Integration of phosphate functionalized Pt/TiO2 and Ru(bpy)32+ sensitization for ultrasensitive assay of adenosine deaminase activity on a novel split-typed PEC aptasensor.

To date, it is still a challenge for high-performance photoelectrochemical (PEC) assay of low-abundance adenosine deaminase (ADA) in fundamental research and clinical diagnosis. Herein, phosphate-functionalized Pt/TiO2 (termed PO43-/Pt/TiO2) was prepared as ideal photoactive material to develop a split-typed PEC aptasensor for detection of ADA activity, coupled by a Ru(bpy)32+ sensitization strategy. We critically studied the effects of the PO43- and Ru(bpy)32+ on the detection signals, and discussed the signal-amplified mechanism. Specifically, hairpin-structured adenosine (AD) aptamer was splited into single chain via ADA-induced catalytic reaction, and subsequently hybridized with complementary DNA (cDNA, initially coating on magnetic beads). The in-situ formed double-stranded DNA (dsDNA) was further intercalated by more Ru(bpy)32+ to amplify the photocurrents. The resultant PEC biosensor showed a broader linear range of 0.05-100 U L-1 and a lower limit of detection (0.019 U L-1), which can fill the blank for analysis of ADA activity. This research would provide some valuable insights for building advanced PEC aptasensors in ADA-related research and clinical diagnosis.

Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study.

BACKGROUND: Chemoprevention of colorectal adenoma and colorectal cancer remains an important public health goal. The present study aimed to investigate the clinical potential and safety of berberine for prevention of colorectal adenoma recurrence. METHODS: This double-blind, randomised, placebo-controlled trial was done in seven hospital centres across six provinces in China. Individuals aged 18-75 years who had at least one but no more than six histologically confirmed colorectal adenomas that had undergone complete polypectomy within the 6 months before recruitment were recruited and randomly assigned (1:1) to receive berberine (0·3 g twice daily) or placebo tablets via block randomisation (block size of six). Participants were to undergo a first follow-up colonoscopy 1 year after enrolment, and if no colorectal adenomas were detected, a second follow-up colonoscopy at 2 years was planned. The study continued until the last enrolled participant reached the 2-year follow-up point. All participants, investigators, endoscopists, and pathologists were blinded to treatment assignment. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. Analysis was based on modified intention-to-treat, with the full analysis set including all randomised participants who received at least one dose of study medication and who had available efficacy data. The study is registered with ClinicalTrials.gov, number NCT02226185; the trial has ended and this report represents the final analysis. FINDINGS: Between Nov 14, 2014, and Dec 30, 2016, 553 participants were randomly assigned to the berberine group and 555 to the placebo group. The full analysis set consisted of 429 participants in the berberine group and 462 in the placebo group. 155 (36%) participants in the berberine group and 216 (47%) in the placebo group were found to have recurrent adenoma during follow-up (unadjusted relative risk ratio for recurrence 0·77, 95% CI 0·66-0·91; p=0·001). No colorectal cancers were detected during follow-up. The most common adverse event was constipation (six [1%] of 446 patients in the berberine group vs one [<0·5%] of 478 in the placebo group). No serious adverse events were reported. INTERPRETATION: Berberine 0·3 g twice daily was safe and effective in reducing the risk of recurrence of colorectal adenoma and could be an option for chemoprevention after polypectomy. FUNDING: National Natural Science Foundation of China.

Efficacy and safety of natural acetylcholinesterase inhibitor huperzine A in the treatment of Alzheimer's disease: an updated meta-analysis.

The objective of this study was to provide an updated meta-analysis of the efficacy and safety of huperzine A (HupA) in Alzheimer's disease (AD). We searched for randomized trials comparing HupA with placebo in the treatment of AD. The primary outcome measures were mini-mental state examination (MMSE) and activities of daily living scale (ADL). Data were extracted from four randomized clinical trials and analyzed using standard meta-analysis and meta-regression methods. Oral administration of HupA for 8-24 weeks (300-500 microg daily) led to significant improvements in MMSE and ADL. The results of meta-regression showed that the estimated effect size of MMSE and ADL was increased over the treatment time. Most adverse events were cholinergic in nature and no serious adverse events occurred. Huperzine A is a well-tolerated drug that could significantly improve cognitive performance and ADL in patients with AD.

[Aldosterone-to-renin ratio threshold for screening primary aldosteronism in Chinese hypertensive patients].

OBJECTIVE: In recent years, the assessment of the plasma aldosterone-to-renin ratio (ARR) has become a most effectively and commonly used method for screening primary aldosteronism from hypertensive patients. It is known that there is a large variance in ARR value between races and ARR is affected by many factors, such as drugs, posture and serum potassium etc. The objective of this study is to establish the threshold of ARR for screening primary aldosteronism in Chinese hypertensive patients. METHODS: A total of 110 hypertensive patients were recruited and divided into essential hypertension group (n=65) and adenoma/hyperplasia group (n=45) according to the adrenal contrast CT scan. Antihypertensive drugs which can affect ARR such as beta-blockers, dihydropyridine calcium channel blockers (CCBs), ACE inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and clonidine, were withdrawn for at least 2 weeks. Washout period for diuretics including spironolactone were 4 weeks. Non-dihydropyridine calcium channel blockers (slow released verapamil) and/or alpha-blocker (terazosin) are allowed for controlling blood pressure when needed. If the serum potassium value<3.6 mmol/L, an oral potassium supplement was prescribed. After keeping upright position for 2 hours, blood samples were drawn for PRA and PAC measurement between 9:00AM-10:00AM. RESULTS: ARR was 100.00+/-48.65 (14.19-285.16) pg/ml vs ngxml-1xh-1 in patients with essential hypertension and 699.33+/-213.33 (185.8-2150) pg/ml vs ngxml-1xh-1 in patients with adenoma/hyperplasia. ARR value was greater than 240 in 42 out of 45 patients (93.3%) with adenoma/hyperplasia and was less than 240 in 59 out of 65 (90.7%) patients with essential hypertension. We used ARR 240 as the cut-off threshold for screening primary aldosteronism in another 178 hypertensive patients and ARR was greater than 240 in all 15 patients with confirmed primary aldosteronism. CONCLUSION: It is suitable to use upright ARR 240 as a cut-off threshold for screening primary aldosteronism in Chinese hypertensive patients.

[Inhibition effects of rhubarb ethanol extract on herpes simplex virus infection in vivo].

OBJECTIVE: To know the anti-viral effects of rhubarb ethanol extract (REE) on herpes simplex virus(HSV) infection in vivo. METHODS: BALB/c mice inoculated from tail vein with 0.15 ml of HSV (TCID50=10(3)) were injected hypodermically with REE next day. After divided into seven groups, three groups of mice were given different doses of REE respectively and the other groups as controls. Pathological sections from the liver, spleen, kidney were made at different times of postinfection, and their pathological changes were observed under microscope; the virus titers in viscera were assayed by using plaque formation technique and the rhubarb inhibitions to the infection of HSV in vivo?were observed. RESULTS: No toxic response to mice were observed for REE injected hypodermically; no pathological changes were observed in different therapy groups of spleens. And those in livers and kidneys at medium- and high-dosed groups disappeared quickly. The effect of low-dosed group was equal to that of positive control group, acyclovir(ACV); the results of the titer tests showed that the virus decreased rapidly by using REE, especially in the medium- and high-dosed groups which were much more marked than the low-dosed group; Q test of the data showed that total mean value had statistical significance (F=49.1459, P<0.01); moreover there were statistical significance between therapy groups (ACV, DH1, DH2, DH3) and non-therapy groups (VC) (P<0.01 ) and between DH2, DH3 and DH1 (P<0.01); no statistical significance were found between DH1, DH2 or DH3 and ACV (P>0.05). Results show that as to the effect of decreasing the average of the total titer, rhubarb is as effective as ACV; furthermore, the medium- and high-dosed groups are superior to the low-dosed group. CONCLUSIONS: REE has significant anti-viral effect on HSV in vivo; there will be a wide application foreground of it in clinical usage.