A new dihydrostilbene from aerial part of Cannabis sativa / 中国中药杂志

The present study investigated the chemical constituents in the aerial part of Cannabis sativa. The chemical constituents were isolated and purified by silica gel column chromatography and HPLC and identified according to their spectral data and physicochemical properties. Thirteen compounds were isolated from the acetic ether extract of C. sativa and identified as 3',5',4″,2-tetrahydroxy-4'-methoxy-3-methyl-3″-butenyl p-disubstituted benzene ethane(1), 16R-hydroxyoctadeca-9Z,12Z,14E-trienoic acid methyl ester(2),(1'R,2'R)-2'-(2-hydroxypropan-2-yl)-5'-methyl-4-pentyl-1',2',3',4'-tetrahydro-(1,1'-biphenyl)-2,6-diol(3), β-sitosteryl-3-O-β-D-glucopyranosyl-6'-O-palmitate(4), 9S,12S,13S-trihydroxy-10-octadecenoate methyl ester(5), benzyloxy-1-O-β-D-glucopyranoside(6), phenylethyl-O-β-D-glucopyranoside(7), 3Z-enol glucoside(8), α-cannabispiranol-4'-O-β-D-glucopyranose(9), 9S,12S,13S-trihydroxyoctadeca-10E,15Z-dienoic acid(10), uracil(11), o-hydroxybenzoic acid(12), and 2'-O-methyladenosine(13). Compound 1 is a new compound, compound 3 is a new natural product, and compounds 2, 4-8, 10, and 13 were isolated from Cannabis plant for the first time.

Pharmacokinetic effects of metformin hydrochloride, food and alcohol on Ramulus Mori (Sangzhi) alkaloids / 药学学报

Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).

Long non-coding RNA LOC101927476 inhibits invasion, migration, and proliferation of ovarian cancer cell lines / 中华肿瘤杂志

Objective: To investigate the expression of long non-coding RNA LOC101927476 (LncRNA LOC101927476) in ovarian cancer and its effect on the biological characteristics of ovarian cancer. Methods: Patients with ovarian cancer who underwent surgery in Cancer Hospital of Chinese Academy of Medical Sciences from 2018 to 2019 were selected. The expressions of LOC101927476 in ovarian cancer cells 3AO, OVCA429, TOV21G, A2780, SKOV3, as well as 22 primary tumor tissues and their matched metastatic tumor tissues were detected by real-time quantitative polymerase chain reaction (RT-PCR). Ovarian cancer transcriptome sequencing data from the TCGA database was used to verify the expressions of LOC101927476 and GATA4. 3AO and OVCA429 cells were infected with lentivirus plasmid containing OE-LOC101927476 and single guide RNA (sg-RNA) targeting LOC101927476, respectively. The effects of LOC101927476 on migration and invasion were detected by Transwell and wound healing assay. The effect of LOC101927476 on cell proliferation was detected by cell counting kit-8 (CCK-8) assay. Results: RT-PCR assay showed that 20 out of 22 patients had significantly lower expression of LOC101927476 in their metastatic tumors compared with primary tumors. Transwell assay showed that overexpression of LOC101927476 significantly inhibited the invasion and migration capacities of 3AO cells. The numbers of invading and migrating 3AO cells infected with OE-LOC101927476 lentivirus were (357±63) and (699±65), respectively, lower than (661±95) and (1 024±76) in OE-EV group (P<0.050). In contrast, the numbers of invading and migrating OVCA429 cells with LOC101927476 knockdown were (512±72) and (472±40), respectively, higher than (309±13) and (363±27) in sg-Control group (P<0.050). Wound healing assay results showed that after 48 hours, the percentage of scratch healing of 3AO cells in OE-LOC101927476 group was (10.86±0.63)%, significantly lower than (57.38±4.42)% of OE-EV group (P=0.009). After 24 hours, the percentage of scratch healing of OCVA429 cells in sg-LOC101927476 group was (59.98±1.34)%, significantly higher than (23.15±2.03)% of sg-Control group (P=0.004). CCK-8 assays showed that the OD value of 3AO cells in OE-LOC101927476 group was (2.07±0.08), significantly lower than (2.29±0.04) of OE-EV group (P=0.009). The OD value of OVCA429 cells in sg-LOC101927476 group was (2.13±0.03), significantly higher than (1.93±0.03) of sg-Control group (P=0.001). The relative expression of GATA4 in OE-LOC101927476 group was (1.86±0.25), significantly higher than 1.00 of OE-EV group (P=0.001). In patients with high expression of LncRNA LOC101927476, the expression level of GATA4 was (2.93±0.35), which was higher than (0.29±0.06) of LOC101927476 low expression group (P=0.001). Conclusion: LncRNA LOC101927476 can inhibit the invasion, migration and proliferation of ovarian cancer cells.

Potential impact of epidural labor analgesia on the outcomes of neonates and children / 中华医学杂志(英文版)

This review summarizes recent evidences regarding the potential influences of epidural labor analgesia (ELA) on the outcomes of neonates and children. Terms and relevant words including "ELA," "ELA and neonatal outcomes," "ELA and children's development," and "ELA and children's neurocognitive development" were used to search articles published in PubMed database up to October 2019. Original articles and reviews regarding potential influences of ELA on neonates and children were identified. Relevant references of the selected articles were also screened. The anesthetics used during ELA can be absorbed, enter the fetus, and produce neonatal depression; however, these effects are less severe than those during systematic opioid analgesia. The impact of anesthetic exposure during ELA on children's neurodevelopment has not been fully studied, but would be mild if any. ELA increases the risk of intrapartum maternal fever; the latter may be harmful to neonatal outcomes. The use of ELA may increase birth injury by increasing instrumental delivery, although long-term adverse events are rare. On the other hand, ELA may reduce maternal depression and, thus, produce favorable effects on neurocognitive development in childhood; but evidences are still lacking in this aspect. ELA may produce both favorable and unfavorable effects on neonates and children. These effects should be discussed with parturient women before making decisions. The potential harmful effects should be carefully managed. The overall impacts of ELA on neonatal and children's outcomes need to be studied further.

Clinical Efficacy of Modified Tongqiao Huoxuetang Combined with Stent Thrombectomy in Treatment of Acute Cerebrovascular Occlusion / 中国实验方剂学杂志

Objective::To observe the effect of modified Tongqiao Huoxuetang combined with stent thrombectomy in treating acute cerebrovascular occlusion. Method::A total of 120 cases were randomly divided into control group and observation group, with 60 cases in each group. The control group received stent thrombectomy, while the observation group received modified Tongqiao Huoxuetang combined with stent thrombectomy. The clinical symptoms [health neural function defect scale stroke scale scores(NIHSS), activities of daily living(ADL), mini mental state examination(MMSE)], hemodynamic indexes [high-shear reduction viscosity(HSRV), medium-shear reduction viscosity(MSRV), low-shear reduction viscosity(LSRV), whole blood plasma viscosity(WBV)], vascular endothelial functions [serum nitric oxide synthase(NOS), endothelin-1(ET-1), vascular endothelial growth factor(VEGF)] were observed. The clinical efficacy and the incidence of adverse reactions were compared between two groups. The blood routine, urine routine, heart, liver and kidney function, incidence of cerebral hemorrhage in two groups were observed during the treatment. Result::There were 4 cases were shed in control group and 2 cases in observation group during the study period. The total effective rate in observation group was 94.8%(55/58), which was higher than 83.9% of the control group(47/56)(P<0.05). The NIHSS in observation group was lower than that in control group(P<0.05), whereas ADL and MMSE were higher than those in control group(P<0.05). The hemorheological indexes in observation group were lower than those in control group(P<0.05), NOS and VEGF in observation group were higher than those in control group(P<0.05), and ET-1 score was lower than that in control group(P<0.05). During the study period, the incidence of cerebral hemorrhage was 7.14%(4/56) in control group and 8.6%(5/58) in observation group, with no significant difference. Conclusion::Modified Tongqiao Huoxuetang combined with stent thrombectomy could significantly improve the clinical symptoms, hemorheology and vascular endothelial function of patients with acute cerebrovascular occlusion, and so is worthy of clinical promotion and application.

Anti-diabetic effects of the fraction of alkaloids from Ramulus Mori, an innovative Sangzhi alkaloids as an α-glucosidase inhibitor / 药学学报

Sangzhi alkaloids (SZ-A) are derived from traditional Chinese medicine Ramulus Mori, serving well as an innovative antidiabetic drug, due to α-glucosidase inhibition. To evaluate the potency of glucosidase inhibitory effect of SZ-A, the enzyme-based screening platforms, including sucrase, maltase and amylase were established, and IC50 was calculated. The effects of SZ-A on postprandial blood glucose at a single dose, oral sucrose, starch and glucose loading were determined in normal ICR mice and alloxan-induced hyperglycemic mice. To confirm the anti-diabetic effects of SZ-A on glucose and lipid metabolism after long-term administration, the postprandial and fasting blood glucose, serum insulin, urinary glucose levels, glycosylated serum proteins and blood lipid levels were determined in high-fat fed C57 obese mice (pre-diabetic HFC57 mice) and diabetic rats induced by streptozotocin (STZ). The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. We found that SZ-A exhibited a significant inhibitory effect on the sucrase and maltase. SZ-A showed no effect on amylase. In normal ICR mice and alloxan-induced hyperglycemic mice, SZ-A at a single dose significantly delayed and reduced the peak of blood glucose after sucrose or starch loading, but showed no effect on the increase of blood glucose after glucose loading. In STZ diabetic rats, SZ-A significantly reduced the postprandial or fasting blood glucose levels, glycosylated serum proteins and urinary glucose. SZ-A also reduced serum triglyceride (TG) and cholesterol (TC) levels after 3 weeks of treatment. SZ-A ameliorated the postprandial blood glucose or the fasting blood glucose elevation, and reduced the incidence of hyperglycemia in HFC57 mice. SZ-A decreased the basal insulin level, improved insulin sensitivity, and ameliorated glucose intolerance in pre-diabetic HFC57 mice. Our results indicated that SZ-A had a novel inhibitory activity on α-glucosidase, especially on disaccharidases. SZ-A at a single dose significantly reduced the peak of blood glucose elevation and delayed the increase of blood glucose in normal and diabetic mice after disaccharide and polysaccharide loading. Long-term SZ-A treatment improved glucose and lipid metabolic profiles by delaying carbohydrate absorption from the intestine and reduced the postprandial blood glucose levels in both pre-diabetic and diabetic animal models. Therefore, SZ-A application may display a beneficial role in preventing the development and complications of diabetes.

Particle Size Distribution of Phenols in Mainstream Cigarette Smoke Aerosol / 分析化学

To measure particle size distribution of phenols in mainstream cigarette smoke aerosol,the particles of cigarette smoke aerosol were divided into 12 stages using single channel smoking machine coupled electrical low-pressure impactor (ELPI) and collected by 12 polyester films.The collected particles were weighted and then analyzed by ultra-high performance liquid chromatography-fluorescence detection (UPLC-FLD) to determine the 14 phenols in the different size particles.The results showed that the aerosols collecting method had good stability with relative standard deviation (RSD) of collected particles mass less than 10%.The analyzing results of 14 phenols by UPLC-FLD showed that the linear correlation coefficients(R2) were greater than 0.9959,with detection limits were less than 1.2 ng/cig and recoveries were 80.1%-115.0%.The distributions of 14 phenols with respect to smoke aerosol particle size were investigated.The results indicated that except 4-ethyl-2-methoxy-phenol not detected,the other 13 phenols were detected in mainstream cigarette smoke aerosol.The content of 13 phenols appeared increasing at first and then decreasing with increase of the particle size which distributed in a pattern similar to that of particle mass.All of 13 phenols were present in higher amounts in the medium size particles (0.261-0.722 μm) with peak content in particles 0.431 μm.The distribution of concentrations (ratio of content to particle mass) of 13 phenols in different size particles was different.The concentrations of phenol and mono-substituted phenol appeared to first increase and then decrease with increasing smoke aerosol particle size and were higher in medium size particles (0.261-0.772 μm).The concentrations of benzenediol and mono-substituted benzenediol were uniformly distributed in medium size particles (0.144-1.166 μm),and the concentration of disubstituted phenol was uniform throughout the particles of varying sizes.

MicroRNA-21 up-regulates expression of occludin by targeting ROCK1 in NCM460 cells / 中国病理生理杂志

AIM:To investigate the role of microRNA-21(miR-21)in regulation of tight junction(TJ)-asso-ciated protein occludin in human normal colon mucosal epithelial cell line NCM 460, and to analyze related target genes. METHODS:Using miR-21 over-expression lentivirus, the NCM460 cells with miR-21 overexpression were established. The expression level of miR-21 was detected by qPCR.The expression of occludin was determined by Western blot.The target genes of miR-21 were predict by bioinformatic method.According to the scores and the appropriate literature search, a target gene was selected for further study.The miR-21 mimic and inhibitor were transfected into NCM 460 cells,and the expression levels of miR-21 and ROCK1 were measured.Dual-luciferase reporter assay was also performed to verify ROCK1 as the target gene of miR-21.RESULTS:In miR-21-overexpressing NCM460 cells,the protein expression level of occlu-din was upregulated.Bioinformatics and literature analysis predicted that the target gene of miR-21 was ROCK1.The mR-NA and protein levels of ROCK1 were down-regulated in the NCM460 cells transfected with miR-21 mimic.Accordingly, the mRNA and protein levels of ROCK1 were up-regulated in the NCM460 cells transfected with miR-21 inhibitor.Lucifer-ase assay confirmed that miR-21-binding sequence was on the 3'UTR of ROCK1,indicating that ROCK1 is the target gene of miR-21.CONCLUSION: In NCM460 cells, miR-21 up-regulates the expression of occludin, which functions in the maintenance of intestinal epithelial mechanical barrier.ROCK1 is a target gene of miR-21,and is involved in the miR-21 regulation of occludin.

Effect of acupoint massage dominant early comprehensive intervention on the prognosis of premature infants with brain injury / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of acupoint massage dominant early comprehensive intervention on the prognosis of premature infants with brain injury.</p><p><b>METHODS</b>Totally 210 premature infants with brain injury were assigned to the intervention group (112 cases) and the control group (98 cases). All patients received routine therapy (medicinal + routine care instructions). Patients in the intervention group additionally received acupoint massage. Those with abnormal early motion received physical sports treatment. Those with upper limbs dysfunction or with fine movement disorders received occupational therapy. Premature infants' development quotient (DQ) was performed at corrected age of 6 and 12 months by using neuropsychological development examination table for 0 - 6 years old children. The incidence of cerebral palsy was statistically calculated.</p><p><b>RESULTS</b>At corrected age of 6 months, DQ of gross motor, fine motor, language three functional areas was higher in the intervention group than in the control group with significant difference (P < 0.05). At corrected age of 12 months, DQ of gross motor, fine motor, language, social and adaptive capacities was higher in the intervention group than in the control groupwith significant difference (P < 0.05). The incidence of cerebral palsy was 4.46% (5/112) in the intervention group and 12.24% (12/98) in the control group (P < 0.05).</p><p><b>CONCLUSION</b>Acupoint massage dominant early comprehensive intervention could obviously improve the intelligence development level and lower the incidence of cerebral palsy in premature infants with brain injury.</p>

Abnormal calcium re-uptake in myocardium sarcoplasmic reticulum in rabbits with heart failure and the influencing factors / 生理学报

The aim of the present study was to investigate the abnormal calcium re-uptake function of myocardium sarcoplasmic reticulum (SR) in rabbits with heart failure, as well as potential mechanisms. Heart failure model was established in rabbits through aortic insufficiency and constriction of abdominal aorta. The SR Ca(2+) re-uptake function was measured with a calcium imaging device. The activity of myocardium SR calcium adenodine triphosphatase 2a (SERCA2a) was measured by inorganic phosphate. The protein expressions of SERCA2a, CaMKII, PKA, PP1α, phospholamban (PLB), PLB-Ser(16) and PLB-Thr(17) were evaluated by Western blot. The activities of PKA and CaMKII were detected by γ-(32)P substrate incorporation. The results showed that, compared with the sham operation group, the heart failure group exhibited reduced Ca(2+) re-uptake amount (P < 0.01) and the expression and activity of SERCA2a (P < 0.05 or P < 0.01), decreased expression of PLB and its phosphorylation status in sites of Ser(16) and Thr(17) (P < 0.05), increased expressions and activities of PKA and CaMKII (P < 0.05 or P < 0.01), and increased expression of PP1α (P < 0.05). These results suggest that the abnormal Ca(2+) re-uptake function in heart failure is related with reduced expression and activities of SERCA2a, as well as reduced expression of PLB and its phosphorylation status. Both PLB-Ser(16) and -Thr(17) may be involved in the regulation of myocardium SR calcium pump activity in heart failure.

Establishment of an aromatase inhibitor letrozole-resistant breast cancer cell model / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish a human breast cancer MCF-7 cell model stably overexpressing the aromatase gene (MCF-7-aromatase) and aromatase inhibitor letrozole-resistant MCF-7 cell model (MCF-7-LR).</p><p><b>METHODS</b>We utilized the lentivirus-mediated gene transfer approach to establish MCF-7-aromatase cell and MCF-7 cell model stably overexpressing green fluorescent protein (GFP) (MCF-7-GFP). The expression of aromatase in the MCF-7-aromatase and MCF-7-GFP cells was determined by reverse transcription polymerase chain reaction (RT-PCR), real time quantitative PCR (RT-qPCR), Western blot and immunoprecipitation (IP) assay. The proliferative ability in vitro of MCF-7-aromatase and MCF-7-GFP cells treated with testostorone and β-estradiol (E2) was determined by WST-1 cell proliferation assay. The proliferative ability of MCF-7-aromatase cells treated with letrozole was determined by WST-1 assay. The half maximal inhibitory concentration (IC50 value) for letrozole was calculated from the nonlinear regression line of the plot of cell viability (percentage of control) versus letrozole concentration using Graphpad Prism software. MCF-7-aromatase cells were continuously cultured in the presence of testosterone and letrozole, thus letrozole-resistant MCF-7-LR cells were obtained. WST-1 assay was performed to determine their chemoresistance to letrozole.</p><p><b>RESULTS</b>RT-PCR and RT-qPCR results revealed that the mRNA expression of aromatase was significantly increased in the MCF-7-aromatase cells compared with that in the MCF-7-GFP cells. Both Western blot and IP assays showed that the expression of aromatase protein was drastically increased in the MCF-7-aromatase cells, compared with that in the MCF-7-GFP cells. WST-1 assay showed that the cell proliferation rate of MCF-7-aromatase cells treated with 1 and 10 nmol/L testosterone was 1.43- and 1.53-fold higher than that of the control cells, respectively. The proliferation rate of MCF-7-aromatase cells treated with 1 and 10 nmol/L E2 was 1.41- and 1.55-fold higher than that of the control cells, respectively. In contrast, the proliferation rate of MCF-7-GFP cells treated with 10 nmol/L testosterone was 1.12-fold higher than that of the control cells, and the proliferation rate of MCF-7-GFP cells treated with 1 and 10 nmol/L E2 was 1.41- and 1.51-fold higher than that of the control cells, respectively. Letrozole treatment significantly inhibited the testosterone-induced proliferation ability of MCF-7-aromatase cells in a dose-dependent manner and the IC50 value was 5.3 nmol/L. In contrast, letrozole treatment showed no inhibitory effect on the proliferative ability of MCF-7-LR cells and the IC50 value was >1000 nmol/L.</p><p><b>CONCLUSIONS</b>MCF-7-aromatase and MCF-7-LR cells exhibit different response to letrozole treatment, which provides an important basis for further investigating the mechanism of letrozole resistance.</p>

Cost-effectiveness analysis on the once-in-a-lifetime cervical cancer screening program for women living in rural and urban areas of China / 中华流行病学杂志

<p><b>OBJECTIVE</b>To estimate the cost-effectiveness of once-in-a-lifetime cervical cancer screening program and to predict the optimal modality for its operation on women living in rural and urban areas of China, based on Markov modeling and simulation.</p><p><b>METHODS</b>Three modalities including visual inspection with acetic acid plus Lugol's iodine (VIA/VILI), conventional Pap Smear (Pap Smear), and simple HPV DNA testing (careHPV) were hypothesized for the rural cohort, whereas other five modalities including Pap Smear, liquid-based cytology (LBC), simple HPV DNA testing (careHPV), Hybrid Capture 2 HPV DNA testing (HC2), and LBC plus HC2 (LBC + HC2) were tested for the urban cohort. A Markov model was constructed based on the factors as natural history, screening, diagnosis and treatment on cervical cancer using data related to the epidemics and the costs from rural and urban areas of the country. Long-term effectiveness and cost-effectiveness were predicted through simulation of the model.</p><p><b>RESULTS</b>Compared to the non-screening scenario, the amount of life years saved were 277.97 - 2727.53 and 134.02 - 1446.84 years per 100 000 women, respectively, for different cohorts in rural and urban areas. The cost-effectiveness ratios were 1520.99 - 2453.74 and 3847.35 - 44 570.35 RMB per life year saved, respectively, for different cohorts in rural and urban areas. The incremental cost-effective ratio for careHPV starting from 40 years old (careHPV@40) and careHPV from 30 years old (careHPV@30) dominated other strategies for the rural cohort, while careHPV@40, careHPV@30, HC2 from 30 years old (HC2@30), and LBC + HC2 from 30 years old (LBC + HC2@30) were dominant for the urban cohort.</p><p><b>CONCLUSION</b>All eight once-in-a-lifetime cervical cancer screening modalities were cost-effective based on our model. In particular, careHPV screening starting from 40 years old seemed to be the most cost-effective one for women living in both rural and urban areas.</p>

Network pharmacology: new opportunity for the modernization of traditional Chinese medicine / 药学学报

Traditional Chinese medicine (TCM) with the characteristics of holistic view and treatment based on syndrome differentiation, has rich clinical experience thousands of years and demonstrates promising effects to cure complex disease. However, due to the features of multi-component, multi-target and synergistic effect existed in TCM, the effective substances and mechanisms of action are not clear, the qualities of TCM are out of control, and scientific and correct assess system is waiting to be established. The network pharmacology is a novel subject based on the construction of multi-layer networks of disease-phenotype-gene-drug to predict the drug targets in a holistic view, and promote efficiency of drug discovery. Methodologically, network pharmacology integrated the notions of comprehensive research and systematic assessment which agree with the characteristics of holistic view and treatment based on syndrome differentiation in Chinese medicine. Our paper reviewed the challenge and chance within the modernization of TCM, the concept and technology of network pharmacology, and its preliminary application in investigation of TCM. The theoretical system of network pharmacology is emphasized, and the potential prospect of its application in modernization in TCM is focused.

Effectiveness and health economic analysis of strategies on cervical cancer screening and early diagnosis and treatment / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the appropriate strategies which are suitable for the areas with diverse health and economic resource settings in China by estimating the life outcomes and cost-effectiveness of several cervical cancer screening strategies.</p><p><b>METHODS</b>Markov model was used to calculate the long-term effectiveness, utility, benefit and cost among screened and unscreened cohorts in rural and urban areas, and then analyses of cost-effectiveness, cost-utility and cost-benefit were performed. The assessed screening strategies were acetic acid of visual inspection combined with Lugol's iodine staining (VIA/VILI), conventional Pap smear and simple HPV DNA testing (careHPV) in rural areas, and conventional Pap smear, simple HPV DNA testing (careHPV), HPV DNA testing (HC2) and liquid-based cytology (LBC) alone or combined with HPV DNA testing (LBC+HC2) in urban areas. We estimated the life outcomes and cost-effectiveness of the above screening strategies at one-year, 3-year and 5-year intervals.</p><p><b>RESULTS</b>All of the screening strategies were effective to decrease cervical cancer mortality and to increase life years, with a trend of shorter screening interval having better effectiveness. However, no matter in urban or rural areas, compared with careHPV testing at 5-year interval, the costs of other screening strategies were 1.28 - 13.86 folds, 1.31 - 14.14 folds, and 1.27 - 12.80 folds higher to avoid one death, to save a year of life, and a QALY, and the benefit per cost of other screening strategies was 9.9%-90.2%.</p><p><b>CONCLUSIONS</b>careHPV testing at 5-year interval has the best cost-effectiveness performance and the highest benefit-cost ratio with the moderate life outcomes. It is the optimal cervical cancer screening strategy to be generalized in our country. careHPV testing at 3 years interval can be considered in more developed areas to achieve better effectiveness.</p>

Effect of metoprolol on sarcoplasmic reticulum Ca2+ leak in a rabbit model of heart failure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Studies have shown that β-blockers can improve cardiac performance in heart failure (HF) by reversing protein kinase A (PKA)-mediated sarcoplasmic reticulum (SR) Ca2+ leak. However, it is being strongly questioned as to whether the PKA-mediated ryanodine receptor (RyR2) hyper-phosphorylation is a critical regulator of SR Ca2+ leak. In this study, we used a rabbit HF model to investigate whether β-blockers affect SR Ca2+ leak by other potential mechanisms.</p><p><b>METHODS</b>New Zealand white rabbits were randomly divided in three groups (n=7 in each group): normal group, metoprolol-untreated group and metoprolol-treated group. Cardiac function was determined by echocardiography and hemodynamic assays. The SR Ca2+ leak was measured by a calcium-imaging device, and the expression and activities of related proteins were evaluated by Western blotting and auto-phosphorylation.</p><p><b>RESULTS</b>In the metoprolol-untreated group, there was significantly increased ventricular cavity size, reduced systolic function, increased SR Ca2+ leak, reduced associated amount of FK506 binding protein 12.6 (FKBP12.6), increased expression and activity of PKA and Ca2+/calmodulin-dependent protein kinase II (CaMKII), and increased phosphorylated RyR2 phosphorylation sites (with unchanged RyR2-P2030). In the treated group, there was partly increased ventricular cavity size with preserved systolic function, but no prominent Ca2+ leak, with unchanged expression and activity of PKA, CaMKII and their RyR2 phosphorylation sites.</p><p><b>CONCLUSION</b>Chronic administration of metoprolol prevented the SR Ca2+ leak by restoring not only PKA-dependent but also CaMKII-dependent hyper-phosphorylation of RyR2, which may be one of the potential mechanisms by which β-blockers improve cardiac function and reduce the incidence of fatal arrhythmia in HF.</p>

Prevalence of high-risk human papillomavirus and incidence of cervical intraepithelial neoplasia in female populations in Shenzhen, Guangdong Province / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the prevalence of high-risk human papillomavirus (HPV) and incidence of cervical intraepithelial neoplasia (CIN) in female populations in Shenzhen, Guangdong Province, China.</p><p><b>METHODS</b>Totally 1137 women aged 15-59 from Shahe Community, Nanshan District, Shenzhen were investigated for cervical cancer during an population-based epidemiological screening from November 2004 to December 2004. Visual inspection with acetic acid (VIA), colposcopy, liquid-based cytology test (LCT), and hybrid capture 2 (HC-) were performed to detect the high-risk HPV types in cervical secretions. Biopsy under colposcope was performed in women who were HPV-positive with LCT >or= atypical squamous cells of undetermined sign (ASCUS) or HPV-negative with LCT >or= low grade squamous intraepithelial lesion (LSIL), with the pathological results as the golden standards.</p><p><b>RESULTS</b>The detection rate of high-risk HPV-DNA was 14.0%. HPV detection rates in 15-24, 25-29, 30-34, 35-39, 40-44, 45-49, and 50-59 age groups were 15.5%, 17.7%, 12.6%, 8.8%, 10.2%, 15.3%, and 21.0%, respectively (P < 0.05). HPV detection rates in 25-29 years group and 50-59 years group were significantly higher than those in other groups (P < 0.05) and 35-39 group had the lowest detection rate. The curve of HPV infection rates in all groups was 'V' type. The overall incidence of CIN was 4.4%. The incidences of CIN , CIN , and CIN were 3.2%, 1.0%, and 0.3%, respectively, in which the incidence of CIN was significantly higher than those of CIN and . HPV detection rates increased with cervical lesion grades, which in >or=CIN groups and normal group were 100.0% and 8.3%, respectively. No cervical cancer was identified in this research. The sensitivities of VIA, colposcopy, LCT, and HC-II for high-risk HPV screening were 35.7%, 50.0%, 92.9%,and 100%, respectively, in detecting high-grade squamous intraepithelial lesion (HSIL), the specificities of these four methods were 96.0%, 87.2%, 88.4%, and 86.9%, respectively. Satisfactory negative predictive values were obtained for all methods.</p><p><b>CONCLUSIONS</b>HPV infection is the main risk factor for CIN. Cervical cancer among female populations in Shenzhen is still in early stages. Prevention of HPV infection and treatment of CIN are key for the prevention of cervical cancer.</p>

Relationship between SLP-2 expression and prognosis in laryngeal squamous cell carcinoma and mammary invasive carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of stomatin like protein-2 (SLP-2) at mRNA and protein levels in two kinds of malignant epithelial tumors, including laryngeal squamous cell carcinoma (LSCC) and invasive breast cancer, and to study the relations of SLP-2 expression and clinicopathologic parameters with the prognosis.</p><p><b>METHODS</b>RT-PCR and Western blot were used to detect the expression of SLP-2 mRNA and protein in LSCC and their normal counterparts (46 and 10 pair, respectively). Immunohistochemistry was carried on tissue array constructed from LSCC (104 cases) and breast cancer (263 cases), respectively. The association between SLP-2 expression and clinicopathologic parameters was analyzed.</p><p><b>RESULTS</b>LSCC showed a higher expression of SLP-2 than that of their normal counterparts (negative expression) at mRNA (83%, 38/46) and protein (7/10) level. Immunohistochemical analysis of LSCC showed that compared with negative expression in normal laryngeal epithelium (0/20), a higher SLP-2 expression was detected in LSCC (36/104, P=0.000) and associated with the advanced clinical stage (P<0.01) and lymph node metastasis (P=0.003). Immunohistochemical study of invasive breast cancer demonstrated that compared with negative expression in normal breast tissue (0/10), more than one half of the cases showed a high SLP-2 expression (52.5%, 138/263, P=0.000) in breast cancer, which correlated with the tumor size (P=0.020), lymph node metastasis (P<0.01), advanced clinical stage (P<0.01), distant metastasis (P=0.002) and HER2/neu protein expression (P=0.037). Survival analysis showed a shorter overall survival probability in patients with a high SLP-2 expression. It was considered that lymph node metastasis, positive HER2/neu expression, and high-level SLP-2 expression may act as the independent prognostic factors for those tumors.</p><p><b>CONCLUSIONS</b>A high expression level of SLP-2 may be associating with the development of invasion and metastasis in LSCC and breast cancer, and SLP-2 is also considered working as an independent factor indicating a poor prognosis clinically in breast cancer.</p>

Expression of SLP-2 protein in esophageal squamous cell carcinoma is associated with cancer invasion / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the expression of stomatin-like protein-2 (SLP-2) in esophageal squamous cell carcinoma (ESCC), and analyze the correlation between SLP-2 expression and clinicopathological features.</p><p><b>METHODS</b>The expression of SLP-2 protein in ESCC tissues (18 and 220 cases respectively) was detected by Western blot and IHC. The association between SLP-2 expression and clinicopathological features was analyzed.</p><p><b>RESULTS</b>Compared with normal epithelium, 13 cases of ESCC tissues showed a higher expression of SLP-2 on the protein level (72.2%, 13/18). IHC analysis on tissue microarray revealed that the expression rate of SLP-2 protein in ESCC was 54.1% and in normal esophageal mucosa was 3.6%, showing a significant difference (P < 0.001). SLP-2 high-level expression correlates with the extent of ESCC invasion (P = 0.033), but not with other clinicopathologic characteristics (P > 0.05).</p><p><b>CONCLUSION</b>SLP-2 as a novel cancer-related gene may play an important role in tumorigenesis of ESCC. The overexpression of SLP-2 may be closely associated with the invasion of esophageal cancer.</p>

The study on the diagnostic value of pregnancy-associated plasma protein-A in acute coronary syndrome patients / 中国医师进修杂志

Objective To investigate the diagnostic value of pregnancy-associated plasma protein-A (PAPP-A) in acute coronary syndrome (ACS) patients. Methods Forty-nine cTnI-negative patients with coronary artery disease who were documented by angiography [31 cases with ACS,18 cases with stable angina (SAP)], and 28 healthy persons were selected as controls. PAPP-A and hs-CRP were analysed with enzyme-linked immunosorbent assay (ELISA). Results Circulating PAPP-A and ha-CRP levels were significandy higher in patients with ACS than those in patients with SAP and controls (P < 0.05). PAPP-A threshold value of 2.79 μg/ml identified patients who had ACS with a sensitivity of 81.0% and a specificity of 84.6%. PAPP-A levels were correlated with hs-CRP levels in patients with ACS (r = 0.418, P < 0.01). Conclusion PAPP-A is a strong candidate marker of ACS, especially to eTnl-negative patients.

Defibrillation efficacy of a newly developed automated external defibrillator in a swine ventricular tachycardia/fibrillation model / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of this study was to evaluate the recognition and defibrillation efficiency of a newly developed automated external defibrillator (AED).</p><p><b>METHOD</b>Ventricular tachycardia (VT)/ventricular fibrillation (VF) was induced by alternating current (50 Hz) through an electrode placed on apex of right ventricle in 23 anesthetized swine and recorded, recognized and defibrillated by a newly developed AED.</p><p><b>RESULTS</b>A total of 96 VF was induced and 145 defibrillations were recorded. We analyzed available 167 electrocardiosignal with a total length of 103,740 seconds. The accuracy, sensitivity and the specificity of the AED on VT/VF recognition are 99.5%, 98.2% and 99.6%, respectively. The success rate of defibrillation was 33.4% which increased in proportion to defibrillation energy. The defibrillation threshold of energy is 29.10-116.91 (78.75 +/- 35.64) J, the defibrillation threshold of electric quantity is (0.11 +/- 0.04) C and the defibrillation threshold of voltage is (1216.67 +/- 260.87) V.</p><p><b>CONCLUSIONS</b>This newly developed AED has high sensitivity and the specificity on recognizing VT/VF. The lower success rate of defibrillation of this AED is associated with the low defibrillation energy during defibrillation which needs to be improved on further development.</p>