Maternal vitamin B1 is a determinant for the fate of primordial follicle formation in offspring.

The mediation of maternal-embryonic cross-talk via nutrition and metabolism impacts greatly on offspring health. However, the underlying key interfaces remain elusive. Here, we determined that maternal high-fat diet during pregnancy in mice impaired preservation of the ovarian primordial follicle pool in female offspring, which was concomitant with mitochondrial dysfunction of germ cells. Furthermore, this occurred through a reduction in maternal gut microbiota-related vitamin B1 while the defects were restored via vitamin B1 supplementation. Intriguingly, vitamin B1 promoted acetyl-CoA metabolism in offspring ovaries, contributing to histone acetylation and chromatin accessibility at the promoters of cell cycle-related genes, enhancement of mitochondrial function, and improvement of granulosa cell proliferation. In humans, vitamin B1 is downregulated in the serum of women with gestational diabetes mellitus. In this work, these findings uncover the role of the non-gamete transmission of maternal high-fat diet in influencing offspring oogenic fate. Vitamin B1 could be a promising therapeutic approach for protecting offspring health.

Differential synthetic illumination based on multi-line detection for resolution and contrast enhancement of line confocal microscopy.

Line confocal (LC) microscopy is a fast 3D imaging technique, but its asymmetric detection slit limits resolution and optical sectioning. To address this, we propose the differential synthetic illumination (DSI) method based on multi-line detection to enhance the spatial resolution and optical sectioning capability of the LC system. The DSI method allows the imaging process to simultaneously accomplish on a single camera, which ensures the rapidity and stability of the imaging process. DSI-LC improves X- and Z-axis resolution by 1.28 and 1.26 times, respectively, and optical sectioning by 2.6 times compared to LC. Furthermore, the spatially resolved power and contrast are also demonstrated by imaging pollen, microtubule, and the fiber of the GFP fluorescence-labeled mouse brain. Finally, Video-rate imaging of zebrafish larval heart beating in a 665.6 × 332.8 µm2 field-of-view is achieved. DSI-LC provides a promising approach for 3D large-scale and functional imaging in vivo with improved resolution, contrast, and robustness.

Effects of Different Concentrations of Ropivacaine Lumbar Plexus-Sciatic Nerve Block on Recovery from Anesthesia, Postoperative Pain and Cognitive Function in Elderly Patients with Femoral Neck Fracture.

Objective: To investigate the effects of lumbar plexus-sciatic nerve block with different concentrations of ropivacaine on recovery from anesthesia, postoperative pain, and cognitive function in elderly patients with femoral neck fracture. Method: A total of 110 elderly patients with femoral neck fractures who were treated in our hospital from January 2020 to January 2022 were selected as the research objects. According to the concentration of ropivacaine, they were divided into low-, medium-, and high-concentration groups (concentrations of ropivacaine were 0.15%, 0.25%, and 0.40%, respectively), with 36, 37, and 37 cases, respectively. Extubation time, anesthesia recovery time, and hospitalization time were recorded. Cognitive symptoms were assessed by the spatial cognitive ability, working memory ability, simple computing ability, and picture recognition ability test. The pain degree of patients was assessed by visual analogue scale (VAS). The occurrence of adverse reactions in patients was recorded. Result: There was no significant difference in extubation time, anesthesia recovery time, and hospitalization time among the three groups (P > 0.05). The PCA time of the patients in the high-concentration group was significantly longer than that in the low- and medium-concentration groups. The dosage of sufentanil within 24 hours and total sufentanil in the high-concentration group were significantly lower than those in the low- and medium-concentration groups, and the dosage of sufentanil within 24 hours and total sufentanil in the medium-concentration group was significantly less than that in the low-concentration group (P < 0.05). The cognitive function score for each entry of the three groups 1 d after surgery was lower than that before surgery (P < 0.05); On the 1 day after operation, the cognitive function score for each entry of the patients in the low-concentration group was significantly higher than that in the middle- and high-concentration groups, and the cognitive function score for each entry in the middle-concentration group was significantly higher than that in the high-concentration group (P < 0.05). There was no significant difference in VAS scores between the three groups at 2 h and 8 h after surgery (P > 0.05); 16 h and 24 h after operation, the VAS score of patients in the high-concentration group was significantly lower than that in the low- and medium-concentration groups, and the VAS score in the medium-concentration group was significantly lower than that in the low-concentration ropivacaine group (P < 0.05). The incidence of adverse reactions in the high-concentration ropivacaine group was significantly higher than that in the low- and medium-concentration groups (P < 0.05). Conclusion: The middle concentration of ropivacaine has good analgesic and nerve block effects and has less influence on cognitive function and less adverse reactions in elderly patients.

A machine-learning approach for predicting the effect of carnitine supplementation on body weight in patients with polycystic ovary syndrome.

The present study aimed to explore the effect of carnitine supplementation on body weight in patients with polycystic ovary syndrome (PCOS) and predict an appropriate dosage schedule using a machine-learning approach. Data were obtained from literature mining and the rates of body weight change from the initial values were selected as the therapeutic index. The maximal effect (Emax) model was built up as the machine-learning model. A total of 242 patients with PCOS were included for analysis. In the machine-learning model, the Emax of carnitine supplementation on body weight was -3.92%, the ET50 was 3.6 weeks, and the treatment times to realize 25%, 50%, 75%, and 80% (plateau) Emax of carnitine supplementation on body weight were 1.2, 3.6, 10.8, and 14.4 weeks, respectively. In addition, no significant relationship of dose-response was found in the dosage range of carnitine supplementation used in the present study, indicating the lower limit of carnitine supplementation dosage, 250 mg/day, could be used as a suitable dosage. The present study first explored the effect of carnitine supplementation on body weight in patients with PCOS, and in order to realize the optimal therapeutic effect, carnitine supplementation needs 250 mg/day for at least 14.4 weeks.

Anemone chinensis Bunge aqueous enema alleviates dextran sulfate sodium-induced colitis via inhibition of inflammation and regulation of the colonic mucosal microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Although the incidence of ulcerative colitis (UC) increases every year, there is still a lack of satisfactory treatment options. Anemone chinensis Bunge (AB), a traditional Chinese herb, is a potent compound that can be prepared as a decoction, and then administered as an enema to relieve UC symptoms. However, the therapeutic effect and mechanisms of aqueous AB on UC are still unknown. AIM OF THE STUDY: This study investigates the potential therapeutic value and mechanism of AB aqueous enema for UC. MATERIALS AND METHODS: First, the practical components in aqueous AB were extracted and identified by UPLC-MS/MS. Second, the potential active targets and target genes related to UC were predicted, mapped, and analyzed by network pharmacology. Then, the effects of AB aqueous enema on UC were assessed using the dextran sulfate sodium (DSS)-induced colitis model with mice. Finally, the level of inflammation, the expression level of proteins associated with the colonic mucosal barrier, and the microbiota associated with the intestinal mucosal were investigated. RESULTS: Fourteen active ingredients in AB were identified. The network pharmacology-based analysis demonstrated that the active ingredients possibly affected ten key targets, such as IL-6, TNF, and PTGS2. They are also related to the tight junction proteins ZO-1, occludin, and claudin-1. Furthermore, mice treated with DSS developed severe mucosal colitis. AB aqueous enema decreased the disease activity index (DAI), significantly inhibited colonic damage, and greatly decreased colon length shortening (p < 0.05). AB also significantly restored tight junction proteins and the associated mucin proteins mucin-2 (MUC2) and mucin-3A (MUC3A). In addition, the diversity of the gut microbiota after administration of DSS was significantly decreased. However, the diversity was entirely restored after AB treatment. Recovery of the abundance of colonic mucosal bacteria, especially Lactobacillus reuteri and Lactobacillus gasseri, occurred at the species level after AB treatment. In vitro, AB can be utilized by the two bacteria, especially under glucose deficiency. CONCLUSIONS: Our study demonstrated that the AB aqueous enema alleviated colitis by restoring intestinal barrier proteins and regulating the gut microbiota.

Theaflavic acid from black tea protects PC12 cells against ROS-mediated mitochondrial apoptosis induced by OGD/R via activating Nrf2/ARE signaling pathway.

Cerebral ischemic stroke is a severe disease afflicting people worldwide. Phytochemicals play a pivotal role in the discovery of novel therapeutic approaches for the prevention of ischemic stroke. In our continual search for bioactive natural products for the treatment of ischemic stroke, we have evaluated the protective effects of theaflavic acid (TFA) from black tea using PC12 cells injured by oxygen and glucose deprivation/restoration (OGD/R), and investigated the possible mechanisms. The results showed that TFA can protect PC12 cells against OGD/R through increasing cell viability and decreasing intracellular lactate dehydrogenase (LDH) release. Further investigations found that TFA could inhibit the overproduction of intracellular reactive oxygen species (ROS), reduce malondialdehyde content, and elevate superoxide dismutase activity, which implied that TFA suppresses oxidative stress in PC12 cells induced by OGD/R. In addition, overload of intracellular calcium and collapse of the mitochondrial membrane potential were improved in the presence of TFA, and the activity of caspase-3 was significantly reduced by TFA. Western blot analysis showed that the expression of Bcl-2 was up-regulated while Bax was down-regulated. Therefore, it can be concluded that TFA can inhibit mitochondria-dependent apoptosis of PC12 cells induced by OGD/R. In addition, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathway was explored to elucidate the mechanism by which TFA inhibits ROS-mediated apoptosis in PC12 cells. The results revealed that TFA promoted the translocation of Nrf2 into nuclei, enhanced the transcriptional activity of ARE, and up-regulated expression of downstream HO-1, which indicates that the Nrf2/ARE signaling pathway is involved in the protection by TFA of PC12 cells injured by OGD/R.

ASSOCIATION BETWEEN ORAL IRON SUPPLEMENTATION AND RETINAL OR SUBRETINAL HEMORRHAGE IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENT TRIALS.

PURPOSE: Because patients often take iron supplements without medical indication, and iron can accumulate in vascular endothelial cells, the authors evaluated the association of oral iron supplementation with retinal/subretinal hemorrhage in patients with neovascular age-related macular degeneration. METHODS: A post hoc secondary data analysis of comparison of age-related macular degeneration treatments trials was performed. Participants were interviewed for use of oral iron supplements. Trained readers evaluated retinal/subretinal hemorrhage in baseline fundus photographs. Adjusted odds ratios from multivariate logistic regression models assessed the association between iron use and baseline hemorrhage adjusted by age, sex, smoking, hypertension, anemia, and use of antiplatelet/anticoagulant drugs. RESULTS: Among 1,165 participants, baseline retinal/subretinal hemorrhage was present in the study eye in 71% of 181 iron users and in 61% of 984 participants without iron use (adjusted odds ratio = 1.47, P = 0.04), and the association was dose dependent (adjusted linear trend P = 0.048). Iron use was associated with hemorrhage in participants with hypertension (adjusted odds ratio = 1.87, P = 0.006) but not without hypertension. The association of iron use with hemorrhage remained significant among hypertensive participants without anemia (adjusted odds ratio = 1.85, P = 0.02). CONCLUSION: Among participants of comparison of age-related macular degeneration treatments trials, the use of oral iron supplements was associated with retinal/subretinal hemorrhage in a dose-response manner. Unindicated iron supplementation may be detrimental in patients with wet age-related macular degeneration.

Combined use of probucol and cilostazol with atorvastatin attenuates atherosclerosis in moderately hypercholesterolemic rabbits.

BACKGROUND: Atherosclerotic cardiovascular disease is one of the major diseases that seriously impacts human health. Combined drug therapy may be efficacious in delaying the occurrence of cardiovascular events. AIM: The current study was designed to investigate whether combined use of probucol (an anti-oxidant agent) with cilostazol (a platelet aggregation inhibitor) would increase the inhibitory effect of statins (a lipid-lowering agent) on atherosclerosis in moderately hypercholesterolemic rabbits. METHODS AND RESULTS: Thirty Japanese white rabbits were fed with a high cholesterol diet for 12 weeks, which was supplemented with either 0.005% atorvastatin alone or 0.005% atorvastatin plus 0.3% probucol and 0.3% cilostazol. Except for high-density lipoprotein cholesterol, no difference was found in plasma lipids among vehicle, statin, and the combined treatment group. However, atherosclerotic lesions were significantly reduced by statin treatment compared with vehicle. Moreover, we found that the anti-atherogenic effect of statin was further enhanced by the combined treatment, which was due to increased anti-inflammatory and anti-oxidant properties. CONCLUSIONS: These data demonstrated that combined drug treatment exhibits potent athero-protective effects via pleiotropic functions, such as anti-inflammatory and anti-oxidative stress, which is independent of the lipid-lowering effect.

Demonstration of an add-on effect of probucol and cilostazol on the statin-induced anti-atherogenic effects.

Statins are often prescribed for treatment of cardiovascular diseases, although there are still many patients who cannot be effectively treated by statins alone. Both probucol and cilostazol exhibit anti-atherogenic effects. In the current study, we attempted to investigate whether a probucol and cilostazol combination had any add-on effects on atorvastatin. To examine this hypothesis, we fed Japanese white rabbits with a cholesterol-rich diet supplemented with atorvastatin alone (Statin group), probucol and cilostazol (PC group), atorvastatin, probucol and cilostazol (APC group), and compared their effects on plasma lipids and aortic atherosclerosis. All three drug-treated groups had lowered total cholesterol levels compared with the vehicle group but high-density lipoproteins cholesterol levels of the atorvastatin group were higher than other groups. Although aortic atherosclerosis was significantly reduced in all drug-treated groups, the most prominent atheroprotective effect was seen in APC group (APC: 67% reduction> PC: 43% reduction> Statin group: 42% reduction over the vehicle). Morphometric analysis revealed that the reduced aortic atherosclerosis in all three groups was mainly attributed to the reduction of intimal macrophages and smooth muscle cells. These results suggest that a combination of probucol and cilostazol with statin enhances statin's anti-atherogenic functions, which may be beneficial for those patients who are less responsive to statin therapy alone.

Effectiveness of Chinese herbal medicine as an adjunctive treatment for dilated cardiomyopathy in patients with heart failure.

OBJECTIVES: To evaluate the effectiveness and safety of Chinese herbal medicine (CHM) as an adjunctive treatment for patients with dilated cardiomyopathy (DCM) and heart failure. DESIGN: Studies on biomedical treatment plus CHM versus biomedical treatment alone in treating patients with DCM and heart failure were retrieved from PubMed and other major databases (1980-2011). Meta-analysis was performed on the overall effects on effective rate, left ventricular ejection fraction, left ventricular diastolic end diameter, and other outcome measures. RESULTS: Twenty-seven studies with 1887 patients were included. Compared with biomedical treatment alone, biomedical treatment plus CHM showed significant improvement in effective rate (relative risk, 1.26; 95% confidence interval [CI], 1.19-1.34), left ventricular ejection fraction (%) (mean difference, 5.88; 95% CI, 3.92-7.85), left ventricular diastolic end diameter (mm) (mean difference, -2.78; 95% CI, -5.15 to -0.42), and other outcome measures. Most adverse events observed in the studies were not severe and resolved without special treatment. CONCLUSIONS: This meta-analysis indicated that biomedical treatment plus CHM is more effective than biomedical treatment alone in treating patients with DCM and heart failure. However, further studies with long-term follow-up, systemic adverse events evaluation, and other ethnic groups are still required to verify the efficacy and safety of CHM as an adjunctive treatment in all patients with DCM and heart failure.

Interferon plus Chinese herbs are associated with higher sustained virological response than interferon alone in chronic Hepatitis C: a meta-analysis of randomised trials.

BACKGROUND/AIMS: Traditional Chinese herbal therapies are widely used for the treatment of chronic hepatitis C (CHC) in Asia. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCTs) comparing interferon therapies with Chinese herbal therapies and/or interferon plus Chinese herb therapies for the treatment of CHC. METHODS: The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang Database and China Biomedical Database were searched to identify RCTs that evaluated the virological response to interferon therapies, Chinese herbal therapies and interferon plus Chinese herb therapies in CHC patients. We statistically combined data using a random-effect meta-analysis according to the intention-to-treat principle. RESULTS: The literature search yielded 770 studies, and 26 RCTs comprising 1905 patients matched the selection criteria. Overall, the sustained virological response (SVR) was significantly higher in patients treated with interferon plus Chinese herbs than in patients treated with interferon alone (49% vs 33%, relative risk, 1.52; 95% confidence interval: 1.23-1.89; p<0.05). Combined therapies of interferon plus Chinese herb therapies were also superior to interferon therapies alone in achieving the end-of-treatment viral response (ETVR), and resulted in fewer relapses, fewer adverse events and more rapid alanine transaminase normalisation. Interferon therapies achieved higher ETVR than Chinese herbal therapies, but they yielded a similar SVR. CONCLUSIONS: The current evidence suggests that combined therapies of interferon plus Chinese herbs yielded a higher SVR, and resulted in fewer relapses and fewer adverse events than interferon therapies.

[Meta analysis on acupuncture treatment of aphasia].

OBJECTIVE: To evaluate the therapeutic effect of acupuncture for the aphasia. METHODS: The publications of acupuncture for the treatment of aphasia are comprehensively searched from relevant domestic medical literature databases, China National Knowledge Infrastructure and Chinese BioMedical Literature Database. Meta analysis was conducted by using the publications. RESULTS: Twenty six trials of 338 matched the selection criteria and their data were suitable for Meta analysis. The total aphasia patients were 1749. The total odds ratio (OR) of the improvement with acupuncture plus language training and drugs compared with language training plus drug intervention was 3.66 (95% confidence interval, 2.81, 4.76), and the funnel plot was approximately symmetry. It is indicated that the curative effect of the acupuncture group is better than that of the control group (Z = 9.60, P < 0.001). CONCLUSION: The effect of acupuncture with language training plus drugs for the treatment of aphasia is better than that of language training plus drugs only.

Application of beta-(2-chloroaroyl)thioacetanilide in synthesis(III): an efficient three-component synthesis of thiochromeno[2,3-b]pyridines catalyzed by KF/neutral Al2O3 co-operated with PEG 6000 under microwave irradiation.

A series of new functionalized thiochromeno[2,3-b]pyridine derivatives have been synthesized via a sequence of Knoevenagel condensation, Michael addition, cyclization, and intramolecular nucleophilic substitution, which is first catalyzed by KF/neutral Al(2)O(3) cooperated with PEG 6000 under microwave irradiation. Experimental results indicated that among the catalysts tested, KF/ neutral Al(2)O(3) with PEG 6000 exhibits the best catalytic activity, which leads to a substantial improvement in the overall yield and purity of the desired final products and significantly shorter reaction time.