of genes involved in ethylene signaling in response to the stresses tested. Moreover, after several gene duplication events, the spatiotemporally differential expression pattern of homologous genes in response to abiotic and biotic stresses may imply their functional diversity as a mechanism for adapting to the environment. Our data provide a framework for further research on the molecular mechanisms of cassava resistance to drought stress and provide a foundation for breeding drought-resistant new cultivars.

[Chemical constituents from Barringtonia racemosa].

To investigate the chemical constituents from Barringtonia racemosa, twelve compounds were isolated by chromatography methods and identified as 3ß-p-E-coumaroymaslinic acid (1), cis-careaborin (2), careaborin (3), maslinic acid (4), 2α, 3ß, 19α-trihydroxyolean-12-ene-24, 28-dioic acid (5), 3ß-p-Z-coumaroylcorosolic acid (6), corosolic acid (7), 1α, 2α, 3ß, 19α-tetrahydroxyurs-12-en-28-oic acid (8), 19α-hydroxyl ursolic acid (9), 3α, 19α-dihydroxyurs-12-en-24, 28-dioic acid (10), tormentic acid (11), 3-hydroxy-7, 22-dien-ergosterol（12） by the NMR and MS data analysis. Among them, compounds 1-4,7-12 were obtained from the genus Barringtonia for the first time. All the compounds didn't show nocytotoxic activity against MCF-7 and A549 cell lines (IC50>50 mg•L⁻¹).

Gout and subsequent increased risk of cardiovascular mortality in non-diabetics aged 50 and above: a population-based cohort study in Taiwan.

BACKGROUND: Limited data are available on the risk ratios for fatal cardiovascular disease (CVD) outcome from gout and chronic kidney disease (CKD) in non-diabetic individuals. METHODS: Nationwide population-based retrospective prospective study with a 5-year follow-up to investigate the association between physician-diagnosed gout and CKD in non-diabetics aged 50 and above who had no pre-existing serious CVD and the subsequent risk of death from CVD. Hazard ratios (HR) of CVD mortality were adjusted for gender, age, smoking- and alcoholism-related diagnoses, hypertension, hyperlipidemia, atrial fibrillation and Charlson's comorbidity index score. RESULTS: A case cohort (n=164,463) having gout and a control cohort (n=3,694,377) having no gout were formed. The prevalence of gout in this study was 4.26% whereas that of gout plus CKD was 8.17%. Male to female ratio among the individuals with gout was 3.2:1. The relative risk (RR) of subsequent cardiovascular mortality between the case and control cohort was 1.71 (95% confidence interval (CI), 1.66-1.75). The presence of CKD in nondiabetic subjects with no gout (control group) has a RR of CVD mortality at 3.05 (95% CI, 2.94-3.15). The presence of gout has protective effect on subjects with CKD with a RR of 1.84 (95% CI, 1.71-1.98). As compared with individuals with no gout, the adjusted HR (aHR) for CVD mortality among the individuals with gout was 1.10 (95% CI 1.07-1.13). In a Cox model, when compared with subjects having neither gout nor CKD, the aHR in subjects with no gout but with CKD is 1.76 (95% CI, 1.70-1.82); in subjects with gout but without CKD, 1.10 (1.07-1.13); interestingly, the aHR is attenuated in subjects with concomitant gout plus CKD which is 1.38 (1.29-1.48). CONCLUSIONS: Among non-diabetic individuals aged 50 years or above who had no preceding serious CVD, those with gout were 1.1 times more likely to die from CVD as were individuals without gout. The presence of gout appears to attenuate the risk of subsequent CV mortality in subjects with CKD. Further studies should focus on finding an explanation for the protective effect of gout on CV mortality in patients with CKD.

Coumarin derivatives from Gerbera saxatilis.

Phytochemical investigation of Gerbera saxatilis (Astraceae) afforded three new coumarin derivatives 1- 3 and a known coumarin 4. Compounds 1 and 2 represent the first examples of the natural occurrence of the novel polycyclic pyrano[3-2c]coumarin carbon skeleton. The structures of compounds 1- 4 were characterized based on extensive spectroscopic analyses as well as comparison to the spectroscopic data reported. The structures of compounds 1 and 3 were further confirmed by X-ray data analyses. The cytotoxic activity of compounds 1- 4 was evaluated against selected cancer cell lines, including human leukemia cell (HL-60), human hepatoma cell (SMMC-7721), and human cervical carcinoma cell (HeLa) lines.