Initiation and duration of folic acid supplementation in preventing congenital malformations.

BACKGROUND: Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. METHODS: A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. RESULTS: Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44-1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21-1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08-5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33-0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36-0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. CONCLUSIONS: The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. TRIAL REGISTRATION: Chictr.org.cn identifier: ChiCTR-SOC-17010976.

Maternal traditional Chinese medicine exposure and risk of congenital malformations: a multicenter prospective cohort study.

INTRODUCTION: The potential teratogenic risk of traditional Chinese medicine (TCM) is of widespread concern; however, related evidence is largely absent in humans. This study aimed to compare the prevalence of congenital malformations between pregnant women with and without TCM exposure. MATERIAL AND METHODS: This was a multicenter prospective cohort study of 17 713 women who participated in a survey on periconceptional TCM exposure. Primary outcome was congenital malformations diagnosed from a survey conducted on the day 42 after delivery. RESULTS: A total of 16 751 pregnant women with 273 congenital malformations were included in the analysis. Fetuses exposed to TCM had an increased risk of congenital malformations compared to those without exposure (odds ratio [OR] 2.10; 95% confidence interval [CI] 1.09-4.02) after controlling for potential confounders. There were significant associations with congenital malformations in women with early pregnant exposure (OR 2.04, 95% CI 1.00-4.20) and for those who received ≥2 TCM formulas (OR 5.84, 95% CI 1.44-23.65). Pre-pregnancy TCM exposure was significantly associated with an increased risk of congenital heart defects (OR 12.69; 95% CI 3.01-53.51). CONCLUSIONS: Periconceptional TCM exposure is associated with an increased risk of congenital malformation. This effect was cumulative and sensitive to periconceptional age. Therefore, TCM deserves more attention and should be used cautiously for pregnant women and those trying to become pregnant.

Comparative study of rapid on-site evaluation performed by cytopathologists and trained endoscopists during endoscopic ultrasound-guided fine needle aspiration for pancreatic solid lesions / 中华消化内镜杂志

Objective:To evaluate rapid on-site evaluation (ROSE) in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic solid lesions, and to compare the difference in ROSE performance between cytopathologists and trained endoscopists.Methods:A total of 168 consecutive patients with pancreatic solid lesions who underwent EUS-FNA from January 2014 to December 2020 at Fuding Hospital, Fujian University of Traditional Chinese Medicine were recruited. The patients who did not receive ROSE from January 2014 to November 2017 were included in N-ROSE group ( n=67). Since December 2017, the patients who intended to receive EUS-FNA were divided into E-ROSE group ( n=59, patients who received EUS-FNA and ROSE by endoscopists trained with cytopathology) and C-ROSE group ( n=42,patients who received EUS-FNA by untrained endoscopists and ROSE by cytopathologists) according to random number table. The number of punctures, sample adequacy, cytological diagnosis, final diagnosis and diagnostic efficiency (including the sensitivity, the specificity, the positive predictive value, the negative predictive value and the accuracy) in 3 groups were compared. Results:(1) The puncture number in N-ROSE group (4.22±0.76) was significantly more than E-ROSE group (3.12±0.79, P<0.001) and C-ROSE group (3.24±0.91, P<0.001). (2) The proportions of adequate samples in N-ROSE group [82.09% (55/67)] was significantly lower than those of E-ROSE group [96.61% (57/59), χ2=5.308, P=0.021] and C-ROSE group [97.62% (41/42), χ2=4.541, P=0.033]. The proportion of negative cytological diagnosis in N-ROSE group [40.30% (27/67)] was significantly higher than those of E-ROSE group [20.34% (12/59), χ2=5.848, P=0.016] and C-ROSE group [19.05% (8/42), χ2=5.348, P=0.021]. (3) The sensitivity of N-ROSE group [74.07% (40/54)] was significantly lower than those of E-ROSE group [94.00% (47/50), χ2=6.151, P=0.013] and C-ROSE group [94.44% (34/36), χ2=4.817, P=0.028]. The accuracy in N-ROSE group [79.10% (53/67)] was significantly lower than those of E-ROSE group [94.92% (56/59), χ2=5.433, P=0.020] and C-ROSE group [95.24% (40/42), χ2=4.155, P=0.042]. (4) There was no significant difference in any observational index between E-ROSE group and C-ROSE group ( P>0.05). Conclusion:ROSE in EUS-FNA can improve sample adequacy, the diagnostic sensitivity and accuracy, and reduce the number of punctures. The sample adequacy and diagnostic efficiency of endoscopists trained with cytopathology are comparable to those of cytopathologists.

Poria cocos polysaccharides exert prebiotic function to attenuate the adverse effects and improve the therapeutic outcome of 5-FU in ApcMin/+ mice.

BACKGROUND: As a first-line chemotherapeutic agent, 5-fluorouracil (5-FU) exhibits many side effects, weakening its efficacy in cancer treatment. In this study, we hypothesize that Poria cocos polysaccharides (PCP), a traditional Chinese herbal medicine with various bioactivities and prebiotic effects, might improve the therapeutic effect of 5-FU by restoring the homeostasis of the gut microenvironment and the commensal gut microflora. METHODS: ApcMin/+ mice were employed to evaluate the anti-cancer effect of 5-FU in conjunction with PCP treatment. Body weight and food consumption were monitored weekly. Polyp count was used to assess the anti-cancer effect of PCP and 5-FU. Expressions of mucosal cytokines and gut epithelial junction molecules were measured using qRT-PCR. 16S rRNA gene sequencing of fecal DNAs was used to evaluate the compositional changes of gut microbiota (GM). Transplantation of Lactobacillus johnsonii and Bifidobacterium animalis were performed to verify the prebiotic effects of PCP in improving the efficacy of 5-FU. RESULTS: The results showed that PCP treatment alleviated the weight loss caused by 5-FU treatment and reduced the polyp burden in ApcMin/+ mice. Additionally, PCP treatment eased the cytotoxic effects of 5-FU by reducing the expressions of pro-inflammatory cytokines, increasing the anti-inflammatory cytokines; and significantly improving the gut barriers by enhancing the tight junction proteins and associated adhesion molecules. Furthermore, 16S rRNA gene sequencing data showed that PCP alone or with 5-FU could stimulate the growth of probiotic bacteria (Bacteroides acidifaciens, Bacteroides intestinihominis, Butyricicoccus pullicaecorum, and the genera Lactobacillus, Bifidobacterium, Eubacterium). At the same time, it inhibited the growth of potential pathogens (e.g., Alistipes finegoldii, Alistipes massiliensis, Alistipes putredinis., Citrobacter spp., Desulfovibrio spp., and Desulfovibrio desulfuricans). Moreover, the results showed that transplantation of L.johnsonii and B.animalis effectively reduced the polyp burden in ApcMin/+ mice being treated with 5-FU. CONCLUSION: Our study showed that PCP could effectively improve the anti-cancer effect of 5-FU by attenuating its side effects, modulating intestinal inflammation, improving the gut epithelial barrier, and modulating the gut microbiota of ApcMin/+ mice.

Clinical application of LASEREO endoscopic system in early gastric cancer / 中华内科杂志

Objective:To evaluate the clinical application of LASEREO endoscopic system in early gastric cancer (EGC).Methods:A total of 68 patients diagnosed with EGC were retrospectively analyzed between August 2017 to December 2020 in Fuding Hospital Affiliated to Fujian University of Traditional Chinese Medicine. There were 50 males and 18 females finally enrolled with a median age of 64 years. EGCs were analyzed from subjective and objective aspect, as well as from magnification and non-magnification status. Six endoscopists evaluated the visibility of the EGC (RSC) and calculated the color difference (ΔEC) between EGC and the surrounding mucosa in white light imaging (WLI), blue light imaging-bright (BLI-Bri) and linked color imaging (LCI) modes. In the case of magnification (×80), the visibility of the microstructures and microvessels (RSV) was analyzed and the color difference (ΔEV) between microvessels and non-vessels areas were calculated in WLI, BLI and LCI modes. The visibility was evaluated using visibility ranking scale(RS) and the color difference (ΔE) was calculated using L*a*b* color space.Results:In WLI, BLI-Bri, and LCI modes, the mean (±SD) RSC were 2.56±0.68, 2.63±0.59 and 3.17±0.50, and the mean(±SD) ΔEC were 15.71±5.58, 12.04±3.73, and 22.84±8.46, respectively, which in LCI were higher than those in WLI and BLI-Bri modes ( P<0.001).Regarding the data evaluated by senior endoscopists, the RSC was higher in BLI-Bri than that in WLI mode (2.98±0.58 vs. 2.79±0.73, P<0.001), but as to those evaluated by junior endoscopists, there were no significant differences between the WLI and BLI-Bri modes(2.29±0.72 vs. 2.23±0.72,P =0.218).In magnifying endoscopy with WLI, BLI, and LCI modes, the mean(±SD) RSV were 2.95±0.28, 3.46±0.40, and 3.38±0.33, and the mean (±SD) ΔEV were 21.68±7.52, 44.29±10.94, and 45.38±14.29, respectively.The RSV and ΔEV in LCI and BLI were higher than that in WLI mode ( P<0.001). Conclusions:LCI improves the visibility of EGC by increasing ΔEC, especially in junior endoscopists. Both BLI and LCI improve the visibility of microstructures and microvessels under magnification.

Diagnostic value of blue light imaging-bright and linked color imaging for early esophageal cancer / 中华消化内镜杂志

Objective To investigate the diagnostic value of blue light imaging-bright (BLI-bright) and linked color imaging (LCI) for early esophageal cancer (EEC).Methods:Data of 63 consecutive patients with EEC who underwent gastroscopy under BLI-bright, LCI and white-light imaging (WLI) and endoscopic submucosal dissection (ESD) from May 2018 to August 2020 at Fuding Hospital Affiliated to Fujian University of Traditional Chinese Medicine were analyzed retrospectively in the cohort study. Subjective visibility analysis was performed by 6 endoscopists who were divided into 2 groups (expert group and trainee group) with 3 endoscopists in each group. The main observation index was the visibility score (ranking score, RS). The objective color difference (Δ E) between lesions of EEC and surrounding mucosa under 3 modes were analyzed by using the L *a *b * color space. Results:The overall RS of 6 endoscopists under WLI mode (2.57±0.81) was significantly lower than that under LCI (3.25±0.67) ( t=9.71, P<0.001) and BLI-bright (3.18±0.67) ( t=9.31, P<0.001). In the expert group, the RS of WLI (2.71±0.80) was significantly lower than that of LCI (3.33±0.66) ( t=7.16, P<0.001) and BLI-bright (3.42±0.62) ( t=8.09, P<0.001). In the trainee group, the RS of WLI (2.40±0.90) was also significantly lower than that of LCI (3.15±0.83) ( t=9.62, P<0.001) and BLI-bright (2.89±0.92) ( t=5.69, P<0.001), and the RS of LCI was higher than that of BLI-bright ( t=4.07, P<0.001). The Δ E between lesions of EEC and surrounding mucosa under WLI (11.52±3.40) was significantly lower than that under LCI (16.64±4.70) ( t=7.10, P<0.001) and BLI-bright (15.72±3.84) ( t=7.88, P<0.001). Conclusion:BLI-bright and LCI can effectively improve EEC visibility and color difference between EEC and surrounding mucosa. Furthermore, LCI is more conducive to the detection of EEC for the trainees.

Nanoparticles composed of the tea polysaccharide-complexed cationic vitamin B12-conjugated glycogen derivative.

Tea polysaccharides exhibit multiple important bioactivities, but very few of them can be absorbed through the small intestine. To enhance the absorption efficacy of tea polysaccharides, a cationic vitamin B12-conjugated glycogen derivative bearing the diethylenetriamine residues (VB12-DETA-Gly) was synthesized and characterized using FTIR, 1H NMR, and UV-vis spectroscopy. An acidic tea polysaccharide (TPSA) was isolated from green tea. The TPSA/VB12-DETA-Gly complexed nanoparticles were prepared, which showed positive zeta potentials and were irregular spherical nanoparticles in the sizes of 50-100 nm. To enable the fluorescence and UV-vis absorption properties of TPSA, a Congo red residue-conjugated TPSA derivative (CR-TPSA) was synthesized. The interactions and complexation mechanism between the CR-TPSA and the VB12-DETA-Gly derivatives were investigated using fluorescence spectroscopy, resonance light scattering spectroscopy, and UV-vis spectroscopy. The results indicated that the electrostatic interaction could play a major role during the CR-TPSA and VB12-DETA-Gly-II complexation processes. The TPSA/VB12-DETA-Gly nanoparticles were nontoxic and exhibited targeted endocytosis for the Caco-2 cells, and showed high permeation through intestinal enterocytes using the Caco-2 cell model. Therefore, they exhibit potential for enhancing the absorption efficacy of tea polysaccharides through the small intestinal mucosa.

Efficacy and safety of moxibustion in the treatment of infertility with polycystic ovary syndrome: A protocol of systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the common diseases of reproductive endocrine metabolism in gynecology, and it is also a common and difficult disease affecting female reproductive endocrine health. PCOS characterized by insulin resistance and hyperandrogenemia, the clinical manifestations are polychaemia, acne, obesity, infertility, menstrual disorders and so on. Clinical treatment of patients with PCOS ovulatory dysfunction infertility is mainly treated with ovulation-promoting drugs, insulin sensitizer, hyperandrogenemia drugs and other drugs Healing. It is found that the sensitivity of patients to ovulation promotion is poor, and it is often necessary to increase the dosage of drugs to increase ovulation rate, thus increasing the risk of ovarian hyperstimulation syndrome, and the recurrence rate is higher after withdrawal. Moxibustion therapy has shown strong advantages in the treatment of PCOS, and the curative effect is accurate. Therefore, this paper will carry out a systematic evaluation and meta-analysis of the efficacy and safety of moxibustion therapy in the treatment of PCOS. METHODS: We will search 8 electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang Database (WF), and Chinese Biomedical Literature Database (CBM). We will search above electronic databases from the beginning to January 2021, without any language restriction. Ovulation rate and pregnancy rate will be accepted as the primary outcomes. The changes of Sex hormone levels, including Luteinizing hormone, follicle-stimulating hormone, serum estradiol, total testosterone will be used as secondary outcomes. RevMan 5.3 software will be used for statistical analysis. The result about the curative effect and safety of moxibustion therapy for PCOS will be presented as risk ratio for dichotomous data and mean differences with a 95% confidence interval for continuous data. RESULTS: Only when we finish this meta-analysis can we get the result. CONCLUSIONS: The results of this study will provide reliable evidence for the efficacy and safety of moxibustion therapy in the treatment of PCOS.

Vitamin C supplementation is necessary for patients with coronavirus disease: An ultra-high-performance liquid chromatography-tandem mass spectrometry finding.

To administer vitamin C (VC) with precision to patients with the coronavirus disease (COVID-19), we developed an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to assess plasma VC concentrations. 31 patients with COVID-19 and 51 healthy volunteers were enrolled. VC stability was evaluated in blood, plasma, and precipitant-containing stabilizers. A proportion of 7.7 % of VC was degraded in blood at room temperature (RT) (approximately 20-25 °C) at 1.5 h post administration with respect to the proportion degraded at 0.5 h, but without statistical difference. VC was stable in plasma for 0.75 h at RT, 2 h at 4 °C, 5 days at -40 °C, and 4 h in precipitant-containing stabilizer (2 % oxalic acid) at RT. The mean plasma concentration of VC in patients with COVID-19 was 2.00 mg/L (0.5-4.90) (n = 8), which was almost 5-fold lower than that in healthy volunteers (9.23 mg/L (3.09. 35.30)) (n = 51). After high-dose VC treatment, the mean VC concentration increased to 13.46 mg/L (3.93. 34.70) (n = 36), higher than that in healthy volunteers, and was within the normal range (6-20 mg/L). In summary, we developed a simple UPLC-MS/MS method to quantify VC in plasma, and determined the duration for which the sample remained stable. VC levels in patients with COVID-19 were considerably low, and supplementation at 100 mg/kg/day is considered highly essential.

Puerarin ameliorates skeletal muscle wasting and fiber type transformation in STZ-induced type 1 diabetic rats.

Puerarin is an isoflavonoid extracted from Pueraria lobate with extensive pharmacological effects in traditional Chinese medicine. The evidence implicates that puerarin mitigates hyperglycemia and various relevant complications. Here, the effect of puerarin on skeletal muscle wasting induced by type 1 diabetes (T1D) was explored. Streptozotocin (STZ)-induced T1D male Sprague Dawley (SD) rats were used in this study. Muscle strength, weight and size were measured. L6 rat skeletal muscle cells were applied for in vitro study. Our results showed that eight-week oral puerarin administration (100 mg/kg) increased muscle strengths and weights accompanied by enhanced skeletal muscle cross-sectional areas in diabetic rats. Simultaneously, puerarin also reduced expressions of several muscle wasting marker genes including F-box only protein 32 (Atrogin-1) and muscle-specific RING-finger 1 (Murf-1) in diabetic group both in vitro and in vivo. Transformation from type I fibers (slow muscle) to type II fibers (fast muscle) were also observed under puerarin administration in diabetic rats. Puerarin promoted Akt/mTOR while inhibited LC3/p62 signaling pathway in skeletal muscle cells. In conclusion, our study showed that puerarin mitigated skeletal muscle wasting in T1D rats and closely related with Akt/mTOR activation and autophagy inhibition. Whether this effect in murine applies to humans remains to be determined.

Corrigendum to "Lycium Berry Polysaccharides Strengthen Gut Microenvironment and Modulate Gut Microbiota of the Mice".

[This corrects the article DOI: 10.1155/2020/8097021.].

Chain conformation of an acidic polysaccharide from green tea and related mechanism of α-amylase inhibitory activity.

An acidic tea polysaccharide (TPSA) isolated from green tea was fractionated using a precipitation-fractionation method into seven fractions with different molecular weights. TPSA was characterized as a hyperbranched polysaccharide with a globular homogeneous conformation by analysis of solution parameters of each fraction using static light scattering and viscosity analyses. Observation by transmission electron microscopy confirmed that TPSA occurred as globular homogeneous particles with size in the range of 20-40 nm. To simulate the branched chain segments of TPSA, four model molecules were designed based on chemical structure of TPSA. Molecular docking analysis indicated that the branched chain segments of TPSA similar to the TPSA-4 model molecule showed preferential binding to α-amylase to form the TPSA/α-amylase complex through hydrogen bonding interactions. Circular dichroism spectroscopy showed that the structure of α-amylase was not significantly affected by TPSA. The mechanism of α-amylase inhibitory activity of TPSA was simulated by molecular docking analysis. The branched chain segments of TPSA similar to the TPSA-4 model molecule likely act as a potential competitor to the starch substrate to inhibit the activity of α-amylase.

Transcription factor YY1 inhibits the expression of THY1 to promote interstitial pulmonary fibrosis by activating the HSF1/miR-214 axis.

Interstitial pulmonary fibrosis (IPF) is a progressive disease of diverse etiology manifesting with proliferation of lung fibroblasts and accumulation of extracellular matrix deposition in pulmonary interstitium. Recent studies show aberrant expression of mRNAs and microRNAs (miRNAs) in human embryonic pulmonary fibroblasts (HEPFs). In this study, we investigated effects of the YY1/HSF1/miR-214/THY1 axis on the functions of HEPFs and IPF. Loss- and gain-of-function tests were conducted to identify roles of YY1, HSF1, miR-214, and THY1 in IPF. As determined by RT-qPCR or western blot assay, silencing YY1 down-regulated HSF1 expression and attenuated the expression of pro-proliferative and fibrosis markers in HEPFs. Meanwhile, viability of HEPFs was impeded by YY1 knockdown. The binding relationship between miR-214 and THY1 was verified using dual-luciferase reporter assay. In HEPFs, down-regulation of HSF1 reduced miR-214 expression to repress proliferation and fibrogenic transformation of HEPFs, while inhibition of miR-214 expression could restrain the fibrogenic transformation property of HEPFs by up-regulating THY1. Subsequently, IPF model in mice was induced by bleomycin treatment. These animal experiments validated the protective effects of YY1 knockdown against IPF-induced lung pathological manifestations, which could be reversed by THY1 knockdown. Our study demonstrates the important involvement of YY1/HSF1/miR-214/THY1 axis in the development of IPF.

A neutral polysaccharide from green tea: Structure, effect on α-amylase activity and hydrolysis property.

A neutral tea polysaccharide (TPSN) was isolated from green tea. Gas chromatography analysis showed that TPSN was composed of d-glucose, l-arabinose and d-galactose residues at a molar ratio of 90.0: 9.1: 0.9. The weight-averaged molecular weight of TPSN was determined as about 2.0 × 105 g mol-1 using static light scattering analysis. The result of nuclear magnetic resonance (NMR) spectroscopy indicated that TPSN and water-soluble starch had similar structures. TPSN exhibited inhibitory activity towards α-amylase through the noncompetitive inhibition mechanism, but the tertiary structure of α-amylase related to enzymatic activity, analyzed using circular dichroism spectroscopy, was not affected by TPSN. Meanwhile, TPSN exhibited hydrolysis properties catalyzed by α-amylase. Molecular docking analysis revealed that the various behaviors of TPSN to α-amylase could be attributed to that the different chain segments of TPSN combined with different amino acid residues of α-amylase.

An Efficient Strategy for Enhancement of Bioactive Compounds in the Fruit Body of Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycetes), by Spraying Biotic Elicitors.

Cordyceps militaris is a mushroom species with high nutritive and medicinal values based on diverse bioactive metabolites. The contents of bioactive ingredients are indicative of the quality of commercially available fruit body of this fungus. Although the application of biotic elicitors has been an efficient strategy to induce the accumulation of valuable bioactive compounds in vivo, related research in C. militaris is rarely reported. In this study, five biotic elicitors in different concentrations (0.05, 0.5, 1, and 2 mg/mL), including chitosan (CHT), 2,4-dichlorophenoxyacetic acid (2,4-D), methyl jasmonate (MeJA), gibberellic acid (GA), and triacontanol (TRIA), were first introduced to enhance the production of 10 kinds of major bioactive components in the fruit body of C. militaris. Results showed that the effect of biotic elicitors on bioactive compounds in the fruit body of C. militaris was elicitor-specific and concentration-dependent. Overall, 1 mg/L CHT was considered the most favorable for the production of 10 bioactive ingredients in C. militaris fruit body, which could increase the content of protein, polysaccharides, polyphenol, triterpenoids, flavonoids, cordyceps acid, cordycepin, and anthocyanins by 20.38-, 1.41-, 0.7-, 0.47-, 11.90-, 1.09-, 0.34-, and 2.64-fold, respectively, compared with the control. The results of this study would provide an efficient strategy for the production of a superior quality fruit body of and contribute to further elucidation of the effects of biotic elicitors on metabolite accumulation in C. militaris.

Maternal periconceptional folic acid supplementation and its effects on the prevalence of fetal neural tube defects / 北京大学学报(医学版)

OBJECTIVE@#To find out the status of folic acid supplementation among women, to evaluate the prevention effects on neural tube defects (NTDs), and to explore the factors impact on folic acid supplementation compliance.@*METHODS@#Based on the routine data of 92 121 women in prenatal health care and birth defect surveillance system in Tongzhou District of Beijing from 2013 to 2018, we described the prevalence of periconceptional folic acid supplementation, pre-pregnancy folic acid supplementation and regularly folic acid supplementation (compliance supplementation). Trend χ2 tests were used to evaluate the change of folic acid supplementation prevalence. The prevalence difference among the women with folic acid supplementation and without supplementation were tested with Fisher's exact test. Factors asso-ciated with folic acid supplementation compliance rate were analyzed with univariate and multivariate Logistic regression model.@*RESULTS@#The prevalence of periconceptional folic acid supplementation during the six years was 90.08% and it was increased from 2013 to 2018, but the rate of pre-pregnancy and regular supplementation was only 41.5% and declined from 2013 to 2018, especially 2013 to 2015. The prevalence of NTDs among the fetuses whose mothers took folic acid during periconceptional period was 5.5/10 000, while the prevalence for the fetuses whose mothers did not take folic acid was 19.7/10 000 (P < 0.001), the rates ratio was 27.9% (χ2=23.74, P < 0.001). The difference between the prevalence of NTDs among the fetuses whose mothers took folic acid only and multiple micronutrients was not statistically significant. After controlling the confounding factors, it was found that the compliant folic acid supplementation rates in women, whose household registrations were outside Beijing and whose education levels were junior high school or below, and who were younger than 25 years old, and who were multiparas and who were pre-pregnancy underweight or obese, were lower than those of the corresponding control groups (P < 0.05).@*CONCLUSION@#The rate of folic acid supplementation among women in Tongzhou District of Beijing was relatively high, but their compliance was poor. Women who did not take folic acid during periconception seriously affected the prevention effect of NTDs. We should focus on women who are younger than 25 years old, lower educated, pre-pregnancy underweight or obese, multiparas and nonlocal household registers, in order to improve the periconceptional folic acid supplementation compliance and improve the effects of NTDs prevention.

Use of Cryopreserved Hepatocytes as Part of an Integrated Strategy to Characterize In Vivo Clearance for Peptide-Antibody Conjugate Inhibitors of Nav1.7 in Preclinical Species.

The identification of nonopioid alternatives to treat chronic pain has received a great deal of interest in recent years. Recently, the engineering of a series of Nav1.7 inhibitory peptide-antibody conjugates has been reported, and herein, the preclinical efforts to identify novel approaches to characterize the pharmacokinetic properties of the peptide conjugates are described. A cryopreserved plated mouse hepatocyte assay was designed to measure the depletion of the peptide-antibody conjugates from the media, with a correlation being observed between percentage remaining in the media and in vivo clearance (Pearson r = -0.5525). Physicochemical (charge and hydrophobicity), receptor-binding [neonatal Fc receptor (FcRn)], and in vivo pharmacokinetic data were generated and compared with the results from our in vitro hepatocyte assay, which was hypothesized to encompass all of the aforementioned properties. Correlations were observed among hydrophobicity; FcRn binding; depletion rates from the hepatocyte assay; and ultimately, in vivo clearance. Subsequent studies identified potential roles for the low-density lipoprotein and mannose/galactose receptors in the association of the Nav1.7 peptide conjugates with mouse hepatocytes, although in vivo studies suggested that FcRn was still the primary receptor involved in determining the pharmacokinetics of the peptide conjugates. Ultimately, the use of the cryopreserved hepatocyte assay along with FcRn binding and hydrophobic interaction chromatography provided an efficient and integrated approach to rapidly triage molecules for advancement while reducing the number of in vivo pharmacokinetic studies. SIGNIFICANCE STATEMENT: Although multiple in vitro and in silico tools are available in small-molecule drug discovery, pharmacokinetic characterization of protein therapeutics is still highly dependent upon the use of in vivo studies in preclinical species. The current work demonstrates the combined use of cryopreserved hepatocytes, hydrophobic interaction chromatography, and neonatal Fc receptor binding to characterize a series of Nav1.7 peptide-antibody conjugates prior to conducting in vivo studies, thus providing a means to rapidly evaluate novel protein therapeutic platforms while concomitantly reducing the number of in vivo studies conducted in preclinical species.

[Developing spectrum-toxicity relationship with rough set theory for hepatotoxicity material basis of Polygonum multiflorum].

Idiosyncratic hepatotoxicity of Polygonum multiflorum has attracted a great attention in the world. The most toxic part of idiosyncratic hepatotoxicity was screened by MTT assay and flow cytometry, which was the 50% ethanol elute by macroporous adsorptive resins from alcohol-extraction of P. multiflorum. The fingerprints were collected by HPLC from 50% ethanol elute of crude and processed P. multiflorum from different habitats, then 14 common peaks were determined. Spectrum-toxicity relationship was analyzed by rough set theory(RST). Two main chemical components were predicted for idiosyncratic hepatotoxicity, in which TSG was the greater contributor. Idiosyncratic hepatotoxicity of TSG was tested in vitro, and the results indicated that TSG was the most important constituent contributed to idiosyncratic hepatotoxicity of P. multiflorum. The study showed the discovery of the main chemical components for idiosyncratic hepatotoxicity, and RST was effective for analyzing the spectrum-toxicity relationship, which could be a new method used in the effective/toxic constituents field of traditional Chinese medicine.

Xiao-Xu-Ming decoction protects against chronic cerebral ischemia injury in rats and profile of differentially expression proteins analysis in hippocampus / 中国药理学与毒理学杂志

OBJECTIVE Vascular dementia (VD) refers to a progressive decline in memory and cognitive function caused by chronic cerebral ischemia. 2-Vessels occlusion (2-VO) has been widely used as a model of VD. Xiao-Xu-Ming decoction, a well-known traditional Chinese medicine prescrip-tion,has been widely used to treat stroke and sequelae of stroke.The present study was to investigate the mechanism of Xiao-Xu-Ming decoction(XXM) against chronic cerebral ischemia injury in rats. METHODS After XXM treatment, rats were performed a memory testing with Morris water maze and motor ability testing using prehensile test and inclined screen test.Neuronal plasticity was observed by immunofluorescent staining with MAP2 antibody. Differentially expressed proteins of rat hippocampus were analyzed by Label-free quantitative proteomics. RESULTS XXM significantly alleviated 2-VO-induced learning and memory deficits, motor ability dysfunction, and neuronal plasticity injury in rats. The mechanism might be involved in up-regulation of 39 proteins and down-regulation of 13 proteins in the hippocampus of rats after XXM treatment vs 2-VO group rats.Gene ontology and pathway analysis showed that the regulated proteins are mainly involved in oxidation reduction process, intracellular signaling cascade process, and protein catabolic process, etc. The signal pathways are mainly involved in ubiquitin mediated proteolysis and phosphatidylinositol signaling system. CONCLUSION Current findings provide new insights into the molecular mechanisms of XXM on chronic cerebral ischemia.