Efficacy and safety of triple therapy containing berberine hydrochloride, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori.

OBJECTIVE: To estimate the effectiveness and safety of triple therapy containing berberine, amoxicillin, and rabeprazole in the eradication of Helicobacter pylori (H. pylori). METHODS: This prospective, randomized controlled, open-label, noninferiority trial included treatment-naive patients with H. pylori infection who were randomly allocated at a ratio of 1:1 into the berberine triple therapy group (berberine hydrochloride 300 mg thrice daily, amoxicillin 1 g twice daily, and rabeprazole 10 mg twice daily) or standard bismuth-containing quadruple therapy group (amoxicillin 1 g twice daily, rabeprazole 10 mg twice daily, clarithromycin 500 mg twice daily, and bismuth tartrate 200 mg twice daily) for 14 days. Negative 13 C/14 C-urea breath test at 4 weeks after completion of the therapy was regarded as successful eradication. RESULTS: Altogether 262 and 262 patients received berberine triple therapy and bismuth-containing quadruple therapy, respectively. Both intention-to-treat (79.8% vs 80.9%, P = 0.742) and per-protocol analyses (83.6% and 85.1%, P = 0.636) showed comparable eradication rate between the two groups, indicating a noninferior eradication rate (the lower limit of the 95% confidence interval over -10% [-7.9% and -7.87%, respectively]). Adverse events more commonly occurred in the bismuth-containing quadruple-therapy group (8.8% vs 16.0%, P = 0.012), while patient compliance and symptom improvement of the two regimens were comparable. CONCLUSION: Triple therapy containing berberine, amoxicillin and rabeprazole is noninferior to bismuth-containing quadruple therapy in the initial treatment for H. pylori eradication.

Homocysteine-Induced Disturbances in DNA Methylation Contribute to Development of Stress-Associated Cognitive Decline in Rats.

Chronic stress is generally accepted as the main risk factor in the development of cognitive decline; however, the underlying mechanisms remain unclear. Previous data have demonstrated that the levels of homocysteine (Hcy) are significantly elevated in the plasma of stressed animals, which suggests that Hcy is associated with stress and cognitive decline. To test this hypothesis, we analyzed the cognitive function, plasma concentrations of Hcy, and brain-derived neurotropic factor (BDNF) levels in rats undergoing chronic unpredicted mild stress (CUMS). The results showed that decreased cognitive behavioral performance and decreased BDNF transcription and protein expression were correlated with hyperhomocysteinemia (HHcy) levels in stressed rats. Diet-induced HHcy mimicked the cognitive decline and BDNF downregulation in the same manner as CUMS, while Hcy reduction (by means of vitamin B complex supplements) alleviated the cognitive deficits and BDNF reduction in CUMS rats. Furthermore, we also found that both stress and HHcy disturbed the DNA methylation process in the brain and induced DNA hypermethylation in the BDNF promoter. In contrast, control of Hcy blocked BDNF promoter methylation and upregulated BDNF levels in the brain. These results imply the possibility of a causal role of Hcy in stress-induced cognitive decline. We also used ten-eleven translocation (TET1), an enzyme that induces DNA demethylation, to verify the involvement of Hcy and DNA methylation in the regulation of BDNF expression and the development of stress-related cognitive decline. The data showed that TET1-expressing viral injection into the hippocampus inhibited BDNF promoter methylation and significantly mitigated the cognitive decline in HHcy rats. Taken together, novel evidence from the present study suggests that Hcy is likely involved in chronic stress-induced BDNF reduction and related cognitive deficits. In addition, the negative side-effects of HHcy may be associated with Hcy-induced DNA hypermethylation in the BDNF promoter. The results also suggest the possibility of Hcy as a target for therapy and the potential value of vitamin B intake in preventing stress-induced cognitive decline.

Mapping thalamic-anterior cingulate monosynaptic inputs in adult mice.

The anterior cingulate cortex (ACC) is located in the frontal part of the cingulate cortex, and plays important roles in pain perception and emotion. The thalamocortical pathway is the major sensory input to the ACC. Previous studies have show that several different thalamic nuclei receive projection fibers from spinothalamic tract, that in turn send efferents to the ACC by using neural tracers and optical imaging methods. Most of these studies were performed in monkeys, cats, and rats, few studies were reported systematically in adult mice. Adult mice, especially genetically modified mice, have provided molecular and synaptic mechanisms for cortical plasticity and modulation in the ACC. In the present study, we utilized rabies virus-based retrograde tracing system to map thalamic-anterior cingulate monosynaptic inputs in adult mice. We also combined with a new high-throughput VISoR imaging technique to generate a three-dimensional whole-brain reconstruction, especially the thalamus. We found that cortical neurons in the ACC received direct projections from different sub-nuclei in the thalamus, including the anterior, ventral, medial, lateral, midline, and intralaminar thalamic nuclei. These findings provide key anatomic evidences for the connection between the thalamus and ACC.

[Non-invasive electrical neuromodulation techniques: analgesic effects and neural mechanisms].

As non-pharmaceutical interventions, non-invasive electrical neuromodulation techniques are promising in pain management. With many advantages, such as low costs, high usability, and non-invasiveness, they have been exploited to treat multiple types of clinical pain. Proper use of these techniques requires a comprehensive understanding of how they work. In this article, we reviewed recent studies concerning non-invasive electrical peripheral nerve stimulation (transcutaneous electrical nerve stimulation and transcutaneous vagus/vagal nerve stimulation) as well as electrical central nerve stimulation (transcranial direct current stimulation and transcranial alternating current stimulation). Specifically, we discussed their analgesic effects on acute and chronic pain, and the neural mechanisms thereof. We then contrasted the four kinds of nerve stimulation techniques, pointing out limitations of existing studies and proposing directions for future research. With more extensive and in-depth research to overcome these limitations, we shall witness more clinical applications of non-invasive electrical nerve stimulations to alleviate patients' pain and ease the crippling medical and economic burden imposed on patients, their families, and the entire society.

Artificial Intelligence Meets Chinese Medicine.

As an interdisciplinary subject of medicine and artificial intelligence, intelligent diagnosis and treatment has received extensive attention. The standardization of Chinese medicine (CM) diagnosis has been always a bottleneck in the modernization and globalization of CM. Studying the application technology of artificial intelligence in CM and solving the problems is an urgent need for the development of modern CM in the era of artificial intelligence. Taking the pneumonia with dyspnea and cough in CM as an example, this article gives an overview of intelligent medical technology and application development, brings forward the present technical problems faced and the new advances in intelligent technology on CM diagnosis and treatment.

Individualized management of hepatic diseases in hereditary hemorrhagic telangiectasia.

Liver involvement in patients with hereditary hemorrhagic telangiectasia (HHT) has not been fully characterized in China. The clinical manifestations, imaging studies, results of treatment in six patients and symptomatic liver involvement were analyzed. Patients included three women and three men with age from 35 to 62 years old. Two patients presented with shortness of breath, one patient with anemia and splenomegaly, and one with chronic gastrointestinal bleeding; the remaining two were asymptomatic. CT and CT angiography (CTA) showed arterioportal and arteriovenous shunting in liver. CTA showed at least one enlarged hepatic artery in all patients. One patient received ligation of the enlarged arteries with subsequent disappearance of symptoms at 56-month follow-up. The patient with gastrointestinal bleeding received interventional embolotherapy and resolved; interventional therapy to embolize the enlarged hepatic arteries was unsuccessful in another patient and the patient died of heart failure and liver dysfunction 38 months later. The patient with splenomegaly received a splenectomy and bandage of an enlarged hepatic artery. One of the two patients with no symptoms died of liver dysfunction 41 months after diagnosis. The other showed abnormal liver function and ascites, and traditional Chinese medicinal herb was used with no effect 21 months later. The symptoms disappeared after systemic medical treatment. Individualized and active therapy is advantageous and proper for patients with HHT.

[Mechanism of combined treatment with Shenkangling Decoction and prednisone in rats with adriamycin-induced nephropathy].

OBJECTIVE: To study the mechanism of Shenkangling (SKL), a compound traditional Chinese herbal medicine, combined with prednisone in treating adriamycin-induced nephropathy in rats. METHODS: Sixty-six SD male rats were randomly divided into normal control group, untreated group, prednisone group, SKL group and SKL plus prednisone group. Except the normal control group, rats were injected once via caudal vein with adriamycin (5.5 mg/kg) to induce nephropathy. Then, the rats were administered with prednisone, SKL, prednisone plus SKL or distilled water for 3 weeks, respectively. After harvest, 24-hour urine protein excretion, tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) contents in serum, and content of nuclear transcription factor-kappa B (NF-kappaB) p65 in mononuclear cells were determined, and correlation analysis among these parameters was performed. The content of NF-kappaB p65 was assayed with the patented method of Active Motif; TNF-alpha was assayed with enzyme-linked immunosorbent assay, and the content of NO was assessed by the method of nitrate reductase. The change of foot process in renal glomerulus was observed under an electron microscope. RESULTS: When the rats were administered with prednisone, SKL correspondingly, the contents of NF-kappaB p65, TNF-alpha and NO as well as 24-hour urine protein excretion were lower than those in the untreated group (P<0.01), and the fusion of foot process only recovered partially. Compared with other treated groups, the contents of NF-kappaB p65 and NO as well as 24-hour urine protein excretion were significantly decreased in SKL plus prednisone group (P<0.01, P<0.05), and the fusion of foot process recovered mostly also. There was no interaction between SKL and prednisone in decreasing the content of TNF-alpha. CONCLUSION: Renal injury can be postponed and improved when treated with SKL plus prednisone; it may contribute to the depression of abnormal activation of NF-kappaB, and the inhibition of production of TNF-alpha and NO.