Serum alkaline DNase activity in normal or nonhospitalised individuals

According to previous observations, the variations in serum alkaline DNase activity (SADA) appeared to be useful in monitoring malignant disease. In this study, SADA was measured in 625 individuals to explore nontumor-related factors which may influence SADA levels. The overall range in SADA was 0.2-82.3 kU/l. Women aged 50-79 years had higher (p less than 0.001) levels of SADA than younger females. A similar but less consistent effect of age was noticed in men (0.01 less than p less than 0.05). Older men had lower (0.01 less than p less than 0.05) SADA levels than the older women. Old women substituted with estrogens had lower (0.01 less than p less than 0.05) levels of SADA than those not treated with estrogens. SADA levels in pregnancy as well as postparturition were lower (p less than 0.001) than SADA values in nonpregnant females of similar age. In fertile women, no SADA variation was observed during the menstrual cycle and there was no significant effect of contraceptive pills. In males, SADA seemed unrelated to testosterone or cortisol levels but varied during the day. Smoking, alcohol consumption and drug therapy appeared to be without effect on SADA.     

Bone mass and biochemical parameters of bone metabolism in men with spinal osteoporosis

With advancing age both sexes have an increased incidence of osteoporotic fractures, although fractures are more common in women than in men. Whereas in women several potential risk factors have been identified, less is known about osteoporosis in men. A total of 27 Austrian men (mean age: 65 +/- 2 years) with atraumatic spine fractures were studied. In all patients, medical history gave no evidence of disease or medications causing osteoporosis. Peripheral bone mass was determined by single-photonabsorptiometry on the distal non-dominant forearm; lumbal bone density was measured by quantitative computed tomography. Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, testosterone, estrogen, parathyroid hormone and 25-hydroxy-vitamin D as well as 2-h-urinary-OH proline and calcium excretion were measured. All data were compared with those of an age and sex matched control group consisting of 19 healthy males. A significant difference in mean peripheral and axial bone mass (SPA: P less than 0.004; QCT: P less than 0.0001) was observed between osteoporotic men and controls. When compared to controls, serum levels of alkaline phosphatase (P less than 0.012), urinary OH proline (P less than 0.05) and urinary calcium excretion (P less than 0.003) were significantly higher in the osteoporotic males. Additionally, there was a significant positive correlation between serum alkaline phosphatase and urinary OH proline excretion (r = 0.32; P less than 0.04) in the osteoporotics. All other biochemical parameters showed no significant differences. Our results may lead to the assumption that osteopenia in men is related to increased bone turnover.     

The acute phase response and its relation to amyloid A degrading activity in serum of patients with rheumatoid arthritis undergoing arthroplasty

The sequential changes in the concentration of specific serum proteins and their relation to amyloid A degrading activity were studied in ten patients with rheumatoid arthritis undergoing arthroplasty of the knee or hip. Serum amyloid A protein increased from a preoperative level of 78 +/- 20 gm/l (mean +/- SEM) to a peak level of 623 +/- 93 mg/l on the third postoperative day (P less than 0.001). The serum amyloid A protein response was greater than that of any other protein including C-reactive protein, to which it was closely related (r = 0.84, P less than 0.001). The concentrations of alpha 1-antitrypsin and alpha 1-antichymotrypsin were highest on the fourth postoperative day (mean changes + 35%, P less than 0.01, and +44%, P less than 0.05, respectively). Serum albumin, pre-albumin and alpha 2-macroglobulin behaved like negative acute phase reactants; the concentrations of albumin and alpha 2-macroglobulin were significantly decreased from the second to sixth and seventh postoperative days, respectively, and the concentration of pre-albumin was significantly decreased on the third and fourth postoperative days. A significant fall in the amyloid A degrading activity of serum occurred during the acute phase reaction. The degradative activity was lowest on the third and fourth postoperative days (P less than 0.001). The results show that the acute phase state in patients with rheumatoid arthritis induces a rise in the concentration of serum amyloid A protein, the putative serum precursor of tissue amyloid A fibrils, and a concomitant reduction in the ability of serum to degrade these fibrils. These factors together may be important in the development of inflammation-associated amyloidosis.     

Antibody-dependent cell-mediated cytotoxicity in selected autoimmune diseases.

Antibody-dependent cell-mediated cytotoxicity mediated by peripheral blood lymphocytes was studied in patients with systemic lupus erythematosus, polyarteritis nodosa. Sjogren's syndrome, and rheumatoid arthritis. The target cells were chicken erythrocytes coated with rabbit anti-chicken erythrocyte antibody. Antibody-dependent cell-mediated cytotoxic activity was normal in Sjogren's syndrome and rheumatoid arthritis but significantly decreased (P is less than 0.001) in active systemic lupus erythematosus and in two patients with polyarteritis nodosa. A partial regeneration of antibody-dependent cell-mediated cytotoxic activity was obtained by treatment with pronase and DNase followed by overnight incubation. Sera from patients with systemic lupus erythematosus inhibited antibody-dependent cell-mediated cytotoxic activity of normal lymphocytes. The inhibitory activity was studied by specific immunoadsorption and sucrose density geadient ultracentrifugation. Removal of IgG but not IgM greatly reduced inhibition. Inhibitory factors were present in 7S and heavier fractions containing IgG. Five systemic lupus erythematosus patients were studied serially to determine if improvement in clinical status could be correlated with a decrease in serum inhibitory factors as studied by inhibition of normal antibody-dependent cell-mediated cytotoxicity. Indeed, a greater serum inhibitory capacity was found in each patient during periods of greater disease activity.     

Increase in serum bone gamma-carboxyglutamic acid protein with aging in women. Implications for the mechanism of age-related bone loss.

Because it is unclear whether age-related bone loss results from increased bone resorption, decreased bone formation or both, we measured the serum level of bone Gla-protein (BGP), a specific marker for bone turnover, in 174 women, ages 30 to 94 yr. Serum BGP increased linearly with aging (r = 0.44, P less than 0.001) from 4.4 +/- 0.4 (mean +/- SE) in the 4th decade to 8.9 +/- 0.9 ng/ml in the 10th decade. This increase correlated inversely (P less than 0.001) with concomitant decreases in bone mineral density at the lumbar spine, midradius, and distal radius. Using partial correlation coefficients, serum BGP still correlated positively with age (r = 0.31, P less than 0.001) after creatinine clearance was fixed but not with creatinine clearance (r = -0.04, NS) when age was fixed. Urinary hydroxyproline (r = 0.29, P less than 0.001), an index of bone resorption, and serum alkaline phosphatase (r = 0.31, P less than 0.001), an index of bone formation, also increased with age and these increases correlated with increases in serum BGP (r = 0.39, P less than 0.001 and r = 0.43, P less than 0.001, respectively). Serum immunoreactive parathyroid hormone concentrations (r = 0.39, P less than 0.001) and urinary cyclic AMP excretion (r = 0.38, P less than 0.001) increased, suggesting that PTH secretion increased with age; these increases correlated significantly with increases in serum BGP. A subgroup of 32 women who were found to have vertebral fractures, hip fractures, or both had significantly higher values for serum BGP than the remainder. These data suggest that overall bone turnover increases in women with aging and, especially considering the concomitant decrease in skeletal mass, do not support the view that age-related bone loss results primarily from decreased bone formation.     

Assessment of copper status in pregnancy by means of determining the specific oxidase activity of ceruloplasmin

BACKGROUND: Conditions not directly related to copper nutriture, such as pregnancy, infections and inflammation, which increase serum copper concentration even during copper deprivation, may be expected to conceal changes in copper status. It has been suggested that the specific enzymatic activity of ceruloplasmin (activity per unit mass of enzyme protein) may be a sensitive indicator of copper status and is not affected by factors such as hormones or sex. In this study, we investigated the behaviour of specific oxidase activity of ceruloplasmin and the copper/ceruloplasmin ratio in pregnant women. METHODS: Copper, immunoreactive ceruloplasmin and its oxidase activity were determined in serum from 52 women in the last trimester of normal pregnancy, and in 50 control women of similar age living in the same area and who were not taking oral contraceptives. The results are expressed as mean+/-S.E.M. RESULTS: In the group of pregnant women, significantly higher serum levels of copper, ceruloplasmin and its oxidase activity were found than in the control group (p < 0.001). In both groups, a high correlation was found between these biochemical variables (r > or =0.905, p < 0.001). However, in the group of pregnant women the specific oxidase activity for ceruloplasmin (364.4+/-3.3 vs. 407.5+/-3.8 U/g) and the copper/ceruloplasmin ratio (2.82+/-0.03 vs. 3.19+/-0.04 microg/mg) were significantly lower than in the control group (p < 0.001). CONCLUSIONS: Although pregnancy accelerates the rate of ceruloplasmin protein synthesis and release with an increase of serum copper, the decrease in specific oxidase activity of circulating ceruloplasmin would be an indicator of the degree of depletion of the mother's copper deposits in order to deal with the foetus' needs.     

Serum levels of C-reactive protein in Crohn''s disease and ulcerative colitis

Prospective measurements were made of serum C-reactive protein levels and erythrocyte sedimentation rate in sixty-four patients with Crohn's disease and fifty with ulcerative colitis. The results were related to clinical assessment of disease activity. C-reactive protein levels were raised in both groups but were significantly higher in Crohn's disease than ulcerative colitis for all categories of disease severity: with mild disease the median and range of C-reactive protein concentration were 4, 0-65 mg/l in Crohn's disease v. 0, 0-15 mg/l in ulcerative colitis, P less than 0.01; in moderate disease the values were 15, 1-100 mg/l v. 3, 0-29 mg/l respectively, P less than 0.05 and in cases of severe disease, 85, 15-183 mg/l v. 12, 2-33 mg/l respectively, P less than 0.001. Erythrocyte sedimentation rate was also higher in Crohn's disease but did not closely reflect disease activity in individual patients. C-reactive protein levels corresponded closely with clinical and pathological indices of relapse, remission and response to therapy in patients with Crohn's disease. The precise assay of serum C-reactive protein provides an objective criterion of inflammatory activity, which may be useful in the assessment, management and study of Crohn's disease.     

Seasonal variation of serum bone GLA protein

The seasonal variation of serum Bone Gla Protein (BGP) was investigated in 15 normal young individuals (seven women and eight men, aged 27-39 years). Serum BGP exhibited a significant seasonal variation of 23% around the yearly mean (p less than 0.001) with zenith in February and nadir in July. Significant seasonal variations were noted also for serum alkaline phosphatase (p less than 0.01) and serum phosphate (p less than 0.01). Serum calcium, bone mineral content (BMC) and creatinine clearance revealed no significant seasonal variation. The seasonal variation of BGP did not follow the variation in serum total alkaline phosphatase. The seasonal variation of BGP has to be taken into account when using the protein as a marker of bone remodelling activity. The variation was probably caused by changes in the production rate of the protein, since the renal excretion of the protein, as reflected in creatinine clearance, remained unchanged throughout the year.     

Assessment of bone turnover in postmenopausal osteoporosis by measurement of serum bone Gla-protein

Controversy persists regarding the abnormality of bone turnover responsible for bone loss in women with postmenopausal osteoporosis. To evaluate this, we measured serum bone Gla-protein (BGP), a specific marker for bone turnover, in 62 untreated patients with postmenopausal osteoporosis. Results were compared with those in 142 normal women and were expressed as standard deviations from the age-adjusted predicted mean (Z score). Serum BGP was increased (+0.48 S.D., p = 0.002) in the osteoporotic patients; 9.7% of patients were greater than 2 S.D. above but none were greater than 2 S.D. below the normal mean. Moreover, when data from normal postmenopausal women (ages 51 to 75 years) and the osteoporotic patients were merged, significant negative correlation existed (r = -0.36, p less than 0.001) between serum BGP and bone density of the lumbar spine assessed by dual photon absorptiometry. Serum alkaline phosphatase, a less specific marker for bone formation, was also increased (+0.96 S.D., p less than 0.001) in the osteoporotic patients. The data suggest that overall bone turnover is increased in patients with postmenopausal osteoporosis and do not support the concept that an absolute decrease in bone formation is the major cause of the bone loss.     

Relationship of the activity of the bone isoenzyme of serum alkaline phosphataseto urinary hydroxyproline excretion in metabolic and neoplastic bone diseases

A significant correlation between the activity of the bone isoenzyme or serum alkaline phosphatase and the urinary hydroxyproline excretion in osteomalacia, osteoporosis, primary hyperparathyroidism with osteodystrophy, Paget's disease, secondary bone tumours, and in a control group was found (P less than 0.001). This close correlation was not observed between these variables in patients with active acromegaly. Diagnosis determined from these indices of formation and turnover of bone matrix agreed with that established by histological and histochemical examination of bone, by X-ray investigation of the skeleton, and by the radionuclear 85Sr test. The relationship between the activity of bone isoenzyme and urinary hydroxyproline excretion differed in metabolic bone diseases with a high bone turnover, in patients with osteoporosis and in patients with early osteoclastic bone metastases.     

Depressed delayed cutaneous hypersensitivity in alcoholic hepatitis.

Delayed cutaneous hypersensitivity was studied in 10 patients with severe alcoholic hepatitis, 9 patients with either inactive alcoholic cirrhosis or alcoholic fatty liver, and 10 agematched controls. The mean response of the alcoholic hepatitis group was significantly less compared to controls for SK-SD (P less than 0.001), mumps (P less than 0.001), trichophyton (P less than 0.025), and Candida albicans (P less than 0.025). Upon clinical recovery, the response of the 6 surviving patients with alcoholic hepatitis was similar to controls for 4 of the 5 antigens tested, and the improvements in response to SK-SD and Candida albicans were significant (P less than 0.02 and P less than 0.05). The mean percentage and absolute numbers of thymus-derived lymphocytes were significantly less in the alcoholic hepatitis group compared with controls. Both the alcoholic hepatitis patients and patients with less advanced alcoholic liver disease had a diminished response to concanavalin A and phytohemagglutinin. This study demonstrates a reversible depression of delayed cutaneous hypersensitivity in alcoholic hepatitis. Several mechanisms may help account for this finding. We recommend that skin tests in patients with alcoholic hepatitis be interpreted with this phenomenon in mind.     

Effects of garlic powder supplementation on insulin resistance,oxidative stress,and body composition in patients with non-alcoholic fatty liver disease: A randomized controlled clinical trial

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Insulin resistance, oxidative stress, and obesity are major contributors to NAFLD pathogenesis. The effects of garlic powder supplementation on these risk factors in patients with NAFLD was investigated.MethodsIn this 12-wk, randomized controlled clinical trial, ninety patients with NAFLD were randomly assigned to two groups. The treatment group received four tablets of garlic (each coated tablet contained 400 mg garlic powder) daily and the control group received four tablets of placebo (each coated tablet contained 400 mg starch).ResultsA significant decrease was seen in the treatment group compared to the control group in waist circumference (P = 0.001), body fat percent (P < 0.001), serum concentration of fasting blood sugar (P = 0.01), insulin (P < 0.001), homeostatic model assessment for insulin resistance (P < 0.001), and malondialdehyde (P < 0.001), as well as significant increase in skeletal muscle mass (P = 0.002), serum concentration of superoxide dismutase (P < 0.001), and total antioxidant capacity (P < 0.001).ConclusionGarlic powder supplementation improved risk factors of NAFLD. Further studies are needed to determine the effects of garlic on hepatic features in patients with NAFLD. The study protocol was registered at Iranian clinical trials website under code IRCT20170206032417N4.     

Changes in calcium and magnesium metabolism in essential arterial hypertension

We studied 60 hypertensive patients (35 men and 25 women with an average age of 40 years) for signs of metabolic changes, with special emphasis on the relationship between the calcium and magnesium levels. The control group comprised 37 normotensive subjects (19 men and 18 women with an average age of 39 years). We studied the total serum calcium level (measured by atomic absorption), the ionized serum calcium level (by Nova 2 testing), and the plasma protein level, and we did coefficiency studies of the creatinine clearance and calcium and magnesium levels in 24-hour urine collections. In the hypertensive group, the ionized calcium level was significantly lower than that of the control subjects (P less than .001); the total serum calcium level was also lower, but the difference was of less statistical significance (P less than .05). There was no difference in serum magnesium levels between the two groups. There was a highly significant correlation between the total serum calcium level and the serum magnesium level (P less than .001) in the normal subjects; this correlation was not found in the hypertensive group. An increase in calcium and magnesium excretion was found in the 24-hour urine collections of the hypertensive group (P less than .001) (coefficient expressed as fractionated excretion of calcium and magnesium). There was also a high correlation between urinary excretion of calcium and magnesium (P less than .001) in the hypertensive subjects. Thus, the hypertensive subjects had changes in calcium metabolism that were related to magnesium levels. We suggest, therefore, that these two factors be studied simultaneously in evaluating patients with essential arterial hypertension.     

Relationship of serum N-acetyl-beta-glucosaminidase activity to oxidative stress in diabetes mellitus.

Serum N-acetyl-beta-glucosaminidase activity was evaluated in 40 Type 1 and 40 Type 2 diabetic patients and compared with parameters of diabetes control and oxidative stress. Significantly increased mean serum N-acetyl-beta-glucosaminidase activity was found in both groups of diabetic patients as compared with the corresponding group of healthy persons (p < 0.01). Oxidative stress measured by plasma malondialdehyde concentration was significantly higher in Type 2 than in Type 1 diabetic patients (p < 0.01) but in comparison with control subjects it was higher only in Type 2 diabetes. Plasma malondialdehyde concentration positively correlated with body mass index (r=0.77, p<0.001) and with serum N-acetyl-beta-glucosaminidase activities (r=0.57, p <0.001). Treatment of 10 Type 2 diabetic patients with antioxidant alpha-tocopherol caused a significant decrease in malondialdehyde concentration (p < 0.001) which was accompanied by a decrease of N-acetyl-beta-glucosaminidase activity (p < 0.01). We conclude that serum N-acetyl-beta-glucosaminidase activity may be influenced by oxidative stress which is more pronounced in Type 2 than in Type 1 diabetic patients.     

Sex-related differences in response of plasma lipids to simvastatin: the Saitama Postmenopausal Lipid Intervention Study. S-POLIS Group

The Saitama Postmenopausal Lipid Intervention Study was a multicenter, uncontrolled, collaborative study that investigated tolerability and sex-related differences in the response of serum lipids to simvastatin administered for 12 months in 122 postmenopausal women and 55 men with serum total cholesterol (TC) levels > or =220 mg/dL. With simvastatin treatment, TC and low-density lipoprotein cholesterol (LDL-C) levels decreased significantly at 1 month in both groups, and these decreased levels were maintained throughout treatment (P < 0.001). A significant decrease in triglyceride (TG) levels was also observed in both groups (P < 0.05). The mean percentage decreases in TC and LDL-C levels in women (20% and 28%, respectively) were significantly greater than those in men (15% and 20%, respectively) (P < 0.001). Mean percentage changes in TC and LDL-C levels in subgroups defined by stratification for baseline TC and LDL-C levels were also greater in women. There were no sex-related differences in the percentage changes in TG or high-density cholesterol levels, although the changes were influenced by baseline levels. Although the median dose of simvastatin (milligrams per kilogram of body weight) in women was significantly higher than in men (P < 0.001), the percentage changes in serum lipids were not correlated with the doses of simvastatin calibrated by body weight. Adverse reactions occurred in 8 men and 7 women, so there appeared to be no significant sex-related difference. Eleven patients had abnormal laboratory values. Simvastatin therapy for 12 months is well tolerated and effective for both women and men with hypercholesterolemia. Sex-related differences occurred in the response to simvastatin therapy of serum lipids, especially TC and LDL-C, with greater changes in lipid levels occurring in women.     

系统性红斑狼疮患者血清sIL-2R、DNase1L3、sCD163水平变化及其联合检测意义

目的探系统性红斑狼疮患者血清可溶性白细胞介素2受体(sIL-2R)、脱氧核糖核酸酶Ⅰ样蛋白3(DNase1L3)、可溶性血红蛋白清道夫受体(sCD163)水平变化及其联合检测意义。方法回顾性选取2018年3月至2020年4月海南西部中心医院收治的系统性红斑狼疮患者123例。根据系统性红斑狼疮疾病活动度评分分为轻度组33例、中度组50例和重度组40例,同期健康体检者42例作为对照组。检测各组对象血清sIL-2R、DNase1L3、sCD163水平。评估sIL-2R、DNase1L3、sCD163联合检测系统性红斑狼疮价值。结果随着病情加重,sIL-2R和sCD163水平逐渐升高,DNase1L3水平逐渐降低,差异均有统计学意义(P <0.05);且轻度组、中度组、重度组sIL-2R和sCD163水平均高于对照组,DNase1L3水平低于对照组,差异均有统计学意义(P <0.05)。根据受试者工作特征(ROC)曲线获得,最佳界限以sIL-2R(146.51 U/mL)、DNase1L3(29.91 ng/m L)、sCD163(465.02 ng/m L)可获得ROC曲线下最大...     

Determination of N-acetyl-glucosaminidase (NAG) in diabetic subjects

NAG activity was measured in the serum of 40 diabetic subjects and 38 normal subjects. Diabetic subjects were divided into 8 groups on the ground of diabetic pattern, therapy and complications. Results showed significantly higher NAG activity in diabetics in comparison with normals. Inside the 8 groups of diabetic subjects, correlation between serum NAG activity and Hg A1 concentration appeared significant (P less than 0.001). Therefore NAG activity in diabetics appears rather related to the degree of glycometabolic control than to the presence of diabetes complications.     

Atrial natriuretic peptide inhibits the aldosterone response to angiotensin II in man

We have investigated the interaction between the recently discovered natriuretic factor alpha human atrial natriuretic peptide (alpha h-ANP) and the renin-angiotensin-aldosterone system in man. Angiotensin II infused with placebo produced a significant rise of plasma aldosterone concentration (mean +/- SEM increment 352 +/- 23 pmol/l, n = 7, P less than 0.001). The infusion of alpha h-ANP together with angiotensin II largely abolished the aldosterone response (P less than 0.001). Diastolic blood pressure rose in response to the infusion of angiotensin II with placebo (mean increment 21.0 +/- 0.9 mmHg, P less than 0.001). Systolic blood pressure increased to a lesser degree (mean increment 12.5 +/- 0.7 mmHg, P less than 0.001). The infusion of alpha h-ANP together with angiotensin II significantly blunted the diastolic pressor response (P less than 0.01). This ability of alpha h-ANP to blunt the pressor effect of angiotensin II may be important in the control of systemic blood pressure. The inhibition of angiotensin II-stimulated aldosterone release demonstrates that alpha h-ANP may not only be a circulating natriuretic factor in its own right but that it may also act as a modulator of a related endocrine system.     

Significant increases in urinary dolichol levels in bacterial infections, malignancies and pregnancy but not in other clinical conditions

The effect of different clinical conditions on urinary dolichols was studied in 219 hospital patients and in 24 pregnant women. Significantly increased urinary dolichol levels were found in patients with severe bacterial infections (mean +/- SEM, 37.5 +/- 8.0 micrograms/mmol creatinine, P less than 0.001), in patients with haematological or metastatic (23.3. +/- 5.1, P less than 0.05) as well as localised (15.4 +/- 1.8, P less than 0.01) malignancies and in pregnant women (22.2 +/- 1.8, P less than 0.001) as compared to healthy controls (6.6 +/- 0.4). These results show that urinary excretion of dolichols may be increased, not only in alcoholics and patients with some rare neurodegenerative storage diseases, but also in patients suffering from various other diseases.     

维持性血液透析患者成纤维细胞生长因子23影响因素探讨

目的 检测维持性血液透析（MHD）患者血中成纤维细胞生长因子23（FGF-23）水平，探讨血磷、血钙、甲状旁腺激素及1，25（OH）2D3等对FGF-23的影响。方法 选择北京市海淀医院MHD患者98例，对照组肾小球过滤率正常共28例，MHD患者根据血磷水平分为低磷组、血磷达标组和高磷组，酶联免疫吸附法测定血中1，25（OH）2D3及FGF-23的水平，测定对照组及MHD患者血中碱性磷酸酶、钙、磷水平，同时测定MHD患者全段甲状旁腺激素。结果 MHD组血清1，25（OH）2D3低于对照组（P〈0．001），FGF-23高于对照组（P〈0．001）；低磷组、血磷达标组和高磷组FGF-23水平无统计学差别（P=0．804），高磷组甲状旁腺激素明显高于低磷组及血磷达标组（P=0．001，0．010）；多元回归分析显示1，25（OH）2D3是MHD患者FGF-23的影响因素（r=0．481，P〈0．001）。结论 MHD患者血中FGF-23水平明显升高，1，25（OH）2D3为MHD患者FGF-23升高的影响因素，血磷不是维持性血液透析患者FGF-23升高的主要影响因素。