[Analysis of the necessity of anticoagulation therapy and influencing factors of stent occlusion after transjugular intrahepatic portosystemic shunt].

Objective: To explore the necessity of anticoagulation therapy and influencing factors of stent occlusion after transjugular intrahepatic portosystemic shunt. Methods: The basic information, laboratory test results, preoperative portal venous pressure, postoperative anticoagulation time, postoperative stent stenosis or occlusion, followed-up and other data of all patients who underwent TIPS surgery in Shandong Provincial Hospital from 2010 to 2019 were retrospectively analyzed. Data were analyzed using t-test, χ2 test, and multivariate analysis (logistic regression and Cox-regression-analysis). Results: A total of 280 cases were finally included in the study, of which 110 (39.3%) had stent stenosis or occlusion, and 170 (60.7%) had stent patency. New or worsening ascites were identified in 194 cases during the follow-up period, including 14 (31.1%) cases in the stent stenosis or occlusion group and 19 (12.8%) cases in the stent patency group. Univariate analysis showed that presence or absence of platelet (P=0.037) and total bilirubin (P=0.038) were correlated with stent stenosis or occlusion. Postoperative continuous anticoagulation was correlated with stent blockage (P=0.029) in patients with partial portal vein thrombosis. Postoperative continuous anticoagulation and stent occlusions were not significantly correlated in patients with preoperative portal cavernoma and preoperative portal vein patency (P=0.848; P=0.744). Multivariate analysis results showed that whether long-term anticoagulation (P=0.017), all-cause rebleeding (P<0.001), postoperative significant hepatic encephalopathy (P<0.012), and postoperative new or worsening ascites (P<0.001) was significantly associated with stent occlusion (P<0.05), while platelets (P=0.134), total bilirubin (P=0.229), international normalized ratio (P=0.436), and portal vein pressure (P=0.230) were not significantly associated with stent occlusion after surgery. Conclusion: In patients with partial portal vein thrombosis before surgery, continuous anticoagulation for 30 days post-TIPS therapy can effectively prevent stent stenosis or occlusion; while in patients with portal vein patency, portal cavernoma and complete portal vein blockage before surgery, postoperative anticoagulation has no significant effect on stent stenosis or occlusion.

[Voxel-based morphometry (VBM) MRI analysis of gray matter in patients with occupational noise-induced hearing loss].

Objective: To investigate the changes of brain gray matter volume in patients with occupational noise-induced hearing loss by voxel based morphometry (VBM) . Methods: 16 age-and education-matched healthy controls and 42 patients with occupational noise induced hearing loss, including 27 in mild group and 15 in severe group, received MRI 3D-FSPGR sequence T1WI sagittal scan, and then underwent VBM of brain gray matter volume data analysis. Results: The brain gray matter volume of the left occipitotemporal lateral gyrus, the anterior cingulate gyrus, the bilateral angular gyrus, the precuneus and the near midline area of cerebellum differed between experimental group and control group (P<0.01) . Conclusion: The volume of gray matter in specific brain areas of patients with occupational noise-induced hearing loss was changed, and the effect of noise on brain structure was revealed from the perspective of imaging.

[Normal values for solid state high resolution anorectal manometry in healthy adult volunteers].

Objective: To explore the normal values for two-dimension solid state high resolution anorectal manometry (HRAM) in healthy adult volunteers. Methods: The healthy adult volunteers were recruited by advertisement and underwent solid state HRAM in the left lateral position. Anorectal pressures and rectal sensation were recorded and analyzed. Results: (1) A total of 126 Chinese healthy adult volunteers (male: 50 cases (39.7%); age: (37.5±14.2) years old ) were recruited in this study. (2) Mean anal resting pressure (MERP) was (71.8±17.3) mmHg (1 mmHg=0.133 kPa). Maximum anal resting pressure (MARP) was (79.3±17.8) mmHg, Maximum anal squeeze pressure (MSP) was (178.7±52.8) mmHg. Anal high pressure zone (HPZ) length was (3.4±0.6) cm. During simulated evacuation, residual anal pressure (RAP) was (63.8±20.5) mmHg, and anal relaxation rate (ARR) was (37.0±11.5)%. Rectal threshold volume for first sensation (FST), desire to defecate (DDT), urgency to defecate (UDT) and maximum discomfort (MDT) was (47.4±10.0) ml, (84.5±18.2) ml, (125.8±28.5) ml, and (175.5±36.1) ml, respectively. (3) Compared with female subjects, male subjects had higher MSP[(211.0±50.7) mmHg vs (157.5±42.5) mmHg], RAP[(71.6±18.1) mmHg vs (58.8±20.5) mmHg]and rectal MDT[(187.0±36.4) mmHg vs (168.0±34.1)mmHg], but lower ARR[(32.1±8.0)% vs (40.2±12.3)%], all P<0.01. (4) MERP, MARP, MSP and rectal MDT were higher in young group (≤40 years old), all P<0.05. Conclusions: These observations provide normal values for two-dimension solid state HRAM, which have significant difference between genders and different age groups.

Impact and clinical significance of Embosphere microsphere artery embolization therapy in serum VEGF expression level of women patients with uterine fibroids.

OBJECTIVE: We aimed to investigate the effect of Embosphere microsphere artery embolization on the serum level of vascular endothelial growth factor (VEGF) in patients with uterine fibroid. PATIENTS AND METHODS: From March 2014 to December 2015, 128 women in child-bearing age with uterine intramural fibroids were enrolled in the patient group. At the same time, 128 healthy cases in child-bearing age were randomly selected and enrolled in the control group. Enzyme-linked immunosorbent assay was used to measure the serum level of VEGF, and immunohistochemical staining method was used to study the expression of VEGF in the uterine fibroids. Embosphere microsphere artery embolization surgery was performed on cases in the patient group. RESULTS: The serum level of VEGF in the patient group was significantly higher than that of the control group. Immunohistochemical staining results showed that in the control group, VEGF expression level in uterine fibroid tissue was significantly higher. Compared with before the treatment, tumor diameter in the patient group reduced significantly 3 months after the treatment. Erythrocyte count, hemoglobin, and menstrual blood volume increased significantly 6 months after treatment. CONCLUSIONS: Serum VEGF level can be considered as a marker for uterine fibroid, and by using VEGF as a marker we can increase the probability of early diagnosis. We showed that, compared with hysterectomy, Embosphere microsphere embolization had an evident advantage and might be an excellent candidate to replace hysterectomy.

Molecular diversity and distribution of anammox community in sediments of the Dongjiang River, a drinking water source of Hong Kong.

AIMS: The aim of this study was to characterize anaerobic ammonium oxidation (anammox) community in sediments of the Dongjiang River, a drinking water source of Hong Kong. METHODS AND RESULTS: The diversity and distribution of the anammox community were investigated based on a comparative analyses of 16S rRNA and hydrazine oxidation (hzo) genes of anammox bacteria. Candidatus Brocadia and two new anammox bacterial clusters were detected based on phylogenetic analysis of 16S rRNA genes. In contrast, the targeting of hzo genes indicated the presence of only Candidatus Jettenia with four different clusters. It was found that the sequence diversities of hzo genes were higher than those of the 16S rRNA genes. The abundance of anammox bacteria varied significantly among the sediment samples based on qPCR. Pearson correlation analysis indicated that nitrite concentration was the key factor influencing the abundance of anammox bacteria. The redundance analysis (RDA) confirmed that the combination of the contents of nitrite and nitrate, and the ratio of total nitrogen vs total carbon (TN/TC) had significant impact on the anammox bacterial community structure. CONCLUSIONS: The results revealed that the diverse anammox bacteria were present in sediments of the Dongjiang River, and the community structures were associated with varied environmental factors caused by urban pollutant invasion. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report about the distribution of anammox bacterial community in sediments of the Dongjiang River, which provides helpful information of anammox niche specificity and influencing factors in the river ecosystem.

Predictors of acid suppression success in patients with chronic laryngitis.

BACKGROUND: Up to 50% of the patients suspected of reflux laryngitis syndrome failed to respond to acid suppression therapy. However, predictors of acid suppression success have not been determined. METHODS: Consecutive patients with chronic laryngitis were enrolled prospectively. All the patients underwent laryngoscopy, esophagogastroduodenoscopy and 24-h multichannel intraluminal impedance and pH (MII-pH) monitoring before receiving rabeprazole 10 mg b.i.d. for 3 months. Patient was considered as a responder to acid suppression if the chief laryngeal complaint score during the last week since last interview had decreased by at least 50% after the start of therapy compared with baseline. Cox regression analysis was used to determine the independent predictors of acid suppression success. KEY RESULTS: Of 92 patients (age 42.4 ± 14.3 years, 50 women), 42 (45.7%) responded to acid suppression after 3 months. Gastroesophageal reflux disease was defined in 22 patients, of whom 19 patients had pathological distal esophageal acid exposure and 5 were defined as erosive esophagitis. The time to response showed a significant hazard ratio for patients with increased distal esophageal acid exposure time (ß: 0.93; HR: 2.55; 95% CI: 1.24-5.24; P = 0.011) and increased laryngopharyngeal bolus exposure time (BET; ß: 0.96; HR: 2.61; 95% CI: 1.36-5.00; P = 0.004). The latter had the best Youden Index (0.34) and accuracy (68.5%). CONCLUSIONS & INFERENCES: The success of acid suppression on chronic laryngitis could be predicted using reflux parameters detected by MII-pH, among which increased laryngopharyngeal BET is the best.

Combined transplantation of neural stem cells and olfactory ensheathing cells for the repair of spinal cord injuries.

Spinal cord repair is a problem that has long puzzled neuroscientists. The failure of the spinal cord to regenerate and undergo reconstruction after spinal cord injury (SCI) can be attributed to secondary axonal demyelination and neuronal death followed by cyst formation and infarction as well as to the nature of the injury environment, which promotes glial scar formation. Cellular replacement and axon guidance are both necessary for SCI repair. Multipotent neural stem cells (NSCs) have the potential to differentiate into both neuronal and glial cells and are, therefore, likely candidates for cell replacement therapy following SCI. However, NSC transplantation alone is not sufficient for spinal cord repair because the majority of the NSCs engrafted into the spinal cord have been shown to differentiate with a phenotype which is restricted to glial lineages, further promoting glial scaring. Olfactory ensheathing cells (OECs) are a unique type of glial cell that occur both peripherally and centrally along the olfactory nerve. The ability of olfactory neurons to grow axons in the mature central nervous system (CNS) milieu has been attributed to the presence of OECs. It has been shown that transplanted OECs are capable of migrating into and through astrocytic scars and thereby facilitating axonal regrowth through an injury barrier. Given the complementary properties of NSCs and OECs, we predict that the co-transplantation of NSCs and OECs into an injured spinal cord would have a synergistic effect, promoting neural regeneration and functional reconstruction. The lost neurocytes would be replaced by NSCs, while the OECs would build "bridges" crossing the glial scaring that conduct axon elongation and promote myelinization simultaneously. Furthermore, the two types of cells could first be seeded into a bioactive scaffold and then the cell seeded construct could be implanted into the defect site. We believe that this type of treatment would lead to improved neural regeneration and functional reconstruction after SCI.

Selective induction of necrotic cell death in cancer cells by beta-lapachone through activation of DNA damage response pathway.

Most efforts thus far have been devoted to develop apoptosis inducers for cancer treatment. However, apoptotic pathway deficiencies are a hallmark of cancer cells. We propose that one way to bypass defective apoptotic pathways in cancer cells is to induce necrotic cell death. Here we show that selective induction of necrotic cell death can be achieved by activation of the DNA damage response pathways. While beta-lapachone induces apoptosis through E2F1 checkpoint pathways, necrotic cell death can be selectively induced by beta-lapachone in a variety of cancer cells. We found that beta-lapachone, unlike DNA damaging chemotherapeutic agents, transiently activates PARP1, a main regulator of the DNA damage response pathway, both in vitro and in vivo. This occurs within minutes of exposure to beta-lapachone, resulting in selective necrotic cell death. Inhibition of PAR blocked beta-lapachone-induced necrosis. Furthermore, necrotic cell death induced by beta-lapachone was significantly reduced in PARP1 knockout cell lines. Our data suggest that selective necrotic cell death can be induced through activation of DNA damage response pathways, supporting the idea of selective necrotic cell death as a therapeutic strategy to eliminate cancer cells.

Protective effects of extract of Ginkgo biloba (EGb 761) on nerve cells after spinal cord injury in rats.

STUDY DESIGN: An experimental animal model was used to assess spinal cord injury following lateral hemitransection at thoracic spinal cord level. OBJECTIVE: To determine whether extract of Ginkgo biloba (EGb) could have a neuroprotective effect in spinal cord injury (SCI) in rats. SETTING: Department of Biological Sciences and Biotechnology, Tsinghua University, China. METHODS: A total of 72 adult rats were divided randomly into three groups: the EGb group, normal saline (NS) group, and sham operation group (sham group). After thoracic spinal cord hemitransection was performed at the level of the 9th thoracic vertebra (T9), rats in the EGb group were given 100 mg/kg EGb 761 daily, while rats in the NS group received NS. The rats in the sham group only underwent laminectomy without spinal cord hemitransection. At various time points after surgery, thoracic spinal cords were sampled and sliced for histochemistry, immunohistochemistry of inducible nitric oxide synthase (iNOS), and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) of apoptotic cells. RESULTS: Myelin staining showed that the area of cavities was small and the demyelinated zones were limited at and around the injury site of the spinal cord in the EGb group, while the area of cavities was large and the demyelinated zones were serious in the NS group. Nissl staining showed that the ratio of bilateral ventral horn neurons (transection side/uninjured side) in the EGb group was higher than that in the NS group (P<0.05). The apoptotic index and the percentage of iNOS-positive cells were lower in the EGb group than in the NS group. Furthermore, the percentage of iNOS-positive cells positively correlated with the apoptotic index (r( 2)=0.729, P<0.01) after SCI. CONCLUSION: This study demonstrated that EGb 761 could inhibit iNOS expression and have neuroprotective effect by preventing nerve cells from apoptosis after SCI in rats.

Leu-enkephalin induced by IL-2 administration mediates analgesic effect of IL-2.

Interleukin-2 (IL-2) was found to have an analgesic effect in both central and peripheral nervous systems. This effect is related to opioid receptors and mediated mainly by IL-2 directly binding to opioid receptors. Using radioimmunoassay, the content of Leu-enkephalin (LEK) in some nuclei were measured at intervals after the injection of IL-2 into the lateral ventricle of rats. Levels of LEK increased in both paraventricular hypothalamic nucleus (PVN) and locus ceruleus (LOC) after IL-2 administration, suggesting that the analgesic effect of IL-2 is also related to the change of LEK in PVN and LOC induced by IL-2 administration.

Tryptophan fluorescence quenching by alkaline earth metal cations in deionized bacteriorhodopsin.

Tryptophan quenching by the addition of alkaline earth metal cations to deionized bacteriorhodopsin suspensions was determined. The results show that the addition of cation primarily quenches fluorescence from surface tryptophan residues. The quenched intensity exhibits a 1/R dependence, where R is the ionic radius of the corresponding metal ion. This observation results from a stronger energy transfer coupling between the tryptophan and the retinal. The membrane curvature may be involved as a result of cations motion and correlated conformational changes.

[Opioid receptor mediated modulation of intrahippocampal enkephalin induced cellular immune function].

In the present work, the effect of intrahippocampal microinjection of opioid receptor antagonist naloxone on the enhancement of cellular immune responses induced by enkephalin was studied in rat. The results showed that (1) the proliferation activity of splenic lymphocytes stimulated by Con A and natural killer (NK) cell activity were decreased with microinjection of 1 microl lipopolysaccharide (LPS,50 ng/microl) into bilateral hippocampus; (2) the decrease of cellular immune responses induced by LPS could be inhibited by a preceding intrahippocampal injection of 1 microl met-enkephalin (10 microg/1 microl); (3) the enhancement of cellular immune responses induced by met-enkephalin could be blocked by an opioid receptor antagonist naloxon (10 microg/microl); and (4) cellular immune responses were also inhibited when naloxon was injected intrahippocampally alone. The above results suggest that the enhancement of cellular immune responses induced by enkephalin was mediated by opioid receptors in hippocampus.

[Effect of intrahippocampal microinjection of enkephalin on cellular immune function and brain IL-1 alpha gene expression in rat].

The effect of intrahippocampal microinjection of enkephalin on cellular immune function and hippocampal IL-1 alpha gene expression was studied in rats. The results showed that: (1) The proliferation activity of splenic lymphocytes stimulated by Con A was significantly increased with microinjection of Leu-enkephalin 1 microliter (18 mmol/L) or Met-enkephalin 1 microliter (18 mmol/L) into bilateral hippocampus, but was inhibited by Lipopolysaccharide 1 microliter (50 ng/microliter). The proliferative response of splenic lymphocytes to Leu-enkephalin still persisted after bilateral adrenalectomy. Low doses of Leu- or Met-enkephalin (10(-10), 10(-11) mol/L) were also capable of causing proliferative activity of the Con A- stimulated cultured splenic lymphocytes in vitro. (2) Using RT-PCR technique, IL-1 alpha gene expression was detected in hippocampus 90 min after bilateral intrahippocampal injection of LPS. The LPS-induced IL-1 alpha gene expression in hippocampus could no longer be detected 30 min after microinjection of Met- or Leu-enkephalin into hippocampus. The above results suggested that intrahippocampal enkephalin might play an important role in neuro-immunomodulation by enhancing the inhibition of IL-1 alpha gene expression in hippocampal formation.

[Possible mechanism of the analgesic effect of interleukin-2 in central nervous system].

The monoclonal antibody against IL-2R (Tac) could not block the analgesic effect of IL-2, and IL-2 mutant that could not bind to beta subunit of IL-2 receptor still had capability of increasing the pain threshold of rats. All these facts suggest that the analgesic effect of IL-2 in CNS is not mediated through the IL-2 receptor, and that the immune and analgesic effects of IL-2 are mediated through different receptor mechanisms. It is suggested that there are common antigenic determinants and similar structure between IL-2 and endogenous opioid peptides (EOP). This implies that the analgesic effect of IL-2 might be mediated by interaction between IL-2 and opioid receptors in CNS. Using radioimmunoassay the contents of EOP of different nuclei were measured at different times after injecting IL-2 into the lateral ventricle of rats. The results suggested that the analgesic effect of IL-2 may be related to beta-EP and LEK in arcuate hypothalamic nucleus, paraventricular hypothalamic nucleus and locus ceruleus.

[Improvement of memory function of fornix-fimbria transected rats by transplantation of the superior cervical ganglion into hippocampus].

Memory impairments of passive avoidance response were observed in 38 Wistar rats with bilateral fornix-fimbria transection. After fornix-fimbria lesions the degree of performance decreased from 65.3% to 13.6% (P < 0.01). Autotransplantation of superior cervical ganglion (SCG) into bilateral dorsal hippocampi improved memory function to a considerable extent. In the end of the behavioral experiments, implanted rats were sacrificed for histofluorescence study of grafts and measurement of norepinephrine (NA) content in the hippocampus. These experiments showed that the hippocampal NA content in implanted rats was considerably higher than that in untransplanted fornix-fimbria transected rats and consequently suggested that improvement of memory function was to some extent due to supplement of monoamine transmitter by the transplanted SCG.

[Effects of morphine on sensitivities of alpha-adrenoceptors in toad spinal ganglion neurons].

Intracellular recordings were performed on 35 neurons from 35 isolated toad spinal ganglia (SG) and the extracellular free calcium ion activities were measured in another 26 isolated toad SG by Ca(2+)-selective microelectrodes. The effects of morphine on the sensitivities of alpha-adrenoceptors were observed. It was found that depolarization of membrane potential induced by norepinephrine (NE 10-100 mumol.L-1) or alpha 1-adrenoceptor agonist phenylephrine (100 mumol.L-1) was depressed by morphine (27 mumol.L-1). Superfusing SG with opioid receptor antagonist naloxone (100 mumol.L-1) blocked the depressing effect of morphine on NE-induced depolarization. The depressing effect of morphine on NE-induced depolarization was not affected by superfusing SG with alpha 2-adrenoceptor antagonist yohimbine (5 mumol.L-1). NE (100 mumol.L-1) reduced the extracellular free calcium ion activity while morphine (27 mumol.L-1) increased the extracellular free calcium ion activity in SG. It is concluded that morphine down-regulates the sensitivity of alpha 1-adrenoceptor in toad SG neuron mediated by opioid receptor and the variation in Ca2+ activity may be involved in this effect.

Dual-enzyme fiber-optic biosensor for glutamate based on reduced nicotinamide adenine dinucleotide luminescence.

Response characteristics are presented for a dual-enzyme fiber-optic biosensor for glutamate. An enzyme layer composed of glutamate dehydrogenase (GDH) and glutamate-pyruvate transaminase (GPT) is used to produce reduced nicotinamide adenine dinucleotide (NADH) at the tip of a fiber-optic probe. NADH luminescence is monitored through this probe and the measured fluorescence intensity is related to the concentration of glutamate. GDH catalyzes the formation of NADH, and GPT drives the GDH reaction by removing a reaction product and regenerating glutamate. Optimal response is obtained in a pH 7.4 Tris-HCl buffer maintained at 25 degrees C in the presence of 4 mM NAD+ and 10 mM L-alanine. The temperature profile reveals a strong negative temperature effect which is attributed to the temperature dependency of NADH luminescence. Under optimal conditions, the sensor sensitivity is 0.127 nA/microM over the 1-10 microM concentration range, the detection limit is 0.13 microM, and response times range from 4 to 8 min. The sensor response is stable for 12 days when stored at 4 degrees C. Selectivity for glutamate is excellent over most of the common amino acids as well as ascorbic acid, uric acid, taurine, and GABA. Only slight responses were observed for glutamine and lysine. The effect of ammonia on the glutamate response was found to be minimal at total ammonia nitrogen concentrations as high as 200 microM.