Objective: To investigate the effects of DFMO on the growth characteristics, apoptosis and activity of telomerase of K562 cells. Methods: The growth rate, phase distribution of cell cycle and apoptosis of treated cells with DFMO were detected by cell count, morphological assay, FCM analysis and DNA electrophoresis, respectively. The telomerase activity was examined by telomeric repeat amplification protocol(TRAP). Results: In K562 cells treated with DFMO, the growth rate was markedly retarded. The increase in G1 -phase cells and decrease in s-phase population and induction of apoptosis were observed. The activity of telomerase of treated cells was inhibited. Conclusion: The growth inhibition and apoptosis induction of K562 cells treated by DFMO were associated with suppressed telomerase activity. It is suggested that inactivation of telomerase in cancer cells conld be one of important events in antitumor molecular mechanism of inhibition of polyamine biosynthesis.

Orinthine decarboxylase (ODC) is a rate-limiting enzyme in polyamine biosynthesis. Abnormal elevation of ODC activity and subsequent polyamine accumulation are intimately associated with the genesis, development and metastasis of cancer. ODC antisense RNA expression plasmid, pCMV/ODCas, was constructed, with which the cells of human lung squamous carcinoma were transfected by the calcium phosphate precipitation method. After G418 selection, two G418 resistant colonies were obtained. The growth rate, the ability to form colony in soft agar, the biosyntheses of DNA, RNA and proteins, and ODC activities of the two antisense transfectants were significantly suppressed in comparison with the parental cell line. It was demonstrated that these changes were associated with the stable integration of exogenous antisense ODC gene in the genomic DNA of transfectants by analysis of Southern blot and PCR.

Background and purpose:With lifestyle shifts, incidence and mortality patterns for cancers have changed. In order to provide scientiifc basis for the government to control the diseases, this study investigated the can-cer mortality among residents of Rugao city for the period 2008 through 2012.Methods:The epidemiological study of cancer mortality rates among residents of Rugao city was carried out. The results were analyzed with Excel and SPSS software.Results:Cancer was the leading cause of death. The crude mortality rate was 264.55/100 000 and the SMR (standardized mortality ratio) was 155.04/100 000. The mortality of cancer was higher in the male than in the female patients. The top 5 causes of cancer death among residents of Rugao city were esophageal cancer, liver cancer, lung cancer, gastric cancer, and pancreatic cancer for the period 2008 through 2012. Pancreatic cancer and colon, rectum and anus cancer were the iffth and sixth leading causes of cancer death in both male and female, respectively. Nervous system tumor was the eight leading cause of cancer death, whereas osteosarcoma was the tenth. Prostate cancer was the ninth leading cause of cancer death in men. The mortality of cancer was signiifcantly higher in the elderly group than in any other age group. The most common causes of cancer death in adolescents and young adults were leukemia,nervous system tumor and osteosarcoma. The top ifve of potential years of life lost (PYLL) were liver cancer, esopha-geal cancer, lung cancer, gastric cancer and leukemia. The top ifve of average years of life lost (AYLL) were leukemia, nervous system tumor, liver cancer, breast cancer and osteosarcoma.Conclusion:Cancer has been the major cause of death in residents of Rugao city. The mortality of cancer was higher in the male than in the female. Cancer mortality was also higher in the elderly group than in any other age group. Pancreatic cancer was the iffth leading cause of cancer death. Researchers should raise awareness of cancer prevention in the residents. Treatment and prevention of pancreatic cancer, nervous system tumor and osteosarcoma should be emphasized in the prevention of the most common types of cancer. Besides, researchers should focus on early diagnosis, early treatment of cancer and screening of high-risk groups to improve the quality of life of cancer patients.

Objective To evaluate the feasibility of endometrial sampler Pipelle for endometrial histologic diagnosis.Methods Using prospective and self-control methods,200 patients with endometrial biopsy firstly used Pipelle endometrial sampler for endometrial tissue,then followed by diagnostic curettage,the same pathologist evaluated the specimen quality and made the histologic diagnosis.Results Totally 200patients completed the observation,the specimen satisfaction of Pipelle was 93.0％ (in this 200 cases,186cases were satisfactory),its pathological accuracy was 85.0％ (in this 200 cases,170 cases' pathological results are highly consistent with diagnostic curettage).There was no significant difference between two kinds of endometrial sampling (P＞0.05).There was no pain for patients during the Pipelle using process.Conclusion Pipelle could obtain satisfactory samples used for histological diagnosis in normal endometrium,simple hyperplasia,complex hyperplasia,atypical hyperplasia and endometrial cancer disease,because its pathological accuracy is so close to the diagnostic curettage,which may be used as a routine screening tool of endometrial diseases.

A 14-week human fetal kidney was studied by the method of freeze-fracture, the results were as follows:1. All the nuclei of various cells at this stage of development possess distinct nuclear pores with the same diameter and they are distributed randomly on the nuclear membrane. The intramembraneous particles on the PF of both the inner and outer nuclear membranes are more numerous than that of the EF. The morphological features of the nuclear pores vary according to the plane of their fracture face; they appear as dimples on the EF and as valcano mouth on the PF. The interior of the nucleus usually contains homogeneously dispersed particles, but no such structures were seen in thin sections. In some nuclei a round vesicle was revealed.2. The cell membrane of various cells, at this stage, shows special structures to manifest their degree of differentiation. In the less differentiated epithelial cells of the renal tubules, the cell membrane is straight and the intramembraneous particles are randomly distributed, the intromembraneous particles on PF are more than on EF, comparetively well developed tight junctions are located at the latexal surface near the apical portion of the cell while in the differentiated proximal tubules, there are many microvilli on their luminal surface, but their lateral cell membrane is still straight without interdigitations. In some tubules small processes near the basal part may be seen, however, basal fold is still absent. The basal membrane of the renal tubules is very prominent. As to the epithelial cells of the viseral layer of the renal corpuscle, gap and tight junctions are revealed while they are columnar in shape, but as they differentiated into podocyte with primary and secondary processes, the structure of tight junctions become simple, less prominent and discontinuous.3. Cytoplasm: In the process of cell differentiation the amount of cytoplasm increases and the ratio of nuclear end cytoplasmic volume decreases. The orgauelles are less in the undifferentiated cells, so the structure of the cytoplasm of them is much simpler than that of the more differentiated ones. The compartmentation phenomenon of the cytoplasm of differentiated cells become distince. In the freeze-fracture micrographs the membraneous structures, such as mitochondria, Golgi complex and secretion granules etc. are more stereoscopic than those in thin sections, but the opportunity to reveal the fine structures of various cells is minimized due to only one fracture face for each specimen and what structure will be fractured is beyond the control of the operator.

The livers from 5 week 14～32 human fetuses were studied. The results are summarized as follows:1. Two kinds of liver cells revealed by EM: the "light" and "dark" cells. The light ones are larger in size, more numerous in number, containing larger mitochondria and obvious RER and SER, but less free ribosomes than the dark ones. Both of them may contain hemosiderin granules and the configuration of mitochondria enclosed by circular or semicircular RER cisternae.2. Bile canaliculus: Beside canaliculi between two adjacent liver cells, canaliculi situated between 3 or 4 liver cells are not infrequently revealed. That is due to the fetal liver cells are arranged in groups rather than in cords. The stereoscopic configurations of bile canaliculus and the tight junction surrounding it are demonstrated more clearly in freeze-fracture micrograph than that of the TEM. In addition, one intracellular bile canaliculus is found in the freeze-fracture preperation.3. The blood sinusoid and hemopoietic focus: In the 4-week fetus, the endothelium of the sinusoid can hardly be recognized While its lumen is quite large. Many erythrocytes accompanied by their immature components can be seen among it. As to the 32-week fetal liver, the endothelium and Kupffer cell may be easily recognized but the lumen of the sinusoid dimenishes enormously. The hemopoietic foci are localized extra-sinusoidially and in close contact with liver cells. Their volume exceeds one half of the fetal liver lobule before the age of 28 weeks, then it dimenishes gradually. In the space of Disse a fat storage cell is revealed.4. The portal canal : The mensenchyma and immature erythrocytes in the portal canal dimenishes with the increase of the fetal age. The portal canal is surrounded by the pigmented limiting plate cells of the liver lobules. The interlobular bile duct is differentiated from the limiting plate cells. Its epithelium is composed of both light and dark cells. The former is more numerous and contains many large mitochondria in its apical portion, while the latter shows higher electron density. Microvilli are located on the surfaces of both kinds of cells and finger like processes in the enlarged intercellular spaces are revealed.

Objective To compare the efficacy and safety of tranexamic acid(TA)and norethisterone(NET)for the treatment of patients with ovulatory menorrhagia in China. Methods Onehundred and thirty one patients with proven ovulatory menorrhagia from gynecologic clinics of 5 teaching hospitals located in 4 different cities in China were enrolled during Jul 2004 to Dec 2006.Ameng them 128 completed the study.Patients were randomly divided into two therapeutic regimen groups:TA 1g thrice daily during menstrual cycle days(D)1-5,69 cases;or NET 5 mg twice daily on D19-26.59 cases.The drugs were administered for 2 consecutive cycles,then withdrawn and patients were followed-up for 1 more cycle.Data on menstrual blood loss [ estimated by pictorial blood assessment chart(PBAC)],length of menstrual periods,quality of life(QOL)evaluated by a 6 item health-related questionnaire were collectedbefore,during each cycle and were compared.Results Both treatments led to significant decreases of mean PBAC scores and shorter duration of menstrual periods,and improved the QOL ranking during the twotreatment cycles.The mean percentages of PBAC decrements in the TA first and second cycles were significantly greater than those in the NET corresponding cycles(35%VS 17%,P=0.004;4J4%VS 34%,P=0.04 respectively).The success rate of TA second cycle was higher than that of the NET second cycle (41%VS 24%,P=0.04).Improvement of QOL ranking in the TA first cycle was also significantly better than those in the NET first cycle ( P=0.03).The percentage of patients with at least 1 adverse event in TA group(19%)was significantly lower than that in NET group(35%,P=0.04).Patients'willingness tocontinue the treatment in the TA second and follow-up cycles(94%,79%respectively)were significantly higher than those in the corresponding cycles of NET groups(79%,59%respectively;P=0.01,P=0.02).Conclusion The regimen of TA 3 g daily during menstrual days 1-5 is a more effective and tolerable treatment than luteal phase norethisterone for patients with ovulatory menorrhagia.

Objective To study the predictive values of the general movements (GMs) assessment in writhing stage for motor development outcomes in infants with severe neonatal jaundice.Method From December of 2012 to December of 2017,infants with severe neonatal jaundice (serum bilirubin reaching the corresponding level of exchange transfusion according to the reference nomogram) in our hospital were enrolled in the study.Inclusion criteria included corrected gestational age of 37 to 48 weeks,serum bilirubin level below phototherapy intervention value after treatment and general and detailed assessment were carried out in writhing stage when the infant was stable.The patients were regularly followed-up until one-year-old to evaluate the predictive values.Result A total of 241 patients with severe neonatal jaundice were enrolled in the study,including 153 males (63.5％) and 88 females (36.5％),with gestational age between 35 and 42 weeks.The mean gestational age was (37.9± 1.8) weeks,the average birth weight was (3 057±480) g,and the mean serum bilirubin value was (458.9± 119.1) μmol/L.The general evaluation of the GMs was normal in 15 cases (6.2％),and abnormal in 226 cases (93.8％) with 217 cases (90.0％) were poor repertoire (PR) and 9 cases (3.7％) were cramped-synchronized (CS).The predictive values of abnormal GMs for abnormal motor development outcomes were as following:sensitivity 100％,specificity 7.6％,negative predictive value(NPV) 100％.The predictive values of CS for cerebral palsy were as following:sensitivity 22.2％,specificity 97.8％,NPV 94.0％.Detailed evaluation of 241 subjects showed that 13 items had statistically significant differences in the prediction of cerebral palsy (P＜0.05),and 18 items in the prediction of abnormal motor development (P＜0.05).Conclusion The CS pattern and detailed assessment of GMs in the writhing stage may be correlated with the outcomes of motor development in infants with severe neonatal jaundice until one-year-old.

Objective: To investigate the dynamic changes of copper and iron contents in brain tissue, body fluids and barriers of rats exposed to lead at different periods in order to provide a theoretical basis for the study of the mechanism of lead nerve injury. Methods: Sixty-four healthy adult SPF male SD rats were randomly divided into control group and lead exposure group, after one week of adaptive feeding, rats in the lead exposure group were treated with 250 mg/L lead acetate, and rats in control group were treated with ordinary drinking water, the experimental period was 12 weeks. After exposure for 3, 6, 9 and 12 weeks, the samples including blood, choroid plexus, cerebrospinal fluid, cortex, hippocampus, striatum, hypothalamus, amygdala, substantia nigra and cerebellum were obtained. Lead, copper and iron content in all kinds of samples were detected by Inductively Coupled Plasma Mass Spectrometry(ICP-MS). The measurement data were presented as Mean±SD, Comparison of metal contents in different tissues of rats at different time analyzed using repeated measurement analysis of variance, Two-variable correlation analysis using Spearman correlation test.The relationship between lead exposure experiod and copper and iron in samples was studied by using trend test. Results: After 12 weeks of lead exposure compared with the control group, lead contents in cortex, hippocampus, striatum, hypothalamus, amygdala, substantia nigra and cerebellum of rats were 2.21, 2.44, 2.95, 3.53, 4.01, 1.85 and 2.86 folds of control group, and the differences were statistically significant(P<0.05). At the same time, lead content in blood, cerebrospinal fluid,choroid plexus, brain microvessels and bones increased. The increase rate in the amygdala and cerebrospinal fluid ranked first among brain tissue or barrier,which were 4.01 and 3.0 folds respectively. Compared with the control group, Compared with the control group, copper content in cortex,hippocampus, striatum, hypothalamus,amygdala, cerebellum,blood,cerebrospinal fluid,choroid plexus and cerebral microvasculature showed an increasing trend among rats following 3,6,9,12 weeks of lead exposure. Copper content change in the striatum was highest among all brain tissue. The increase rate of copper content in the striatum was at the top among brain tissues. After 12 weeks of lead exposure,copper content in brain microvessels was 4.98 folds higher than that of the control group (P<0.05). After lead exposure at different periods,the iron content in the cortex, hippocampus, striatum,cerebrospinal fluid,choroid plexus and brain microvessels of experimental rats all increased(P<0.05). And the iron increase rate in the hypothalamus or cerebrospinal fluid increase ranked first among brain tissues or body fluid the most obviously. Conclusion With the increase of exposure time, lead exposure can changes in the contents of copper and iron in different brain tissues,body fluids and barriers in rats,among which, the contents of copper and iron in the amygdala,cerebrospinal fluid and brain microvessels increase significantly. This may be related to nerve damage from lead exposure.

Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.
Humans ; Pyrazinamide/therapeutic use* ; Isoniazid/therapeutic use* ; Antitubercular Agents/therapeutic use* ; Tuberculosis, Multidrug-Resistant/microbiology* ; Mycobacterium tuberculosis/genetics* ; Tuberculosis/drug therapy* ; Rifampin/therapeutic use* ; Mutation ; Drug Resistance, Multiple, Bacterial/genetics*