Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

Gastric cancer (GC) is associated with high morbidity and mortality rates. Thus, early diagnosis is important to improve disease prognosis. Endoscopic assessment represents the most reliable imaging method for GC diagnosis; however, it is semi-invasive and costly and heavily depends on the skills of the endoscopist, which limit its clinical applicability.Therefore, the search for new sensitive biomarkers for the early detection of GC using noninvasive sampling collection methods has attracted much attention among scientists.Urine is considered an ideal biofluid, as it is readily accessible, less complex, and relatively stable than plasma and serum. Over the years, substantial progress has been made in screening for potential urinary biomarkers for GC. This review explores the possible applications and limitations of urinary biomarkers in GC detection and diagnosis.

Dihydropyridine (DHP) calcium channel blockers drugs (dipine in drug names) are currently used in the treatment of hypertension clinically. In recent years, with the emergence of generic drugs, it has been found that the drug efficacy is quite different from that of the original drug, and the reason is closely related to the difference in the crystal forms of the oral preparations. This paper reviews the polymorphic phenomenon of some DHP calcium channel blockers in the domestic market, introduces the clinical application and research progress of the DHP drugs, analyzes the differences between different crystal forms of the same drugs. This work may provide references and ideas for the research and development of generic drugs or new crystalline drug of DHP drugs.

Objective To investigate the effects of the microbubbles combined with different mechanical index ultrasound irradiation on ultrastmcture and migration of colon cancer cells.Methods The experimental study was conducted.Colon cancer cells inn vitro (Lovo ceils) were cultured and divided into 4 groups,ceils in the A group were not treated and cells in the B,C and D groups were treated by microbubbles combined with different mechanical index ultrasound irradiation (mechanical index were 0.20,0.80 and 1.45).The changes of ultrastructure and migration of cells were observed using laser scanning confocal microscope and MilliceIl-PCF cell culturechamber method,respectively.Measurement data with normal distribution were represented as (x)±s.Comparisons among groups were analyzed by the one-way ANOVA.Pairwise comparisons were done by the t test.Results (1)Effects of the microbubbles combined with different mechanical index ultrasound irradiation on ultrastructure of Lovo cells:Lovo cells in the A group showed big nucleus,less plasma,regular arrangement,jagged-like or more irregular varicosity surrounding nucleus,twisted euchmmatin,expansion of nucleus cisternal space,homogeneous distribution and normal development of granular soil and clear mitochondrial ridge-like structures.Lovo cells in the B group showed big nucleus with regular arrangement,obvious nucleolus margination,endoplasmic reticulum dilatation,normal development of mitochondrion and clear mitochondrial ridge-like structures.Lovo cells in the C group showed broadening nucleus space,abnormal nucleus with karyopycnosis,chromatin condensation,a few remaining or obvious dilatation of rough endoplasmic reticulum,typically consisting of different fragments or bubbles,cytoplasmic vacuoles changes and decreasing mitochondrial ridge-like structures.Lovo cells in the D group showed big and irregular nucleus,nucleolus margination,obvious endoplasmic reticulum dilatation,fewer mitochondrion with extended cell area and swelling shape,rare mitochondrial ridge-like structures with disordered or broken arrangement,even disappearing.(2) Effects of the microbubbles combined with different mechanical index ultrasound irradiation on migration of Lovo cells:Millicell-PCF cell culture chamber method showed that number of migration of Lovo cells were respectively 63±7,61±4,21±3 and 19±5 in the A,B,C and D groups,with a statistically significant difference (F=55.040,P＜0.05).There were no statistically significant difference in migration of Lovo cells between group A and B (t =1.571,P＞0.05) and between group C and D (t =2.013,P＞0.05).There were statistically significant differences in migration of Lovo cells between group A and C or D (t=7.861,10.652,P＜0.05) and between group B and group C or D (t=7.161,10.453,P＜0.05).Conclusion Microbubbles combined with high mechanical index ultrasound irradiation can make the ultrastructural alterations in the cancer cells,resulting in tumor cell degeneration and death,ultimately inhibit tumor cell migration and metastasis.

Aim To evaluate the vasorelaxant effect of two new chemical entities, J35242 and J35243, on iso-lated rat thoracic aorta rings as Rho-kinase inhibitors, and further to explore the underlying mechanisms of these two compounds. Methods Isolated rat thoracic aorta rings pre-contracted by KCl or norepinephrine ( NE) were used to evaluate the vasodilatory effect of J35242 and J35243 . Through the interventions of sev-eral tool drugs, the mechanisms of compounds concern-ing endothelium, K+ channels and Ca2+ were studied. Results J35242 and J35243 showed potent relaxant effect on both KCl and NE pre-contracted vessels, and exhibited partial endothelium dependency. L-NAME and Methylene Blue( MB) could influence the relaxant effect of these compounds. Meanwhile, the compounds could inhibit intracellular Ca2+ release and extracellu-lar Ca2+ influx, which indicated that the compounds might block the calcium channels to relax the vessels. In addition, the two compounds probably did not dilate the aorta rings through opening potassium channels. Conclusions J35242 and J35243 have vasorelaxant effects on vessels in vitro and the potency of J35242 is stronger than that of J35243 . The underlying mecha-nisms might be endothelium-dependent. Also the com-pounds might block Ca2+ channels, lowering intracel-lular Ca2+ concentration to relax the vessels.

Objective To investigate the awareness rate of knowledge related with vascular cognitive impairment (VCI) in community residents in Shuangjing District,Beijing.Methods 5 communities were randomly selected from 12 communities in Shuangjing District.According to roster,512 residents were selected randomly.Among them,there were 197 males and 315 females with an average age of (64.71±8.22) years.87.9％ of subjects had junior high school culture and over.The awareness rate of knowledge related with VCI was investigated by questionnaires from January 2013 to March 2013.Results Although the awareness rate of knowledge related with vascular dementia was only 36.9％,the awareness rates of symptoms of impairment in memory,orientation,language,execution,calculation,visuospatial and judgement were 43.8％-89.3％.The awareness rates of four outpatient clinics among dementia patients were 21.5％-38.9％,however,the awareness rate of dementia which was not curable was 47.5％.The awareness rates of 5 risk factors for stroke were 54.5％-83.4％,but the awareness rate of cognition impairment caused by hypotension and hypoglycemia was 42.8％ and 43.2％,respectively.About VCI-related preventive knowledge,the awareness rates of VCI population with high risk factors,cognitive abilities screening,and primary prevention were 35.5％-95.5 ％.The main routes taking healthy knowledge were the television and newspapers with the awareness rate of 86.9％ and 60.2％,respectively.85.9％ of subjects agreed that healthy education was helpful to their life qualities.Multiple linear regression analysis showed a significant relationship of accumulated points of VCI-related knowledge with gender and education degree (P＜0.05).Conclusions The awareness rates of risk factors,diagnosis and therapy and primary prevention for VCI are lower in Shuangjing community,and the health education about VCI should be strengthened.

OBJECTIVETo evaluate the accuracy and direct medical cost of different screening modalities of physical examination (PE), mammography (MAM), and high-frequency ultrasonography (US) for breast cancer among Chinese women.

METHODSThis study was designed as a blindly carried outcom parative parallel screening trial for breast cancer among Chinese women aged 35 years or older. Physical examination was conducted with the subjects in the first round of breast cancer screening. The negative cases were followed up approximately 1 year later and moved into the second round of screening. Using the results of biopsies and 1-year follow-up as the gold standards, the accuracy and cost indexes of different screening modalities were calculated. Data were analyzed by McNemar test.

RESULTSA total of 2 471 eligible women were included in this trial, and 14 breast cancers were identified among them. Mammography enabled to detect 11 cancers, high-frequency ultrasonography detected 9 cancers and physical examination detected 8 cancers. Considering the three modalities separately, MAM identified the fewest suspicious cases (52 cases) and detected the most cancers (11 cases). Using US alone at the first stage, followed by MAM when indicated, offered the highest specificity (99.7%)and correct positive predictive value (11.4%), meanwhile the sensitivity was 78.6%, and the mean costs of the screening modality in urban and rural areas were 291, 210 yuan and 886,050 yuan per cancer case detected.

CONCLUSIONSThe strategy of screening with US alone at the first stage, followed by MAM when indicated, may be the most suitable modality of breast cancer detection in most regions of China, but the cost is still too high to develop the breast cancer screening in some low incidence regions with limited health resources.

Adult ; Breast Neoplasms ; diagnosis ; economics ; China ; Early Detection of Cancer ; economics ; methods ; Female ; Follow-Up Studies ; Humans ; Mammography ; economics ; Middle Aged ; Physical Examination ; economics ; Sensitivity and Specificity ; Ultrasonography, Mammary ; economics

Aim To investigate the in vitro vasorelax-ant effect of DL0805-0, a Rho kinase inhibitor, on iso-lated rat thoracic aorta and explore its underlying mechanism. Methods Tension was measured to eval-uate the vasorelaxant effect of DL0805-0 on rat endo-thelium-intact and endothelium-denuded thoracic aorta rings. Rho kinase inhibitor fasudil, nitric oxide syn-thase inhibitor Nω-nitro-L-arginine methyl ester ( L-NAME), guanylate cyclase inhibitor methylene blue, cyclooxygenase inhibitor indomethacin, calcium-activa-ted potassium channel blocker tetraethyl ammonium ( TEA ) , ATP-sensitive potassium channel blocker glibenclamide and voltage-dependent potassium chan-nel blocker 4-aminopyridine ( 4-AP ) were used to il-lustrate the mechanisms of vasorelaxant effect of DL0805-0 . Results DL0805-0 exerted vasorelaxation in a dose-dependent manner in KCl (60 mmol·L-1 ) or NE ( 0. 1 μmol · L-1 ) -induced contraction. DL0805-0-induced vasorelaxation was significantly re-duced by L-NAME. However, methylene blue and in-domethacin did not significantly affect vasorelaxation of DL0805-0. In endothelium-denuded rings, TEA re-markably attenuated the vasorelaxant effect of DL0805-0 , while glibenclamide and 4-AP did not affect vasore laxation of DL0805-0 significantly. DL0805-0 also re-duced NE-induced transient contraction and inhibited contraction induced by increasing extracellular calci-um. Conclusion These results suggest that DL0805-0 induces vasorelaxation through an endothelium-depend-ent pathway. The opening of calcium-activated K+channels and blocking of Ca2+ channels in vascular smooth muscle cells may be one of the mechanisms of DL0805-0-induced vasorelaxation.

Aim ToestablishthemethodofHighper-formance liquid chromatography ( HPLC ) for detecting plasma concentration of indazole compound DL0805-1 , a Rho kinase inhibitor, and to investigate its pharma-cokinetics in rats with intravenous injection. Methods ThedetectingsystemwasAgilent1200-DAD;chro-matographic column was Agilent TC-C18 ( 4. 6 mm × 250 mm, 5 μm); the ultraviolet detection wavelength was 235 nm; the column temperature was 35 ℃; the flow rate was 1 ml·min-1;the mobile phase was ace-tonitrile-0. 05% H3 PO4 gradient elute. Rat blood sam-ples were collected at different intervals after intrave-nous injection of a single dose of DL0805-1 , and the concentration of DL0805-1 in rat plasma were deter-mined by HPLC method for estimating pharmacokinetic parameters.Results Afterintravenousinjectionof DL0805-1 in rats, prototype and its metabolite were detected in plasma. T1/2 of DL0805-1=(2. 34 ± 1. 42) h, Cmax=(3. 51 ± 0. 44) mg·L-1, T1/2 of metabolite of DL0805-1 = ( 1. 27 ± 0. 45 ) h, Cmax = ( 3. 55 ± 0.22)mg·L-1.Conclusion Theseresultssuggest that DL0805-1 may be metabolized into another sub-stance in vivo and play biological functions. The meth-od is sensitive, simple, and accurate, and can be used for the determination of DL0805-1 in rat plasma and pharmacokinetic studies.

ObjectiveTo compare the effects of dexmedetomidine and propofol for stereotactic brain surgery in patients with intractable psychosis.MethodsThirty male patients with intractable psychosis,aged 22-33 yr,weighing 60-90 kg,scheduled for stereotactic surgery,were randomized to receive either propofol (group P,n =15) or dexmedetomidine (group D,n =15).Anesthesia was induced with iv injection of midazolam 0.05-0.10 mg/kg and fentany 1-2 μg/kg in the two groups,and in addition,dexmedetomidine was infused at 0.3-0.7μg· kg- 1 · h- 1 after a loading dose of 1 μg/kg (duration of infusion ＞ 10 min) and propofol 1-2 mg/kg was injected intravenously before endotracheal intubation in group D and propofol 2-3 mg/kg was injected intravenously and then propofol was infused at a rate of 3-4 mg· kg- 1 · h- 1 in group P.Orotracheal intubation was performed under the guidance of direct laryngoscope.The patients kept spontaneous breathing.The adverse events such as body movement,bucking,apnea,adverse cardiac events and hypoxemia were recorded during location.ResultsThe incidence of body movement,bucking,apnea,tachycardia,hypotension and hypoxemia was significandy lower,while the incidence of bradycardia was significantly higher in group D than in group P ( P ＜ 0.01 ).There was no significant difference in the incidence of hypertension between the two groups (P ＞ 0.05).ConclusionDexmedetomidine provides better anesthesia,exerts less effect on the respiratory and circulatory functions and is safer than propofol for stereotactic surgery in patients with intractable psychosis.