OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Objective To investigate the expression levels and clinical significance of microRNA-383(miR-383),microRNA-4458(miR-4458),and microRNA-93(miR-93)in colorectal cancer tissue.Methods From October 2018 to October 2020,124 colorectal cancer patients who underwent surgical treatment in our hospital were regarded as the colorectal cancer group,and their adjacent normal tissues were as the adjacent control group.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)method was applied to detect the expression levels of miR-383,miR-4458,and miR-93 in tissues;the relationship between the expression of miR-383,miR-4458,and miR-93 in colorectal cancer tissue and patient prognosis was analyzed using Kaplan-Meier curve;Cox regression was applied to analyze the prognostic factors of colorectal cancer patients.Results Compared with the adjacent control group,the expression levels of miR-383,miR-4458,and miR-93 in the colorectal cancer group were obviously lower(P＜0.05).The expression of miR-383,miR-4458,and miR-93 in colorectal cancer tissue was related to clinical and pathological features such as tumor diameter,TNM staging,lymph node metastasis,and depth of invasion(P＜0.05).The three-year survival rate of patients with high expression of miR-383 in colorectal cancer tissue(55/63,87.30％)was higher than that of patients with low expression of miR-383(41/61,67.21％)(x2=7.650,P＜0.05);the three-year survival rate of patients with high expression of miR-4458 in colorectal cancer tissue(53/60,88.33％)was higher than that of patients with low expression of miR-4458(43/64,67.18％)(x2=8.566,P＜0.05);the three-year survival rate of patients with high expression of miR-93 in colorectal cancer tissue(51/59,86.44％)was higher than that of patients with low expression of miR-93(45/65,69.23％)(x2=5.612,P＜0.05).According to multivariate Cox regression analysis,miR-383,miR-4458,and miR-93 are protective factors for the prognosis of colorectal cancer patients(P＜0.05),while tumor diameter,TNM staging,lymph node metastasis,and depth of infiltration were risk factors for the prognosis of colorectal cancer patients(P＜0.05).The area under the curve(AUC)predicted by Cox regression model is 0.917,95％CI is 0.854～0.959(Z=12.338,P＜0.05),the sensitivity is 94.29％,and the specificity is 87.64％.Conclusion The expression levels of miR-383,miR-4458,and miR-93 in colorectal cancer tissue are obviously reduced,and their expression levels are related to the clinical pathological characteristics and prognosis of colorectal cancer patients.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To investigate the expression levels and clinical significance of microRNA-383(miR-383),microRNA-4458(miR-4458),and microRNA-93(miR-93)in colorectal cancer tissue.Methods From October 2018 to October 2020,124 colorectal cancer patients who underwent surgical treatment in our hospital were regarded as the colorectal cancer group,and their adjacent normal tissues were as the adjacent control group.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)method was applied to detect the expression levels of miR-383,miR-4458,and miR-93 in tissues;the relationship between the expression of miR-383,miR-4458,and miR-93 in colorectal cancer tissue and patient prognosis was analyzed using Kaplan-Meier curve;Cox regression was applied to analyze the prognostic factors of colorectal cancer patients.Results Compared with the adjacent control group,the expression levels of miR-383,miR-4458,and miR-93 in the colorectal cancer group were obviously lower(P＜0.05).The expression of miR-383,miR-4458,and miR-93 in colorectal cancer tissue was related to clinical and pathological features such as tumor diameter,TNM staging,lymph node metastasis,and depth of invasion(P＜0.05).The three-year survival rate of patients with high expression of miR-383 in colorectal cancer tissue(55/63,87.30％)was higher than that of patients with low expression of miR-383(41/61,67.21％)(x2=7.650,P＜0.05);the three-year survival rate of patients with high expression of miR-4458 in colorectal cancer tissue(53/60,88.33％)was higher than that of patients with low expression of miR-4458(43/64,67.18％)(x2=8.566,P＜0.05);the three-year survival rate of patients with high expression of miR-93 in colorectal cancer tissue(51/59,86.44％)was higher than that of patients with low expression of miR-93(45/65,69.23％)(x2=5.612,P＜0.05).According to multivariate Cox regression analysis,miR-383,miR-4458,and miR-93 are protective factors for the prognosis of colorectal cancer patients(P＜0.05),while tumor diameter,TNM staging,lymph node metastasis,and depth of infiltration were risk factors for the prognosis of colorectal cancer patients(P＜0.05).The area under the curve(AUC)predicted by Cox regression model is 0.917,95％CI is 0.854～0.959(Z=12.338,P＜0.05),the sensitivity is 94.29％,and the specificity is 87.64％.Conclusion The expression levels of miR-383,miR-4458,and miR-93 in colorectal cancer tissue are obviously reduced,and their expression levels are related to the clinical pathological characteristics and prognosis of colorectal cancer patients.

OBJECTIVE: To investigate the therapeutic effect of Epothilone D on traumatic optic neuropathy (TON) in rats. METHODS: Forty-two SD rats were randomized to receive intraperitoneal injection of 1.0 mg/kg Epothilone D or DMSO (control) every 3 days until day 28, and rat models of TON were established on the second day after the first administration. On days 3, 7, and 28, examination of flash visual evoked potentials (FVEP), immunofluorescence staining and Western blotting were performed to examine the visual pathway features, number of retinal ganglion cells (RGCs), GAP43 expression level in damaged axons, and changes of Tau and pTau-396/404 in the retina and optic nerve. RESULTS: In Epothilone D treatment group, RGC loss rate was significantly decreased by 19.12% (P=0.032) on day 3 and by 22.67% (P=0.042) on day 28 as compared with the rats in the control group, but FVEP examination failed to show physiological improvement in the visual pathway on day 28 in terms of the relative latency of N2 wave (P=0.236) and relative amplitude attenuation of P2-N2 wave (P=0.441). The total Tau content in the retina of the treatment group was significantly increased compared with that in the control group on day 3 (P < 0.001), showing a consistent change with ptau-396/404 level. In the optic nerve axons, the total Tau level in the treatment group was significantly lower than that in the control group on day 7 (P=0.002), but the changes of the total Tau and pTau-396/404 level did not show an obvious correlation. Epothilone D induced persistent expression of GAP43 in the damaged axons, detectable even on day 28 of the experiment. CONCLUSION Epothilone D treatment can protect against TON in rats by promoting the survival of injured RGCs, enhancing Tau content in the surviving RGCs, reducing Tau accumulation in injured axons, and stimulating sustained regeneration of axons.
Animals ; Disease Models, Animal ; Epothilones ; Evoked Potentials, Visual ; Nerve Regeneration/physiology* ; Optic Nerve Injuries/metabolism* ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells/physiology*

As a new type of cell death, necroptosis is initiated by tumor necrosis factor receptor 1(TNFR1), and then activated receptor-interacting protein kinase 1(RIP1) and receptor-interacting protein kinase 3 (RIP3), following by the activation of mixed lineage kinase domain-like protein(MLKL) to deliver cell death signal. When necroptosis happens, damage associated molecular patterns (DAMPs) enter into extracellular area through the ruptured cytomembrane, followed by the disordered tissue hemeostasis. In recent years, many researches showed that necroptosis playimportant roles in a few bone related diseases, such as osteoporosis, osteonecrosis, osteosarcoma, etc. Thus, we try to briefly review the researches in this field.
Apoptosis ; Necroptosis ; Protein Kinases

Objective To study the effect of stress on the degradation rate in vitro of novel magnesium alloy bone screw. Methods A three-dimensional （3D） model of the tibia fracture was established using the reverse engineering method. Then, based on the FE model, the in vitro degradation experimental device for bone screws was designed. The stress distribution of the screw by finite element calculation was used as the in vitro experimental load, which effectively improved the accuracy and efficiency of the experiment. The experimental samples were divided into four groups. Group A was treated as control group without force application, while Groups B, C and D were subjected to 150, 250 and 350 N axial forces. The influence of different mechanical environment on the degradation rate in vitro of bone screws was investigated. Finally, combining the stress distributions with the degradation experiment results in vitro, the curve between the stress and the degradation rate in vitro of novel magnesium alloy bone screws was obtained. Results Degradation experiments in vitro showed that Group A had the lowest weight loss and hydrogen production, and the average degradation rate was (0.315±0.005) mm/a. While in the stress groups, the weight loss and hydrogen production increased gradually with the axial force increasing. The average degradation rates of Groups B, C and D were (0.379±0.006), (0.469±0.007) and (0.547±0.009) mm/a, respectively. Conclusions When the novel magnesium alloy bone screw was degraded in mechanical environment, the greater stress on the screw would cause the faster degradation rate in vitro. The obtained relationship between the maximum stress and the average degradation rate in vitro of the novel megnesium alloy bone screw provided data support and theoretical guidance for material selection, design and clinical application of magnesium alloy bone screws.

Objective: To prospectively explore the relationship between resting heart rate (RHR) and risk of new-onset heart failure. Methods: It was a prospective cohort study. People who attended the physical examination of Kailuan Group Company in 2006 and with complete electrocardiography (ECG) recordings were eligible for this study. A total of 88 879 participants aged 18 years old or more who were free of arrhythmia, a prior history of heart failure and were not treated with β-blocker were included. Participants were divided into 5 groups according to the quintiles of RHR at baseline (Q(1) group, 40-60 beats/minutes (n=18 168) ; Q(2) group, 67-70 beats/minutes (n=18 970) ; Q(3) group, 71-74 beats/minutes (n=13 583) ; Q(4) group, 75-80 beats/minutes (n=22 739) ; and Q(5) group,>80 beats/minutes (n=15 419) ) .The general clinical data and laboratory test results were collected. The outcome was the first occurrence of heart failure at the end of follow-up (December 31, 2016) .We used Cox regression model to examine the association between RHR and the risk of new-onset heart failure. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling. Results: Among the included patients 68 411 participants were male, mean age was (51.0±12.3) years old, and RHR was (74±10) beats/minutes. Statistically significant differences among the RHR quintiles were found for the following variables: age, gender, systolic blood pressure, diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, body mass index, the level of high-sensitivity C-reactive protein, education status, physical activity, smoking status, drinking status, history of diabetes, history of hypertension and history of use antihypertensive drugs (all P<0.01) . Higher RHR was linked with higher prevalence of diabetes, hypertension history, and higher systolic blood pressure, diastolic blood pressure and FBG levels (all P<0.01). After a mean follow-up of 9.5 years, the incidence of new-onset heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.60%(290/18 168), 1.36%(258/18 970), 1.80%(245/13 583), 1.76%(400/22 739) and 2.35%(362/15 419),respectively (P<0.01) . The person-year incidence of heart failure in Q(1), Q(2), Q(3), Q(4) and Q(5) groups was 1.7, 1.5, 1.9, 1.9 and 2.6 per 1 000 person-years respectively. Compared with the Q(2) group, multivariate analysis with adjustment for major traditional cardiovascular risk factors showed that HRs of Q(3),Q(4),and Q(5) group were 1.23 (95%CI 1.03-1.48, P<0.05) , 1.19 (95%CI 1.01-1.41, P<0.05) , 1.39 (95%CI 1.18-1.65, P<0.01) , respectively. In the absence of hypertension, diabetes, smoking and acute myocardial infarction, the Cox regression model showed that compared with Q(2) group, the HR of new-onset heart failure in Q(5) group was 1.58 (95%CI 1.02-2.45, P<0.05) . Conclusion: Increased RHR is associated with increased risk of new-onset heart failure in this cohort.
Adult ; Blood Pressure ; Cohort Studies ; Female ; Heart Failure ; Heart Rate ; Humans ; Male ; Middle Aged ; Prospective Studies ; Risk Factors

【Objective】 The purpose of this study was to investigate puberty development in β-TM patients and to analyze its clinical characteristics and influencing factors. 【Methods】 A total of 42 β-TM patients aged ≥10 years old were evaluated for their stages of puberty development by reviewing follow-up data(using the REDCAP system, the thalassemia follow-up database), questionnaire, physical examination and laboratory tests. To investigate The correlations between multiple factors, such as age, beginning age of iron chelation, iron overload and so on, and abnormal puberty development in β-TM patients, were investigated. 【Results】 Twenty-four cases of β-TM patients were diagnosed as abnormal puberty development, including 11 girls and 13 boys. The common clinical manifestations of β-TM patients with abnormal puberty development were delayed puberty development and primary amenorrhea for girls and short penis and small testicles for boys. The prevalence rate of abnormal puberty development was significantly higher in β-TM patients who had older beginning age of iron chelation, β0β0 genotype, a history of splenectomy, vitamin D deficiency and diabetes(χ² = 3.966, 5.196, 5.567, 4.714, P = 0.046, 0.023, 0.018, 0.030). The result of logistic regression analysis indicated that cardiac MRT2* < 20 ms was an independent risk factor for abnormal puberty development in β-TM patients. 【Conclusions】 Abnormal puberty development in β-TM patients is very common. Influencing factors include beginning age of iron chelation, β0β0 genotype, vitamin D deficiency, diabetes and cardiac iron deposition. Moreover, hypogonadotropic hypogonadism may be an important pathogenesis of abnormal puberty development in β-TM patients.

With the globalisation of Chinese medicine (CM), the local CM education institutions were established in many other countries outside of China. These CM education institutions have formed a new mode in CM education after integrating with local culture, law and national conditions. This article takes New Zealand CM education institutions as an example to discuss the characteristics of CM education under the British education system, aiming to provide ideas on CM education in China and other countries.