Multidrug resistance (MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein (P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp, WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel (PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4 (CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft (PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.

Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

ARNTL Transcription Factors ; deficiency ; metabolism ; Animals ; Cyclic AMP ; metabolism ; Gluconeogenesis ; Glucose ; biosynthesis ; HEK293 Cells ; Histone Deacetylases ; metabolism ; Humans ; Liver ; metabolism ; Mice ; Mice, Knockout

No abstract available.
Animals ; Calcium ; Interstitial Cells of Cajal ; Jejunum ; Mice

Huperzine A is a potent,reversible,and blood-brain barrier permeable acetylcholinesterase irhibitor.The aim of this study was to compare the pharmacokinetics,tolerability,and bioavailability of two formulations with the established reference formulation of huperzine A in a fasting,healthy Chinese male population.This was a randomized,single-dose,3-period,6-sequence crossover study.The plasma concentrations of huperzine A were determined by liquid chromatography tandem mass spectrometry.Tolerability was assessed based on subject interview,vital sign monitoring,physical examination,and routine blood and urine tests.The mean (SD) pharmacokinetic parameters of the reference drug were Cmax,1.550 (0.528) ng/mL;t1/2,12.092 (1.898) h;AUC0-72h,17.550 (3.794) ng.h/mL.Those of the test formulation A and test formulation B were Cmax,1.412 (0.467),1.521 (0.608) ng/mL;t1/2,12.073 (2.068),12.271 (1.678) h;AUC0-72h,15.286 (3.434) ng.h/mL,15.673 (3.586) ng.h/mL.The 90％ confidence intervals for the AUC0-72h and Cmax were between 0.80 and 1.25.No adverse events were reported by the subjects or found with results of clinical laboratory test.The test and reference products met the regulatory criteria for bioequivalence in these fasting,healthy Chinese male volunteers.All three formulations appeared to be well tolerated.

Members of the genus Anaplasma are important emerging tick-borne pathogens in both humans and animals in tropical and subtropical areas. Here, we investigated the presence of Anaplasma spp. in 621 sheep and 710 goats from six provinces of China. Polymerase chain reaction (PCR) and DNA sequencing were conducted to determine the prevalence of Anaplasma (A.) phagocytophilum, A. ovis and A. bovis targeting the 16S ribosomal RNA or the major surface protein 4 gene. PCR revealed Anaplasma in 39.0% (240/621) of sheep and 45.5% (323/710) of goats. The most frequently detected species was A. ovis (88/621, 14.2% for sheep; 129/710, 18.2% for goats), followed by A. bovis (60/621, 9.7% for sheep; 74/710, 10.4% for goats) and A. phagocytophilum (33/621, 5.3% for sheep; 15/710, 2.1% for goats). Additionally, eight sheep and 20 goats were found to be infected with three pathogens simultaneously. DNA sequencing confirmed the presence of these three Anaplasma species in the investigated areas, and phylogenetic analysis indicated that there was geographic segregation to a certain extent, as well as a relationship between the host and cluster of A. ovis. The results of the present study provide valuable data that helps understand the epidemiology of anaplasmosis in ruminants from China.
Anaplasma ovis ; Anaplasma phagocytophilum ; Anaplasma* ; Anaplasmosis ; Animals ; China* ; Epidemiology ; Goats* ; Humans ; Polymerase Chain Reaction ; Prevalence ; RNA, Ribosomal, 16S ; Ruminants ; Sequence Analysis, DNA ; Sheep*

?AlM: To investigate the outcome and safety of Ahmed glaucoma valve implantation treatment in uncontrolled primary congenital glaucoma ( PCG) .
? METHODS: Twenty - two eyes in 22 children with uncontrolled PCG were reviewed retrospectively and underwent Ahmed glaucoma valve implantation treatment from January 2011 to December 2014. Main checking index included intraocular pressure ( lOP ) before and after operation, corneal diameter and complications.
?RESULTS: Preoperative mean age was 3. 74±2. 24y, and 2. 59 ± 1. 78y apart from the last operation. Postoperative average lOP was 35. 22 ± 6. 36mmHg. Average corneal diameter was 12. 79 ± 0. 75mm. Mitomycin C ( 0. 3 - 0. 5mg/mL ) was used in all operations for 3-5min. Glaucoma valves were implanted in the temporal or nose above the equator sclera. Postoperative lOP was 11. 4±4. 45mmHg at 1wk, and 16. 73± 7. 23mmHg after 12mo. As lOP< 21mmHg for success criteria, lOP of 16 eyes ( 73%) were controlled after 12mo. Preoperative 6 cases had shallow anterior chamber, recovered spontaneously. No serious complication was recorded, such as rejection of glaucoma valve, endoophthalmitis and corneal decompensation.
?CONCLUSlON:Ahmed glaucoma valve implantation in uncontrolled PCG is a safe and viable treatment.

PURPOSE: This study aims to analyze the clinical-pathological characteristics of multifocal and multicentric breast cancer (MMBC) in Chinese women. METHODS: Sixty-seven cases with MMBC were randomly collected and reviewed at seven hospitals in representative districts of China during 1999 to 2008. RESULTS: The incidence of MMBC in breast cancer in China was 1.75%. Compared to those with unifocal breast cancer, women with MMBC were more likely to have larger tumor size, lymph node metastasis (59.70% vs. 45.62%) and stage III to IV (46.26% vs. 21.10%). The peak age at onset of MMBC was 40 to 49 years old and has been gradually increasing during 1999 to 2008. Most of the MMBC women were treated with surgery and adjuvant therapy. CONCLUSION: In China, the incidence of MMBC in breast cancer is significantly lower than that in Western countries. Compared to unifocal breast cancer, MMBC is biologically more aggressive. Most MMBC women underwent mastectomy, instead of breast conservation surgery.
Asian Continental Ancestry Group ; Breast ; Breast Neoplasms ; China ; Cohort Studies ; Female ; Humans ; Incidence ; Lymph Nodes ; Mastectomy ; Neoplasm Metastasis ; Pathology, Clinical ; Retrospective Studies

Animals ; Antibodies, Monoclonal ; immunology ; Atrazine ; analysis ; immunology ; Chromatography, Gas ; Chromatography, High Pressure Liquid ; Enzyme-Linked Immunosorbent Assay ; Food Contamination ; analysis ; Herbicides ; analysis ; immunology ; Mass Spectrometry

Phytochemical investigation was carried out on the seeds of Vigna umbellata. The 70% ethanol extract of the seeds of V. umbellata was subjected to silica gel, Sephadex LH-20, ODS column chromatographies and preparative HPLC. The structures of the isolated compounds were elucidated on the basis of NMR and ESI-MS spectroscopic data Eight compounds were obtained and identified as carboxyatractyligenin (1), 2beta-O-beta-D-glucopyranosyl-15alpha-hydroxy-kaur-16-ene-18,19-dicarboxylic acid (2), 2beta-O-(beta-D-glucopyranosyl) atractyligenin (3), 3R-O-[beta-L-arabinopyranosyl-(1-6) -beta-D-glucopyranosyl] oct-1-ene-3-ol (4), (6S, 7E, 9R) -roseoside (5), liriodendrin (6), resveratrol (7) and maltol (8). Compounds 1-7 were isolated from Vigna genus for the first time, and compound 8 was isolated from V. umbellata for the first time.
Fabaceae ; chemistry ; Seeds ; chemistry