[Progress in treatment for malignant pleural mesothelioma].

Malignant pleural mesothelioma (MPM) is a kind of invasive malignant tumor originated from pleural tissue. The incidence of MPM is not high in the population, but the prognosis is very poor. The median survival time is only about 12 months. Pemetrexed combined with platinum is the first-line chemotherapy regimen recommended by the current guidelines. The use of bevacizumab will further prolong the survival of chemotherapy. Once resistance happened, no anti-tumor treatment has been confirmed to achieve survival benefits. Therefore, there is no recommended standard second-line MPM regimen in international and domestic guidelines, including National Comprehensive Cancer Network (NCCN) guidelines. Vinorelbine, gemcitabine and other monotherapy regimens are commonly used in clinical practice, but the median progression free survival (PFS) is only about 3 months. Immune checkpoint inhibitors (ICIS) have been proved to have a significant inhibitory effect on tumor growth in a variety of malignant tumors, and their efficacy is related to the expression of programmed death-ligand 1(PD-L1). In unresectable MPM, programmed death 1 (PD-1)/PD-L1 inhibitors have been used in a series of clinical studies in the first-line, second-line and above treatment. Some of the results have been cited and recommended by international guidelines, but the overall efficacy improvement is still limited. This review summarizes the latest clinical studies and researches in the field of MPM treatment and predicts the directions and prospect of improving the therapeutic effect in the future.

[Study on the effectiveness of implementation: the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

Objective: To assess the implementation and impact of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases. Methods: Both sociological and epidemiological methods were used to collect qualitative and quantitative data in November and December, 2016 in order to conduct on process and outcome evaluation of the above mentioned objective. In the meantime, case study was also conducted. Results: All the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were found well implemented across the country, with health education and health promotion, surveillance and safeguard measures in particular. A government-led and inter-sector coordination and communication mechanism had been well established, with more than 16 non-health departments actively involved. 28.7% of the residents living in the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases were aware of the key messages related to chronic diseases. Among the residents, 72.1% of them consumed vegetables and 53.6% consumed fruits daily, with another 86.9% walked at least 10 minutes per day. Over 70% of the patients with hypertension or diabetes reported that they were taken care of by the Community Health Centers, and above 50% of them were under standardized management. Residents, living in the National Demonstration Areas under higher ranking of implementation scores, were more likely to be aware of relevant knowledge on chronic disease control and prevention (OR=6.591, 95%CI: 5.188-8.373), salt reduction (OR=1.352, 95%CI: 1.151-1.589), oil reduction (OR=1.477, 95%CI: 1.249-1.746) and recommendation on physical activities (OR=1.975, 95%CI: 1.623- 2.403). Conclusion: The implementation of programs carried out by the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases had served a local platform for the control and prevention of non-communicable diseases, and thus become an important 'carrier' for chronic disease prevention and control programs in China.

[Study on the overall implementation status of the National Demonstration Areas for Comprehensive Prevention and Control of Non-communicable Diseases].

Objective: To understand the current overall status of implementation on the National Demonstration Areas of Comprehensive Prevention and Control of Non-communicable Diseases. Methods: According to the scheme design of the questionnaires, all the National Demonstration Areas were involved in this study. For each National Demonstration Areas, eight departments were selected to complete a total of 12 questionnaires. Results: Scores related to the implementation of the National Demonstration Areas accounted for 71.8% of the total 170 points. Based on the scores gathered from this study, the 23-items-index-system that represented the status of project implementation was classified into seven categories. Categories with higher percentile scores would include: monitoring (88.0%), safeguard measures (75.0%), health education and health promotion (75.0%). Categories with lower percentile scores would include: the national health lifestyle actions (67.7%), community diagnosis (66.7%), discovery and intervention of high-risk groups (64.7%), and patient management (60.9%). There were significant differences noticed among the eastern, central and western areas on items as safeguard measures, health education/promotion, discovery and intervention of high-risk groups. In all, the implementation programs in the eastern Demonstration Areas seemed better than in the central or western regions. As for the 23 items, five of the highest scores appeared on policy support, mortality surveillance, tumor registration, reporting system on cardiovascular/cerebrovascular events, and on tobacco control, respectively. However, the lowest five scores fell on healthy diet, patient self-management program, oral hygiene, setting up the demonstration units and promotion on basic public health services, respectively. The overall scores in the eastern region was higher than that in the central or the western regions. The scores in the central and western regions showed basically the same. Conclusions: The overall status of implementation on the National Demonstration Areas was satisfactory. Future attention should be focusing on patient management as well as discovery and intervention of high-risk groups, which also presented the lowest scores, in this survey.

[Current status of folic acid supplementation in women at child-bearing age in suburban area of Beijing].

Objective: To access the current status of folic acid supplementation in women at childbearing age in suburban area of Beijing, 2016. Methods: In this cross-sectional study, a total of 722 women aged 17-41 years from six hospitals in suburban areas of Beijing were selected through cluster sampling. A questionnaire survey was conducted. Results: The rates of folic acid intake and regular folic acid intake among women under survey were 63.9% (456/714) and 83.3% (380/456). In women who remembered the duration of folic acid supplementation, the overall rate of preconceptional folic acid supplementation was 35.5% (159/450), in whom 27.3% (123/450) began to take folic acid 0-3 months before pregnancy; 8.0% (36/450) began to take folic acid 3 months before pregnancy. Multivariate logistic regression analysis indicated that household registering type, preparation for pregnancy or pregnancy, parity, smoking and alcohol use were the influencing factors for folic acid supplementation. Conclusions: The rate of folic acid supplementation remained low in childbearing aged women in suburban area of Beijing. It is necessary to further strengthen the health education about the importance of folic acid supplementation to improve the intake rate and the regular intake rate of folic acid in pregnant women and to promote maternal infant health and reduce the related complications.

[Effect of magnesium and selenium on the expression of matrix metalloproteinases-20 and kallikrein 4 in fluorosis mice].

OBJECTIVE: To study the effect of magnesium/selenium on the expression of matrix metalloproteinases-20(MMP-20) and kallikrein 4(KLK4) during fluorosis in mice and to explore the formation mechanism of dental fluorosis. METHODS: Eighty SPF male ICR mice were randomly divided into 8 groups according to body weight: control group, magnesium group, selenium group, magnesium-selenium group, fluoride group, magnesium-fluorine group, selenium-fluorine group and magnesium-selenium-fluorine group. Mice in control, magnesium, selenium and magnesium-selenium groups were fed double steamed water, and mice in the other four groups were feddouble steamed water with 50 mg/L F(-). Mice in control and fluoride groups were fed conventionally. Mice in magnesium and magnesium-fluorine groups were fed conventionally by adding MgSO4·7H2O 162.5 mg/kg. Mice in selenium and selenium-fluorine groups were fed conventionally by adding Na2SeO3·5H2O 2 mg/kg. Mice in magnesium-selenium and magnesium-selenium-fluorine groups were fed conventionally by adding MgSO4·7 H2O 162.5 mg/kg + Na2SeO3·5H2O 2 mg/kg. Incisor specimens were obtained after the mice were put into death when they were 42 days. The expressions of MMP-20 and KLK4 were observed by using immunohisto-chemicalstain. RESULTS: The meangray value of MMP-20 of fluoride group(133.1±10.3) was significantly higher than that of control group(116.8±10.0), magnesium group (113.6 ± 9.6), magnesium-selenium group(108.2 ± 15.2), magnesium-fluorine group(111.1 ± 8.1) and magnesium-selenium-fluorine group(108.2 ± 11.0), respectively(F=3.864, P<0.05). The mean gray value of MMP-20 of magnesium-selenium-fluorine group(108.2±11.0) was significantly lower than that of selenium group(125.4 ± 7.9), fluoride group (133.1 ± 10.3) and selenium-fluorine group(126.2 ± 2.8), respectively(F= 3.864, P<0.05). The mean gray value of KLK4 of magnesium-selenium group(117.2±11.7) was significantly lower than others(137.3±7.9 of control group, 144.2±7.7 of magnesium group, 138.9±13.3 of selenium group, 149.7 ± 12.4 of fluoride group, 148.9 ± 7.5 of magnesium-fluorine group, 140.6 ± 17.0 of selenium-fluorine group and 140.7 ± 7.3 of magnesium-selenium-fluorine group, F=3.668, P<0.05). In factorial analysis of fluorosis mice, magnesium had effect on the expression of MMP-20(F=42.613, P<0.05), selenium had effect on the expression of KLK4(F=6.649, P<0.05). CONCLUSIONS: The excessive fluoride could inhibit the expressions of MMP-20. The excessive fluoride hadno significant influence on the expression of KLK4. Magnesium and selenium had antagonistic effect on the dental fluorosis.

Breeding of new Rehmannia glutinosa variety.

Huaidi 81, a new variety of Rehmannia glutinosa with excellent comprehensive characters, was screened by space mutation of hybrid seeds of 85-5 and Beijing No.1. The fresh weight, index composition, resistance, chlorophyll, anthocyanin and photosynthetic characteristics of Huaidi 81 and the main cultivars were determined. The results showed that: the per plant fresh weight of Rehmannia ranked in the order as follows: Huaidi 81 > 85-5 > Golden Nine >Huaifeng >Qinhuai>Beijing No.3, there was extremely significant difference between Huaidi 81 and others. The catalpol content ranked in the following order: Beijing No.3 (1.601%)> Qinhuai (1.588%)> Huaidi 81 (1.314%)> Golden Nine > 85-5 (1.073%)> Huaifeng (0.924%). There was no significant difference between Huaidi 81 and Golden Nine, but extremely significant difference between was found in Huaidi 81 and other varieties; The acteoside content ranked in the following following order: Huaidi 81 (0.096%) > Qin Huai (0.069%) >85-5 (0.047%) > Beijing No.3 (0.035%) > Huaifeng (0.023%) > Golden Nine (0.022%). There was significant difference between Huaidi 81 and other varieties. Huaidi 81 showed high resistance to Septoris digitalis Pass and middle resistance against leaf ring rot, which indicated that Huaidi 81 had good resistance to leaf diseases. Huaidi 81 with highest chlorophyll content and moderate anthocyanin content showed the highest photosynthetic rate. All these results indicated that the new variety Huaidi 81 with best comprehensive properties was suitable for popularizing as a new Rehmannia glutinosa variety.

L-carnitine enhances oocyte maturation and development of parthenogenetic embryos in pigs.

The objective was to determine whether adding L-carnitine in IVM/IVC medium enhanced maturation and developmental competence of porcine oocytes in vitro. Oocyte maturation rates did not differ significantly among groups supplemented with 0, 0.25, 0.5, or 1 mg/mL of L-carnitine added during IVM (although 2 mg/mL of L-carnitine reduced maturation rate). Compared with control oocytes, those treated with 0.5 mg/mL of L-carnitine during IVM had greater (P < 0.05) rates of blastocyst formation after parthenogenetic activation, and these blastocysts had less (P < 0.05) apoptosis. Adding 0.5 mg/mL of L-carnitine during IVM also significantly reduced intracellular reactive oxygen species (ROS), and increased glutathione (GSH) concentrations. With or without glucose supplementation, 0.5 mg/mL of L-carnitine in the IVM medium significantly hastened nuclear maturation of oocytes. Moreover, supplementing the IVM medium with either glucose or L-carnitine increased (P < 0.05) percentages of oocytes that reached the metaphase II (MII) stage, relative to a control group. Final maturation rates in IVM medium containing either glucose or L-carnitine were not significantly different. Adding L-carnitine (0 to 2 mg/mL) to IVC medium for activated porcine oocytes did not significantly affect development. However, 0.5 mg/mL of L-carnitine in IVC medium significantly reduced reactive oxygen species levels and apoptosis in activated blastocysts, although glutathione concentrations were not significantly altered. In conclusion, adding L-carnitine during IVM/IVC improved developmental potential of porcine oocytes, and also the quality of parthenogenetic embryos, probably by accelerating nuclear maturation, and preventing oxidative damage and apoptosis.

Changes in pubococcygeus muscle tension in the pelvic floor of rats after spinal cord injury.

STUDY DESIGN: The purpose of this study was to explore the changes in pelvic floor muscle tension at different times after suprasacral spinal cord injury (SS) and sacral cord injury (SC), and learn more about pelvic floor dysfunction (PFD) after spinal cord injury (SCI). METHOD: A total of 70 healthy female Sprague-Dawley (SD) rats, weighing between 250 and 280 g, were randomly divided into seven groups with 10 rats in each group, which included five SS groups (3 days and 2, 4, 8 and 12 weeks after injury), one SC group (4 weeks after injury) and one normal group. Muscle tension, including muscle compliance, and contraction activity elicited using electrostimulation under two initial lengths were measured at different time points. RESULTS: (1) Muscle compliance decreased within 4 weeks in the SS group (P>0.05), began to increase at 8 weeks (P<0.05) and reached the peak at 12 weeks, which were all lower than the normal level; (2) contraction activity under both initial lengths tended to decrease within 4 weeks, peak at 8 weeks (P<0.05) and decline again at 12 weeks , which were all lower than that of the normal group as well; and (3) the SC group showed similar compliance with the normal group (P>0.05) and less contraction activity when compared with other SS groups (P<0.05). CONCLUSION: Measurement for the compliance and contraction activity of pubococcygeus indicates the changes from decreasing to increasing after suprasacral cord injury, and similar compliance combined with rather low contraction activity compared with the normal group after sacral cord injury, both of which are in accordance with PFD after spinal cord injury.

[Inhibitory activity of Dianthus superbus L. and 11 kinds of diuretic Traditional Chinese medicines for urogenital Chlamydia trachomatis in vitro].

OBJECTIVE: To detect the susceptibility of urogenital chlamydia trachomatis(CT) to 12 kinds of diuretic traditional Chinese medicines. METHODS: The inhibitory activity of these medicines for CT was detected by microculture technique of McCoy cell in vitro. RESULTS: All the 12 kinds of diuretic traditional Chinese medicines had inhibitory activities for urogenital CT, with minimal inhibitory concentrations (MICs) from 0.122 mg.ml-1 to 62.5 mg.ml-1. The activities of Dianthus superbus L., Poria cocos(Shcw.) Woft, Polyporus umbellatus and Artemissia capillaris were stronger. The number and volume of CT inclusions reduced gradually and disappeared finally with the rise of concentration. CONCLUSION: All the 12 kinds of diuretic traditional Chinese medicines possess some inhibitory activity for urogenital CT.

Maspin gene expression in tumor suppression induced by overexpressing manganese-containing superoxide dismutase cDNA in human breast cancer cells.

We have reported the tumor suppressive effects of manganese-containing superoxide dismutase (MnSOD) in human breast cancer cells. In order to understand the molecular mechanism of this anti-tumor effect, we asked whether tumor suppressor gene(s), especially the ones inhibiting tumor invasion and motility, are involved in MnSOD-induced tumor suppression. Maspin is one of the serpin family of protease inhibitors that has been shown to function as a tumor-suppressor in human breast epithelium. In the present study, we demonstrated that maspin expression was up-regulated in human breast cancer MCF-7 cells that overexpress a normal MnSOD gene. The induced maspin transcripts were detected by RT-PCR and Northern blot and identified by sequencing. Maspin gene expression was induced in parallel with the level of exogenous MnSOD protein, which was induced by transfection with varied amounts of cDNA. In order to analyze cell invasion ability, which may be related to the induced maspin gene expression, MnSOD stable transfectants were tested using a matrigel invasion chamber. The invasion ability was reduced to 24% and 36% in the cloned (MCF + SOD) and pooled MnSOD-transfectants (MCF + SODp) respectively, compared with the wild-type MCF-7 cell line. In conclusion, these results suggest that overexpression of a normal MnSOD cDNA in human breast cancer cells up-regulates the gene expression of the protease inhibitor, maspin, which may play a role in the inhibitory function of MnSOD on tumor invasion.

Overexpression of manganese-containing superoxide dismutase confers resistance to the cytotoxicity of tumor necrosis factor alpha and/or hyperthermia.

Human breast cancer cells (MCF-7) overexpressing manganese-containing superoxide dismutase (MnSOD) by stable or transient transfection were challenged with the cytotoxicity of tumor necrosis factor alpha (TNF-alpha), hyperthermia, and a combination of both. In contrast to the vector control and wild-type MCF-7 cells, the stable MnSOD transfectants showed significant resistance to the cytotoxicity of TNF-alpha (100 units/ml), heat at 43 or 45 degrees C, and a combination of TNF-alpha and heat at 43 degrees C. To probe the correlation of MnSOD levels with cell survival, cell sensitivity to TNF-alpha, heat at 43 degrees C, or a combination of both was also measured after MnSOD cDNA transient transfection. The data showed that the level of cell resistance was proportional to the exogenous MnSOD gene expression. These results suggest that superoxide free radicals or their reaction products are responsible for much of the synergistic cytotoxicity of TNF-alpha and hyperthermia.

Novel terphenyls as selective cyclooxygenase-2 inhibitors and orally active anti-inflammatory agents.

A novel series of terphenyl methyl sulfones and sulfonamides have been shown to be highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. The sulfonamide analogs 17 and 21 were found to be much more potent COX-2 inhibitors and orally active anti-inflammatory agents than the corresponding methyl sulfone analogs 16 and 20, respectively, albeit with some decrease in COX-2 selectivity. Structure-activity relationship studies have determined that incorporation of two fluorine atoms in the central phenyl group, as in 20 and 21, is extremely advantageous for both in vitro COX-2 potency and selectivity as well as in vivo activity. Several noticeable examples in the 1,2-diaryl-4,5-difluorobenzenesulfonamide series are 21a-c,k,l,n (COX-2, IC50 = 0.002-0.004 microM), in which all have in vitro COX-1/COX-2 selectivity > 1000. In addition, sulfonamides 21a,b,d,g,j,m,n,q were shown to have greatly enhanced oral activity with more than 90% inhibition of prostaglandin E2 production in the air pouch model of inflammation. Furthermore, sulfonamide 21b was found to be very active in the rat adjuvant-induced arthritis model (ED50 = 0.05 mg/kg) and carrageenan-induced hyperalgesia assay (ED50 = 38.7 mg/kg) with no indication of gastrointestinal toxicity in rats at doses as high as 200 mg/kg.

The use of RT-PCR to distinguish between plasmid MnSOD transcripts and endogenous MnSOD mRNA.

We report here a convenient RT-PCR method to distinguish plasmid human MnSOD cDNA transcripts from the endogenous MnSOD gene products without engineering the cDNA insert. When a specific antisense primer for the carrier vector sequence was paired with a sense primer for the human MnSOD cDNA in RT-PCR analysis, a unique amplicon with the expected size was generated in MnSOD cDNA transfected cells but not in the wild type or vector control cells. The same primers were also used in genomic DNA-PCR to demonstrate genomic incorporation of cDNA in stably transfected cells. This method is convenient and specific in determining exogenous cDNA incorporation and expression in transfectants especially when transcripts of cDNA are difficult to separate from the endogenous mRNA by other methods.

[Pharmacognostical studies on the medicinal parts of Panax quinquefolius L].

The pharmacognostical identification of Panax quinquefolius was carried out. The microscopic characteristics of its root, stem, leaves, flowers and fruit were described and illustrated.

[Quantitative determination of total alkaloids in radix Gelsemii and its preparation using a colorimetric method with acid dye].

This paper deals with the quantitative determination of the total alkaloids in Radix Gelsemii and its preparation by colorimetric method with acid dye. It is shown that the mean contents of total alkaloids in Radix Gelsemii and its alkaloids injection were 0.621% and 5.02 mg/ml respectively, and the mean recovery was 96.87%.

Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney.

Both synthetic and natural estrogens have been studied for their ability to induce renal carcinomas in castrated male hamsters after 9.0 months of treatment. Tumor foci were detected in frozen serial sections stained histochemically for estrase activity. Both diethylstilbestrol (DES) and 17 beta-estradiol had equal ability (100%) to induce renal tumors [approximately 20.5 +/- 3 (S.E.) tumor foci] in these animals. Hexestrol induced the same incidence and number of renal carcinoma foci as DES or 17 beta-estradiol. However, alpha -dienestrol and DES 3,4-oxide showed an 86 to 88% incidence of renal tumors in hamsters (approximately 10.8 +/- 3). When equilin and d-equilenin, components of therapeutic conjugated estrogens, were tested, only equilin had a 76% incidence of renal tumor foci (5.5 +/- 0.9). The ability of these stilbene and steroidal estrogens to compete for renal tumor estrogen receptor generally correlated well with their ability to cause renal tumorigenesis in the hamster with one notable exception. Although ethinyl estradiol competed as well as did DES or 17 beta-estradiol for estrogen receptor, had similar ability to induce renal progesterone receptor, and led to similar high serum prolactin levels as either DES or 17 beta-estradiol, it had only weak carcinogenic activity (21%) in the hamster kidney (0.6 +/- 0.5 foci). These data represent the first detailed analysis of the relative carcinogenic activity of different estrogens within a given tumor-inducing system, and based on the carcinogenicity data of hexestrol and alpha-dienestrol presented herein, they suggest that epoxidation of the olefinic double bond and the p-quinone metabolite of DES probably are not involved significantly in its carcinogenic activity. Moreover, the poor carcinogenic activity of ethinyl estradiol in this system, despite strong estrogenicity, suggests that estronic activity alone may not be sufficient to effect renal tumorigenesis in the hamster.

Biochemical comparison of estrogen receptors of the hamster hypothalamus and uterus.

Comparison of the soluble estradiol receptor proteins in the hypothalamus and uterus of the golden Syrian hamster revealed that both have sedimentation coefficients of 8S in a low ionic strength buffer and migrate similarly on analytical disc-gel electrophoresis in both 5% and 7% acrylamide gels. The competition of [3H]-17beta-estradiol binding by unlabeled estrogenic as well as nonestrogenic compounds was similar with the receptors present in the two tissues. The affinity constants for the hypothalamic and uterine receptors were 4.3 X 10-9M-1 and 1.6 X 10-10M-1, respectively; the number of binding sites when expressed on an equivalent protein basis (i.e. 1 mg/ml) was 0.18 X 10-10M and 3.1 X 10-10M, respectively. Identical amounts of soluble receptors with similar sedimentation characteristics were found in hypothalami from male and female animals gonadectomized 64 h prior to use. A titration of binding sites in the uteri of intact and ovariectomized animals revealed decreased binding in the supernatant preparation from intact animals, probably due to the presence of bound endogenous unlabeled hormone.