Objective To detect and explore the expression and clinical significance of dual specificity tyrosine phosphorylation regulated kinase1b (Dyrk1b) in the specimens and cells of cervical lesions. Methods (1)All the data were collected from 75 patients with cervical cancer and 52 cases with squamous intraepithelial lesion(SIL)admitted in the First Affiliated Hospital of Dalian Medical College during Jan. 2011 to Dec. 2013 and confirmed by pathological examination, included 60 cases of stageⅠand 15 cases of stageⅡ, 12 cases with low-grade squamous intraepithelial lesion(LSIL)and 40 cases with high-grade squamous intraepithelial lesion(HSIL). While, 28 cases with chronic cervicitis were chosen as the control group. The protein expression of Dyrk1b was detected by immunohistochemistry among the four groups.(2)The expression of Dyrk1b in HeLa and SiHa cells were detected by western blot method and the expression of Dyrk1b protein were also detected after treatment of AZ191 (5, 10 μmol/L) for 48 hours in HeLa and SiHa cells.(3)The cellular survival and proliferation of HeLa and SiHa cells treated by different concentrations of AZ191(2.5, 5, 10, 25, 50, 100 μmol/L)for 48 hours were detected by methyl thiazolyl tetrazolium (MTT) assay.(4)The rate of apoptosis of HeLa and SiHa cells was detected by flowcytometry after treatment of AZ191 (5, 10μmol/L) for 48 hours. Results (1)The positive rates of Dyrk1b protein in chronic cervicitis, LSIL, HSIL and cervical squamous cancer by immunohistochemistry were 11%(3/28), 1/12, 42%(17/40)and 71%(53/75), respectively. The expression of Dyrk1b in cervical squamous cancer and HISL were higher than those in LSIL and chronic cervicitis (P<0.01), there were significant difference between cervical squamous cancer and HSIL, or between HSIL and LSIL(all P<0.05), while there were not significant difference between LSIL and chronic cervicitis(P>0.05). Expression of Dyrk1b was correlated with stromal invasion depth of cervical cancer (P<0.05), but not with age, clinical stage, lymph node metastasis, and serum squamous cell carcinom antigen(SCC-Ag)levels (all P>0.05). (2) Dyrk1b protein was expressed in different levels in HeLa and SiHa cells, and the expression of Dyrk1b was decreased gradually as the increased of the concentration of AZ191 in both HeLa and SiHa cells by treatment of AZ191 for 48 hours. (3) Different concentration of AZ191 treated on cervical cancer cells could inhibit the cellular proliferation and induce cell apoptosis in a concentration-dependent manner(P<0.01), concomitant to the decreased cell survival rate. The apoptosis rate of HeLa and SiHa were increased significantly after 10μmol/L AZ191-treatment for 48 hours, but no any difference induced by 5 μmol/L AZ191-treatment compared to control group. Also,there was no any difference between Hela and SiHa cells in either inhibitory effect or apoptosis rate induced by AZ191. Conclusions Dyrk1b is over-expressed in either specimens or cells of cervical cancer. The expression of Dyrk1b protein in cervical lesions is increased as the progression of disease. Dyrk1b inhibitor AZ191 could inhibit cellular proliferation and induce apoptosis in a concentration-dependent manner in cervical cancer cells.

A fluorescent immunochromatographic test strip based on the quantum dots submicrobeads (QBs) was developed for quantitative detection of chloramphenicol (CAP). In this method, monoclonal antibody of CAP and OBs complex fluorescent probe was first prepared using 1-ethyl-3-( 3-dimethylaminopropyl ) carbodiimide / N-hydroxysuccinimide coupling approach, then complete antigen CAP-HS-BSA was synthesized and sprayed on nitrocellulose membrane as test line (T line). Similarly, goat anti-mouse antibody was sprayed as control line (C line). The time required for the analysis was 15 min, and the limit of detection (LOD) for CAP was 0. 1 μg / L, with a working range of 0. 1 - 100 μg / L. In spiked milk samples, the test strip demonstrated high recoveries in the range from 93. 3% to 97. 9% with relative standard deviations of less than 7% .

This research was aimed to explore the effects of blocking B7/CD28 and CD40/CD154 co-stimulatory signals on engraftment of hematopoietic stem cell in the sensitized recipient so as to provide the experimental evidence for the treatment of sensitized recipient's immune rejection after clinical allogeneic hematopoietic stem cell transplantation (HSCT). The BALB/c mice were divided into 4 groups: (1)mice sensitized on 7 day before transplant; (2)mice were sensitized on 7 day before transplant, and injected CTLA4Ig+anti-CD154 applied; (3)normal mice injected by corresponding isotype control IgG of CTLA4Ig and anti-CD154; (4)normal blank control mice. Each group had 15 mice. On day 0, mice of each group were irradiated lethally 8 Gy by linear accelerator, and the bone marrow cells of C57BL/6 labeled by fluorescence staining were injected via the tail vein. The fluorescent cell level in peripheral blood and organ tissue at different time points were detected by flow cytometry (FCM) for homing assessment. Survival rates and hematopoietic reconstitution were also monitored and recorded. The results showed that application of CTLA4Ig anti-CD154 could promote implantation of allogeneic HSC in sensitized recipients, induce the immune tolerance, prolong their survival time and accelerate the hematopoietic reconstitution within 28 days, compared with the sensitized group. It is concluded that applying CTLA4Ig and anti-CD154 can enhance the engraftment of HSCT and induce immune tolerance in the sensitized recipient after allogeneic HSCT and accelerate the hematopoietic reconstitution.
Abatacept ; Animals ; B7 Antigens ; antagonists & inhibitors ; CD28 Antigens ; antagonists & inhibitors ; CD40 Antigens ; antagonists & inhibitors ; CD40 Ligand ; antagonists & inhibitors ; Graft Rejection ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Immune Tolerance ; Immunoconjugates ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Transplantation, Homologous

Objective The objective of this study was to explore the association between human papillomavirus( HPV) and prognosis of lung cancer by meta-analysis. Methods The PubMed,Embase and Cochrane literature databases studies were searched using a combination of subject terms and free words. As of October 2018,a total of 123 related documents were obtained. After screen-ing the literature according to inclusion and exclusion criteria,the basic information of the study,HPV detection methods,lung cancer patients,hazard ratio(HR)values and 95% confidence interval(CI)were extracted from each study. The meta-analysis of random effects models was used to evaluate the correlation between HPV infection and prognosis in patients with lung cancer. Heterogeneity was assessed using the Q test and I2statistics,and publication bias was tested using Egger′s linear regression test and Begg′s rank cor-relation test. Results The study finally included 11 articles(9 in Asia,2 in Europe and US),and 1439 patients with lung cancer. Meta-analysis using a random-effects model showed no significant association between HPV infection and prognosis of lung cancer (HR=0. 90,95% CI:0. 71~1. 13). A stratified analysis of lung cancer pathological subtypes showed that the prognosis of patients with HPV-infected lung adenocarcinoma was significantly better than that in patients without HPV-infected lung adenocarcinoma (HR=0. 65,95% CI:0. 49~0. 85). Sensitivity analysis was performed by sequentially removing the included studies,and the results were not statistically significant. The results of Egger′s test(P=0. 708)and Begg′s test(P=0. 784)suggest that there is no publica-tion bias in this study. Conclusion HPV infection may be related to the prognostic of patients with lung adenocarcinoma. More basic and clinical studies are needed to further explore the association between HPV infection and lung adenocarcinoma as well as the corre-sponding mechanisms in the future.

Objective:To investigate the safety and efficacy of sacral neuromodulation(SNM)therapy for the treatment of lower urinary tract dysfunction(LUTD)in elderly patients.Methods:Clinical data of 91 elderly patients with LUTD from multiple medical institutions who received SNM during the period from January 2012 to December 2016 were retrospectively analyzed.Patients were divided into four groups: the interstitial cystitis(IC)group(n=28), the neurogenic bladder(NB)group(n=36), the overactive bladder syndrome(OAB)group(n=13)and the idiopathic dysuria(ID)group(n=14). Different sets of evaluation parameters were used for different diseases.Patients’ baseline data and data in stage I(test phase)and stage Ⅱ(permanent SNM)were recorded, statistically analyzed and compared.Results:Ninety-one people underwent SNM treatment.Of them, 53 patients received permanent implants(stage Ⅱ), and the total conversion rate of stage I to stage Ⅱ was 58.2%(53/91). Patients receiving permanent implants(stage Ⅱ)had a preoperative period ranging from 3 months to 30 years, and were followed up for 2 to 58 months after treatment, with an average follow-up of 19.6 months.The improvement rates in stage I for urinary urgency, daily urination frequency, daily nocturnal urination frequency, maximum urine volume, daily average urine volume, daily urine leakage frequency, and quality of life score were 35.4%, 31.6%, 33.7%, 32.6%, 49.2%, 43.2% and 13.2%, respectively.The improvement rates in stage Ⅱ for urinary urgency, daily urination frequency, daily nocturnal urination frequency, maximum urine volume, daily average urine volume, daily urine leakage frequency, and quality of life score were 43.2%, 40.0%, 37.8%, 50.5%, 70.5%, 70.4% and 43.2%, respectively.Three adverse events occurred, including 1 case of recurrent symptoms, 1 case of moderate infection, and 1 case of electrical lead dislocation.Conclusions:Sacral nerve stimulation has definitive and consistent curative effects on LUTD in elderly people.The follow-up time should be extended to further study the safety of sacral nerve stimulation.

Objective To investigate the efficacy of Fuzheng Hejie Prescription(composed of Scutellariae Radix,Lonicerae Japonicae Flos,Agastachis Herba,Bupleuri Radix,Atractylodis Rhizoma,Glycyrrhizae Radix et Rhizoma,etc.)in the treatment of respiratory viral infections in children and to observe its effect on inflammatory factors and immune function.Methods A total of 203 children with respiratory viral infection of H1N1 virus were randomly divided into 101 cases in the observation group and 102 cases in the control group.Both groups were given the routine treatment for subsiding fever,maintaining water-electrolyte balance,and ensuring enough sleep.And additionally,the control group was given Ribavirin Granules and Ibuprofen Granules,and the observation group was given Fuzheng Hejie Prescription based on the treatment for the control group.The course of treatment covered 7 days.The changes of traditional Chinese medicine(TCM)syndrome scores and the levels of immunological indicators and inflammatory factors in the two groups were observed before and after the treatment.Moreover,the clinical efficacy,symptom resolution time and the incidence of adverse reactions were compared between the two groups of children.Results(1)In the course of the trial,one case fell off in the observation group and 2 cases fell off in the control group,and eventually 100 children in each group were included in the trial.(2)After 7 days of treatment,the total effective rate of the observation group was 93.00%(93/100),and that of the control group was 88.00%(88/100),and the intergroup comparison showed that the therapeutic effect of the observation group was superior to that of the control group,but the difference was not statistically significant(χ2= 1.454,P = 0.228).(3)After treatment,the scores of primary symptoms and secondary symptoms as well as the total TCM syndrome scores in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the time for the resolution of clinical symptoms such as fever,cough,expectoration and sore throat in the observation group was significantly shorter than that in the control group(P＜0.01).(5)After treatment,the levels of immunological indicators of T lymphocyte subset CD3+ and CD4+ in the two groups were increased compared with those before treatment(P＜0.05),and the levels of CD8+ and B cells were decreased compared with those before treatment(P＜0.05).The intergroup comparison showed that the increase in the levels of CD3+ and CD4+ as well as the decrease in the levels of CD8+ and B cells of the observation group was significantly superior to that of the control group(P＜0.01).(6)After treatment,the levels of inflammatory factors of serum amyloid A(SAA),C-reactive protein(CRP),serum tumor necrosis factor alpha(TNF-α),soluble interleukin 2 receptor(SIL-2R),and interleukin 6(IL-6)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels of interleukin 2(IL-2)and interferon γ(IFN-γ)ls were all significantly increased compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum SAA,CRP,TNF-α,SIL-2R,and IL-6 levels and the increase of serum IL-2 and IFN-γ levels in the observation group were significantly superior to those in the control group(P＜0.01).(7)The incidence of adverse reactions in the observation group was 2.00%(2/100),which was significantly lower than that of 8.00%(8/100)in the control group,but the difference was not statistically significant(χ2 = 3.789,P = 0.052).Conclusion Fuzheng Hejie Prescription exerts certain effect in treating children with respiratory viral infection of H1N1 virus,which can effectively decrease children's TCM syndrome scores,regulate the inflammatory response,improve the immune function,accelerate the relief of clinical symptoms and shorten the course of the disease.

The 2017 China (Lianyungang) International Medical Technology Conference was held in Lianyungang,Jiangsu Province during November 15-17,2017.During this conference,the Division for Traditional Chinese Medicine and Natural Products Pharmacology of Chinese Pharmacological Society (CNPHARS) and Jiangsu Kanion Pharmaceutical Co. Ltd.jointly held the Forum on R&D and Interna-tionalization of New Drugs and Health Products of Traditional Chinese Medicine.The forum was co-chaired by Professor ZHANG Yong-xiang, President of CNPHARS, Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Chair of the Natural Product Section of Inter-national Union of Basic&Clinical Pharmacology(IUPHAR), Professor DU Guan-hua,former President of CNPHARS and Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS,and Dr.XIAO Wei,Chairman of the Board of Jiangsu Kanion Pharmaceutical Co. Ltd. And Vice-Chair of Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS. More than 70 scholars attended the forum, including four foreign experts [Michael SPEDDING, Secretary-General of IUPHAR; Professor Valérie B. SCHINI-KERTH, Vice-Chair of the Natural Product Section of IUPHAR; Professor Cherry WAINWRGHT, Director of Centre for Natural Product Drugs of Robert Gordon University; Professor InKyeom KIM, Director of the Korean Society of Pharmacology], members of the Division for Traditional Chinese Medicine and Natural Products Pharmacology of CNPHARS and leading researchers at Jiangsu Kanion Pharmaceutical Co.,Ltd.GU Jin-hui,Director of the Division of National Science and Technology Major Project for Drug Innovation,Department of Health Science,Technology and Education,National Health and Family Planning Commission of the People's Republic of China was also invited to attend the forum. Representatives discussed the R&D and internationalization of new drugs and health products of traditional Chinese medicine.The summary of views and advice of some experts was published here for the purpose of promoting domestic and overseas academic exchange, and playing an active role in improving the level of R&D and internationalization of new drugs and health products of traditional Chinese medicine in China.

BACKGROUNDWith the progress of perinatal medicine and neonatal technology, more and more extremely low birth weight (ELBW) survived all over the world. This study was designed to investigate the short-term outcomes of ELBW infants during their Neonatal Intensive Care Unit (NICU) stay in the mainland of China.

METHODSAll infants admitted to 26 NICUs with a birth weight (BW) < l000 g were included between January l, 2011 and December 31, 2011. All the data were collected retrospectively from clinical records by a prospectively designed questionnaire. The data collected from each NICU transmitted to the main institution where the results were aggregated and analyzed. Categorical variables were performed with Pearson Chi-square test. Binary Logistic regression analysis was used to detect risk factors.

RESULTSA total of 258 ELBW infants were admitted to 26 NICUs, of whom the mean gestational age (GA) was 28.1 ± 2.2 weeks, and the mean BW was 868 ± 97 g. The overall survival rate at discharge was 50.0%. Despite aggressive treatment 60 infants (23.3%) died and another 69 infants (26.7%) died after medical care withdrawal. Furthermore, the survival rate was significantly higher in coastal areas than inland areas (53.6% vs. 35.3%, P = 0.019). BW < 750 g and GA < 28 weeks were the largest risk factors, and being small for gestational age was a protective factor related to mortality. Respiratory distress syndrome was the most common complication. The incidence of patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia, retinopathy of prematurity was 26.2%, 33.7%, 6.7%, 48.1%, and 41.4%, respectively. Ventilator associated pneumonia was the most common hospital acquired infection during hospitalization.

CONCLUSIONSOur study was the first survey that revealed the present status of ELBW infants in the mainland of China. The mortality and morbidity of ELBW infants remained high as compared to other developed countries.

China ; Female ; Humans ; Infant ; Infant Mortality ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; statistics & numerical data ; Male ; Morbidity ; Respiratory Distress Syndrome, Newborn ; mortality ; Retrospective Studies ; Surveys and Questionnaires

Objective:To explore the correlation between the occurrence of colorectal cancer and different internal environment （cold and heat）. Method:The 70 Wistar rats （male and female） were randomly divided into blank group （10 cases）， cold model group （30 cases） and heat model group （30 cases）. The cold syndrome model was made by intragastric infusion of cold water （0 ℃） and soaking in cold water （10 ℃）. The heat model was made by ethanol （30%） and capsaicin solution （0.9 g·L^-1）. The blank group was given normal saline by gavage， 10 mL·kg^-1·d^-1， for 5 consecutive weeks. The colorectal cancer model was made by subcutaneous injection of DMH solution in the back of neck in the cold model group and heat model group at the 6^th week， 25 mg·kg^-1，once a week，for 12 consecutive times. During the carcinogenesis， only 30% ethanol solution was given to the heat model group， and the modeling was maintained in cold model group， 10 mL·kg^-1·d^-1， for 38 weeks. The general state of the rats in each group was observed， and the changes of food intake and body weight were measured. At the 27^th， 29^th， 32^th， 35^th and 38^th weeks， samples were collected in batches. Intestinal tissues were subjected to hematoxylin-eosin staining （HE） and detection of sodium， potassium-adenosine triphosphate （Na⁺ K⁺-ATP）， calcium， magnesium-adenosine triphosphate （Ca²⁺ Mg²⁺-ATP） activity， lactate dehydrogenase （LDH） activity and succinate dehydrogenase （SDH） activity. Result:The symptoms of hematochezia and ascites in cold model group were earlier than those in heat model group. As compared with the blank group， the food intake and body weight were decreased in cold model group and heat model group. As compared with the blank group， the length of the large intestine was shorter in cold model group at the 32^nd and 35^th week （P<0.05）， the activities of Na⁺ K⁺-ATP， Ca²⁺ Mg²⁺-ATP increased significantly in heat model group at the 27^th， 29^th and 38^th week （P<0.05， P<0.01）， the SDH enzyme activity was decreased in the cold model group at the 29^th and 35^th week （P<0.05， P<0.01）， the SDH enzyme activity was significantly increased in the heat model group at the 38^th week （P<0.01）. At the 27^th week， LDH enzyme activity was significantly reduced in cold model group （P<0.01）. The LDH activity was increased significantly in heat model group at 29^th and 32^nd week （P<0.05， P<0.01）. As compared with the heat model group， the large intestine texture of the cold model rats showed greater brittleness， aggravated fibrosis， more obvious fibroproliferative characteristics， higher tumor incidence， and more serious tumor differentiation. The Na⁺ K⁺-ATP， Ca²⁺ Mg²⁺-ATP enzyme activities of the cold model rats were significantly reduced at 27^th， 29^th， and 38^th weeks （P<0.01）， the SDH enzyme activity was significantly reduced in the cold model rats at 29^th and 38^th weeks （P<0.01）， the LDH activity was reduced in the cold model group at 32^nd week （P<0.05）. Conclusion:Cold environment for colorectal cancer promotes tumorigenesis， and the hot environment can also promote tumorigenesis in a later stage.