Narrow Results

H-type hypertension (HHT) is closely associated with cardiovascular and cerebrovascular complications, as well as peripheral vascular sclerosis. However, the mechanism underlying the relationship between HHT and cardiac remodeling is not completely clear. Therefore, this study aimed to investigate the structural differences in a cardiac ultrasound between patients with HHT and those with non-H-type hypertension (NHHT). This study was performed on 300 elderly patients ($\ge 60$ years) with essential hypertension and stratified into two groups based on their homocysteine (Hcy) levels: 150 with HHT and 150 with NHHT. The cardiac structure was assessed using color Doppler echocardiography. The key parameters were measured, including interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular mass index (LVMI), and others. The chi-square test was employed to examine the differences in cardiac ultrasound outcomes between HHT and NHHT groups. Left ventricular hypertrophy (LVH) was observed in 118 patients (78.7%) in the HHT group and 75 patients (50.0%) in the NHHT group. The HHT group demonstrated a significantly higher prevalence of LVH (${\chi }^2=5.183$, $p<0.0001$). Patients with HHT had significantly higher systolic blood pressure, Hcy levels, LVPWT, IVST, and LVMI compared with those with NHHT: systolic blood pressure ($165.2\pm 13.15$ mm Hg versus $148.6\pm 11.06$ mm Hg), Hcy ($15.36\pm 3.15\mu$mol/L versus $8.15\pm 3.12$  $\mu$mol/L), LVPWT ($12.5\pm 1.16$ mm versus $10.2\pm 1.22$ mm), IVST ($13.6\pm 1.25$ mm versus $11.2\pm 1.15$ mm), and LVMI ($121.3\pm 22.15$ g/m² versus $110.5\pm 23.36$ g/m²). The correlation analysis showed a notable positive relationship between Hcy levels and LVMI ($r=0.386$, $p<0.001$), and between systolic blood pressure and LVMI ($r=0.536$, $p<0.001$). The occurrence of LVH was notably greater in patients with HHT than in those with NHHT. Furthermore, Hcy and systolic blood pressure levels were positively correlated with LVMI.

A study was designed to elucidate the mechanism of anti-hypertensive effects of Danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive model, which is the renin-angiotensin system (RAS)-dependent hypertensive model. We investigated the effects of water extracts of Danshen on the angiotensin converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of Danshen extract in a dose-dependent manner. SBP was decreased significantly after administration of Danshen extract in 2K1C, whereas plasma renin activity (PRA) was not changed. The plasma concentration of aldosterone (PAC) was decreased significantly in 2K1C group administered with Danshen extract, whereas the plasma concentration of ANP was increased by administration of Danshen extract for three weeks. These results suggest that Danshen has an anti-hypertensive effect through the inhibition of ACE, an essential regulatory enzyme of RAS.

Hawthorn (Crataegus) may play a role in the prevention and treatment of cardiovascular diseases such as hypertension, hyperlipidemia, and in particular, congestive heart failure. Evidence is accumulating that hawthorn may induce anti-ischemia/reperfusion-injury, anti-arrhythmic, hypolipidemic and hypotensive effects. These beneficial effects may in part be due to the presence of antioxidant flavonoid components. While a number of studies have been performed to evaluate the clinical efficacy of hawthorn, an international, multi-center, prospective clinical study including a large number of New York Heart Association (NYHA) class II/III heart failure patients is ongoing to test hawthorn's long-term therapeutic effects. Further clinical trials as well as pharmacokinetic and mechanistic studies are needed to explore and confirm its effectiveness, safety and pharmacological mechanism.

Experiments were conducted to establish the safety and efficacy of Eucommia ulmoides (Du-Zhong) extract in the treatment of hypertension. Pilot experiments using rats demonstrated that E. ulmoides extract was safe to the saturation limits of the compound. The maximum tolerated dose (MTD) was 1200 mg/kg when administered by gastric gavage at a concentration of 1200 mg/ml. Also, rats given 200 mg/kg, 600 mg/kg or 1200 mg/kg doses of E. ulmoides extract daily for 28 days demonstrated no evidence of acute toxicity as determined by clinical appearance, histopathology and serum chemistry evaluation. Lastly, spontaneous hypertensive rats (SHRs) were administered E. ulmoides extract daily for 22 days. Systolic blood pressure (BP) was measured on treatment days 1, 8, 15 and 22 at 0, 1, 2 and 3 hours post-treatment. Beginning on day 8, E. ulmoides extract administered at the mid or high dosages lowered BP in male, but not female, rats. BP declined at a rate of approximately 10 mmHg per hour. The mid dosage of 600 mg/kg was found to be the minimum effective dose. In conclusion, E. ulmoides extract was non-toxic and effective in reducing systolic BP in the SHR.

Hypertension is one of the modifiable risk factors for stroke. Lowering blood pressure is helpful for primary and secondary prevention of stroke. This study is aimed to assess the efficacy of Chunghyul-dan on stroke patients with stage 1 hypertension using 24 hours ambulatory blood pressure monitoring (24ABPM). Forty hospitalized stroke patients with stage 1 hypertension were included in the study and they were randomly assigned into two groups: group A was treated with Chunghyul-dan 1200 mg once a day for 2 weeks, while group B was not. Twelve subjects were dropped out because of unexpected early discharge or data errors, thus the remaining 28 subjects were included in the final analysis (15 in group A and 13 in group B). Blood pressure was monitored every 30 minutes for 24 hours at baseline and 2 weeks after medication. Blood pressure, pulse rate, trough/peak ratio (TPR) [the value calculated by dividing the blood pressure change at trough (22 to 24 hours after drug intake) by the change at peak (2 adjacent hours with a maximal blood pressure reduction between the second and eighth hour after drug intake)] and smoothness index (SI) (the value calculated as the ratio between the average of the 24 hours, treatment-induced blood pressure changes and its standard deviation) were compared to assess the efficacy of Chunghyul-dan. To assess the safety of Chunghyul-dan, any adverse effects during medication period were monitored. There was no significant difference in the baseline assessment between the two groups. Systolic blood pressure was lower in group A than in group B (141.37 ± 8.96 mmHg versus 132.28 ± 9.46 mmHg, P = 0.03), while diastolic blood pressure and pulse rate had no significant difference between the two groups. Systolic TPR and SI was 0.87 and 1.04 in group A, respectively. This suggests that Chunghyul-dan have anti-hypertensive effect on stroke patients with stage 1 hypertension.

Recent findings of a link between high blood pressure (BP) and dementia have given new prospects. The aim of this study is to analyze a mixture of Chinese herbs, Tianma Gouteng Decoction (TGD), which was traditionally used to treat hypertension, and investigate its relation to ameliorating cognitive impairment. We discovered that TGD also had properties involving enhancement of memory acquisition (learning) skills in mice, but not memory consolidation. It was observed that TGD could prolong the step-through latency at doses of 1.0 and 2.5 g/kg on passive avoidance task in mice. TGD could be developed further to treat mice with amnesia, which was induced by scopolamine at the same dose under long-term (8 days) administration.

Accumulating evidence indicates that the high blood pressure (BP) is a potent risk factor for dementia in the elderly. In line with this theory, we had found the mixture of Chinese herbs (TGD) which were traditionally used to treat hypertension, could enhance the cognitive function. The aim of this study was to decrease the number of herbs used from 11 (TGD) to 4 herbs (TGDS) and further to search the active constituents. After administering a dose of 10 g/kg of TGDS0 to ICR mice, no cholinergic symptoms of lacrimation, salivation, emesis, eyeclosure, increased respiration and fibrillation were observed. All the mice survived without any deaths after 24 hours and 7 days. No changes were observed in control and experimental groups on locomotor activity (no stimulant or sedative effects). It was also revealed that TGDS could prolong the step-through latency at the dose of 1.0 and 2.5 g/kg on passive avoidance tasks in mice. This result was the same as the previous study. The active constituents which enhanced the memory acquisition were discovered in the butanol layer and ethyl acetate layer after the extraction.

Lindera strychnifolia (Tendai-Uyaku), a medicinal plant, has long been used for the treatment of cardiac, renal and rheumatic diseases in Japan. We investigated the effect of Lindera strychnifolia on systolic blood pressure, cardiac function, and plasma noradrenaline levels in rats. Spontaneously hypertensive rats (SHR) were given free access to water or extract solution of Lindera strychnifolia, which was extracted with a ratio of 10 g Lindera strychnifolia roots/20 ml water. Systolic blood pressure was measured by using a tail-cuf sphygmomanometer twice a week from 10 to 30 weeks of age, and compared to the age-matched Wistar Kyoto rats (WKY) as a control group. At 30 weeks of age, heart function was measured by echocardiography and blood samples were taken for detection of plasma noradrenaline levels, and rats were then sacrificed. Systolic blood pressure gradually increased from 10 to 30 weeks of age in the SHR group, while it did not change in the WKY group. In the Lindera-treated SHR group, the increase in systolic blood pressure was significantly attenuated from 21 to 30 weeks of age. Echocardiography showed a significant increase in ejection fraction in the Lindera-treated SHR group (60.4 ± 7.8%) as compared to the SHR group (39.7 ± 23.4%). Plasma noradrenaline levels were significantly decreased in Lindera-treated SHR group compared to the SHR group. These results suggest that Lindera strychnifolia has an anti-hypertensive effect and improves cardiac function in spontaneous hypertensive rats. These effects may be related to the decrease in plasma noradrenaline levels by Lindera strychnifolia.

Morus alba L. has been used in traditional Chinese medicine and almost all parts of this plant are useful in cardiovascular, liver and spleen disorders. The present study was designed to investigate the inhibitory effect of a water extract from Morus alba L. (WMA) on vascular dysfunction in rat models fed a high fat and high cholesterol diet. Male rats were fed an atherogenic diet consisting of food with 7.5% cocoa butter and 1.25% cholesterol, with or without 100 or 200 mg/day/kg WMA, for 14 weeks. Chronic treatment with low (100 mg/kg/day) or high (200 mg/day/kg) doses of WMA markedly attenuated hypertension and the impairments of acetylcholine-induced relaxation of aortic rings in rats fed an atherogenic diet. WMA reduced intima/media thickness in rats fed an atherogenic diet. WMA improved plasma levels of triglyceride (TG) and augmented plasma levels of high-density lipoprotein (HDL) and plasma low-density lipoprotein (LDL), but did not affect blood glucose levels. Interestingly, WMA suppressed increased cell adhesion molecules such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) expression in the aorta. Taken together, these results suggested that Morus alba L. could improve an atherogenic diet-induced hypertension, hyperlipidemia, and vascular dysfunction through inhibition of cell adhesion molecules expression and induction of vascular relaxation.

Diabetes mellitus is the leading cause of vascular complications such as atherosclerosis. This study was designed to investigate whether Prunella vulgaris (APV) would inhibit diabetic atherosclerosis in db/db mice with type 2 diabetes. The db/db mice were treated with high fat/high cholesterol (HFHC) diet and an aqueous extract of APV (100 and 200 mg/kg/day) for eight weeks to examine the long-term effect on metabolic abnormalities and diabetic atherosclerosis. APV treatment markedly lowered blood glucose and systolic blood pressure. The db/db mice experienced an increase in blood urea nitrogen as well as a decrease of creatinine clearance, the latter of which was restored by treatment with APV. Treatment with APV markedly decreased total plasma cholesterol, triglyceride, and LDL-cholesterol and also increased the HDL-cholesterol. In addition, malondialdehyde and TGF-β1 were decreased by treatment of APV. On the other hand, total NO level was decreased in db/db mice. However, the NO level was increased by treatment with APV, suggesting an association with vascular dysfunction. Vascular relaxation of aortic rings by acetylcholine or SNP-inducement was ameliorated by APV in a dose-dependent manner. Damage of vascular intima and hypertrophic of media were observed in db/db mice; however its dysfunction was improved by the treatment of APV. APV treatment significantly reduced the aortic expressions of ICAM-1, VCAM-1, ET-1, and nitrotyrosine. Furthermore, expression of eNOS in aortic was remarkably increased by APV treatment. Taken together, APV suppressed hyperglycemia and diabetic vascular dysfunction in HFHC diet-db/db mice. The present data suggest that Prunella vulgaris may prevent development of diabetic atherosclerosis.

A prospective multicenter clinical trial was conducted to compare the beneficial effects of a Chinese herbal medicine formula Jiangzhuoqinggan (JZQG) and western antihypertension drug irbesartan. JZQG is mainly composed of rhubarb, coptis, cassia, and uncaria. A total of 240 patients with mild to moderate hypertension were enrolled in the trial. Patients were assigned into two groups after screening: JZQG group and the irbesartan group. After four weeks of treatment, we compared the changes in routine blood pressure, 24 h ambulatory blood pressure, and waist circumference. There was a significant reduction in systolic blood pressure and diastolic blood pressure in the JZQG group (both p < 0.01). There were no significant differences between the reduction of systolic and diastolic blood pressures in the two treatment groups. From the 24 h ambulatory blood pressure measurement, the JZQG group showed a greater reduction in both systolic and diastolic blood pressures (in both daytime and nighttime) than the irbesartan group. Furthermore, there was a significant difference in waist circumference in the JZQG group (1.51 cm reduction; P < 0.05) but not the irbesartan group (0.42 cm). Thus, the JZQG formula may have therapeutic value in patients with both hypertension and metabolic syndrome.

The constitution of traditional Chinese medicine was established in 1970s by Chinese scholars, in which the constitutions of Chinese people were classified into nine types for study. The phlegm-dampness constitution is one of the nine constitutions and is the most common type in constitution study. Genomics studies found four upregulated genes: COPS8, GNPDA1, CD52 and ARPC3; and six downregulated genes: GSPT2, CACNB2, FLJ20584, UXS1, IL21R and TNPO in the phlegm-dampness constitution. Gene functional analyses on genes affecting the differences between the phlegm-dampness constitution and the balanced constitution indicated that people with phlegm-dampness constitution were susceptible to hyperlipemia and diabetes. Results of epidemiological surveys also revealed that people with phlegm-dampness constitution have a much higher risk of obesity, metabolic syndrome, hypertension and diabetes than people with a balanced constitution. Therefore, differentiation of phlegm-dampness constitution could be performed in the normal population with the Constitution of Chinese Medicine Scale to estimate the risks of those diseases for prediction. For people with phlegm-dampness constitution, Chinese medicine could be used to reduce risk of related diseases. Constitution-based strategies in disease prevention and treatment are consistent with the current proposed 4P medical mode (personalized, predictive, preventive and participatory). With the rising burden of global disease and increasing medical expenditure, the objectives of medicine are transforming from treatment to prevention. Thus, studies on the phlegm-dampness constitution of traditional Chinese medicine are significantly important for the prediction and prevention of related diseases and maintenance of human health.

The lignan extracts from the tree bark of Eucommia ulmoides Oliv., a famous traditional Chinese medicine, have been demonstrated to have inhibitory effects on aldose reductase activity in spontaneously hypertensive rat myocardium. This study was aimed to investigate the hypertensive cardiac remodeling effects of the lignan extracts together with epalrestat. Ten-week-old male spontaneously hypertensive rats were randomly divided into three groups (n = 12, each) and administered 100 mg/kg/d of captopril (angiotensin converting enzyme inhibitor), 100 mg/kg/d of epalrestat (aldose reductase inhibitor) or 300 mg/kg/d of lignan extracts by gavage for 16 weeks. Sex-, age-, and number-matched normotensive Wistar Kyoto rats with spontaneously hypertensive rats were treated with distilled water (vehicle) as controls. Systolic blood pressures were measured periodically. Echocardiography examination was taken when rats were 24 weeks old. We found that both captopril and lignan extracts lowered blood pressure, and inhibited aldose reductase activity similarly to epalrestat. Echocardiography examination and histomorphometry indices were improved in all treated groups (p < 0.05). Therefore, lignan extracts could prevent hypertensive cardiac remodeling, which is likely related to aldose reductase inhibition.

Puerarin is an isoflavonoid isolated from the Chinese herb, Kudzu roots (also known as Gegen), which has been widely used for the treatment of hypertensive diseases and diabetic mellitus in traditional Chinese medicine. Dahl salt-sensitive (DS) rat is a genetic model of salt-sensitive hypertension with cardiovascular injury and vascular insulin resistance. Here, we investigated whether puerarin improved vascular insulin resistance and attenuated cardiac and aortic remodeling in salt-sensitive hypertension. DS rats were given a normal (NS) or high salt diet (HS) for five weeks. An additional group of DS rats was pretreated with puerarin and NS for 10 days, then switched to HS plus puerarin for five weeks. HS for five weeks increased systolic blood pressure (SBP), cardiac hypertrophy and fibrosis, and aortic hypertrophy with increased the expression of phosphor-ERK1/2 in the aorta and heart; puerarin attenuated cardiac and aortic hypertrophy, cardiac fibrosis and phosphor-ERK1/2 with a mild reduction in SBP. Hypertensive rats also manifested impairment of acetylcholine- and insulin-mediated vasorelaxation and insulin-mediated Akt and eNOS phosphorylation associated with the activation of NF$\kappa$B/TNF$\alpha$/JNK pathway. Puerarin improved acetylcholine- and insulin-mediated vasorelaxation and insulin-stimulated Akt/NO signaling with the inhibition of the NF$\kappa$B inflammatory pathway. Our results demonstrated that in salt-sensitive hypertension, puerarin improved vascular insulin action with cardiovascular beneficial effects. Our results found that the underlying mechanisms may involve its inhibition of NF$\kappa$B/JNK and ERK1/2 pathway. These results suggest that puerarin could be used as a new antihypertensive agent to expand our armamentarium for the prevention and treatment of end-organ damage in individuals with hypertension and metabolic diseases.

Platycodin D (PD) is the main active saponin isolated from Platycodon grandiflorum (PG) and is reported to exhibit anticancer, anti-angiogenic, anti-inflammation and anti-obesity biological effects. The current study aims to evaluate the therapeutic efficacy of PD in cardiac fibrosis and for hypertrophy in spontaneous hypertension rats (SHRs) and to verify inhibition of the signaling pathway. Significant increases in the cardiac functional indices of left ventricular internal diameter end diastole (LVIDd) and left ventricular internal diameter end systole (LVIDs); the eccentric hypertrophy marker p-MEK5; concentric hypertrophy markers, such as CaMKII$\alpha$ and calcineurin; and expression levels of NFATc3, p-GATA4 and BNP were observed in spontaneously hypertensive groups. PD treatment reversed these increases in SHRs. In addition, an increase in the fibrosis markers FGF2, uPA, MMP2, MMP9, TGF$\beta$-1 and CTGF during cardiac hypertrophy was detected by western blotting analyses. These results demonstrated that PD treatment considerably attenuates cardiac fibrosis. Histopathological examination revealed that PD treatment remarkably reduced collagen accumulation in contrast to spontaneously hypertensive groups. This study clearly suggests that PD provides myocardial protection by alleviating two damaging responses to hypertension, fibrosis and hypertrophy, in the heart.

Puerarin is an isoflavonoid isolated from the root of Pueraria lobata (Gegen in Chinese) that has been widely used to treat cardiovascular and cerebrovascular diseases in China. Here, we investigated the hypotensive effects and mechanisms of puerarin in spontaneously hypertensive rats. The qPCR array technique was used to determine the expression of hypertension-related genes. Then, the differentially expressed genes were analyzed using the STRING database. The systolic blood pressure and diastolic blood pressure of rats decreased after the administration of puerarin for nine weeks. Puerarin, but not losartan, also slowed the heart rate of rats. NO and cGMP levels were improved by puerarin. Eighteen differentially expressed hypertension-related genes were identified by comparing the model group with the control group and the high-dose puerarin group with the model group. NO and cGMP levels were increased by high-dose puerarin. High-dose puerarin increased the levels of the phosphorylated eNOS protein and decreased AT1 and Cav1 levels. Based on our results, eNOS was a key target in the mechanism by which puerarin reduced blood pressure, and puerarin represents a potential antihypertensive agent.

The endothelium covers the internal lumen of the entire circulatory system and plays an important modulatory role in vascular homeostasis. Endothelium dysfunction, characterized by a vasoconstrictive, pro-inflammatory, and pro-coagulant state, usually manifests as a significant pathological process of vascular diseases, including hypertension, atherosclerosis (AS), stroke, diabetes mellitus, coronary artery disease, and cancer. Therefore, there is an urgent necessity to seek promising therapeutic drugs or remedies to ameliorate endothelial dysfunction-induced vascular ailments and complications. Recently, much attention has been attached to ginsenosides, the most significant active components of ginseng, which have always been referred to as “all-healing” and widely used for its extensively medicinal value. Surprisingly, ginsenosides have diverse biological activity which might be related to inflammation, apoptosis, oxidative stress, and angiogenesis. In this review, a brief introduction about endothelial dysfunction and ginsenosides was demonstrated, and the emphasis was put on summarizing multi-faceted pharmacological effects and underlying molecular mechanisms of ginsenosides on the endothelium, including vasorelaxation, anti-oxidation, anti-inflammation, and angio-modulation. Beyond that, nanotechnology to improve efficacy and the existing clinical trials of ginsenosides were concluded. Hopefully, our work will give suggestions for promoting clinical application of traditional Chinese medicine, e.g., hypertension, AS, diabetes, ischemic stroke, and cancer. This review provides a comprehensive base of knowledge for ginsenosides to prevention and treatment of vascular injury- related diseases with clinical significance.

Red yeast rice (RYR) is known for its lipid-lowering effects in patients with hypercholesterolemia; however, its comparative efficacy with statins and risk reduction remains uncertain. This retrospective study analyzed data from 337,104 patients with hyperlipidemia in the Chang Gung Research Database cohort, spanning from January 2016 to December 2021. Exclusion criteria were applied to ensure data completeness and compliance, including an age limit of $<18$ years, absence of RYR or statin treatment, and a treatment duration of $<30$ days. Propensity score matching was employed to minimize bias based on baseline factors, with one patient matching with four patients in the comparison group. The study encompassed a total of 5,984 adult hyperlipidemic patients, with 1,197 in the RYR group and 4,787 in the statin group. The patients were also stratified into statin ($n=880$) or combined use ($n=220$) groups for further comparison. Following one year of treatment, both the RYR and statin groups exhibited reductions in total cholesterol and triglyceride levels. Most biochemical parameters showed no significant differences, except for elevated glutamic oxaloacetic transaminase levels in the RYR group ($p=0.026$) and increased glycohemoglobin levels in the statin group at the three-month mark ($p=0.035$). In patients with comorbid diabetes, hypertension, kidney, or liver diseases, RYR and statins demonstrated comparable risks for emergency room (ER) visits, stroke, and myocardial infarction (MI). However, the combination of RYR and statins was associated with reduced stroke-related hospitalizations in patients with diabetes, hypertension, and kidney disease, as well as decreased MI-related hospitalizations in patients with hypertension and kidney disease (all $p<0.0001$). In conclusion, both RYR and statins effectively lower blood lipid levels and mitigate related complications. Combining these therapies may lead to fewer ER visits, reduced stroke frequency, and fewer MI hospitalizations in hypertensive and kidney disease patients, and they decreased all-cause mortality in the kidney disease population. Further research on combined therapy is warranted.

We present evidence against the well-established education–health gradient by relating education to measured hypertension status in 5,873 men and 6,152 women aged 40$+$ in Indonesia. Once a basic set of covariates was controlled for, the two variables were not statistically significantly related. We argue that this lack was due to neglect of chronic diseases. It appears that the assumption of full information in theories on the education–health gradient is too strong to be applied to the developing world. Therefore, more information needs to be provided to the public regarding the seriousness of chronic diseases and preventive and curative methods.

There are certain difficulties and unpleasant issues related to conventional diagnostic tools. These factors tilted the researchers toward finding an alternative non-invasive way of diagnosis. This alternate approach usually involves physiological and lifestyle-related data. The non-invasive tools are more convenient for common people as they are user-friendly and have no side effects. At the same time, they are cost-effective as well. The non-invasive diagnosis is also preferred by the people who live in places where medical facilities are not abundant. This study concentrates on detecting a person as hypertensive by analyzing certain parameters in speech using machine learning approaches. We identify some phonemes and features of speech that are more sensitive to capture the distortions in speech due to hypertension. Four different machine learning methods involving both classical and state-of-the-art methods in our study show the effectiveness of both types of machine learning methods in different dimensions. The study shows inspiring results in terms of prediction accuracy ($\sim$95%) as well as identifying a minimal set of hypertension-sensitive features. It is also found that when we combine the predictions of both classical and state-of-the-art methods, the result gives more reliable predictions.