A Correlation Analysis Between Adult Hepatic Fibrosis and Bone Mineral Density of the Lumbar Spine and Hip.

Context: Osteoporosis (OP) is a common complication for patients who have liver cirrhosis or cholestatic liver disease or who have received a liver transplantation. Osteoporotic fractures are serious clinical consequences of OP, and they often occur in the spine, hip, and wrist; have a high disability and mortality rate; cause a serious, social, medical burden; and threaten people's health. Objective: The study intended to explore the correlation between different degrees of liver fibrosis and bone mineral density (BMD) of the lumbar spine and hip as well as the factors influencing those differences. Design: The research team performed a retrospective observational study. Setting: The study took place at the First Affiliated Hospital of the Medical College at Ningbo University (Bund Courtyard) in Ningbo, China. Participants: Participants were 164 patients who had received two-dimensional shear wave elastography (2D-SWE) to measure liver stiffness and dual-energy X-ray absorptiometry (DEXA) to measure bone density at the First Affiliated Hospital of Ningbo University (Bund Courtyard) in Ningbo from May 2020 to April 2022. Groups: According to the liver-stiffness value, the research team divided participants into three groups: (1) the F0-F1 group with no or mild liver fibrosis, (2) the F2 group with significant liver fibrosis, and (3) F3-F4 group with severe liver fibrosis. For the three groups, the research team also compared the differences between the groups-F0-F1 to F2, F0-F1 to F3-F4, and F2 to F3-F4-in the BMD of the lumbar spine-Total, L2, L3, L4-and of the hip-Total, Neck, and Troch. Outcome Measures: The research team: (1) determined participants' degrees of liver fibrosis to create the F0-F1, F2, and F3-F4 groups and compared the BMDs of the lumbar spine and hip among those groups; (2) compared the degrees of liver fibrosis for three age groups-<40, 40-60, and ≥60 years old; (3) compared the degrees of liver fibrosis for participants with two etiologies of the disease-hepatitis or other causes; and (4) analyzed the correlations between different degrees of liver fibrosis and BMD of the lumbar spine and hip and the factors influencing those relationships. Results: The study revealed significant differences among the F0-F1, F2, and F3-F4 groups in terms of age group, degree of liver fibrosis, and bone mineral density (BMD) at various sites. Specifically, there were significant age group differences between individuals aged 40-60 years and those aged ≥60 years (P < .05). There were also significant differences noted in the degree of liver fibrosis with mean values of 5.59 ± 0.81, 7.43 ± 0.26, and 15.48 ± 10.02 for the F0-F1, F2, and F3-F4 groups, respectively (P < .05). The BMDs of the lumbar spine (L2, L3, L4, and Total values) and hip (Total values, right femoral neck (Neck), and trochantor (Troch)) showed significant differences (all P < .05). However, no significant differences were found in the BMDs for the L1 vertebra and Ward's triangle among the groups (both P > .05). The analysis also revealed that the mean BMDs of the F2 group were significantly higher than those of the F0-F1 and F3-F4 groups. Furthermore, there was a positive correlation between the F2 and F0-F1 groups and a negative correlation between the F2 and F3-F4 groups (P < .05). The logistic regression analysis showed that age group (OR = 2.047, 95% CI: 0.135-1.298, P = .016) and Total BMD for the hip (OR = 176.368, 95% CI: 0.233-10.112, P = .040) were significantly, independently correlated with the degree of liver fibrosis. Conclusions: According to the findings of the present study, a positive correlation was observed between liver stiffness and bone mineral density (BMD) values in patients at the F0-F1 to F2 stage of liver fibrosis. In contrast, a significant negative correlation was identified between these parameters in patients at the F2 to F3-F4 stage, indicating that BMD tends to decrease as the degree of liver fibrosis increases. These results suggest a potential link between liver fibrosis and bone health. The comparisons between groups F0-F1 and F3-F4 with group F2. Specifically, the study found that the BMD values of the F2 group were significantly higher than those of the F0-F1 and F3-F4 groups.

Identification and analysis of differential miRNA-mRNA interactions in coronary heart disease: an experimental screening approach.

Objective: This aim of this study is to screen the differential molecules of kidney deficiency and blood stasis (KDBS) syndrome in coronary heart disease by high-throughput sequencing. In addition, the study aims to verify the alterations in the expression levels of miR-4685-3p and its regulated downstream, namely, C1QC, C4, and C5, using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA), and to determine whether the complement and coagulation cascade pathway is the specific pathogenic pathway. Methods: Patients diagnosed with unstable angina pectoris with KDBS syndrome, patients with non-kidney deficiency blood stasis (NKDBS) syndrome, and a Normal group were recruited. The clinical symptoms of each group were further analyzed. Illumina's NextSeq 2000 sequencing platform and FastQC software were used for RNA sequencing and quality control. DESeq software was used for differential gene expression (DGE) analysis. qPCR and ELISA verification were performed on DGE analysis. Results: The DGE profiles of 77 miRNA and 331 mRNA were selected. The GO enrichment analysis comprised 43 biological processes, 49 cell components, and 42 molecular functions. The KEGG enrichment results included 40 KEGG pathways. The PCR results showed that, compared with the Normal group, the miR-4685-3p levels decreased in the CHD_KDBS group (P = 0.001), and were found to be lower than those observed in the CHD_NKDBS group. The downstream mRNA C1 regulated by miR-4685-3p showed an increasing trend in the CHD_KDBS group, which was higher than that in the Normal group (P = 0.0019). The mRNA C4 and C5 in the CHD_KDBS group showed an upward trend, but the difference was not statistically significant. ELISA was utilized for the detection of proteins associated with the complement and coagulation cascade pathway. It was found that the expression level of C1 was significantly upregulated in the CHD_KDBS group compared with the Normal group (P < 0.0001), which was seen to be higher than that in the CHD_NKDBS group (P < 0.0001). The expression levels of C4 and C5 in the CHD_KDBS group were significantly lower than the Normal group, and were lower than that in the CHD_NKDBS group (P < 0.0001). Conclusion: The occurrence of CHD_KDBS might be related to the activation of the complement and coagulation cascade pathway, which is demonstrated by the observed decrease in miR-4685-3p and the subsequent upregulation of its downstream C1QC. In addition, the expression levels of complement C4 and C5 were found to be decreased, which provided a research basis for the prevention and treatment of this disease.

Hedyotis diffusa-Sculellaria barbata (HD-SB) suppresses the progression of colorectal cancer cells via the hsa_circ_0039933/hsa-miR-204-5p/wnt11 axis.

Our previous study confirmed that the combination of Hedyotis diffusa (HD) and Scutellaria barbata (SB) significantly inhibited colorectal cancer cell proliferation and the WNT signaling pathway. However, the exact molecular modulation remains unclear. In this study, colorectal cancer cells (SW620) were treated with 1 mg/mL HD-SB for 24 h, and high-throughput sequencing of circRNAs was performed. The level of hsa_circ_0039933 in three colorectal cancer cell lines (HT-29, SW620, and HCT116) was verified by qPCR. After transfection of hsa_circ_0039933 overexpression plasmids or small interfering RNAs, CCK8, apoptosis, cell migration, and cell invasion were utilized to evaluate the function of hsa_circ_0039933 in the progression of colorectal cancer cells. We identified hsa_circ_0039933, which was downregulated in HD-SB-induced colorectal cancer cells and positively related to colorectal cancer progression. In SW620 cells with relatively high expression of hsa_circ_0039933, interfering with the expression of hsa_circ_0039933 inhibited the proliferation, invasion, and migration of SW620 cells. In HCT116 cells with relatively low expression of hsa_circ_0039933, overexpression of hsa_circ_0039933 promoted the proliferation and invasion and migration ability of HCT116. Mechanistically, hsa_circ_0039933 targeted hsa-miR-204-5p to increase the expression of wnt11, leading to the activation of the Wnt pathway, thereby promoting the proliferation of colorectal cancer cells. This work revealed the potential molecular mechanism of HD-SB for the treatment of colorectal cancer, which was to inhibit the Wnt signaling pathway through the hsa_circ_0039933/hsa-miR-204-5p/wnt11 axis, then suppressing proliferation, migration, and invasion in the colorectal cancer cell.

Xihuang pill induces pyroptosis and inhibits progression of breast cancer cells via activating the cAMP/PKA signalling pathway.

Xihuang pill (XHP), a traditional Chinese medicine, has been shown to be effective for breast cancer (BC) therapy in clinical trials. However, the molecular mechanism of XHP in BC remains unclear. The molecular mechanism of XHP in BC was investigated in vivo by generating murine mammary carcinoma 4T1 cell xenografts. Enzyme-linked immunosorbent assay (ELISA) and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were used to detect pyroptosis-related indicators. Transcriptome sequencing was used to identify potential targets of XHP. Cell counting kit-8 (CCK-8), EdU, cell wound-healing, and transwell assays were performed to investigate the role of XHP in BC cells. Western blotting was performed to identify proteins related to the cAMP/PKA signalling pathway. XHP inhibited the growth of BC and induced pyroptosis. Western blotting confirmed the significant association between XHP and the cAMP/PKA signalling pathway revealed by Kyoto Encyclopedia of Genes and Genomes pathway analysis. XHP inhibited BC cell proliferation, migration, and invasion, and induced pyroptosis. Inhibiting the cAMP/PKA signalling pathway reversed the anti-cancer activity of XHP. XHP inhibits proliferation, migration, and invasion, and induces pyroptosis of BC cells via activating the cAMP/PKA signalling pathway.

Effects of Tai Chi Chuan on Cognitive Function in Adults 60 Years or Older With Type 2 Diabetes and Mild Cognitive Impairment in China: A Randomized Clinical Trial.

Importance: Type 2 diabetes (T2D) is associated with the progression of cognitive dysfunction. Physical activity benefits cognition, but no evidence from randomized clinical trials has shown whether tai chi chuan has better long-term benefits than fitness walking in cognitive function for patients with T2D and mild cognitive impairment (MCI). Objective: To compare the effectiveness of tai chi chuan, a mind-body exercise, for improving cognitive function in older adults with T2D and MCI, with fitness walking. Design, Setting, and Participants: This randomized clinical trial was conducted between June 1, 2020, and February 28, 2022, at 4 sites in China. Participants included 328 adults (aged ≥60 years) with a clinical diagnosis of T2D and MCI. Interventions: Participants were randomized in a 1:1:1 ratio to a tai chi chuan group, a fitness walking group, or a control group. The tai chi chuan group received 24-form simplified tai chi chuan. The fitness walking group received fitness walking training. Both exercise groups took the training for 60 min/session, 3 times/wk, for 24 weeks in a supervised setting. All 3 groups were provided with a 30-minute diabetes self-management education session, once every 4 weeks for 24 weeks. The participants were followed up for 36 weeks. Main Outcomes and Measures: The primary outcome was the global cognitive function measured at 36 weeks by the Montreal Cognitive Assessment (MoCA). Secondary outcomes included MoCA at 24 weeks and other cognitive subdomain measures and blood metabolic indices at 24 and 36 weeks. Results: A total of 328 participants (mean [SD] age, 67.55 [5.02] years; mean [SD] T2D duration, 10.48 [6.81] years; 167 [50.9%] women) were randomized to the tai chi chuan group (n = 107), fitness walking group (n = 110), or control group (n = 111) and included in the intention-to-treat analysis. At 36 weeks, the tai chi chuan group showed improved MoCA scores compared with the fitness walking group (mean [SD], 24.67 [2.72] vs 23.84 [3.17]; between-group mean difference, 0.84 [95% CI, 0.02-1.66]; P = .046) in the intention-to-treat analysis. The per-protocol analysis data set and subgroup analysis at 36 weeks showed similar results. Based on the generalized linear models, the treatment effects were similar in each group after adjusting for self-reported dietary calories and physical activity. There were 37 nonserious adverse events (tai chi chuan group, 8; fitness walking group, 13; control group, 16) unrelated to the study with no statistically significant difference among the 3 groups (P = .26). Conclusions and Relevance: In this randomized clinical trial including older adults with T2D and MCI, tai chi chuan was more effective than fitness walking in improving global cognitive function. The findings support a long-term benefit, suggesting the potential clinical use of tai chi chuan as an exercise intervention to improve cognitive function for older adults with T2D and MCI. Trial Registration: ClinicalTrials.gov Identifier: NCT04416841.

Comparative study on the effects of crystalline L-methionine and methionine hydroxy analogue calcium supplementations in the diet of juvenile Pacific white shrimp (Litopenaeus vannamei).

An 8-week feeding trial was conducted to evaluate the effects of L-methionine and methionine hydroxy analogue calcium (MHA-Ca) supplements in low-fishmeal diet on growth performance, hepatopancreas morphology, protein metabolism, anti-oxidative capacity, and immunity of Pacific white shrimp (Litopena eus vannamei). Four isonitrogenous and isoenergetic diets were designed: PC (203.3 g/kg fishmeal), NC (100 g/kg fishmeal), MET (100 g/kg fishmeal +3 g/kg L-methionine) and MHA-Ca (100 g/kg fishmeal +3 g/kg MHA-Ca). White shrimp (initial body weight 0.23 ± 0.00 g, 50 shrimp per tank) were allocated to 12 tanks and divided among 4 treatments in triplicates. In response to L-methionine and MHA-Ca supplementations, the shrimp exhibited higher weight gain rate (WGR), specific growth rate (SGR), condition factor (CF), and lower hepatosomatic index (HSI) compared to those fed the NC diet (p < 0.05). The WGR and SGR of shrimp fed L-methionine and MHA-Ca showed no difference with those in the PC diet (p > 0.05). Both of L-methionine and MHA-Ca supplementary diets significantly decreased the malondialdehyde (MDA) levels of shrimp when compared with the NC diet (p < 0.05). L-methionine supplementation improved the lysozyme (LZM) activity and total antioxidant capacity (T-AOC) of shrimp, while the MHA-Ca addition elevated the reduced glutathione (GSH) levels in comparison with those fed the NC diet (p < 0.05). Hypertrophied blister cells in hepatocytes were observed in shrimp fed the NC diet, and alleviated with L-methionine and MHA-Ca supplementations. Shrimp fed the MET and MHA-Ca diets had higher mRNA expression levels of target of rapamycin (tor) than those fed the NC diet (p < 0.05). Compared to the NC group, dietary MHA-Ca supplementation upregulated the expression level of cysteine dioxygenase (cdo) (p < 0.05), while L-methionine supplementation had no significant impact (p > 0.05). The expression levels of superoxide dismutase (sod) and glutathione peroxidase (gpx) were significantly upregulated by L-methionine supplemented diet in comparison with those in the NC group (p < 0.05). Overall, the addition of both L-methionine and MHA-Ca elevated the growth performance, facilitated protein synthesis, and ameliorated hepatopancreatic damage induced by plant-protein enriched diet in L. vannamei. L-methionine and MHA-Ca supplements enhanced anti-oxidants differently.

[Evaluation of calcium intake levels and sources among pregnant women in a Chengdu hospital in 2017].

OBJECTIVE: Investigate and evaluate the levels and sources of calcium intake of pregnant women in Chengdu during three trimesters. METHODS: Use the data of a cohort study in Chengdu in 2017. The healthy singleton pregnant women with 8-14 weeks of pregnancy in an obstetrical clinic of a maternal-and-child health care institution in Chengdu were selected as the object of the study. Data on maternal demographic characteristics and the use information of calcium supplements in the past month of each trimester were collected by questionnaire investigation. The dietary intakes data of pregnant women in each trimester was collected by the 3-day 24-hour dietary recall method. The dietary calcium intake and the contribution of calcium from different foods were calculated based on the Chinese Food Composition Table(2018). The total calcium intake was obtained by adding the dietary calcium and supplement calcium intake. The calcium intake was evaluated with reference to the Chinese Dietary Nutrient Reference Intakes(2013). RESULTS: Valid samples of 1653 cases in early pregnancy, 1024 cases in middle pregnancy and 1017 cases in late pregnancy were finally included. The median intake of total calcium was 523.3, 1280.5 and 1491.3 mg/d in three trimesters, respectively. The adequate rate of total calcium intake was 16.3%, 63.2% and 67.1%, the insufficient rate was 69.0%, 15.7% and 11.2%, the excess rate was 0.2%, 9.1% and 14.4%, respectively. The median intake of dietary calcium was 453.0, 613.0 and 723.0 mg/d in three trimesters respectively. The dietary calcium adequate rates were 7.1%, 9.7% and 16.2%, the dietary calcium deficiency rates were 82.0%, 75.0%, 62.6%, respectively. The main food sources of dietary calcium in each pregnancy were dairy foods, vegetables, tubers and grains. The contribution of dairy foods to the dietary calcium was 33.8%, 37.7% and 40.2%, respectively. The median intake of milk was 125.0, 235.3 and 250.0 g/d, respectively. Among all pregnant women, the calcium supplement use in three trimesters was 36.2%, 93.4% and 91.7%, respectively; the median intake of supplement calcium was 0.0, 625.0 and 750.0 mg/d, respectively. Among pregnant women who met the dietary calcium standard, the use of calcium supplements in the three trimesters was 38.1%, 95.0% and 94.5%, respectively; the median intake of supplemental calcium was 0.0, 725.0 and 750.0 mg/d, respectively. CONCLUSION: The insufficient and excessive total calcium intake coexisted among pregnant women in Chengdu, with the insufficient dietary calcium intake prominent in all trimesters. The use of calcium supplements was common in middle and late pregnancy.

Enhanced phosphorus release from waste activated sludge using ascorbic acid reduction and acid dissolution.

Due to the widespread application of various iron (Fe)-derived substances used in phosphorus (P) removal during wastewater treatment, Fe-P species generated in this process constitute an important part of P speciation in non-digested sludge. SEM-EDS and sequential extraction methods were utilized to analyze the speciation, distribution, and spatial variation of P contained in the sludge. Inorganic P accounted for 91.3% of the total P, and Fe(III)-P represented the greatest percentage (68.5%) in the inorganic P fraction. Ascorbic acid, also known as vitamin C (VC), performed well in releasing P from sludge, especially in combination with subsequent pH adjustment to 3.0 using HCl. Fe(III)-P in sludge was first reduced to Fe(II)-P by VC, then dissolved in acidic conditions to release Fe2+ and PO43-. Other metal-P compounds were also partially dissolved and released. VC disrupted the sludge floc structure, releasing organic P via organic efflux. There was a positive correlation (R2>0.97, p<0.05) between the amount of released P and the amount of reductant (VC). There was a synergistic effect between 120 mmol/L VC and acidity, producing the greatest P release of 67.1% of total sludge P. The P release efficiency achieved in this study was higher than other reported methods. Additionally, VC provides a more sustainable option due to its natural biodegradability. Released P and Fe2+ can be recovered as vivianite with recovery rates of 88% and 99%, respectively. This finding provides a new direction for effective, sustainable sludge P recovery and utilization.

Role of Mitophagy in Myocardial Ischemia/Reperfusion Injury and Chinese Medicine Treatment.

Mitophagy is one of the important targets for the prevention and treatment of myocardial ischemia/reperfusion injury (MIRI). Moderate mitophagy can remove damaged mitochondria, inhibit excessive reactive oxygen species accumulation, and protect mitochondria from damage. However, excessive enhancement of mitophagy greatly reduces adenosine triphosphate production and energy supply for cell survival, and aggravates cell death. How dysfunctional mitochondria are selectively recognized and engulfed is related to the interaction of adaptors on the mitochondrial membrane, which mainly include phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced kinase 1/Parkin, hypoxia-inducible factor-1 α/Bcl-2 and adenovirus e1b19k Da interacting protein 3, FUN-14 domain containing protein 1 receptor-mediated mitophagy pathway and so on. In this review, the authors briefly summarize the main pathways currently studied on mitophagy and the relationship between mitophagy and MIRI, and incorporate and analyze research data on prevention and treatment of MIRI with Chinese medicine, thereby provide relevant theoretical basis and treatment ideas for clinical prevention of MIRI.

The concentrations of bone calcium, phosphorus and trace metal elements in elderly patients with intertrochanteric hip fractures.

Introduction: Trace metal elements may play a crucial role in bone mineralization and metabolism. However, the quantification of trace element concentrations in human bone tissue has received little attention. Materials and methods: Bone tissue samples were collected from 55 elderly patients (15 males and 40 females) with intertrochanteric hip fractures. The calcium, phosphorus, manganese, iron, copper, and zinc concentrations in the cortical bone zone, cancellous bone zone, and junction zone between cortical and cancellous bone were determined by energy-dispersive X-ray fluorescence (EDX). The differences in trace element concentrations in the three regions were compared, and the correlation between gender and bone trace element contents of the bones was analyzed using the Kruskal-Wallis's test. The correlation between age, body mass index (BMI), and bone calcium, phosphorus concentrations, and trace elements in three bone zones was determined using Spearman correlation analysis. Results: The Kruskal-Wallis test showed no difference in bone phosphorus concentration among the three regions. In contrast, the difference in the concentrations of bone calcium and four metal elements was statistically significant (P<0.01). In addition, no statistical differences were observed in the concentrations of trace elements among the three regions in elderly male and female patients. Spearman correlation analysis showed a strong negative correlation between bone calcium and phosphorus in three bone regions (r=-0.999, -0.95, -0.998, P < 0.01) and a significant positive correlation between trace metal elements in the cancellous bone zone. In the junction zone, the BMI showed a strong positive correlation with bone calcium content (r=0.347, P=0.009) and a significant negative correlation with phosphorus content (r=-0.349, P=0.009). Conclusion: Bone calcium and phosphorus were the main components of hydroxyapatite, and these two elements accounted for the majority of bone mineral salts. Trace metal elements are essential for bone metabolism and specific synergistic interactions. BMI may be associated with bone calcium and phosphorus contents in elderly patients with osteoporosis.

Application of network pharmacology and molecular docking approach to explore active compounds and potential pharmacological mechanisms of Aconiti Lateralis Radix Praeparata and Lepidii Semen Descurainiae Semen for treatment of heart failure.

BACKGROUND: Heart failure (HF) is the end stage of the development of heart disease, whose prognosis is poor. The previous research of our team indicated that the formulae containing Aconiti Lateralis Radix Praeparata and Lepidii Semen Descurainiae Semen (ALRP-LSDS) could inhibit myocardial hypertrophy, inhibit cardiomyocyte apoptosis, delay myocardial remodeling (REM), and improve the prognosis of patients with HF effectively. In order to explore the mechanism of ALRP-LSDS for the treatment of HF, a combined approach of network pharmacology and molecular docking was conducted. METHODS: Public database TCMSP was used to screen the active compounds of ALRP-LSDS. The targets of screened active compounds were obtained from the TCMSP database and predicted using the online analysis tool PharmMapper. The targets of HF were obtained from 6 databases including GeneCards, OMIM, DrugBank, TTD, PharmGKB, and DisGeNET. Protein-protein interaction and enrichment analysis were performed, respectively, by STRING and Metascape online tools after merging the targets of active compounds and HF. Cytoscape software was used to conduct networks. Finally, molecular docking was performed by Vina to verify the correlation between key targets and active compounds. RESULTS: Final results indicated that the active compounds including ß-sitosterol, isorhamnetin, quercetin, kaempferol, and (R)-norcoclaurine, the targets including AKT1, CASP3, and MAPK1 might be the main active compounds and key targets of ALRP-LSDS for the treatment of HF separately. The binding ability of AKT1 to the main active compounds was better compared with the other 2 key targets, which means it might be more critical. The pathways including AGE-RAGE signaling pathway in diabetic complications, Pathways in cancer, and Fluid shear stress and atherosclerosis might play important roles in the treatment of HF with ALRP-LSDS. In general, ALRP-LSDS could inhibit cardiomyocyte apoptosis, delay REM, and improve cardiac function through multicompound, multitarget, and multipathway, which contributes to the treatment of HF. CONCLUSIONS: Based on the combined approach of network pharmacology and molecular docking, this study screened out the main active compounds, key targets, and main pathways of ALRP-LSDS for the treatment of HF, and revealed its potential mechanisms, providing a theoretical basis for further research.

Xiongshao Zhitong Recipe Attenuates Nitroglycerin-Induced Migraine-Like Behaviors via the Inhibition of Inflammation Mediated by Nitric Oxide Synthase.

Migraine is a major cause of disability worldwide, particularly in young adults and middle-aged women. Xiongshao Zhitong Recipe (XZR) is a traditional Chinese medicine prescription used for treating migraine, but its bioactive components and therapeutic mechanisms remain unclear. We aimed to confirm the therapeutic effect of XZR on migraine and to determine the possible mechanism and bioactive components of XZR. Here, a sensitive UHPLC-LTQ-Orbitrap MS assay was carried out to analyze the ingredients of XZR, and a total of 62 components were identified, including coumarins, phenolic acids, phthalides, flavonoids, and terpenoids; among them, 15 components were identified in the serum samples after XZR treatment. We established a rat model of migraine via nitroglycerin (NTG) injection. The in vivo experiments demonstrated that XZR attenuated allodynia and photophobia in rats with NTG-induced migraine, and XZR also demonstrated analgesic effects. XZR reversed the abnormal levels of nitric oxide, 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP), and substance P (SP) to normal levels. XZR also downregulated inflammatory reactions, including mast cell degranulation and serum IL-1ß, IL-6, and TNF-α levels. In terms of mechanism, we revealed that XZR treated NTG-induced migraine through the inhibition of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in both the trigeminal nucleus caudalis (TNC) and periaqueductal gray matter (PAG), as well as the total NOS enzyme activity, which regulated the NF-κB signaling pathway. Additionally, imperatorin and xanthotoxin, two major ingredients of XZR, showed a high binding affinity to nNOS (Gly468-Leu616). In vitro, XZR, imperatorin, and xanthotoxin inhibited the nNOS expression and the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated PC12 cells. In conclusion, we demonstrated the therapeutic effects of XZR and provided evidence that XZR played a critical anti-inflammatory role by suppressing NOS and NF-κB signaling pathway activation. Imperatorin and xanthotoxin were potential bioactive components of XZR. The findings from this study supported that XZR was a candidate herbal drug for migraine therapy.

Pharmacokinetics and Main Metabolites of Anwulignan in Mice.

Anwulignan is a representative component of Chinese traditional medicine Schisandra sphenanthera, with strong pharmacological activities. However, there are few reports on its pharmacokinetics and metabolites in the body. In this study, a metabolomic method based on UHPLC-Q-Orbitrap-MS was used to study the pharmacokinetics of anwulignan in the blood, organs, urine, and feces samples of mice after the intragastric administration of anwulignan (10 mg/kg). The pharmacokinetic parameters were calculated, and the distribution characteristics and main metabolites of anwulignan in the body of mice were analyzed. The results showed that the retention time of anwulignan in the body of mice was longer (t 1/2 = 7.1 h), and anwulignan was widely distributed in the body (Vz/F = 32.81 L/kg), especially in the liver. The order of anwulignan concentration in the tissues of mice from high to low was the liver > heart > brain > kidney > lung > spleen. Anwulignan was mainly excreted through the digestive tract in the form of its prototype and metabolites, indicating that it might experience an enterohepatic circulation. A total of seven metabolites were identified, and the demethylation, hydroxylation, dehydroxylation, and demethoxylation were considered to be the main metabolic ways of anwulignan in the body of mice.

[Intakes and sources of fat and fatty acids among pregnant women in Chengdu in 2017: a longitudinal study].

OBJECTIVE: To analyze the intake of fat and fatty acids and their food sources of pregnant women in Chengdu. METHODS: Participants were from a cohort study in 2017, which was conducted among 1652 healthy singleton pregnant women within 6-14 weeks of gestation in a maternity out-patient clinic of maternal-and-child health care institution in Chengdu, Sichuan Province. Data on maternal demographic characteristics was collected by questionnaire. In three trimesters, 3-day 24-hour dietary recall method was applied to collect dietary intakes data, with the information of docosahexaenoic acid(DHA) supplement intake being collected by questionnaire. The intakes and sources of daily fat and fatty acids in three trimesters were calculated using the National Nutrient Database of USDA and China Food Composition Tables(6th edition). The intake levels of fat and fatty acids were evaluated according to 2013 Chinese Dietary Reference Intakes. RESULTS: The study showed that the intakes of total fat and fatty acids increased during pregnancy. The mean intake of total daily fat was 64.8 g/d, 81.2 g/d, 88.5 g/d in three trimesters, respectively. The proportion of energy from total fat >30%E during three trimesters were 67.7%, 77.6%, 82.9%, respectively. The proportions of energy from saturated fatty acids(SFA) were 7.9%E, 8.9%E, 9.7%E, and those higher than 10%E were 20.9%, 31.9%, 44.7% in three trimesters, respectively. The proportions of energy from monounsaturated fatty acids(MUFA) were 12.9%E, 13.5%E, 14.2%E, and the proportions of energy from polyunsaturated fatty acids(PUFA) were 8.5%E, 8.4%E, 8.8%E in three trimesters, respectively. The proportion of DHA intake meeting recommendation(200 mg/d) in three trimesters were 3.6%, 21.7%, 21.1%, respectively. The radio of SFA, MUFA and PUFA(S∶M∶P) was 1∶1.6∶1.1 in the early trimester, and S∶M∶P was 1∶1.5∶1 in the second trimester and third trimester. Total fat and MUFA mainly came from edible oil and meat, and PUFA mainly came from edible oil and nuts. SFA mainly came from meat and milk, and the contribution of milk to SFA increased during pregnancy. CONCLUSION: The excessive intakes of total fat and SFA and the inadequate intake of DHA among pregnant women in Chengdu deserve attention.

Melatonin intervention to prevent delirium in hospitalized patients: A meta-analysis.

BACKGROUND: Evaluation of the effectiveness of melatonin is necessary to prevent the development of delirium in hospitalized patients. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone produced by the pineal gland of the brain from the amino acid tryptophan. Synthetic melatonin supplements have been used for various medical conditions, especially sleep-related diseases, and have proved to be successful. AIM: To determine the effect of melatonin on the prevention of delirium in hospitalized patients. METHODS: A literature search of the CNKI, Wanfang Database, VIP Database, China Biomedical Literature Database, PubMed, Embase, Cochrane Library, Web of Science, and other databases was conducted. The CNKI, Wanfang Database, VIP Database (VIP), and China Biomedical Literature Database were searched for Chinese studies, and PubMed, Embase, Cochrane Library, Web of Science and other databases were searched for international studies. It will be established in June 2021 in a randomized controlled trial (RCT) whether melatonin treatment for 6 mo prevents delirium in hospitalized patients. Literature screening, quality review, and data extraction were carried out using the Cochrane Manual 5.1.0 systematic evaluation method, and Stata 15.0 software and Review Manager 5.3 were used for meta-analysis and processing. RESULTS: A total of 18 new RCT articles and 18 experimental subjects were identified. The results of the meta-analysis showed that following the occurrence of delirium, melatonin reduced the incidence of delirium in patients (RR = 0.69, 95%CI: 0.60-0.80), which is of significance, but heterogeneity was significant I 2 = 62%. Subgroup analysis was performed to examine the source of heterogeneity, and it was found that different patient types were the source of heterogeneity; the research on subgroup analysis was of high quality and homogeneous. To determine the reliability and robustness of the research results, a sensitivity analysis was carried out. The results showed that after excluding individual studies one by one, the effect size was still within 95%CI, which strengthened the reliability of the original meta-analysis results. Melatonin has a significant preventive effect on delirium in hospitalized medical patients [RR = 0.60, 95%CI: 0.47-0.76), P < 0.001]. CONCLUSION: Melatonin can reduce the rate of delirium in medical patients, and the role of melatonin in reducing the incidence of delirium in surgical patients and critical care unit patients requires further study.

Anoectochilus roxburghii flavonoids extract ameliorated the memory decline and reduced neuron apoptosis via modulating SIRT1 signaling pathway in senescent mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus roxburghii (A. roxburghii) is a precious herb and folk medicine in many Asian countries. It has been used traditionally to treat diabetes, etc., and also used as a dietary therapy to delay senescence. AIM OF THE STUDY: This study was to evaluate the neuroprotective effects of A. roxburghii flavonoids extract (ARF) and whether its effects were due to the regulation of SIRT1 signaling pathway in senescent mice and in D-galactose (D-gal) induced aging in SH-SY5Y cells. MATERIALS AND METHODS: 18-month-old mice were randomly divided into senescent model, low-dose ARF, high-dose ARF and vitamin E group. 2-Month-old mice were as a control group. After 8 weeks treatment, Morris water maze (MWM) was performed. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), monoamine oxidase (MAO) and acetylcholinesterase (ACh-E) in the cortex were determined. Hippocampus morphologic changes were observed with haematoxylin and eosin (H&E), Nissl, senescence-associated-galactosidase (SA-ß-gal) and terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining. Apoptosis-related molecular expressions in the hippocampus were performed by western blotting. Furthermore, after stimulated by EX527 (a SIRT1 inhibitor), the SIRT1-dependent neuroprotective effects of ARF were determined by measuring SRIT1 and p53 expression in SH-SY5Y aging cells induced by D-gal. RESULTS: ARF could significantly ameliorate memory decline in senescent mice and reduce the generations of ROS, MDA and the activities of MAO and ACh-E, while increasing SOD activities in the cortex of aging mice. ARF obviously improved hippocampus pathological alterations, increased the number of Nissl bodies, while reducing senescent and apoptotic cells in senescent mice hippocampus. Further, ARF positively regulated SIRT1 expression, and reduced apoptosis-related molecules p53, p21 and Caspase-3 expression, while increasing the ratio of Bcl-2/Bax. In D-gal-induced SH-SY5Y cells, the effects of ARF on SIRT1 and p53, and the ability of scavenging ROS were mostly abolished after incubation with the EX527. CONCLUSIONS: ARF, in a SIRT1-dependent manner, exerted neuroprotection via modulating SIRT1/p53 signaling pathway against memory decline and apoptosis due to age-induced oxidative stress damage in senescent mice.

Characterization of a new (Z)-3:(E)-2-hexenal isomerase from tea (Camellia sinensis) involved in the conversion of (Z)-3-hexenal to (E)-2-hexenal.

Two major green leaf volatiles (GLVs) in tea that contribute greatly to tea aroma, particularly the green odor, are (E)-2-hexenal and (Z)-3-hexenal. Until now, their formation and related mechanisms during tea manufacture have remained unclear. Our data showed that the contents of (E)-2-hexenal and (Z)-3-hexenal increased more than 1000-fold after live tea leaves were torn. Subsequently, a new (Z)-3:(E)-2-hexenal isomerase (CsHI) was identified in Camellia sinensis. CsHI irreversibly catalyzed the conversion of (Z)-3-hexenal to (E)-2-hexenal. Abiotic stresses including low temperature, dehydration, and mechanical wounding, did not influence the (E)-2-hexenal content in intact tea leaves during withering, but regulated the proportions of (Z)-3-hexenal and (E)-2-hexenal in torn leaves by modulating CsHI at the transcript level. For the first time, this work reveals the formation of (E)-2-hexenal during tea processing and suggests that CsHI may play a pivotal role in tea flavor development as well as in plant defense against abiotic stresses.

[Influencing factors of insufficient and excessive folate intake in early pregnancy in Chengdu in 2017].

OBJECTIVE: To investigate the folate intake level of early pregnant women and its influencing factors in Chengdu. METHODS: The healthy singleton pregnant women with 8-14 weeks of pregnancy in an obstetrical clinic of maternal-and-child health care institution in Chengdu in 2017 were selected as the object of the study. The basic information of pregnant women was collected by questionnaire survey, and the dietary intake of all kinds of food in early pregnancy was collected by 3-day 24-hour dietary recall method, and the average daily intake of folate was calculated according to China Food Composition(2018). A self-designed questionnaire was used to collect the use of folic acid supplements in pregnant women in the past one month, and the average daily intake of folic acid supplements was calculated. According to the Chinese Dietary Reference Intakes(2013), the folate intake <600 µg DFE/d was defined as insufficient, and folic acid supplements intake ≥1000 µg/d was defined as excessive. The influencing factors of folate intake were analyzed by binary Logistic regression model. RESULTS: A total of 1579 valid samples were included. The average folate intake of early pregnant women in Chengdu was 865.8(778.6, 1461.0) µg DFE/d, the average dietary folate intake was 145.4(101.9, 200.7) µg/d, and the average folic acid supplements intake was 400.0(400.0, 800.0) µg/d. The rate of insufficient intake of folate in early pregnancy was 12.1%, and the rate of excessive intake of folic acid supplements was 13.0%. Compared with the primiparous group, the risk of insufficient folate intake was higher in the multiparous group(OR=1.708, 95%CI 1.175-2.482). Compared with the low income group, risk of insufficient folate intake in the medium and high income group was lower(OR=0.660, 95%CI 0.477-0.913); taking folic acid supplements before pregnancy has a lower risk of overdose of folic acid than the non-taking group(OR=0.594, 95%CI 0.423-0.835). CONCLUSION: The phenomenon of insufficient intake of total folate and excessive intake of folic acid supplements coexists among women in early pregnancy in Chengdu, and the rational use of folic acid supplements is worthy of attention.

"Efficacy-Nature-Structure" Relationship of Traditional Chinese Medicine Based on Chemical Structural Data and Bioinformatics Analysis.

Traditional Chinese medicines (TCMs) have wide pharmacological activities, and the ingredients in individual TCMs determine their efficacies. To understand the "efficacy-nature-structure" relationship of TCM, compounds from 2444 kinds of herbs were collected, and the associations between family, structure, nature, and biological activities were mined and analyzed. Bernoulli Naïve Bayes profiling and a data analysis method were used to predict the targets of compounds. The results show that genetic material determined the representation of ingredients from herbs and the nature of TCMs and that the superior scaffolds of compounds of cold nature were 2-phenylochrotinone, anthraquinone, and coumarin, while the compounds of hot nature were cyclohexene. The results of the similarity analysis and distribution for molecular descriptors of compounds show that compounds associated with the same nature were similar and compounds associated with different natures occurred as a transition in part. As for integral compounds from 2-phenylochrotinone, anthraquinone, coumarin, and cyclohexene, the value of the shape index increased, indicating the transition of scaffolds from a spherical structure to a linear structure, with various molecular descriptors decreasing. Three medicines and three recipes prescribed based on "efficacy-nature-structure" had a higher survival rate in the clinic and provided powerful evidence for TCM principles. The research improves the understanding of the "efficacy-nature-structure" relationship and extends TCM applications.

Mitochondria-Targeted Nanocarriers Promote Highly Efficient Cancer Therapy: A Review.

Mitochondria are the primary organelles which can produce adenosine triphosphate (ATP). They play vital roles in maintaining normal functions. They also regulated apoptotic pathways of cancer cells. Given that, designing therapeutic agents that precisely target mitochondria is of great importance for cancer treatment. Nanocarriers can combine the mitochondria with other therapeutic modalities in cancer treatment, thus showing great potential to cancer therapy in the past few years. Herein, we summarized lipophilic cation- and peptide-based nanosystems for mitochondria targeting. This review described how mitochondria-targeted nanocarriers promoted highly efficient cancer treatment in photodynamic therapy (PDT), chemotherapy, combined immunotherapy, and sonodynamic therapy (SDT). We further discussed mitochondria-targeted nanocarriers' major challenges and future prospects in clinical cancer treatment.