Macrophages promote cell proliferation in colorectal cancer via IL-1ß-mediated downregulation of miR-28-3p.

Infiltration of macrophages is associated with tumor progression and poor prognosis in multiple malignancies, but the underlying mechanisms by which macrophages contribute to colorectal cancer (CRC) have not yet been elucidated. The purpose of this study was to discuss the potential mechanisms of macrophages in CRC. The MTT assay was used to assess cell viability. The expression of the proliferation-related marker PCNA was detected by Western blot analysis. The 10 most important factors (PDGF, VEGF, TNFα, bFGF, IL-8, TGF-ß, IFN-γ, SPARC, IL-1ß and IL-6) secreted by macrophages were knocked down by RNA interference (RNAi), and the mRNA expression levels of these 10 factors were analyzed by qRT-PCR. The effect of these factors on cell proliferation was assessed by the MTT assay. The miRNAs regulated by IL-1ß in CRC cells were identified by miRNA microarray and qRT-PCR analyses. The proliferation ability of miR-28-3p inhibitor on CRC cells was detected by colony formation assay. The association of IL-1ß and miR-28-3p expression with the clinicopathological characteristics in patients with CRC was analyzed by TCGA RNA-seq data. As a result, macrophages promoted the proliferation of CRC cells in a time- and number-dependent manner, and these effects were associated with the upregulation of PCNA and the macrophage-secreted cytokine IL-1ß, which had the most significant effect on CRC cell proliferation. Furthermore, downregulation of miR-28-3p was induced by IL-1ß in CRC cells. The miR-28-3p inhibitor promoted the proliferation in CRC cells. Moreover, upregulation of IL-1ß expression or downregulation of miR-28-3p expression was associated with poor survival in patients with CRC. Therefore, these data demonstrated that macrophages promoted CRC cell proliferation via IL-1ß-mediated downregulation of miR-28-3p.

[Iodine status of vulnerable populations in Henan Province of China three years after the implementation of new iodized salt standard].

Iodine nutrition surveillance of vulnerable population was conducted in 18 cities of Henan Province in 2015. The medians and quartiles of urinary iodine concentration in women of reproductive-age (n=3 318), pregnant women (n=36 366), lactating women (n=4 153), infants <2 years of age (n=1 017), and children aged 8-10 years (n=4 806) were 202.1(124.0, 310.0), 192.4(133.6, 262.4), 168.3(119.1, 248.3), 214.2(156.1, 272.3) and 90.0 (121.8, 285.6) µg/L, respectively. Iodine status of the vulnerable populations was generally regarded as adequate in Henan Province. But the median of urinary iodine concentration of reproductive-age women were slightly above the adequate level. The proportions above iodine adequate level were 26.7% in reproductive-age women, 29.4% in pregnant women and 22.5% in children aged 8-10 years.

[Clinical observation of postprandial hypotension in patients with hypertensive and coronary heart disease].

Objective: To explore the prevalence and clinical characteristics of postprandial hypotension(PPH) in patients with essential hypertension and coronary heart disease. Methods: A total of 197 patients with essential hypertension and coronary heart disease, who had been treated in the First Department of Cardiology of the Second Hospital of Hebei Medical University from December, 2013 to December, 2014 were included. The patients' blood pressure before breakfast, lunch and dinner and 30, 60, 90, 120 minutes after the meal were monitored. Subjects were classified into PPH group (n=37) and non-PPH group (NPPH, n=160) according to postprandial decrease in systolic blood pressure, to explore the clinical characteristics and related factors and the major adverse cardiac and cerebral vascular events of PPH. Results: Among 197 patients, 37 cases (18.8%) showed at least once postprandial decline in systolic blood pressure greater than and equal to 20 mmHg. The incidence of PPH after breakfast and dinner were higher than lunch (P<0.05). There was no significant difference in the incidence of PPH among different age groups, among patients accompanied with different diseases, and among patients with different dining position (all P>0.05). According to the baseline systolic blood pressure, patients can be divided into 4 groups(<120 mmHg, 120-129 mmHg, 130-139 mmHg, >140 mmHg), the higher the level of the baseline systolic blood pressure was, the higher the incidence of PPH was. And the incidence of major adverse cardiac and cerebral vascular events in patients during hospitalization were increased by PPH. Conclusions: The prevalence of PPH in the patients with essential hypertension and coronary heart disease is 18.8%. The incidence of PPH after breakfast and dinner is higher than lunch. The baseline systolic blood pressure is considered to be the risk factor of PPH. And PPH could lead to an increase of the incidence of major adverse cardiac and cerebral vascular events.

Fabrication and evaluation of porous coatings doped with bioactive elements on titanium surfaces.

OBJECTIVE: Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve the biological activity of titanium implants through surface modification. MATERIALS AND METHODS: Titanium was processed into titanium discs, where the titanium discs served as anodes and stainless steel served as cathodes, and a copper- and cobalt-doped porous coating [pure titanium model (PTM)] was prepared on the surface of titanium via plasma electrolytic oxidation. The surface characteristics of the coating were evaluated using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and profilometry. The corrosion resistance of PTM was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of coated bone marrow mesenchymal stem cells (BMSCs) were evaluated through in vitro cell experiments. RESULTS: A copper- and cobalt-doped porous coating was successfully prepared on the surface of titanium, and the doping of copper and cobalt did not change the surface topography of the coating. The porous coating increased the surface roughness of titanium and improved its resistance to corrosion. In addition, the porous coating doped with copper and cobalt promoted the adhesion and spreading of BMSCs. CONCLUSIONS: A porous coating doped with copper and cobalt was prepared on the surface of titanium through plasma electrolytic oxidation. The coating not only improved the roughness and corrosion resistance of titanium but also exhibited good biological activity.

[Evaluation of the impact of the Japanese encephalitis vaccine included in an expanded immunization program on the reported incidence rate of Japanese encephalitis in Gansu province-based on interrupted time series].

Objective: To evaluate the impact of the Japanese encephalitis vaccine included in an expanded immunization program on the reported incidence rate of Japanese encephalitis in Gansu province. Methods: Information on the reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was collected through the National Population Health Science Data Center and the China Disease Prevention and Control Information System. In addition, the trend of Japanese encephalitis reported incidence rate in Gansu province before and after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program was analyzed using an interrupted time-series design. Results: The annual reported incidence rate of Japanese encephalitis in Gansu province from 1987 to 2019 was 0.448/per 100 000. However, after the inclusion of the Japanese encephalitis vaccine in the expanded immunization program in Gansu province in 2008, the amount of change in the level of Japanese encephalitis reported incidence rate was -2.223/per 100 000 (t=-2.90, P=0.007), the amount of change in the slope of Japanese encephalitis reported incidence rate was 0.082 (t=2.87, P=0.008) with the slope of Japanese encephalitis reported incidence rate as 0.071 (ß1+ß3=0.071). Conclusions: The Japanese encephalitis vaccine has achieved good prevention and control effects in Gansu province in the short term after its inclusion in the expanded immunization program, but outbreaks of Japanese encephalitis have still occurred. Therefore, in the future, Gansu province should promptly adjust the immunization strategy of the Japanese encephalitis vaccine, and strengthen the vaccination of the adult population, especially the rural adult population in the southeastern region of Gansu province, based on the continued focus on the works on Japanese encephalitis vaccination for children and adolescents.

[Radio frequency catheter ablation of arrhythmias with low dose X-ray guided by three-dimensional mapping system in 14 children].

Objective: To assess the feasibility and efficacy of radiofrequency catheter ablation (RFCA) of arrhythmias with low dose X-ray in children guided by three-dimensional mapping system. Methods: Fourteen children with tachyarrhythmia who were transferred to Tianjin Medical University General Hospital after being hospitalized in Tianjin Children's Hospital and underwent RFCA from April 2017 to May 2018 were included.The results of intraoperative electrophysiological examination, intraoperative X-ray dosage,the immediate success rateand complications of RFCA,and the recurrence during the follow-up for at least 6 months were recorded. Results: Among the 14 children, 11 cases were diagnosed with supraventricular tachycardia.Five cases had atrioventricular reentrant tachycardia (AVRT) which included two cases with left accessory pathway and three cases with right accessory pathway, and four cases had atrioventricular nodular reentrant tachycardia (AVNRT), one case had atrial flutter (AFL), one case had both AFL and AVNRT. One case had focal atrial tachycardia, one case had ventricular tachycardia, and one case had premature ventricular contraction. Eleven cases underwent RFCA with zero radiation, and 3 cases underwent atrial septal puncture with low dose X-ray. The exposure amounts were 3.85, 3.23 and 4.67 mGy, respectively. No complications occurred except for one case with AVRT had atrioventricular block and recovered to normal in 25 days after operation.During the follow-up of 7 to 20 months, no arrhythmias had been found in 13 cases, and one case with AVRT and AFL recurred. Conclusion: Under the guidance of three-dimensional mapping system, RFCA of tachyarrhythmia with low dose X-ray in children is feasible.

Direct Growth of Al2O3 on Black Phosphorus by Plasma-Enhanced Atomic Layer Deposition.

Growing high-quality and uniform dielectric on black phosphorus is challenging since it is easy to react with O2 or H2O in ambient. In this work, we have directly grown Al2O3 on BP using plasma-enhanced atomic layer deposition (PEALD). The surface roughness of BP with covered Al2O3 film can reduce significantly, which is due to the removal of oxidized bubble in BP surface by oxygen plasma. It was also found there is an interfacial layer of PO x in between amorphous Al2O3 film and crystallized BP, which is verified by both X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) measurements. By increasing temperature, the PO x can be converted into fully oxidized P2O5.

The POU homeodomain protein Oct-1 binds Cis-regulatory element essential for the human GnRH upstream promoter activity in JEG-3 cells.

In previous studies, we have localized four specific nuclear protein-binding elements in the human GnRH upstream promoter. To test whether these four elements are reproductive tissue specific, we placed the four elements upstream to a thymidine kinase (TK) promoter/luciferase reporter gene, and transfected the constructs into human placental choriocarcinoma (JEG-3) cells. The 272-bp fragment (-994 to -723) containing the four elements can drive heterologous TK promoter expression in JEG-3 cells about 15 times more than that of basal TK promoter activity. Deletion of element 4 (E4, -987/-968) significantly decreased (4-fold) the luciferase activity. Further deletion of the other elements (E3 individual, -960/-940 or E3 and E2 in combination, -919/-896) only slightly decreased the luciferase activity. In contrast, deletion of element 1 (E1, -876/-851) caused a 2-fold loss of luciferase activity and elimination of E2 and E3 only lost less than 2-fold of the luciferase activity. Study performed with 5' end deletion of this region confirmed these observations. Furthermore, E4 DNA-protein complex can be supershifted by Oct-1 antibody, indicating that Oct-1 binds to E4. These results clearly demonstrated that all four elements are required to confer tissue-specific expression of the hGnRH gene in JEG-3 cells. However, the E4 is the most important for the tissue-specific expression of the hGnRH gene in JEG-3 cells. Oct-1 factor binds with E4 element and may be involved in the mediation of the human GnRH upstream promoter activity.

Estrogen receptor-mediated repression of gonadotropin-releasing hormone (gnRH) promoter activity in transfected CHO-K1 cells.

To examine the transcriptional regulation of gonadotropin-releasing hormone (GnRH) gene in reproductive tissues, the expression of human GnRH gene promoter in cultured human granulosa cells and a Chinese hamster ovary-derived CHO-K1 tumor cells was studied. Transfection of luciferase reporter gene construct containing either upstream (hU) or downstream (hD) human GnRH gene promoter into both human granulosa and CHO-K1 cells showed that the upstream promoter, hU, was more active than hD in directing luciferase expression in these ovarian tissues. CHO-K1 cells transfected with either hU or hD construct showed insignificant changes in luciferase activity in response to 17beta-estradiol and GnRH. However, cotransfection of hU construct with a vector expressing a human estrogen receptor-alpha (ER-alpha) cDNA results in dose-dependent decreases in luciferase activity in response to both 17beta-estradiol and a GnRH agonist. By functional analysis of a series of deletion constructs, the ER-mediated suppression of GnRH promoter activity by 17beta-estradiol was localized to a region between -169 and -548 bp 5' of the upstream transcription start site of the human GnRH gene. Results of this study demonstrated that estrogen receptor can mediate the negative feedback regulation of human GnRH upstream promoter activity by both estrogen and GnRH in the ovary.

A randomized multicenter study comparing the efficacy and bleeding pattern of a single-rod (Implanon) and a six-capsule (Norplant) hormonal contraceptive implant.

To compare the contraceptive efficacy, tolerability, and bleeding patterns, 200 healthy female volunteers received, in an open, comparative, randomized, multicenter study in China, either a single-rod (Implanon) or a six-capsule (Norplant) contraceptive implant for 2 years with an optional extension of up to 4 years. Women were exposed to Implanon for 341.6 woman-years and Norplant for 329.1 woman-years. There were no pregnancies during the study. Per 90-day reference period, the median number of bleeding/spotting days with Implanon decreased from 33.5 in the first period to 19.0-21.5 days in the last year. Similarly, with Norplant, the median number of bleeding/spotting days decreased from 34.5 to 18.0-23.0 days, respectively. The number of bleeding/spotting episodes during year 1 was 2.0 per 90-day reference period with Implanon and 3.0 per period with Norplant (p < 0.05 for periods 1-4). For the remaining 90-day periods, there was no statistical difference between the two groups. In general, there was less frequent bleeding with Implanon compared with Norplant, whereas the incidences of amenorrhea and infrequent bleeding were higher with Implanon than with Norplant. The mean overall incidence of prolonged bleeding fell markedly during the study, from 66.0% in reference period 1 to 27.3% in period 16 with Implanon and from 69.0% to 21.7% with Norplant, respectively. The most common adverse events were related to disturbed bleeding patterns, which were also the major reasons for discontinuation (Implanon n = 8; Norplant n = 14). Normal menses returned in almost all subjects within 3 months after removal of the implants. Implanon was inserted in a mean time of 0.61 min and Norplant in 3.90 min (p < 0.001). Similarly, the mean time required to remove the implant was significantly shorter for Implanon than for Norplant (2.18 min vs 11.25 min, p < 0.001). The maximum time required for removal of the implant was 10 min for the Implanon group and 60 min for the Norplant group. In both groups, blood pressure and hemoglobin were not affected, whereas body weight tended to increase. It can be concluded that both contraceptive systems demonstrated excellent contraceptive efficacy and were well tolerated. Compared with Norplant, there was less frequent bleeding with Implanon, whereas the incidence of infrequent bleeding and amenorrhea was higher. Implanon was significantly quicker to insert and to remove than was the multiple capsule system.

PIP: This study compares the contraceptive efficacy and bleeding patterns of a single-rod (Implanon) and a six-capsule (Norplant) contraceptive implant for 2 years, with an optional extension of up to 4 years, among 200 healthy female volunteers in China. Women were administered with Implanon for 341.6 woman-years and Norplant for 329.1 woman-years. No pregnancies occurred during the study, demonstrating excellent contraceptive efficacy. The median number of bleeding/spotting (B/S) days with Implanon decreased from 33.5 in the first period to 19.0-21.5 days in the last year. With Norplant, the median number of B/S days decreased from 34.5 to 18.9-23.0 days. There was less frequent bleeding with Implanon than with Norplant. The most common adverse effects were related to disturbed bleeding patterns, which were also the main reasons for discontinuation (Implanon, n = 8; Norplant, n = 14). Normal menses returned in almost all subjects within 3 months after removal of the implants. Lastly, Implanon required less time for insertion and removal as compared to Norplant.

Study of Norplant implants in Shanghai: three-year experience.

A clinical follow-up study conducted in Shanghai, China confirmed earlier reports that the Norplant implants, Norplant-1 and Norplant-2, are both highly effective with high continuation rates. The implants, however, tend to cause menstrual disturbance, spotting and bleeding. The mean hemoglobin value, however, did not change and the blood pressure remained stable. The report of 8 cases of thrombocytopenia among 301 Norplant-2 users is a source of concern.

A 10-year follow-up study of contraceptive Norplant implants.

OBJECTIVES: To evaluate the long-term efficacy and health problems associated with Norplant implants and re-implants after 5 full years of first implants. METHOD: From 1984 to 1988, 1657 women accepted first implants of Type I and Type II of Norplant, and 394 first acceptors had a re-implant, at a clinic for study. The clinical records and annual follow-up data of acceptors were analyzed. The life-table technique was the main method used. RESULTS: The continuation rates were very high. The cumulative pregnancy rates at 1, 3 and 5 full years of use were 0.0%, 0.1% and 0.7%, respectively. Users with heavier body weight had higher pregnancy rates. The rate of menstrual disturbances peaked at 73% after 3 months and consistently decreased to 20% at 5 years of use. Rates of menstrual disturbances associated with re-implants were much lower. CONCLUSION: Norplant is extremely effective and safe for long-term use.

Rigid spine syndrome. Report of 4 cases.

Four cases of rigid spine syndrome are reported for the first time in China. They are 2 males and 2 females. One girl has a positive family history. Limitation of flexion of the cervical and dorsolumbar spine, contractures of joints, especially the elbow joints, extreme flattening of the chest and scoliosis are the prominent symptoms of this syndrome. The clinical criteria for this rigid spine syndrome tally with those described by Dubowitz (1965). Symptomatology, diagnosis, differential diagnosis and genetics are discussed. However, the question whether rigid spine syndrome is a single, well defined disease entity remains to be explored.

[Experimental study of Ligusticum wallichii on cerebrovascular hemodynamic parameters].

The model of experimental atherosclerosis was established by means of dietary hyperlipidemia and repeated intravenous injection of heterologous serum to make the immunologic injuries of arterial endothelium, in which the effect of Ligusticum wallichii (LW) on the cerebrovascular hemodynamic parameters (CVHP) was observed. All CVHP indexes in LW group were near that of normal group, and there was no significant difference between these two groups. The carotid arteries' mean flow (Qmean), mean velocity (Vmean), maximal velocity (Vmax), cerebrovascular peripheral compliance for zero pressure and cerebrovascular peripheral resistance (R) in LW group were significantly better than that of atherosclerotic control group (P < 0.05-0.01). The results showed that LW had protective effects on cerebral vessels.

[Changes in serum FSH, LH and ovarian follicular growth during electroacupuncture for induction of ovulation].

Changes in serum FSH, LH and follicular sizes were observed in chronically anovulatory patients during electroacupuncture treatment (EAT) for induction of ovulation. 7 cases were diagnosed as PCOD, 3 as dysfunctional uterine bleeding, and 1 as hypogonadotropic amenorrhea. Among them 8 cases complained of infertility for 2.7 years on average. Ovulation was confirmed by pregnancy or the combination of biphasic BBT and ultrasonographic evidence. During one cycle with 3-day EAT on acupoints Ren 3, 4, Extra 16 and Sp 6, ovulation resulted in 5 patients (ovulatory group) and among the 5 cases, 3 of 4 infertile cases became pregnant. The other 5 cases remained in anovulation (anovulatory group); of them 3 cases got biphasic BBT, but no typical ovulatory signs were found on ultrasonography; 2 cases remained in monophasic BBT. Serum FSH, LH values were elevated in ovulatory group, and FSH pulsatile frequency increased significantly during EAT (from 2.10 +/- 0.42/4h to 3.70 +/- 1.64/4h), but not in anovulatory group. No apparent changes were found in serum LH pulsatile frequency and pulsatile amplitudes of FSH and LH in this study. In ovulatory group diameters of ovarian follicles increased markedly, while diameters of anovulatory group stopped to grow at 14-16 mm. It is suggested that ovulation may be induced by EAT via a regulation on hypothalamic-pituitary function leading to normal secretion of FSH and LH.

An analysis of vaginal bleeding patterns in users of Norplant implants.

PIP: A 5-year prospective study of 548 Norplant acceptors at Shanghai (China) Medical University assessed self-reported vaginal bleeding patterns over time. Between the first 90-day reference period and the last such period, spotting decreased from an average of 21.5 to 9.5 days, bleeding declined from an average of 11 to 9.9 days, and heavy bleeding remained relatively constant at 0.5-1.0 days. Overall, the average total of bleeding and spotting days decreased from 33 days in the first 90-day period to 26.7 days in the fourth 90-day period and to 20.2 days in the 20th reference period. Only 0.5-5.4% of women experienced amenorrhea during the various reference periods. Careful counseling of Norplant acceptors about the likelihood of increased vaginal bleeding during the early period of method use is essential to reduce requests for removal.^ieng

[Termination of pregnancy with 16,16-dimethyl-trans-delta2 PGE1 methyl ester vaginal suppositories: an analysis of 182 cases].

PIP: The results of pregnancy termination with ONO 802 as a vaginal suppository in 182 cases are presented. The drug was tested during the different phases of pregnancy, as well as in abnormal pregnancies (intrauterine fetal death and hydatidiform mole) and normal pregnancy. 1 suppository containing 1 mg of the drug was inserted in the posterior vaginal fornix every 3 hours, with 1 full course consisting of 5 suppositories. Cases which did not terminate spontaneously were administered the same treatment the next day. A success rate of 90.5% was obtained; 91.6% for the 1st trimester, 88.8% for the 2nd, 94.7% for intrauterine fetal death, and 100% for hydatidiform mole and 3rd trimester cases. A dosage of between 1-5 mg was successful in 83.9%. 75% terminated within 24 hours. In the 34 patients who were given 2 suppositories and whose surgical termination followed 6 hours later, the cervix was so soft and dilated that a No. 8 Hegar dilator was easily inserted and blood loss was reduced to an average of 12.5 ml. After termination, vaginal bleeding ceased within 2 weeks and menses resumed in 6 weeks. Few complications and side effects occurred. Of the 8 cases which later became pregnant, 2 have delivered normal fetuses spontaneously. In light of these results, the use of ONO 802 vaginal suppository is 1 of the better methods of pregnancy termiantion. (author's modified)^ieng

Viral induction of low frequency interferon-alpha producing cells.

The human peripheral blood mononuclear cells responsible for IFN-alpha production in response to viral stimuli have been most often described as either monocytes (as typified by the response to Sendai virus) or as a light density, HLA-DR+ population which is negative for most cell surface markers characteristic of mature T cells, B cells, monocytes, or natural killer cells (as typified by the response to Herpes simplex virus (HSV)). The frequency of IFN-alpha-producing cells (IPC) responding to Sendai virus is typically 10-fold or more higher than those responding to HSV. In the current study, we have used ELISpot assays to determine the frequency of IPC responding to DNA and RNA viruses including HSV, Sendai, vesicular stomatitis virus, cytomegalovirus, adenovirus, SV40, influenza, measles, mumps, Newcastle disease virus (NDV) and human immunodeficiency virus (HIV). The enveloped viruses but not the nonenveloped viruses (adenovirus and SV40) elicited an IFN-alpha response. The frequency of IPC for each of the other viruses was more similar to the low frequency HSV-responding population than to the higher frequency Sendai virus response. These included several viruses in the same family as Sendai virus, namely the paramyxo viruses measles, mumps, and NDV. IPC were also tested for sensitivity to the lysosomotropic drug chloroquine, which diminishes IFN-alpha produced in response to HSV but not Sendai virus. With the exception of Sendai virus, chloroquine treatment abrogated the majority of IFN-alpha produced and IPC against each of the viruses. We conclude that low frequency, nonmonocytic NIPC account for the majority of IFN-alpha production in response to different viruses.