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 compare the efficacy of linaclotide and procalcitide in the treatment of adult constipation IBS-C.Methods:A retrospective study was conducted on 80 IBS-C patients admitted from May 2021 to May 2024.All patients were treated with novel secretagogues,and were divided into four groups according to the different treatment methods:linarotinib group and Pucanapide group,with 40 patients in each group.The clinical efficacy of oral administration of 290 μg of Nallotide capsules and 3 mg of Pucanapeptide in the Linalotide group and Pucanapeptide group was compared after one month of continuous treatment.The scores of IBS-C symptoms related to stool frequency,stool characteristics,upper abdominal pain,early satiety,and bloating were evaluated before and Post-treatment.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of vasoactive intestinal peptide(VIP),substance P(SP),5-hydroxytryptamine(5-HT),motilin,and gastrin IBS-C related serum markers in feces.The 16s rDNA fluorescence quantitative polymerase chain reaction method was used to detect Escherichia coli and lactate in feces.Compare the incidence of adverse reactions between the two groups based on the levels of Bacillus and Bifidobacterium.Results:There was no difference in the total effective rate between linagliptin group and Pucanotide group(P＞0.05);Post-treatment,the fecal frequency scores of the linaclotide group and the procalcitonin group were higher than pretherapy,while the fecal characteristics,upper abdominal pain,early satiety,and fullness scores were lower than pretherapy(P＜0.05).There was no difference in the fecal frequency,fecal characteristics,early satiety,and fullness scores between the linaclotide group and the procalcitonin group(P＞0.05),and the upper abdominal pain score of the linaclotide group was lower than that of the procalcitonin group(P＜0.05);Post-treatment,VIP,SP,5-HT,motilin and gastrin levels in linagliptin group and Pucanotide group were all lower than that pretherapy(P＜0.05),and there was no significant difference between linagliptin group and Pucanotide group(P＞0.05);Post-treatment,the levels of Escherichia coli in the linaclotide group and the procaine group were lower than pretherapy,while the numbers of Lactobacilli and Bifidobacteria were higher than pretherapy(P＜0.05).There was no difference between the linaclotide group and the procaine group(P＞0.05);There was no difference in the incidence of headache,bloating/abdominal pain between the linaclotide group and the procaine group(P＞0.05),and the incidence of diarrhea in the procaine group was lower than that in the linaclotide group(P＜0.05).Conclusion:Linalotide and Pucanatide have similar therapeutic effects in treating adult IBS-C,both of which can improve patients' clinical symptoms,serum biomarker levels,and intestinal microbiota structure.However,Linalotide has a better effect on improving abdominal pain,while Pucanatide can reduce the risk of diarrhea.Therefore,the clinical application of different new secretagogue drugs can be determined based on individualized symptoms and diarrhea risk of patients.

Objective:To compare the efficacy of linaclotide and procalcitide in the treatment of adult constipation IBS-C.Methods:A retrospective study was conducted on 80 IBS-C patients admitted from May 2021 to May 2024.All patients were treated with novel secretagogues,and were divided into four groups according to the different treatment methods:linarotinib group and Pucanapide group,with 40 patients in each group.The clinical efficacy of oral administration of 290 μg of Nallotide capsules and 3 mg of Pucanapeptide in the Linalotide group and Pucanapeptide group was compared after one month of continuous treatment.The scores of IBS-C symptoms related to stool frequency,stool characteristics,upper abdominal pain,early satiety,and bloating were evaluated before and Post-treatment.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of vasoactive intestinal peptide(VIP),substance P(SP),5-hydroxytryptamine(5-HT),motilin,and gastrin IBS-C related serum markers in feces.The 16s rDNA fluorescence quantitative polymerase chain reaction method was used to detect Escherichia coli and lactate in feces.Compare the incidence of adverse reactions between the two groups based on the levels of Bacillus and Bifidobacterium.Results:There was no difference in the total effective rate between linagliptin group and Pucanotide group(P＞0.05);Post-treatment,the fecal frequency scores of the linaclotide group and the procalcitonin group were higher than pretherapy,while the fecal characteristics,upper abdominal pain,early satiety,and fullness scores were lower than pretherapy(P＜0.05).There was no difference in the fecal frequency,fecal characteristics,early satiety,and fullness scores between the linaclotide group and the procalcitonin group(P＞0.05),and the upper abdominal pain score of the linaclotide group was lower than that of the procalcitonin group(P＜0.05);Post-treatment,VIP,SP,5-HT,motilin and gastrin levels in linagliptin group and Pucanotide group were all lower than that pretherapy(P＜0.05),and there was no significant difference between linagliptin group and Pucanotide group(P＞0.05);Post-treatment,the levels of Escherichia coli in the linaclotide group and the procaine group were lower than pretherapy,while the numbers of Lactobacilli and Bifidobacteria were higher than pretherapy(P＜0.05).There was no difference between the linaclotide group and the procaine group(P＞0.05);There was no difference in the incidence of headache,bloating/abdominal pain between the linaclotide group and the procaine group(P＞0.05),and the incidence of diarrhea in the procaine group was lower than that in the linaclotide group(P＜0.05).Conclusion:Linalotide and Pucanatide have similar therapeutic effects in treating adult IBS-C,both of which can improve patients' clinical symptoms,serum biomarker levels,and intestinal microbiota structure.However,Linalotide has a better effect on improving abdominal pain,while Pucanatide can reduce the risk of diarrhea.Therefore,the clinical application of different new secretagogue drugs can be determined based on individualized symptoms and diarrhea risk of 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.

Aiming at the hysteresis and destructiveness of off-line static detection of critical quality attribute of the moisture content of the raw material unit of the traditional Chinese medicine manufacturing process, honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis were used as the research carriers, and the drying method was used to measure the moisture content as a reference value. The moving stage was used to simulate the movement process of samples on the conveyor belt in the actual on-site production process, and near-infrared (NIR) spectra were collected, combined with machine learning, to establish NIR on-site dynamic detection model of moisture content in multi-variety honey-processed Chinese herbal slice. The results show that the second derivative method is used to preprocess the spectrum. The number of decision trees (ntree), the number of random features (max feature), and the minimum number of samples for generating leaf nodes (node size) are selected: 46, 76, and 8, respectively. The quantitative analysis model of moisture content has the best effect. The prediction coefficient of determination (the prediction coefficient of determination, R²_pre) and the root mean square error of prediction (root mean square error of prediction, RMSEP) of the model were 0.903 2 and 0.330 2, respectively. The NIR quantitative model for the moisture content of multi-variety honey-processed Chinese herbal slice established in this study has good predictive performance, and can achieve rapid, accurate and non-destructive quantitative analysis of the moisture content of honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis at the same time, and provides a method for determining the moisture content of honey-processed Chinese herbal slice of the raw material unit of the traditional Chinese medicine manufacturing process.

OBJECTIVE: To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms. METHODS: Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD). RESULTS: MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD. CONCLUSIONS MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.
Rats ; Mice ; Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; Ghrelin/metabolism* ; Antidepressive Agents/therapeutic use* ; Hippocampus ; Stress, Psychological ; Mammals/metabolism*

OBJECTIVE: To analyze the independent risk factors of long-term ischemic stroke and establish a nomogram for predicting the long-term risks in elderly patients with obstructive sleep apnea (OSA). METHODS: This multicenter prospective cohort study was conducted from January, 2015 to October, 2017 among consecutive elderly patients (≥60 years) with newly diagnosed OSA without a history of cardio-cerebrovascular diseases and loss of important clinical indicators. The follow-up outcome was the occurrence of ischemic stroke. The baseline demographic and clinical data, sleep parameters, laboratory and ultrasound results were collected from all the patients, who were randomized into the modeling group (n=856) and validation group (n=258) at a 3∶1 ratio. LASSO regression was used for variable reduction and dimension screening, and the risk score prediction model of ischemic stroke was established based on Cox proportional hazard regression. RESULTS: In the total of 1141 patients enrolled in this study, 58 (5.08%) patients experienced ischemic stroke during the median follow-up of 42 months (range 41-54 months). The cumulative incidence of ischemic stroke was 5.14% in the model group and 4.91% in the verification group (P < 0.05). Age (HR=3.44, 95% CI: 2.38- 7.77), fasting blood glucose (FPG) (HR=2.13, 95% CI: 1.22-3.72), internal diameter of the ascending aorta (HR=2.60, 95% CI: 1.0- 4.47), left atrial anteroposterior diameter (HR=1.98, 95% CI: 1.75-2.25) and minimum oxygen saturation (LSpO₂) (HR=1.57, 95% CI: 1.20-1.93) were identified as independent risk factors for ischemic stroke (P < 0.05 or 0.01). A long-term ischemic stroke risk score model was constructed based the regression coefficient ratios of these 5 risk variables. Before and after the application of the Bootstrap method, the AUC of the cohort risk score model was 0.84 (95% CI: 0.78- 0.90) and 0.85 (95% CI: 0.78- 0.89) in the model group and was 0.83 (95% CI: 0.73-0.93) and 0.82 (95%CI: 0.72-0.90) in the verification group, respectively, suggesting a good prediction efficiency and high robustness of the model. At the best clinical cutoff point, the cumulative incidence of ischemic stroke was significantly higher in the high-risk group than in the low-risk group (P=0.021). CONCLUSION This model can help to identify high-risk OSA patients for early interventions of the risks of ischemic stroke associated with OSA.
Aged ; Humans ; Ischemic Stroke ; Middle Aged ; Prospective Studies ; Risk Factors ; Sleep ; Sleep Apnea, Obstructive/complications* ; Stroke/complications*

OBJECTIVE: To examine whether the combination of Naoxintong Capsule with standard care could further reduce the recurrence of ischemic stroke without increasing the risk of severe bleeding. METHODS: A total of 23 Chinese medical centers participated in this trial. Adult patients with a history of ischemic stroke were randomly assigned in a 1:1 ratio using a block design to receive either Naoxintong Capsule (1.2 g orally, twice a day) or placebo in addition to standard care. The primary endpoint was recurrence of ischemic stroke within 2 years. Secondary outcomes included myocardial infarction, death due to recurrent ischemic stroke, and all-cause mortality. The safety of drugs was monitored. Results were analyzed using the intention-to-treat principle. RESULTS: A total of 2,200 patients were enrolled from March 2015 to March 2016, of whom 143 and 158 in the Naoxintong and placebo groups were lost to follow-up, respectively. Compared with the placebo group, the recurrence rate of ischemic stroke within 2 years was significantly lower in the Naoxintong group [6.5% vs. 9.5%, hazard ratio (HR): 0.665, 95% confidence interval (CI): 0.492-0.899, P=0.008]. The two groups showed no significant differences in the secondary outcomes and safety, including rates of severe hemorrhage, cerebral hemorrhage and subarachnoid hemorrhage (P>0.05). CONCLUSION The combination of Naoxintong Capsule with standard care reduced the 2-year stroke recurrence rate in patients with ischemic stroke without increasing the risk of severe hemorrhage in high-risk patients. (Trial registration No. NCT02334969).
Adult ; Humans ; Secondary Prevention/methods* ; Ischemic Stroke ; Stroke/prevention & control* ; Cerebral Hemorrhage/complications* ; Double-Blind Method ; Platelet Aggregation Inhibitors

Objective: To investigate the daily variation of LPR and the significance of 48-hour oropharyngeal pH monitoring in the diagnosis of LPRD. Methods: 72 subjects with suspected LPRD who were treated in our department from June 2018 to June 2021 were included. All patients were hospitalized to complete continuous 48-hour oropharyngeal Dx-pH monitoring. The consistency of Ryan index and W index and the correlation of various reflux parameters between the first and second 24-hour were compared. SPSS 24.0 was used for statistical analysis. Results: All 72 subjects successfully completed 48-hour oropharyngeal Dx-pH monitoring. Ryan index was positive in 11 cases (15.2%) in the first 24-hour, in 17 cases (23.6%) in the second 24-hour, in 5 cases (6.9%) both first and second, and in 23 cases (31.9%) in either 24-hour, Kappa=0.211 (P=0.064), 18 cases (25%) had inconsistent results of the first 24-hour and the second 24-hour, and there was no significant difference in the positive rate between the first and second (P=0.234). The number of positive cases in 48-hour monitoring increased by 109.1% compared with 24-hour monitoring.For W index, 49 cases (68.1%) were positive in the first 24-hourf 53 cases (73.6%) were positive in the second 24-hour, 42 cases (58.3%) were positive both first and second, and 58 cases (80.6%) were positive in either 24-hour, Kappa=0.477 (P<0.001), 16 cases (22.2%) had inconsistent results of the first and second, and there was no significant difference in the positive rate between the first and second (P=0.804). The number of positive cases in 48-hour monitoring increased by 18.4% compared with 24-hour monitoring. There was no significant difference in all the reflux parameters of first and second (P>0.05). The correlation comparison showed that the correlation of various reflux parameters in the upright position was lower than that in the supine position. Conclusion: Laryngeal reflux has daily variability. Extending the monitoring time of Dx-pH to 48-hour can help reduce the missed diagnosis caused by daily variability; the use of W index can reduce the influence of daily variability on the diagnostic results of LPRD.
Humans ; Laryngopharyngeal Reflux/diagnosis* ; Hydrogen-Ion Concentration ; Hypopharynx ; Larynx

Chronic psychological stress can promote vascular diseases, such as hypertension and atherosclerosis. This study aims to explore the effects and mechanism of chronic psychological stress on aortic medial calcification (AMC). Rat arterial calcification model was established by nicotine gavage in combination with vitamin D₃ (VitD₃) intramuscular injection, and rat model of chronic psychological stress was induced by humid environment. Aortic calcification in rats was evaluated by using Alizarin red staining, aortic calcium content detection, and alkaline phosphatase (ALP) activity assay. The expression levels of the related proteins, including vascular smooth muscle cells (VSMCs) contractile phenotype marker SM22α, osteoblast-like phenotype marker RUNX2, and endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP), were determined by Western blot. The results showed that chronic psychological stress alone induced AMC in rats, further aggravated AMC induced by nicotine in combination with VitD₃, promoted the osteoblast-like phenotype transformation of VSMCs and aortic ERS activation, and significantly increased the plasma cortisol levels. The 11β-hydroxylase inhibitor metyrapone effectively reduced chronic psychological stress-induced plasma cortisol levels and ameliorated AMC and aortic ERS in chronic psychological stress model rats. Conversely, the glucocorticoid receptor agonist dexamethasone induced AMC, promoted AMC induced by nicotine combined with VitD₃, and further activated aortic ERS. The above effects of dexamethasone could be inhibited by ERS inhibitor 4-phenylbutyrate. These results suggest that chronic psychological stress can lead to the occurrence and development of AMC by promoting glucocorticoid synthesis, which may provide new strategies and targets for the prevention and control of AMC.
Rats ; Animals ; Glucocorticoids/metabolism* ; Rats, Sprague-Dawley ; Nicotine/metabolism* ; Hydrocortisone/metabolism* ; Muscle, Smooth, Vascular ; Dexamethasone/metabolism* ; Vascular Calcification/metabolism* ; Myocytes, Smooth Muscle/metabolism* ; Cells, Cultured