[Performance of point-of-care testing for cervical cancer screening].

Objective: To evaluate the performance of point-of-care testing for cervical cancer and precancerous lesions screening. Methods: In September 2020, 197 and 273 women were selected by using simple random sampling method from "self-sampling" cohort and "physician-sampling" cohort established in Xiangyuan county, Shanxi Province, China, respectively. Cervical exfoliated cells were collected by women themselves or gynecologists. All samples were detected by POCT and women with positive result were directly referred for colposcopy. Subsequently, all the samples were detected by careHPV and PCR test. Colposcopy and punch biopsy were performed for women with POCT negative but careHPV or PCR test positive at another visit. Using histopathological diagnosis as the gold standard, we calculated sensitivity, specificity and drew the receiver operating characteristic (ROC) curves. The accuracy of POCT was analyzed and compared to that of careHPV and conventional PCR test in cervical cancer and precancerous lesions screening. Results: The median (Q1 , Q3) age of 470 women was 51 (45, 57) years old. Based on self-sampling, the sensitivity and specificity of POCT for CIN2+ were 100.00% (95%CI: 56.56%-100.00%) and 28.95% (95%CI: 22.97%-35.76%), respectively. Compared with POCT, POCT HPV16/18 test had similar sensitivity and higher specificity of 89.47% (95%CI: 84.30%-93.08%). Self-sampling POCT HPV16/18 test had an AUC of 0.947 (95%CI:0.910-0.985), which was higher than that of careHPV and PCR test. Physician-sampling POCT test had 100.00% sensitivity (95%CI: 64.57%-100.00%) and 55.85% specificity (95%CI: 49.83%-61.70%) for detecting CIN2+. POCT HPV16/18 test had lower sensitivity (71.43%, 95%CI: 35.90%-91.76%) and higher specificity (92.45%, 95%CI: 88.63%-95.06%). POCT HPV16/18 test generally showed similar AUC on both self-collected samples and clinician-collected samples (0.947 vs 0.819, P=0.217). Conclusion: POCT HPV16/18 test is an effective method with relatively high sensitivity and specificity for cervical cancer screening.

Factors influencing QTL mapping accuracy under complicated genetic models by computer simulation.

The accuracy of quantitative trait loci (QTLs) identified using different sample sizes and marker densities was evaluated in different genetic models. Model I assumed one additive QTL; Model II assumed three additive QTLs plus one pair of epistatic QTLs; and Model III assumed two additive QTLs with opposite genetic effects plus two pairs of epistatic QTLs. Recombinant inbred lines (RILs) (50-1500 samples) were simulated according to the Models to study the influence of different sample sizes under different genetic models on QTL mapping accuracy. RILs with 10-100 target chromosome markers were simulated according to Models I and II to evaluate the influence of marker density on QTL mapping accuracy. Different marker densities did not significantly influence accurate estimation of genetic effects with simple additive models, but influenced QTL mapping accuracy in the additive and epistatic models. The optimum marker density was approximately 20 markers when the recombination fraction between two adjacent markers was 0.056 in the additive and epistatic models. A sample size of 150 was sufficient for detecting simple additive QTLs. Thus, a sample size of approximately 450 is needed to detect QTLs with additive and epistatic models. Sample size must be approximately 750 to detect QTLs with additive, epistatic, and combined effects between QTLs. The sample size should be increased to >750 if the genetic models of the data set become more complicated than Model III. Our results provide a theoretical basis for marker-assisted selection breeding and molecular design breeding.

Influence of various quantitative trait loci (QTL) mapping methods on the mapping accuracy under varying heritability levels.

The study of quantitative trait effects is of great significance for molecular marker-assisted breeding. The accuracy of quantitative trait loci (QTL) mapping is the key factor affecting marker-assisted breeding, and is extremely significant. The effect of different heritability rates (10, 30, 50, 70, and 90%) on the accuracy of QTL mapping of five recombinant inbred lines (RILs) were analyzed via computer simulation. RILs display additive and epistatic genetic effects. The QTLs were analyzed using four different mapping procedures: multiple QTL model (MQM), composite interval mapping (CIM), multiple interval mapping (MIMR), and inclusive composite interval mapping (ICIM). The results revealed an increase in the QTL mapping accuracy and QTL detection power, and a decrease in the QTL interval range with the increase in heritability; conversely, an irregular number of false positive QTLs were generated. CIM and MQM only screen the additive and dominant effects; MIMR and ICIM screen the additive, dominant, and epistatic effects. The highest QTL detection power obtained using MQM and CIM was only 75%, while MIMR and ICIM showed a detection power of 100%. At heritability rates of more than 50 and less than 10%, the detection powers of the MIMR and ICIM procedures were >95 and <35%, respectively. QTL mapping has no significance at heritability rates <10%. The results of this study suggest that QTL mapping has significance at a heritability rate >30% (at least >10%) for practical marker-assisted breeding.

Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion.

Poly (ADP-ribose) synthase or polymerase (PARS and PARP, respectively) is a cytotoxic enzyme which causes cellular damage. Nicotinamide, a compound of vitamin B complex, has been reported to exert an inhibitory effect on PARS or PARP. The present study tests the effects of nicotinamide on acute lung injury and associated alterations following ischaemia/reperfusion (I/R) of the isolated perfused rat's lung. I/R increased the lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, pulmonary arterial pressure and capillary permeability. The insult also increased nitrate/nitrite, methyl guanidine, tumour necrosis factor-alpha and interleukin-1beta in lung perfusate, while it decreased adenosine triphosphate content with an increase in PARP activity in lung tissue. Most of the I/R-induced changes were abrogated by post-treatment (30 min after I/R) with nicotinamide (100 mg.kg(-1) body weight). However, the increase in pulmonary arterial pressure was enhanced by nicotinamide post-treatment. Following I/R, the inducible nitric oxide synthase (iNOS) mRNA expression was enhanced. Nicotinamide reduced the iNOS expression. The results suggest that nicotinamide exerted a protective effect on the acute lung injury caused by ischaemia/reperfusion. The mechanisms may be mediated through the inhibition on the poly (adenosine diphosphate-ribose) polymerase activity, inducible nitric oxide synthase expression and the subsequent suppression of nitric oxide, free radicals and pro-inflammatory cytokines with restoration of adenosine triphosphate.

Mediation of beta-endorphin in exercise-induced improvement in insulin resistance in obese Zucker rats.

BACKGROUND: Aerobic exercise including treadmill running has long been used to successfully treat and/or prevent insulin resistance and type-2 diabetes. Increase of plasma beta-endorphin is observed with exercise. The present study was designed to clarify the role of endogenous beta-endorphin in exercise-induced improvement in insulin resistance. METHODS: We used a moderate exercise program consisting of treadmill running at 20 m/min and 0% grade for 1 h/day, 7 days/week, for 8 weeks. Plasma glucose concentration was assessed by the glucose oxidase method. The enzyme-linked immunosorbent assay was performed to quantify the plasma level of beta-endorphin-like immunoreactivity (BER). The glucose disposal rate (GDR) was measured by the hyperinsulinemic euglycemic clamp technique. Changes of the insulin signaling in isolated soleus muscle were then detected by immunoprecipitation and immunoblotting. RESULTS: An increase of plasma BER in parallel with the reduction of plasma glucose was obtained in exercise-trained obese Zucker rats. Different from a marked reduction in sedentary obese rats, the value of insulin-stimulated GDR obtained from the exercised obese rats was reversed to near that of the sedentary lean group, eight weeks after the last period of exercise. This effect of exercise was inhibited by naloxone or naloxonazine at doses sufficient to block opioid micro-receptors. Signaling-related defects in the soleus muscle of sedentary obese Zucker rats, which impaired glucose transporter subtype 4 (GLUT 4), included decreased phosphorylation of insulin receptor substrate (IRS)-1, as well as an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3 kinase) and Akt serine phosphorylation. In contrast, exercise training failed to modify the levels of insulin receptor (IR), IRS-1, and IR tyrosine autophosphorylation in obese Zucker rats. CONCLUSION: Enhanced insulin sensitivity via exercise training might be mediated by endogenous beta-endorphin through an increase of postreceptor insulin signaling related to the IRS-1-associated PI3-kinase step that leads to the enhancement of GLUT 4 translocation and improved glucose disposal in obese Zucker rats.

Infusion of beta-endorphin improves insulin resistance in fructose-fed rats.

In an attempt to probe the effect of beta-endorphin on insulin resistance, we used Wistar rats that were fed fructose-rich chow to induce insulin resistance. Insulin action on glucose disposal rate (GDR) was measured using the hyperinsulinemic euglycemic clamp technique, in which glucose (variable), insulin (40 mU/kg/min), and beta-endorphin (6 ng/kg/min) or vehicle were initiated simultaneously and continued for 120 min. A marked reduction in insulin-stimulated GDR was observed in fructose-fed rats compared to normal control rats. Infusion of beta-endorphin reversed the value of GDR, which was inhibited by naloxone and naloxonazine each at doses sufficient to block opioid mu-receptors. Opioid mu-receptors may therefore be activated by beta-endorphin to improve insulin resistance. Next, soleus muscle was isolated to investigate the effect of beta-endorphin on insulin signals. Insulin resistance in rats induced by excess fructose was associated with the impaired insulin receptor (IR), tyrosine autophosphorylation, and insulin receptor substrate (IRS)-1 protein content in addition to the significant decrease in IRS-1 tyrosine phosphorylation in soleus muscle. This impaired glucose transportation was also due to signaling defects that included an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) and Akt serine phosphorylation. However, IR protein levels were not markedly changed in rats with insulin resistance. beta-endorphin infusion reversed the fructose-induced decrement in the insulin-signaling cascade with increased GDR. Apart from IR protein levels, infusion of beta-endorphin reversed the decrease in protein expression for the IRS-1, p85 regulatory subunit of PI3-kinase, and Akt serine phosphorylation in soleus muscle in fructose-fed rats. The decrease in insulin-stimulated protein expression of glucose transporter subtype 4 (GLUT 4) in fructose-fed rats returned to near-normal levels after beta-endorphin infusion. Infusion of beta-endorphin may improve insulin resistance by modulating the insulin-signaling pathway to reverse insulin responsiveness.

Assessment of intragastric pH value changes after early nasogastric feeding.

Studies have suggested that early feeding after injury decreases morbidity and mortality. Few reports, however, have focused on the change in pH inside the stomach after early tube feeding. The aim of the present study was the assessment of 1) the change in intragastric pH after surgery, and 2) the effect of early nasogastric tube feeding on intragastric pH value. From April 1997 to February 1998, 80 patients who underwent colon resection for colorectal cancer by a single surgeon entered the study and were randomized into four groups. Twenty patients (group I) were kept on NPO for 1 wk, and 20 patients per group (groups II, III, and IV) were fed through a nasogastric tube from the second to the seventh postoperative day with low-residual (Osmolite HN), high-fat (Pulmocare), and glutamine-containing (AlitraQ) enteral formulas. Feeding started at 500 kcal/500 cc/d. If the patient tolerated the formula well, feeding increased to 1500 kcal/1500 cc(-1)/d(-1) the following day. Intragastric pH was measured preoperatively and then twice daily until the sixth postoperative day. The pH value of intragastric juice increased significantly once feeding started (3. 67 +/- 1.33 on the third postoperative day; 4.28 +/- 1.26 on the six postoperative day). The pH value seemed only mildly affected by the patient's tolerance for tube feeding (poorly tolerated group, pH 3. 52 +/- 1.75 versus 3.75 +/- 1.21 in the well-tolerated group on the third postoperative day; poorly tolerated group, pH 3.67 +/- 1.02 versus 4.45 +/- 1.27 in the well-tolerated group on the sixth postoperative day). The pH value of intragastric juice was higher in group II than in groups III and IV (4.51 +/- 1.57, 3.90 +/- 1.20, 4. 42 +/- 0.89 respectively, on the sixth postoperative day). This series suggests that early nasogastric feeding can significantly elevate the intragastric pH value in patients after resection of colorectal cancer. Nasogastric feeding may decrease the incidence of stress ulceration by elevating the pH value of intragastric juice.

Effects of intracranial hypertension on steady and pulsatile haemodynamics in dogs.

1. Intracranial hypertension (ICH) tends to elicit various cardiovascular changes. Previous studies on the haemodynamic responses to ICH have been confined mainly to measurements of arterial pressure (AP), cardiac output (CO) and total peripheral resistance (TPR). In the present study, we used the technique of arterial impedance analysis for a complete assessment of steady and pulsatile haemodynamics in ICH. 2. In anaesthetized dogs, aortic pressure and flow waves were obtained with high-fidelity Millar sensors. The pressure and flow waves were subjected to Fourier transformation (frequency analysis) for an analysis of impedance spectra. Intracranial pressure (ICP) was elevated by inflation of an epidural balloon. At an ICP of 50 mmHg, the changes in steady and pulsatile haemodynamics were slight. 3. Haemodynamic changes became evident at an ICP of 100 mmHg. The mean AP was elevated by 31 mmHg (+32%) and heart rate (HR) was reduced by 25 b.p.m. (-18%). There was also a significant decrease in CO by 27% and large increase in TPR by 82%. With respect to pulsatile haemodynamics, an elevation of ICP to 100 mmHg caused significant increases in characteristic impedance by 45% and wave reflection by 53%. Arterial compliance was reduced by 50%. The ventricular oscillatory work was increased without a significant change in steady work. 4. The results indicate that ICH causes constriction of resistance vessels to affect AP and TPR. Because the pulsatile haemodynamics reflect mainly the Windkessel functions, ICH also induces stiffness of the large vessels to affect arterial impedance, pulse wave reflection and ventricular oscillatory work.

[Neural and hemodynamic mechanisms of neurogenic pulmonary edema].

Acute pulmonary edema has been reported in man and animals with intracranial disorders, head trauma or cerebral compression. In anesthetized rats, cerebral compression produced acute, fulminating and fatal lung injury. Intense activation of the sympathetic mechanism in the brain stem induced systemic hypertension and a series of hemodynamic changes. Pulmonary volume loading was the result of drastic decrease in aortic flow accompanying a decline in pulmonary arterial flow. The acute increase in pulmonary blood volume caused severe rises in pulmonary arterial and venous pressures leading to disruption of lung vessels.

Epidemiological study of moyamoya disease in Taiwan.

From January 1978 to December 1995, 92 cases of Moyamoya disease were collected from seven major medical centers in Taiwan. The data gave an annual incidence rate of 0.048 per 100,000 population. There were 40 males and 52 females and the ages ranged from 2 to 62 years with the peak incidence in the 31-40 year age group (23 cases). Cerebral infarction occurred in 20 out of 24 juvenile patients (83%), and in 24 out of 68 adult patients (35%). The difference was statistically significant. Haemorrhagic stroke was more frequent in adult patients. Computed tomographic scans following stroke showed cerebral infarction in 44 cases, ventricular haemorrhage in 26 cases, intracerebral haemorrhage in 14 cases and pure subarachnoid haemorrhage in eight. The most frequent initial symptom was motor disturbance (59%), followed by headache (49%) and impaired consciousness (35%). This survey showed an incidence rate much lower than that in Japan, but comparable with those in other Oriental countries and higher than those in Western countries. The male-to-female ratio once differed considerably from that of the Japanese series, but from the present study is now quite similar.

[Moyamoya disease in Taiwan].

From January 1978 to December 1993, 73 patients with moyamoya disease were collected from seven neurological centers in Taiwan. The annual incidence of this disease in Taiwan is 0.024 per 100,000 population. There were 33 males and 40 females. The ages ranged from 2 to 62 years with a peak incidence in the 31 to 40 year age group (18 cases). Cerebral infarction occurred in 16 out of 19 juvenile patients (84.2%); by contrast, only 19 out of 54 adult patients (35.2%) presented with infarction. Hemorrhagic strokes were more frequent in adult patients. Computed tomographic scans following stroke showed cerebral infarction in 35 cases, ventricular hemorrhage in 21 cases, intracerebral hemorrhage in 11 cases and pure subarachnoidal hemorrhage in 6 cases. The most frequent initial symptom was motor disturbance (58.9%), followed by headaches (49.3%), and impaired consciousness (34.2%). Compared with reports from Japan, this survey showed a lower incidence of moyamoya disease in Taiwan.

Interleukin-1 beta production during the onset of heat stroke in rabbits.

During the onset of heat stroke, rabbits displayed hyperthermia (42.8 degrees C), decreased arterial blood pressure, increased intracranial pressure, decreased cerebral perfusion pressure and increased interleukin-1 beta production (in both the hypothalamus and plasma), compared to those of normothermic, control rabbits. In addition, the heat-stroke animals which received an i.v. injection of interleukin 1-receptor antagonist (200 micrograms/kg) had a survival time (interval between onset of heat stroke and death) longer than that of the heat-stroke animals which received control-vehicle solution. The data indicate that interleukin-1 production plays a role in pathogenesis of heat stroke in rabbits.

Spinal 5-HT pathways and the antinociception induced by intramedullary clonidine in rats.

The possible involvement of spinal 5-hydroxytryptamine (5-HT) pathways in antinociception induced by microinjection of clonidine into the ventrolateral surface of the medulla oblongata was investigated in rats. Microinjection of clonidine (10-20 micrograms), but not yohimbine (1 microgram) or 0.9% saline, into the lateral medulla prolonged the hot plate latency in rats. This clonidine-induced antinociception was abolished by intramedullary injection of the alpha 2-adrenoceptor antagonist, yohimbine. Selective destruction of spinal 5-HT neurons produced by intraspinal injection of 5,7-dihydroxytryptamine (5,7-DHT; 10 micrograms) or postsynaptic blockade of spinal 5-HT receptors produced by intrathecal injection of cyproheptadine (1 microgram; a mixed 5-HT1/5-HT2 antagonist) also abolished clonidine-induced antinociception. Rats given 5,7-DHT intraspinally or cyproheptadine intrathecally showed a decrease in hot plate latency as compared with the controls. In anesthetized rats, the 5-HT release from the thoracic spinal cord was enhanced by microinjection of clonidine into the lateral medulla. This enhanced spinal 5-HT release evoked by intramedullary injection of clonidine was abolished by pretreatment of rats with intraspinal injection of 5,7-DHT. These results indicate that 5-HT pathways to the spinal cord mediate the antinociceptive effect induced by microinjection of clonidine into the ventrolateral surface of the medulla oblongata in rats.

"Backfiring" in spinal cord monitoring. High thoracic spinal cord stimulation evokes sciatic response by antidromic sensory pathway conduction, not motor tract conduction.

Spinal cord stimulation has been advocated as an alternative to motor cortex stimulation for motor tract activation. To test this theory, evoked responses were recorded from lumbar spinal cord (L2; n = 14), spinal roots (L4-L7; n = 112), peripheral nerves (sciatics; n = 28), and hind limb muscles (n = 28) after epidural stimulation of the T1-T2 segment of the spinal cord in dogs (n = 12), cats (n = 2), and monkeys (n = 2). The spinal response evoked by spinal cord stimulation was resistant to a dorsal hemisectioning (depth, 7-8 mm) of the midthoracic spinal cord. A minimal attenuation of latency and amplitude occurred with dorsal hemisectioning, suggesting signal transmission through descending or ascending pathways in the ventrolateral and ventral quadrants of the spinal cord. The sciatic nerve response was abolished by a dorsal column transection (depth, 3-4 mm) or ipsilateral lumbar dorsal rhizotomy (four dorsal roots). This shows that the evoked response recorded from the sciatic nerve in our animals was not travelling, as we expected, through the ventral roots, but rather was conducted antidromically through sensory fibers in dorsal roots.

The antinociceptive role of a bulbospinal serotonergic pathway in the rat brain.

The antinociceptive role of spinal serotonin (5-HT) neurons descending from 5-HT cells near the ventrolateral surface of the medulla oblongata was investigated by stimulating these cells in normal rats, in rats with generalized or selective chemical ablation of 5-HT nerves, and in rats with postsynaptic blockade of 5-HT receptors. Electrical stimulation of the lateral medulla elicited analgesia in normal rats; the increase in pain threshold was proportional to the intensity and to the frequency of stimulation. In addition, microinjection of kainic acid or L-glutamate at the same sites also produced analgesia. However, generalized destruction of CNS 5-HT nerves produced by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) or selective destruction of spinal 5-HT nerves produced by intraspinal injection of 5,7-DHT reduced the magnitude of the antinociceptive responses to electrical stimulation. Postsynaptic blockade of CNS 5-HT receptors produced by intraventricular injection of cyproheptadine also reduced the stimulation-produced analgesia. The specificity of the lesions for 5-HT nerves is demonstrated by the lack of effect on the levels of noradrenaline in the same brain regions. The results indicate that the activity of 5-HT nerve cells adjacent to the ventrolateral surface of the medulla oblongata and projecting to the spinal cord serves to elevate pain threshold.

Intraventricular morphine produces pain relief, hypothermia, hyperglycaemia and increased prolactin and growth hormone levels in patients with cancer pain.

The effects of analgesic, thermoregulatory and endocrine functions of administering morphine sulphate (0.3 mg) into the lateral cerebral ventricle via an Ommaya catheter were assessed in eight patients with cancer pain. Satisfactory control of intractable pain was obtained in these patients, without any change in other sensory modalities. The delay in the onset of pain relief and the duration of analgesia ranged, respectively, from 20 to 40 min and from 12 to 16 h after drug injection. In addition, intraventricular administration of morphine caused a reduction in rectal temperature in these patients at an ambient temperature of 24 degrees C. The hypothermia in response to the injection of morphine was due to cutaneous vasodilation and sweating. There was no change in metabolism or in respiratory evaporative heat loss after morphine injection. Further, 10 to 20 min after intraventricular administration of morphine, the blood levels of prolactin, growth hormone and glucose were elevated in these patients. The changes in temperature and endocrine levels lasted for 1-3 h. In addition to the pain relief, these side-effects of morphine treatment were short-lasting and disappeared as the morphine treatment continued. The results indicate that activation of opiate receptors in the brain produced pain relief, hypothermia (due to cutaneous vasodilation and sweating), and increased blood levels of prolactin, growth hormone and glucose in patients with cancer pain.