The role and application of vesicles in triple-negative breast cancer: Opportunities and challenges.

Extracellular vesicles (EVs) carry DNA, RNA, protein, and other substances involved in intercellular crosstalk and can be used for the targeted delivery of drugs. Triple-negative breast cancer (TNBC) is rich in recurrent and metastatic disease and lacks therapeutic targets. Studies have proved the role of EVs in the different stages of the genesis and development of TNBC. Cancer cells actively secrete various biomolecules, which play a significant part establishing the tumor microenvironment via EVs. In this article, we describe the roles of EVs in the tumor immune microenvironment, metabolic microenvironment, and vascular remodeling, and summarize the application of EVs for objective delivery of chemotherapeutic drugs, immune antigens, and cancer vaccine adjuvants. EVs-based therapy may represent the next-generation tool for targeted drug delivery for the cure of a variety of diseases lacking effective drug treatment.

Breaking the mold: Overcoming resistance to immune checkpoint inhibitors.

Immune checkpoint blockade-based therapies are effective against a sorts of cancers. However, drug resistance is a problem that cannot be ignored. This review intends to elucidate the mechanisms underlying drug tolerance induced by PD-1/PD-L1 inhibitors, as well as to outline proposed mechanism-based combination therapies and small molecule drugs that target intrinsic immunity and immune checkpoints. According to the differences of patients and types of cancer, the optimization of individualized combination therapy will help to enhance PD-1/PD-L1-mediated immunoregulation, reduce chemotherapy resistance, and provide new ideas for chemotherapy-resistant cancer.

Mechanisms of drug resistance in breast cancer liver metastases: Dilemmas and opportunities.

Breast cancer is the leading cause of cancer-related deaths in females worldwide, and the liver is one of the most common sites of distant metastases in breast cancer patients. Patients with breast cancer liver metastases face limited treatment options, and drug resistance is highly prevalent, leading to a poor prognosis and a short survival. Liver metastases respond extremely poorly to immunotherapy and have shown resistance to treatments such as chemotherapy and targeted therapies. Therefore, to develop and to optimize treatment strategies as well as to explore potential therapeutic approaches, it is crucial to understand the mechanisms of drug resistance in breast cancer liver metastases patients. In this review, we summarize recent advances in the research of drug resistance mechanisms in breast cancer liver metastases and discuss their therapeutic potential for improving patient prognoses and outcomes.

Synthesis and crystal structure of catena-poly[[hexa-aqua{µ3-2-[bis-(carboxyl-atometh-yl)amino]-terephthalato}dicobalt(II)] penta-hydrate] containing water tapes and penta-mers.

The title coordination polymer, {[Co2(C12H7NO8)(H2O)6]·5H2O} n , was crystallized at room temperature from an aqueous solution of 2-aminodi-acetic terephthalic acid (H4adtp) and cobalt(II) nitrate. The asymmetric unit consists of one adtp4- ligand, one and two half CoII ions, six water ligands coordinated to CoII ions and five uncoordinated water mol-ecules. Two of the cobalt cations lie on centres of inversion and are coordinated in octa-hedral O2(OH2)4 environments, whereas the other adopts a slightly distorted octa-hedral NO3(OH2)2 environment. The crystal structure contains parallel stacked, one-dimensional zigzag chains, {[Co2(C12H7NO8)(H2O)6]} n , which assemble into a three-dimensional supra-molecular architecture via networks of hydrogen bonds involving the coordinated and free water mol-ecules. One-dimensional 'water tapes' are formed, containing alternating six-membered and twelve-membered rings of water mol-ecules, together with water penta-mers, in which a central uncoordinated water mol-ecule is hydrogen bonded to two coordinated and two free water mol-ecules in a tetra-hedral arrangement.

Alterations of Prefrontal-Posterior Information Processing Patterns in Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is a heterogeneous disorder characterized by different levels of repetitive and stereotypic behavior as well as deficits in social interaction and communication. In this current study, we explored the changes in cerebral neural activities in ASD. The purpose of this study is to investigate whether there exists a dysfunction of interactive information processing between the prefrontal cortex and posterior brain regions in ASD. We investigated the atypical connectivity and information flow between the prefrontal cortex and posterior brain regions in ASD utilizing the entropy connectivity (a kind of directional connectivity) method. Eighty-nine patients with ASD and 94 typical developing (TD) teenagers participated in this study. Two-sample t-tests revealed weakened interactive entropy connectivity between the prefrontal cortex and posterior brain regions. This result indicates that there exists interactive prefrontal-posterior underconnectivity in ASD, and this disorder might lead to less prior knowledge being used and updated. Our proposals highlighted that aforementioned atypical change might accelerate the deoptimization of brain networks in ASD.

Effect of SecinH3 on lung injury induced by sepsis of rats.

OBJECTIVE: To study effect of SecinH3 on lung injury induced by the sepsis of rats. METHODS: A total of 30 SPF Wistar rats were randomly divided into two groups, including 5 rats in the control group and 25 in the model group. The intraperitoneal injection of endotoxin-lipopolysaccharide (LPS) was performed to build the animal model of sepsis. The blood gas analysis was carried out. Afterwards, change in the expression of pro-inflammatory factors of IL-1, IL-6 and TNF-α in the serum were detected. To study the mechanism of SecinH3 in the process of lung injury induced by the sepsis, the rats with the successful modeling of sepsis were randomly divided into two groups. Rats in the SecinH3 group were given the intraperitoneal injection of 100 µg/12 h SecinH3 for 24 h; while rats in the control group were given the injection of same solvent by the same dosage. The blood was drawn from the heart by 500 µL for the blood gas analysis to detect the change in the expression of pro-inflammatory factors of IL-1, IL-6 and TNF-α in the treatment group and control group. After separating the lung tissue, the Real-time PCR and western blotting were performed to analyze the effect of SecinH3 on the expression of cytohesins and also discuss the change of epidermal growth factor receptor (EGFR) and p-EGFR related to the signaling pathway of EGFR-p38 mitogen-activated protein kinase that is regulated by cytohesins. RESULTS: Three rats died within 4 h after the injection of LPS, while other 22 ones had the successful modeling, with the success rate of 88%. After being stimulated by LPS, compared with the control group, the arterial partial pressure of oxygen of rats in the treatment group was significantly reduced (P < 0.05), while the partial pressure of CO2 was significantly increased (P < 0.01). After being treated by SecinH3, Pa/O2 was increased with the sepsis, while Pa/CO2 was decreased with the action of SecinH3, which indicated that SecinH3 had the certain 'repairing' ability for the lung injury. SecinH3 might inhibit the cytohesins and then inhibit the phosphorylation of EGFR. CONCLUSIONS: SecinH3 can significantly inhibit the cytohesins and then relieve the lung injury induced by the sepsis of rats.

Acute hypervolemic hemodilution effect on oxygen metabolism and blood pharmacokinetics in patients undergoing acute laparotomy during induction of general anesthesia.

BACKGROUND/AIMS: To investigate acute hypervolemic hemodilution effect on oxygen metabolism and blood pharmacokinetics in patients undergoing acute laparotomy during Induction of general anesthesia. METHODOLOGY: Forty ASA I-II patients undergoing acute laparotomy were randomly divided into 2 groups (n=20 each): Patients of group A received Voluven 7 ml/kg in 20 mins before induction and 8 ml/kg after induction. Patients of group B received 6 ml/kg/h Plasmalyte A. Hemodynamic parameters MAP, HR and CVP were collected at 6 set points during the surgery: T1: before AHH; T2: before anesthesia induction; T3: right intubation; T4: 10 min after intubation; T5: 20 min after intubation; T6: skin incision. Arterial and venous blood samples were taken for blood gas analysis and determination of lactic acid, Hb and Hct: T1: before AHH, T2: right after AHH, T3: 0.5 h after AHH, T4: l h after AHH. Arterial Oxygen Content (Ca02), Central Venous Oxygen Content (Ccv02) and Oxygen Extraction Ratio (ER02) were calculated. RESULTS: The hemodynamic parameters were maintained within normal limits during operation in group A (P <0.05). CaO2, CcvO2, ERO2 and Lac between the two groups were no significant difference (P> 0.05). Compared with T1, CaO2/CcvO2 atT 2~4 reduced in both groups (P <0.05). Compared with group A, Hb and Hct in group B increased at T2~4 (P <0.05). CONCLUSIONS: Acute hypervolemic hemodilution in patients undergoing acute laparotomy during Induction of general anesthesia have some preventive hypotension effect, more conducive to the smooth blood pharmacokinetics; Voluven induced expansion of applications is safe and effective, and has no effect on the body's metabolic rate of oxygen.

[Optimal culture conditions of transgenic Polygonium multiflorum hairy root and the effect of elicitor on its growth].

OBJECTIVE: To optimize the culture medium of transgenic Polygonium multiflorum hairy root and the effect of different elicitors on its growth. METHODS: Measured the growth curve of hairy root in four media, including MS, 1/2 MS, B5 and White and estimated the effects of elicitors on the hairy root biomass. RESULTS: MS medium was the most suitable of the four media for hairy root growth. The different concentrations of elicitors, salicylic acid and methyl jasmonate, inhibited the biomass accumulation of hairy root. CONCLUSION: MS is the optimum medium for transgenic Polygonium multiflorum hairy root. Two usual plant elicitors, salicylic acid and methyl jasmonate, can inhibit the growth of transgenic hairy root.

A bioluminescence assay for DNA methyltransferase activity based on methylation-resistant cleavage.

DNA methyltransferase (MTase) is a kind of important regulatory factor in various biological processes. Current methods to investigate DNA MTase activity are still limited in the sensitivity and/or generality. Therefore, developing methods with high sensitivity and improved generality is needed. Here, we develop a new bioluminescence strategy based on methylation-resistant cleavage and protein expression in vitro to detect DNA MTase activity. In the strategy, Dam MTase was used as a model enzyme and MboI as the methylation-resistant endonuclease, and luciferase reporter DNA (LR-DNA) was used as their action target. Because the completely methylated LR-DNA could be expressed as detectable luciferase, Dam MTase activity was quantified by measuring the luminescence intensity of the expressed luciferase. The assay provides a very low detection limit (0.08 U/ml) as well as a wide linear range (0.2-100 U/ml). Besides, the analysis mode has improved generality and could be extended to the detection of other DNA MTases and the corresponding inhibitor screening.

Effect of selective inflow occlusion on hemodynamic conditions during laparoscopic left hemihepatectomy effect of selective inflow occlusion on hemodynamic conditions during laparoscopic left hemihepatectomy.

BACKGROUND/AIMS: Selective inflow occlusion instead of portal triad clamping was used during laparoscopic left hemihepatectomy in our institution. This study observed its hemodynamic effects during operation. METHODOLOGY: Hemodynamic parameters including heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were collected at 6 time points: after induction, after insufflation with CO2, after patient in reverse Trendelenburg position, after left branch of hepatic artery was occluded, after left branch of portal vein was occluded and after desufflation with patient supine. RESULTS: No severe perioperative cardiopulmonary complications were observed. Occlusion of left branch of hepatic artery brought no significant hemodynamic change. Occlusion of left branch of portal vein increased CVP and CI and decreased SVR. CO2 inflation caused HR, MAP and SVR to increase. The change to reverse Trendelenburg position caused CVP and PAP to decrease. When placed in the supine position with deflation, MAP, CVP, PAP, PCWP and CI went to a higher than base level. HR and SVR returned to base level. CONCLUSIONS: Using selective inflow occlusion in laparoscopic left hemihepatectomy caused few hemodynamic changes before and after occlusion in patients without cardiopulmonary diseases. However, the change of position and inflation or deflation caused significant changes.

[Biotransformation of 4-methyl-7-allyloxy coumarin by transgenic hairy roots of Polygonum multiflorum].

OBJECTIVE: To synthesis 4-methyl-7-allyloxy coumarin by Williamson etherification from 4-methyl-7-hydroxy coumarin and apply as a substrate in hairy roots of Polygonum multiflorum. METHODS: The synthesis reaction of 4-methyl-7-allyloxy coumarin used the allyl bromide and potassium carbonate as catalysts, and acetone as solvent reacted for 17 hours, then the product was isolated. 4-methyl-7-allyloxy coumarin was added into the media of supension transgenic hairy roots of Polygonum multiflorum which had been precultured for 8 d, and then co-cultured for another 7 d. The biotransformation products were detected by TLC and HPLC and isolated by various chromatographic methods. RESULTS: Two biotransformation products, 4-methyl-7-hydroxy coumarin and 4-methyl-coumarin-7-O-beta-D-glucoside were isolated and identified. CONCLUSION: Hairy roots of Polygonum multiflorum contains not only glycosyltransferase but also hydrolysis enzymes.

Ventricular fibrillation caused by electrocoagulation in monopolar mode during laparoscopic subphrenic mass resection.

BACKGROUND: Monopolar is usually a safe and effective electrosurgical unit used in laparoscopic general surgery. However, it can cause adverse outcomes and even cardiac arrest. We present a video of laparoscopic subphrenic mass resection using monopolar coagulation during which ventricular fibrillation occurred and from which the patient was successfully resuscitated. METHODS: Our patient was a 39-year-old man who was admitted to our institution for treatment of a liver mass. The mass was located in the left subphrenic region and was 3.31 cm × 2.7 cm according to B ultrasound. He had had a spleen resection after a car accident 14 years before. He was otherwise healthy and a physical examination was negative. He was scheduled for "laparoscopic exploration, mass resection." General anesthesia was induced and the operation began. While dissecting the mass from the diaphragm there was some bleeding; monopolar electrocoagulation with 68 W was performed upon which ventricular fibrillation occurred. The operation was stopped and closed-chest compression began immediately. Defibrillation (200-J shock) was performed in 1 min and rhythm returned to sinus. RESULTS: The operation was resumed carefully and uneventfully. The patient was sent to the postoperative acute care unit and was extubated 10 min after operation. The patient recovered uneventfully without any signs of permanent cardiac injury and was discharged on postoperative day 3. The final pathology was accessory spleen. CONCLUSIONS: We present a video of a patient who experienced ventricular fibrillation during laparoscopic surgery which was successfully defibrillated leaving no permanent cardiac injury. We assume the reason for the ventricular fibrillation was the low-frequency leakage current from electrocoagulation which may be conducted by Swan-Ganz catheter to the heart. It is important that we be familiar with the character of electrosurgical unit when performing laparoscopic surgery. We should be careful when using an electrosurgical unit near the cardiac region, especially when the patient has an indwelling catheter. We recommend performing hemostasis in bipolar mode or use an ultrasonic scalpel if bleeding is close to the heart. Also, an easily available defibrillator should be ready for use.

[The purification and characterization of polysaccharides isolated from Ginkgo biloba and their in vitro antioxidant activities].

OBJECTIVE: To isolate and identify the polysaccharides of Ginkgo biloba and determine their antioxidant activities in vitro. METHODS: Used hot extraction and alcohol precipitation to get the crude polysaccharides, removed protein with Sevag method, further purify by column chromatography packed with DEAE-52 and DEAE-Sepharose Fast Flow. The homogeneity and molecular weights were evaluated, configuration and monosaccharide composition were measured by IR and high performance ion chromatography analysis, the scavenging activities of GBPB-S on hydroxyl radical and DPPH were measured. RESULTS: The molecular weights of GBPB-W and GBPB-S were 26 300 and 19 100, and both of them were composed of rhamnose, arabinose, galactose, glucose and mannose with the ratios of (3.48: 8.47:3.73: 1.76: 1) and (5.34: 5.37: 5.27: 1:1.68). GBPB-S had certain scavenging effect on hydroxyl radical and DPPH. CONCLUSION: The polysaccharide isolated from Ginkgo biloba has a direct antioxidant activities in vitro.

[Clinical observation on acupoint injection therapy for chronic gastritis of gastric blood stasis type].

OBJECTIVE: To objectively evaluate the clinical effect of acupoint injection therapy for chronic gastritis of gastric blood stasis type. METHODS: One hundred and two cases arranged by registration order were randomly divided into an acupoint injection group and a medicine group, 51 cases in each group. The acupoint injection group was treated with acupoint injection of compound Danshen injection, and Zusanli (ST 36) and Weishu (BL 21) were selected, and the medicine group with oral administration of Omeprazole. After 2 weeks of treatment, the clinical effect and improvement of endoscopic gastric mucosal lesions were observed. RESULTS: The clinical total effective rate of 96.1% (49/51) in the acupoint injection group was better than 76.5% (39/51) in the medicine group (P < 0.01). The symptom score decreased significantly after treatment and the gastric mucosal lesion was significantly improved in both of the two groups (all P < 0.05), and the acupoint injection group was superior to the medicine group (all P < 0.05). CONCLUSION: Acupoint injection has outstanding effect for treatment of chronic gastritis of gastric blood stasis type and this therapy is worth generalizing and applying.

Factor analysis-based relationship analysis between geographical factors and value of FEV1. 0% in aged Chinese males / 第二军医大学学报

Objective: To provide a scientific basis for establishing a standard reference value of FEV1. 0% for aged Chinese males. Methods: The reference values of FEV1. 0% of 4 342 healthy aged Chinese males were collected from hospitals, research units, and higher institutions of 72 counties or cities. Correlation analysis, factor analysis and GIS software were used to investigate the relationship between the reference values of FEV1. 0% with six geographical factors. Results: It was found that the reference values of FEV1. 0% in aged Chinese males were significantly associated with geographical factors. Factor analysis and regression analysis yielded a regression equation as: y = 79.279 8 + 0.000 901 5X1 -0. 001 931 4X2 + 0. 001 966 8X 3 - 0.002 615X4+0.001 293 4X5+0.001 650 3X 6 ±1.032 8. The fitting degree between the predicted and the measured values was high. With the aid of geostatistical analysis module of GIS spatial analysis and Kriging interpolation method, we interpolated the geographical distribution map of the reference value of FEV1. 0% in aged Chinese males. Conclusion: The regression equation can be used to accurately calculate the reference value of FEV1. 0% for aged Chinese males, if the geographical values for an area are available. The reference value of FEV1. 0% can also be obtained by the geography Trend-surface distribution map of an area.

[Expression of MMP-2 and its clinical significance in cervical squamous carcinoma].

OBJECTIVE: To investigate the relationship of the expression of matrix metalloproteinase-2 (MMP-2) with tumorigenesis, development and metastasis of cervical squamous carcinoma. METHODS: The expression and distribution of MMP-2 protein were detected by using immunohistochemical SP method. The active protein and mRNA of MMP-2 were determined by using gelatin Zymography and RT-PCR, respectively. The relationships between those indexes and the factors related to clinical pathology of cervical carcinoma were analyzed statistically. RESULTS: Immunohistochemical studies demonstrated that MMP-2 was expressed in 81.13% of squamous cell carcinomas (SCC), but was less frequently expressed in high-grade squamous intraepithelial lesions (HSIL, 47.62%, 10/21) and low-grade squamous intraepithelial lesions (LSIL, 10.00%, 1/10, P<0.01). In SCC, MMP-2 protein was expressed in 91.30%(21/23) of patients, which positively correlated with lymph node metastasis significantly (P<0.05). And the expression of MMP-2 was not significantly related to the pathological grade, or stage status. By direct analysis of enzyme activities we found that the gelatinolytic activity of MMP-2 was significantly higher in SCC [(5.81 +/- 2.17)x10(4)] than in HSIL [(2.28 +/- 0.83) x10(4), P<0.01] and LSIL [(1.94 +/- 0.71)x10(4), P<0.01]. Expression of MMP-2 mRNA was significantly higher in carcinoma(0.87 +/- 0.44) than in HSIL(0.46 +/- 0.22, P<0.01) and in LSIL(0.37 +/- 0.20, P<0.01). CONCLUSION: The positive expression of MMP-2 can be used to estimate the metastatic potentiality and help the adjuvant treatment. MMP-2 is related well with the occurrence, invasion and metastasis of cervical squamous carcinoma.

Fingerprint analysis of anti-tumor active polypeptides from Arca subcrenata by HPLC.

RP-HPLC was applied to analyze active polypeptides in Arca subcrenata, and the optimal condition for separation was also set up: temperature: 30 degrees C; wavelength: 280 nm; flow rate: 1.0 ml/min; Solvent A consisted of 80% acetonitrile and 0.1% trifluoroacetic acid (TFA) and solvent B contained 0.1% TFA. In this condition, ten samples' fingerprints were gained, in one of which the genuine fraction exhibited fourteen "common peaks" representing the characteristics of the constituents.

[Biotransformation of furannoligularenone by hairy root cultures of Polygonum multiflorum].

OBJECTIVE: To investigate the biotransformation of furannoligularenone by hairy roots of Polygonum multiflorum. METHODS: Furannoligularenone was added to the medium of hairy roots of P. multiflorum after precultured for 9 days, then they were co-cultured. The products were isolated and identified on the basis of their physical chemical properties and spectroscopic data. The T-C curve of biotransformation was investigated with HPLC. RESULTS: The hairy roots of P. multiflorum transformed the substrate to two products, 3-oxo-eremophila-1,7(11)-dien-12,8-olide(II) and 3-oxo-8-hydroxy-eremophila-1,7(11)-dien-12,8-olide(III). After co-cultured for 3 days, the mole conversion ratio of the substrate reached the highest (27.2%). CONCLUSION: It's possible to biotransform furannoligularenone by hairy roots of P. multiflorum.

[Therapeutic effects of acupoint drug-finger pressing on gastroesophageal reflux].

OBJECTIVE: To observe the clinical effects and possible mechanism of acupoint drug-finger pressing (ADFP) on gastroesophageal reflux (GER). METHODS: Eighty patients were randomly assigned to the treatment group and the control group, 40 in each group. The treatment group was treated by ADFP on Ganshu (BL18), Danshu (BL19), Weishu (BL21) and Pishu (BL20) acupoint of bilateral Foot-taiyang Bladder Meridians with pressing and kneading maneuver for 15 min each time, twice per day, while the control group was treated with acid-inhibitory and gastrokinetic drugs as omeprazole enteric-coated tablets (20 mg, once administration at a 12-h interval) and cisapride tablets (10 mg, thrice daily, taken 15 min before meals). The treatment course for both was 3 weeks. RESULTS: The symptom score and esophageal pressure obviously decreased (P < 0.05), esophageal pressure was relieved remarkably (P < 0.05) in both groups after treatment with insignificant difference between the groups (P > 0.05). The ratio of 24-h esophageal reflux times and total reflux time, the times of reflux lasting for more than 5 min and the maximum reflux time were all lowered obviously in all patients after treatment, and the improvements was significantly different between the two groups (P < 0.05). Upper gastrointestinal endoscopy suggested obvious amelioration in esophagitis. The total effective rate was 97.5% in the treatment group, significantly higher than that in the control group (80.0%) (P < 0.05). And no obvious adverse reaction was found. CONCLUSION: Therapy of ADFP provides a new approach for GER treatment with TCM characteristics, prominent effects and less adverse reaction, and is easily be accepted by patients, so, it is worthy to be generalized.

[Studies on biotransformation of arbutin by 4-hydroxy phenol in hairy root of Polygonum multiflorum].

OBJECTIVE: To study the biotransformation of arbutin by 4-hydroxy phenol in hairy root of Polygonum multiflorum. METHOD: 4-hydroxy phenol was used as substrate, the standard curve was made by HPLC, and the influences of the co-culture time, the concentration of substrate added and the volume of culture flasks on biotransformation of arbutin were measured by the index of the production yield and transform rate of arbutin. RESULT: Arbutin could be detected from both of the cultures and medium. The correlation curve of arbutin: Y = 440740X - 1.473 (r = 0.9997). The production yield (2.22 g x L(-1)) and conversion ratio (81.45%) of arbutin reached the maximum amount as co-culture time at 72 h, substrate added in medium for 1100 mg x L(-1). Furthermore a large-scale culture of 3 L was also successful in our experiment. CONCLUSION: It was firstly to biosynthesis arbutin in hairy root of P. multiflorum. The production yield and trasfer rate of arbutin were increased largely. And large-scale production (3 L culture flask) of arbutin was achieved in the experiment and it would be valuable for the industrial production of arbutin by biotechnological method in the future.