The impact of blinding on estimated treatment effects in randomized clinical trials on acupuncture: A meta-epidemiological study.

OBJECTIVE: To evaluate the sole impact of blinding patients and outcome assessors in acupuncture randomized controlled trials (RCTs) on treatment effects while considering the type of outcome measures. METHODS: We searched databases for the meta-analyses on acupuncture with both blinded and non-blinded RCTs. Mixed-effects meta-regression models estimated the average ratio of odds ratios (ROR) and differences in standardized mean differences (dSMD) for non-blinded RCTs versus blinded mixed-effects meta-regression model. RESULTS: The study included 96 meta-analyses (1012 trials). The average ROR for lack of patient blinding was 1.08 (95% confidence intervals 0.79-1.49) in 18 meta-analyses with binary patient-reported outcomes. The average ROR for lack of outcome assessor blinding was 0.98 (0.77-1.24) in 43 meta-analyses with binary subjective outcomes. The average dSMD was -0.38 (-0.96 to 0.20) in 10 meta-analyses with continuous patient-reported outcomes. The average dSMD was -0.13 (-0.45 to 0.18) in 25 meta-analyses with continuous subjective outcomes. The results of the subgroup analysis were consistent with the primary analysis findings. CONCLUSIONS: Blinding of participants and outcome assessors does not significantly influence acupuncture treatment efficacy. It underscores the practical difficulties of blinding in acupuncture RCTs and the necessity to distinguish between trials with and without successful blinding to understand treatment expectations' effects. Enhancing blinding procedures' quality and assessment in future research is crucial for improving RCTs' internal validity and reliability.

Visual tracking of label-free microplastics in wheat seedlings and their effects on crop growth and physiology.

The effects of microplastics on crop plants have attracted growing attention. However, little is known about the effects of microplastics and their extracts on the growth and physiology of wheat seedlings. In this study, hyperspectral-enhanced dark field microscopy and scanning electron microscopy were used to accurately track the accumulation of 200 nm label-free polystyrene microplastics (PS) in wheat seedlings. The PS accumulated along the root xylem cell wall and in the xylem vessel member and then moved toward to the shoots. In addition, lower concentration (≤ 5 mg·L-1) of microplastics increased root hydraulic conductivity by 80.6 %- 117.0 %. While higher PS treatment (200 mg·L-1) considerably decreased plant pigments content (chlorophyll a, b, and total chlorophyll) by 14.8 %, 19.9 %, and 17.2 %, respectively, and decreased root hydraulic conductivity by 50.7 %. Similarly, catalase activity was reduced by 17.7 % in root and 36.8 % in shoot. However, extracts from the PS solution showed no physiological effect on wheat. The result confirmed that it was the plastic particle, rather than the chemical reagents added in the microplastics, contributed to the physiological variation. These data will benefit to better understanding on the behavior of microplastics in soil plants, and to providing of convincing evidence for the effects of terrestrial microplastics.

Proteomics analysis reveals promotion effect of 1α,25-dihydroxyvitamin D3 on mammary gland development and lactation of primiparous sows during gestation.

1α,25(OH)2VD3 is the most active form of vitamin D3 in animals, and it plays an important role in regulating mineral metabolism and reproduction. In this study, 140 crossbred gilts (Landrace × Yorkshire) were selected, randomly divided into four groups, and fed with a commercial diet supplemented with 0, 1, 2, and 4 µg/kg of 1α,25(OH)2VD3 in the form of 1α,25(OH)2VD3-glycosides. The mammary gland tissues were sampled from sows on day 114 of gestation. The production data of sows in each group were analyzed, and the colostrum quality was evaluated. Differentially abundant proteins (DAPs) in the mammary tissues were identified by tandem mass tag (TMT) technique and were verified by Western blot and parallel reaction monitoring (PRM). The results showed that 4 µg/kg 1α,25(OH)2VD3-glycosides significantly promoted the piglet birth weight, weaning weight, colostrum quality, and lactation ability of primiparous sows. The proteomics analysis showed that of the identified 53,118 peptides, 48,868 were unique peptides. A total of 5029 DAPs were identified, of which 4292 DAPs contained quantitative information. Our data indicated that 1α,25(OH)2VD3 was involved in the regulation of the mammary gland development and lactation in a dose-dependent manner through multiple pathways during gestation of primiparous sows. SIGNIFICANCE: The mammary gland is an important lactation organ of female mammals. Our research aims to reveal the effect of dietary supplementation with 1α,25(OH)2VD3 on mammary gland development and lactation of primiparous sow. This study identified potential signaling pathways and DAPs involved in regulating the mammary gland development and lactation in sows. Our findings provides theoretical basis for improving the fecundity of sows.

Identification and bioactivity evaluation of flavan-3-ols in the milk of dairy sheep fed Cynomorium songaricum.

Cynomorium songaricum is a traditional medicine and also a food material that is eaten raw or processed as tea or beverages. As a featured plant in semi-desert grasslands, C. songaricum is also eaten by the cattle and sheep in the area. This research study fed dairy sheep C. songaricum to determine the flavan-3-ols in sheep milk. Catechin (Cat), epicatechin (Epi), procyanidin A1 (A1), procyanidin A2 (A2), and procyanidin B1 (B1) were detected in sheep milk with the concentration being Epi > A2 > Cat > B1 > A1 at 24 h after the administration of C. songaricum. Neither A1 nor A2 were detected in the methanol extract of C. songaricum. Cysteine degradation of the plant revealed that in addition to Epi, A2 was the extending unit of the polymeric flavan-3-ols in C. songaricum, indicating that A2 is released digestively from the polymers and enters the milk. Procyanidin B-1 was converted to A1 on incubation in raw but not heated milk, indicating that the A1 in milk is the enzymatically transformed product of B1. Accelerated oxidation showed that the flavan-3-ols, B1, Cat, and Epi significantly protects the unsaturated triacyglycerols in the milk from oxidation. The flavan-3-ol could slow down the oxidation of glutathione and the latter may play an important role in preventing the milk triglycerides from oxidation. Flavan-3-ols are polyphenols with many health benefits. The present research revealed the antioxidant activities of flavan-3-ols that could be absorbed to sheep milk, adding new evidences for the values of these flavan-3-ols and for the milk.

Combination of Ephedra sinica stems and Terminalia chebula fruits produces new ephedrine derivatives in vivo that diminish the permeability to BBB while retaining airway dilation and hepatoprotective effects.

ETHNOPHARMACOLOGICAL RELEVANCE: The stems of Ephedra sinica and the fruits of Terminalia chebula are combined using in traditional Mongolian medicine formula "Gurigumu-7" for liver diseases. E. sinica stems contains ephedrine with broncho-dilatory activity. However, ephedrine can pass through the blood-brain barrier (BBB) and excite the central nervous system (CNS) to cause insomnia and restlessness. AIM OF THE STUDY: The present study was to investigate the structures and bioactivities of new compounds formed in vivo after co-administration of E. sinica stems and T. chebula fruits. MATERIALS AND METHODS: Pharmacokinetic investigation was carried out in rats. A parallel artificial membrane permeability measurement system was used to determine BBB permeability. Ex vivo experiments using tracheal rings of guinea pig was performed to examine the tracheal relaxation effect. In vivo hepatoprotective tests were carried out in Tg (fabp10a: dsRed) liver transgenic zebrafish. The fluorescent probe, 2,7-dichlorodihydrofluorescein diacetate, was used to measure reactive oxygen species, and UHPLC-MS was used to determine glutathione concentrations after derivatization with N-ethylmaleimide. RESULTS: New ephedrine derivatives (1 and 2) formed in vivo and reached their maximum serum concentrations at 0.5 h after administration of the two herbal drugs. Compounds 1 and 2 showed lower BBB permeability than ephedrine, suggesting that they have less adverse effects on the CNS. Compounds 1 and 2 relaxed the tracheal rings and had strong hepatoprotective effect on transgenic zebrafish with liver specific expression of RFP. Compounds 1 and 2 significantly reduced the level of reactive oxygen species while increasing that of glutathione in thioacetamide-treated zebrafish, which might be the hepatoprotective mechanism. CONCLUSION: These results provided evidences that the chemical constituents in various herbal drugs in a medicinal formula can interact to generate new compounds with fewer side effects and increased or additive bioactivity.

Effect of Tongxinluo on Nephrin Expression via Inhibition of Notch1/Snail Pathway in Diabetic Rats.

Podocyte injury is an important mechanism of diabetic nephropathy (DN). Accumulating evidence suggests that nephrin expression is decreased in podocyte in DN. Moreover, it has been demonstrated that tongxinluo (TXL) can ameliorate renal structure disruption and dysfunction in DN. However, the effect of TXL on podocyte injury in DN and its molecular mechanism is unclear. In order to explore the effect of TXL on podocyte injury and its molecular mechanism in DN, our in vivo and in vitro studies were performed. Our results showed that TXL increased nephrin expression in diabetic rats and in high glucose cultured podocyte. Meanwhile, TXL decreased ICN1 (the intracellular domain of notch), HES1, and snail expression in podocyte in vivo and in vitro. More importantly, we found that TXL protected podocyte from injury in DN. The results demonstrated that TXL inhibited the activation of notch1/snail pathway and increased nephrin expression, which may be a mechanism of protecting effect on podocyte injury in DN.