[Ningmitai Capsules combined with doxycycline hydrochloride for Ureaplasma urealyticumpositive chronic prostatitis].

OBJECTIVE: To investigate the effects of Ningmitai Capsules (NMT) combined with doxycycline hydrochloride (DH) on chronic prostatitis induced by Ureaplasma urealyticum (Uu). METHODS: This randomized controlled trial included 240 male patients with Uupositive chronic prostatitis, treated orally with NMT at 4 capsules tid (n= 35), DH at 100 mg bid (n = 78), and NMT+DH at the corresponding doses (n = 127), respectively, all for 2 successive weeks. At 1 week after drug withdrawl, we conducted routine urine analysis, EPS examination, and drug sensitivity test of the cultured Uu. RESULTS: The positivetonegative rate of Uu was significantly higher in the NMT+DH group than in the NMT and DH groups (89.0% ［113/127］ vs 54.3% ［19/35］ and 71.8% ［56/78］, P< 0.05), so were the cure rate (25.2% vs 20.0% and 20.5%, P< 0.05) and total effectiveness rate (89.0% vs 54.3% and 71.8%, P< 0.05). CONCLUSIONS: The combination of Ningmitai Capsules and doxycycline hydrochloride is more effective than either Ningmitai Capsules or doxycycline hydrochloride used alone in the treatment of Uupositive chronic prostatitis.

All-magnetic control of skyrmions in nanowires by a spin wave.

Magnetic skyrmions are topologically protected nanoscale objects, which are promising building blocks for novel magnetic and spintronic devices. Here, we investigate the dynamics of a skyrmion driven by a spin wave in a magnetic nanowire. It is found that (i) the skyrmion is first accelerated and then decelerated exponentially; (ii) it can turn L-corners with both right and left turns; and (iii) it always turns left (right) when the skyrmion number is positive (negative) in the T- and Y-junctions. Our results will be the basis of skyrmionic devices driven by a spin wave.

Blockade of corticotropin-releasing hormone receptor 1 attenuates early-life stress-induced synaptic abnormalities in the neonatal hippocampus.

Adult individuals with early stressful experience exhibit impaired hippocampal neuronal morphology, synaptic plasticity and cognitive performance. While our knowledge on the persistent effects of early-life stress on hippocampal structure and function and the underlying mechanisms has advanced over the recent years, the molecular basis of the immediate postnatal stress effects on hippocampal development remains to be investigated. Here, we reported that repeated blockade of corticotropin-releasing hormone receptor 1 (CRHR1) ameliorated postnatal stress-induced hippocampal synaptic abnormalities in neonatal mice. Following the stress exposure, pups with fragmented maternal care showed retarded dendritic outgrowth and spine formation in CA3 pyramidal neurons and reduced hippocampal levels of synapse-related proteins. During the stress exposure, repeated blockade of glucocorticoid receptors (GRs) by daily administration of RU486 (100 µg g(-1) ) failed to attenuate postnatal stress-evoked synaptic impairments. Conversely, daily administration of the CRHR1 antagonist antalarmin hydrochloride (20 µg g(-1) ) in stressed pups normalized hippocampal protein levels of synaptophysin, postsynaptic density-95, nectin-1, and nectin-3, but not the N-methyl-d-aspartate receptor subunits NR1 and NR2A. Additionally, GR or CRHR1 antagonism attenuated postnatal stress-induced endocrine alterations but not body growth retardation. Our data indicate that the CRH-CRHR1 system modulates the deleterious effects of early-life stress on dendritic development, spinogenesis, and synapse formation, and that early interventions of this system may prevent stress-induced hippocampal maldevelopment.

Short-term exposure to air pollution and outpatient visits for conjunctivitis: a time-series analysis in Urumqi, China.

Conjunctivitis is an inflammatory disease of the conjunctival tissue caused by a variety of causes; despite the conjunctiva being directly exposed to the external atmospheric environment, the important role of air pollution is not fully evaluated, especially in areas with poor air quality undergoing rapid economic and industrial development. Information on 59,731 outpatient conjunctivitis visits from 1 January 2013 to 31 December 2020 was obtained from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China), and data on six air pollutants including particulate matter with a median aerometric diameter of less than 10 and 2.5 mm (PM10 and PM2.5, respectively), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) from eleven standard urban background fixed air quality monitors were also recorded. A time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) were used to fit the effect of exposure to air pollutants on the risk of conjunctivitis outpatient visits. Further subgroup analyses were conducted for gender, age, and season, as well as the type of conjunctivitis. Single and multi-pollutant models showed that exposure to PM2.5, PM10, NO2, CO, and O3 was associated with increased risk of outpatient conjunctivitis visits on the lag 0 day and various other lag days. Variations in the effect estimates on direction and magnitude were found in different subgroup analyses. We conducted the first time-series analysis with the longest duration as well as the largest sample size in Northwest China, which provides evidence that outpatient conjunctivitis visits is significantly associated with air pollution in Urumqi, China. Meanwhile, our results demonstrate the effectiveness of SO2 reduction in reducing the risk of outpatient conjunctivitis visits in the Urumqi region and reaffirm the need to implement special air pollution control measures.

[Changes of nerve growth factor and M3 subtype muscarinic receptor in the seminal vesicle of diabetic rats].

OBJECTIVE: To investigate the effect of diabetic autonomic neuropathy on the seminal vesicle and search for the theoretical evidence for the prevention and treatment of diabetic infertility by observing changes in the contents of the nerve growth factor (NGF) and muscarinic M3 receptor in the seminal vesicle of diabetic rats. METHODS: Diabetic models were established in 10 of the 15 male adult SD rats by intraperitoneal injection of streptozotocin (STZ), and the other 5 were included in a normal control group. Eight weeks after modeling, seminal vesicles were collected from the rats for HE and immunohistochemical staining. RESULTS: Compared with the normal controls, the diabetic models showed a decreased number of smooth muscle cells, thinner cytoplasm of glandular epithelial cells and disordered structure in the seminal vesicle. The intensity of NGF-positive staining was significantly enhanced, but that of M3 markedly reduced in the diabetic group. There were statistically significant differences in the mean integrated optical density (IA) of muscarinic M3 receptors and NGF between the control and diabetic groups (0.0187 +/- 0.0024 vs 0.0100 +/- 0.0015 and 0.0209 +/- 0.0085 vs 0.0412 +/- 0.0117, P<0.01). CONCLUSION: The changes in the expressions of NGF and M3 receptors in the seminal vesicle of diabetic rats suggest that diabetes mellitus may induce autonomic neuropathy of the seminal vesicle.

MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma.

This study investigates the influence expression of the MYCN oncogene has on the DNA damage response, replication fork progression and sensitivity to PARP inhibition in neuroblastoma. In a panel of neuroblastoma cell lines, MYCN amplification or MYCN expression resulted in increased cell death in response to a range of PARP inhibitors (niraparib, veliparib, talazoparib and olaparib) compared to the response seen in non-expressing/amplified cells. MYCN expression slowed replication fork speed and increased replication fork stalling, an effect that was amplified by PARP inhibition or PARP1 depletion. Increased DNA damage seen was specifically induced in S-phase cells. Importantly, PARP inhibition caused a significant increase in the survival of mice bearing MYCN expressing tumours in a transgenic murine model of MYCN expressing neuroblastoma. Olaparib also sensitized MYCN expressing cells to camptothecin- and temozolomide-induced cell death to a greater degree than non-expressing cells. In summary, MYCN expression leads to increased replication stress in neuroblastoma cells. This effect is exaggerated by inhibition of PARP, resulting in S-phase specific DNA damage and ultimately increased tumour cell death. PARP inhibition alone or in combination with classical chemotherapeutics is therefore a potential therapeutic strategy for neuroblastoma and may be more effective in MYCN expressing tumours.

[Isolation, Culture and Biological Characteristics of Endothelial Progenitor Cells from Cryopreserved Umbilical Cord Blood].

OBJECTIVE: To establish a novel method to isolate endothelial progenitor cells（EPC） from cryopreserved umbilical cord blood (cryoUCB), to investigate the biological characteristics of EPC and to improve the rate of EPC obtained from cryoUCB. METHODS: Twelve cryoUCB samples during 2000 to 2001 years were collected from allogeneic cord blood bank, cryoUCB was thawed rapidly in a water bath at 37 ℃, total nucleated cells (TNCs) were washed by phosphate-buffered saline (PBS). TNCs were seeded onto fibronectin-coated dishes to isolate EPC. Flow cytometry and immunofluorescence were used to identify EPC. The function of EPC was identified in vitro, such as the incorporation of Dil-Ac-LDL and FITC-UEA-I, the formation of capillary-like structure in matrigel, and the release of VEGF by ELISA. RESULTS: One to five cluster of cobble stone-like cells appeared at 2-3 weeks after seeding. Flow cytometric analysis showed that positive rates of CD31, CD34, CD144, and VEGFR (CD309) were（92.91±5.20）%, （30.0±23.27）%, （88.55±3.83）% and （67.21±12.12）% in passage 1 to passage 3 of EPC. EPC could uptake Dil-Ac-LDL and FITC-UEA-I, form capillary-like network on Matriget and release VEGF. CONCLUSION: EPC had been successfully isolated from cryopreserved umbilical cord blood by this method with high stability and reproducibility. EPC can be obtained in 85% frozen umbilical cord blood. This method may lay a foundation to supply abundant EPC for clinical application.

A Preclinical Model to Assess Brain Recovery After Acute Stroke in Rats.

The purpose of this study was to establish and validate an animal brain ischemia model in the recovery and sequela stages. A middle cerebral artery occlusion/reperfusion (MCAO/R) model in male Sprague-Dawley rats was chosen. By changing the rat's weight (260-330 g), the thread bolt type (2636/2838/3040/3043) and the brain infarct time (2-3 h), a higher Longa's score, a larger infarct volume and a greater model success ratio were screened using the Longa's score and TTC staining. The optimum model condition (300 g, 3040 thread bolt, 3 h brain infarct time) was acquired and used in a 1-90 day observation period after reperfusion via assessment of sensorimotor functions and infarct volume. At these conditions, the bilateral asymmetry test had a significant difference from 1 to 90 days, and the grid-walking test had a significant difference from 1 to 60 days; both differences could be a suitable sensorimotor functional test. Thus, the most appropriate condition of a novel rat model in the recovery and sequela stages of brain ischemia was found: 300 g rats that underwent MCAO with a 3040 thread bolt for a 3 h brain infarct and then reperfused. The appropriate sensorimotor functional tests were a bilateral asymmetry test and a grid-walking test.

Early postnatal stress suppresses the developmental trajectory of hippocampal pyramidal neurons: the role of CRHR1.

Adverse experiences early in life hamper the development and maturation of the hippocampus, but how early-life stress perturbs the developmental trajectory of the hippocampus across various life stages and the underlying molecular mechanisms remain to be investigated. In this study, we stressed male mice from postnatal day 2 (P2) to P9, and examined the potential role of CRHR1 in postnatal stress-induced structural remodeling of hippocampal CA3 pyramidal neurons directly after stress (P9), in mid-adolescence (P35) and in adulthood (P90). We found that early-life stress exposure significantly reduced apical dendritic arborization and spine density in CA3 neurons on P9 and P90. Moreover, postnatally stressed neurons underwent increased pruning of spines, especially thin spines, between P35 and P90. These stress-induced immediate and long-term structural abnormalities could be abolished by daily systemic administration of the CRHR1 antagonist antalarmin (20 µg/g of body weight) during stress exposure. However, such treatment strategy failed to attenuate the deleterious stress effects in mid-adolescence on P35. We then extended antalarmin treatment until the end of the second postnatal week, and found that prolonged blockade of CRHR1 could prevent the mid-term impact of early postnatal stress on structural remodeling of CA3 neurons. Our study characterized the influences of early-life stress on the developmental trajectory of hippocampal pyramidal neurons, and highlighted the critical role of CRHR1 in modulating these negative outcomes evoked by early-life stress.

[Expansion and function of MHC restricted killer T cells derived from umbilical cord blood].

OBJECTIVE: This study was to expand the cytotoxic T lymphocytes (CTL) through inducing the differentiation of umbilical blood monomuclear cells (UBMNC) by using various combination of cytokines, and to investigate the functions of expanded CTL. METHODS: The MNC were isolated by ficoll density gradient centrifugation. Then, the PHA-P, IFN-γ combined with IL-2, IL-15 and other cytokines were used for induction and expansion of the cord blood-derived CTL. The biological function of CTL was examined by phenotype analysis, cytotoxic tests and real-time fluorescence quantitative PCR. RESULTS: After expansion for 15 days, the cell number increased by 1522% ± 137%. The content of CD3(-)CD8(-) cells in uncultured cord blood MNC was 95%, and the CD3(+)CD8(+) CTL cells reached 82.77% in cultured cord blood MNC after expansion for 15 days. The expanded CTL cell showed the cytotoxic activity against K562 and HeLa cell line. The killing rate of MNC was 61.88 ± 1.08%. After expansion, the killing rate could reach to 90% with the average value of 90.33 ± 2.02%. The expanded CTL cells highly expressed some key cytokines, such as granzyme A, granzyme B, GM-CSF, granulysin, IFN-γ, TGF-ß, TNF-α and perforin. Compared with the control group, the expression of IFN-γ and TGF-ß significantly increased (P < 0.05), and the other factors dramatically increased (P < 0.01). CONCLUSION: The cord blood-derived CTL can be expanded by different combinations of cytokines. These protocols may provide alternative choices for CTL cell expansion in tumor adoptive immunotherapy.

Stress during a critical postnatal period induces region-specific structural abnormalities and dysfunction of the prefrontal cortex via CRF1.

During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin administration (20 µg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF1 in modulating early-life stress-induced prefrontal abnormalities.

Randomized, double-blind, controlled trial of mifepristone in capsule versus tablet form followed by misoprostol for early medical abortion.

OBJECTIVE: To compare the efficacy and side-effects of mifepristone 75 mg in capsule form versus 150 mg in tablet form followed by misoprostol for medical termination of early pregnancy. STUDY DESIGN: In a prospective randomized, double-blind, placebo-controlled trial, a total of 480 women who were 49 days or less pregnant were randomized by means of a random number table to receive either two tablets in the morning and one tablet 12 h later for 2 days (group A) or three capsules orally twice daily for 2 days, the first dose being double all subsequent doses (group B). After a further 48 h, 600 microg misoprostol was given orally. Successful abortion was defined as complete abortion with no need for surgical aspiration. RESULTS: There were no significant differences between the two study groups in the rates of complete abortion (95.4% in group A versus 96.3% in group B), incomplete abortion (3.8% in group A, 3.3% in group B) and continued pregnancy (0.8% in group A, 0.4% in group B). No significant difference in the duration and amount of vaginal bleeding was observed. The incidence of side-effects, such as vomiting, nausea, headache, diarrhea and lower abdominal pain was similar in the two groups. CONCLUSIONS: Our results indicate that 75 mg mifepristone in capsule form combined with 600 microg misoprostol is as effective and safe as 150 mg mifepristone in tablet form for the termination of pregnancy up to 49 days.

Picosecond electric field pulse induced coherent magnetic switching in MgO/FePt/Pt(001)-based tunnel junctions: a multiscale study.

Combined methods of first-principles calculations and Landau-Lifshitz-Gilbert (LLG) macrospin simulations are performed to investigate the coherent magnetization switching in the MgO/FePt/Pt(001)-based magnetic tunnel junctions triggered by short pulses of electric field through the control of magnetic anisotropy energy (MAE) electrically. First-principles calculations indicate that the MAE of MgO/FePt/Pt(001) film varies linearly with the change of the electric field, whereas the LLG simulations show that the change in MAE by electric field pulses could induce the in-plane magnetization reversal of the free layer by tuning the pulse parameters. We find that there exist a critical pulse width τmin to switch the in-plane magnetization, and this τmin deceases with the increasing pulse amplitude E0. Besides, the magnetization orientation cannot be switched when the pulse width exceeds a critical value τmax, and τmax increases asymptotically with E0. In addition, there exist some irregular switching areas at short pulse width due to the high precessional frequency under small initial angle. Finally, a successive magnetization switching can be achieved by a series of electric field pulses.

[IFN-γ stimulation enhances immunosuppressive capability of human umbilical cord mesenchymal stem cells].

This study was objective to explore the effect of IFN-γ on immunosuppressive capability of mesenchymal stem cells (MSC) derived from umbilical cord. The immunomodulating capability of MSC was changed by stimulating cell surface receptors like Toll-like receptors (TLR). The inhibition of T-lymphocyte proliferation by MSC was tested via cell co-cultures. Further RT-PCR and ELISA were performed to examine the expression changes in gene and protein level. The results showed that the IFN-γ could promote the immunosuppressive effect of umbilical cord derived MSC. IFN-γ-stimulated MSC could suppress the proliferation of T cells more effectively. IFN-γ stimulation up-regulated the expression of immunosuppressive genes like IDO1, COX2, HLA-G, and soluble suppressive proteins such as HLA-G, KYN, IL10, PGE2 of MSC. And the immuno suppression capability of IFN-γ-stimulated MSC was 2-7 folds higher than control in MSC and lymphocyte co-culture tests. It is concluded that IFN-γ can effectively enhance the immunosuppressive capability of MSC.