OBJECTIVETo synthesize cyclin-dependent kinase (CDKs) inhibitors and assay their antitumor activities.

METHODSA series of pyrimidines containing different arylamino and 1-(methylsulfonyl)piperidin moieties were designed by combining the segments 1-(methylsulfonyl)piperidin and pyrimidine heterocycles according to the super-position principle of the reinforcement of biological activities.

RESULTSTheir structures were characterized by MS and 1H NMR spectra and all the synthesized compounds were screened for their antimicrobial activity with MTT assay.

CONCLUSIONThe preliminary bioassay showed that compound 3 b displayed good antitumor activity (IC(50)=13.6 µmol/L). The preliminary structure activity relationship analysis of these analogues suggest that the steric factor may have important impact on the anti-tumor activity.

Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Humans ; Pyrimidines ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

BACKGROUNDKetanserin (KT), a selective serotonin (5-HT) 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method was used to investigate the effect of KT and potassium ion on Kv1.3 potassium channels and explore the role of blocker KT in the alteration of channel kinetics contributing to the potassium ion imbalances.

METHODSKv1.3 channels were expressed in xenopus oocytes, and currents were measured using the two-microelectrode voltage-clamp technique.

RESULTSKCl made a left shift of activation and an inactivation curve of Kv1.3 current and accelerated the activation and inactivation time constant. High extracellular [K(+)] attenuated the blockade effect of KT on Kv1.3 channels. In the presence of KT and KCl the activation and inactivation time constants were not influenced significantly no matter what was administered first. KT did not significantly inhibit Kv1.3 current induced by tetraethylammonium (TEA).

CONCLUSIONSKT is a weak blocker of Kv1.3 channels at different concentrations of extracellular potassium and binds to the intracellular side of the channel pore. The inhibitor KT of ion channels is not fully effective in clinical use because of high [K(+)](o) and other electrolyte disorders.

Animals ; Electrophysiology ; Female ; Ketanserin ; pharmacology ; Kv1.3 Potassium Channel ; drug effects ; metabolism ; Oocytes ; Patch-Clamp Techniques ; Potassium ; pharmacology ; Serotonin Antagonists ; pharmacology ; Xenopus laevis

OBJECTIVETo evaluate the impact of universal salt iodization using monitoring data on correctional status of iodine deficiency and hospitalized thyroid diseases.

METHODSRetrospective survey was conducted to collect medical records of hospitalized thyroid disease cases. Routine monitoring data on population iodine nutrition status and goiter prevalence were analyzed.

RESULTSThe coverage of adequately iodized salt was consistently above 95%. Hospitalization rate of thyroid diseases rose steadily, and peaked at 54.5 per 100,000. The proportion of hospitalized thyroid disease among hospitalized diseases also rose with female and those aged above 40 years old mostly affected. The proportion of hospitalized hyperthyroidism among total hospitalized thyroid disease rose from 13.6% to 34.7%.

CONCLUSIONSUniversal salt iodization might eliminate iodine deficiency while other impact still exists. However, the benefits of universal salt iodization should be far overweight the adverse effects.

China ; epidemiology ; Female ; Humans ; Iodine ; therapeutic use ; Male ; Sodium Chloride, Dietary ; therapeutic use ; Thyroid Diseases ; epidemiology ; prevention & control

OBJECTIVETo assess the value of preoperative neutrophil-lymphocyte ratio (NLR) for prognosis in patients with colorectal cancer after radical operation.

METHODSClinical data of 140 patients with colorectal cancer undergoing radical operation in the Department of General Surgery of General Hospital of PLA from July 2005 to July 2011 were analyzed retrospectively. According to preoperative NLR, patients were divided into the low NLR group (NLR<5, n=105) and the high NLR group (NLR≥5, n=35). The overall 5-year survival rates of two groups were compared and the independent risk factors were examined by univariate analysis and Cox model.

RESULTSThe overall 5-year survival rates of the low and high NLR groups were 74.8% and 54.7% respectively with significant difference (P=0.03). Univariate analysis revealed depth of tumor, lymph nodes metastasis, TMN stage and NLR were associated with survival (P<0.05, P<0.01). Cox model showed that NLR was independent risk factor of prognosis (RR=1.068, 95%CI:1.009-1.129, P=0.02).

CONCLUSIONPreoperative NLR≥5 predicts poorer prognosis of colorectal cancer patients.

Aged ; Colorectal Neoplasms ; blood ; diagnosis ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Lymphocytes ; pathology ; Male ; Neutrophils ; pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate

OBJECTIVETo explore the prognostic factors of anorectal malignant melanoma (ARMM).

METHODSMedical records and follow-up data of 34 patients with ARMM treated in the Chinese PLA General Hospital from March 1993 to November 2011 were analyzed retrospectively.

RESULTSThere were 26 abdominoperineal resections(APR) and 8 wide local excisions (WLE). Twenty patients underwent postoperative adjuvant therapy, including chemotherapy in 14 cases, radiotherapy in 2 cases, traditional Chinese medicine therapy in 4 cases and immunotherapy in 16 cases. Postoperative follow-up was carried out in all the patients and the mean follow-up period was 27 months. The 1-, 3- and 5-year overall survival rates were 76.3%, 39.6% and 20.6% respectively, while the 1-, 3- and 5-year disease-free survival rates were 60.6%, 30.8% and 12.8% respectively. APR and postoperative immunotherapy could significantly reduce the local recurrence rate. According to the Kaplan-Meier method, gross type of tumor, mural involvement, lymph metastasis, and clinical staging had significant effects on overall survival, while lymph metastasis and postoperative immunotherapy on disease-free survival. Cox proportional hazards model indicated that the clinical staging and postoperative immunotherapy were significant predictive factors.

CONCLUSIONSEarly diagnosis and correct choice of surgical method are the keys to the treatment. Postoperative immunotherapy can prolong disease-free survival.

Disease-Free Survival ; Humans ; Lymphatic Metastasis ; Melanoma ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Survival Rate

OBJECTIVETo provide evidence for more accurate diagnosis of birth defects based on the pathoanatomy of congenital malformations.

METHODSData used in this study were obtained from Luliang City Hospital and three county hospitals of Shanxi province between February 2004 and March 2006. Autopsy and pathological examination of 160 dead fetuses and stillbirths were performed. Photos of dead fetuses and stillbirths were taken, tissues were cut into sections for pathological examination under microscope, all pathological information was recorded, and percentage of birth defects was calculated.

RESULTSThe proportion of dead fetuses and stillbirths with or without congenital malformations was 84.4% (135/160) and 15.6% (25/160), respectively. There were 16 categories of major external and internal birth defects in 135 cases of such defects. Congenital heart defects, anencephaly and spina bifida had a higher prevalence rate in the study period. The prevalence rate of non-malformation death and birth defects < 28 gestational weeks and internal anomalies > or = 28 gestational weeks was 14.61% (61/4175) and 17.25% (72/4175), respectively. A total of 413 in situ anomalies were found in 135 cases of autopsy. Spina bifida, anencephaly, congenital heart defects, aplasia or accessory lobe of lung, renal agenesis and dysplasis and congenital hydrocephaly were more closely associated with severe malformations than with mitis malformations. The cases of dead fetuses and stillbirths with multiple malformations (> or = 2 in situ anomalies) had a higher proportion (74.1%), whereas those with isolated malformations had a lower proportion (25.93%).

CONCLUSIONThe occurrence of congenital malformations in different embryonic developmental stages affects multiple organs. Postmortem examination of internal and multiple malformations of fetal deaths and stillbirths can provide more accurate diagnostic information for birth defects.

Cause of Death ; China ; epidemiology ; Congenital Abnormalities ; diagnosis ; epidemiology ; Female ; Humans ; Infant, Newborn ; Male ; Population Surveillance ; Pregnancy ; Stillbirth

Objective: To determine the association between physical health fitness with Chinese reading ability of schoolaged children, so as to provide evidence for improving children s reading ability. Methods: A questionnaire survey was conducted among 1 923 school aged children in grades 2-6 in a primary school in Wuhan, Hubei Province, China. The questionnaire included basic demographic information and Dyslexia Checklist for Chinese Children and the Pupil Rating Scale Revised Screening. At the same time, participants underwent physical fitness tests which included an assessment of height, weight, and lung capacity, as well as a 50 meter run, sit forward bend, one minute skipping rope task, sit ups, and a 50 × 8 round trip. Results: A total of 59 children were identified with dyslexia. Normal children achieved higher scores than children with dyslexia in the total physical health score, as well as the one minute skipping rope score, one minute sit up score, and sitting forward score ( P <0.05). Multiple linear regression analyses showed that the reading ability of girls was higher than that of boys ( β =-3.04, P <0.01), and the children who regularly participated in more intense physical activity and who had higher fitness scores had a higher reading ability ( β =-1.68, -0.08, P <0.01). Children s reading ability increased significantly with parental educational level( P <0.05). Conclusion Gender, parents education level, physical exercise intensity, and children s physical fitness were identified as influencing factors of school age children s reading ability. A positive correlation was found between children s physical health level and reading ability.

Objective To investigate the effect of empathy in compliance of inserting gastric canal in emergency treatment to patients of taking poison, so that raise the achievement ratio of inserting gastric canal.Methods From July 2008, to October 2009, empathy nursing was applied for inserting gastric canal to 125 patients of taking poison who were conscious, through comparing the time of inserting gastric canal, patients' compliance, and achievement ratio of bout, we investigated the effect of empathy nursing. Results Afetr empathy nursing, the time of inserting gastric canal was shorter than before, the difference was statistically significant ( P ＜ 0. 01 ). Patients' complian and chievement ratio of insertiny gastric canal were better than before,the difference was statistically significant ( P ＜ 0. 01 ). Conclusions In emergency treatment to patients of taking poison, by empathy nursing, we can raise the patients' compliance, shorten the time of inserting gastric canal, accordingly raise achievement ratio of bout of inserting gastric canal.

Objective: To examine the changes of depressive and anxiety symptoms in school aged children during home confinement and to identify possible influence of learning and lifestyle behaviors on mental health changes. Methods: The population of this study were obtained from the "Tongji Mental Health Cohort". Two primary schools in Wuhan were selected through cluster sampling and students in grade 2-5 were surveyed. This study was divided into two stages. In the first stage (T1=during home learning), a total of 2 588 valid questionnaires were collected. In the second phase (T2=during school learning), 2 424 children were followed up successfully. Combining the results of the depression and anxiety symptoms of the two surveys of children respectively to classify the children s psychological outcomes. Association between home learning and lifestyle behaviors with the change of psychological symptoms in school aged children were estimated by disordered multi classification Logistic regression. Results: The prevalence of depressive and anxiety symptoms were 28.9% and 21.0% in school aged children at T1, 35.6% and 30.6% at T2, respectively. The aggravation and persistence of depressive and anxiety symptoms in children were partly related to their home learning and lifestyle behaviors. Concentration in class（ OR=0.63，95%CI =0.45-0.89）, frequent interaction with teachers ( OR =0.74, 95% CI = 0.57- 0.95 ), participation in physical exercise at home ( OR =0.60, 95% CI =0.41-0.87) was negatively associated with depressive symptoms in children. Time spent on playing video games ( OR =1.15, 95% CI =1.06-1.24) and fear of infection with coronavirus disease 2019 ( OR =1.83, 95% CI =1.39-2.42) were positively associated with anxiety in children. Boys（ OR=0.70， 0.63 ） were more likely to suffer from depression and anxiety symptoms than girls. Conclusion The prevalence of depressive and anxiety symptoms among school aged children increased when they went back to school after home confinement, suggesting more attention are needed for mental health intervention among school aged children.

Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4％)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P＜0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P＜0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P＜0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P＜0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P＞0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P＜0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P＜0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.