Effects of vitamins and polyunsaturated fatty acids on cognitive function in older adults with mild cognitive impairment: a meta-analysis of randomized controlled trials.

PURPOSE: Vitamins and polyunsaturated fatty acids (PUFAs) have been studied extensively as safe and manageable nutrient interventions for mild cognitive impairment (MCI). The purpose of the current meta-analysis was to examine the effects of vitamins and PUFAs on cognition and to compare the effects of single and multiple nutrient subgroups in patients with MCI. METHODS: Randomized controlled trials (RCTs) written in English and Chinese were retrieved from eight databases, namely, PubMed, CENTRAL, Embase, CINAHL, Web of Science, SinoMed, CNKI, and Wanfang Data, from their respective dates of inception until 16 July 2023. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool 2.0. Meta-analyses were performed to determine the standardized mean differences (SMDs) in global cognitive function, memory function, attention, visuospatial skills, executive function, and processing speed between the supplement and control groups using 95% confidence intervals (CI) and I2. Prospero registration number: CRD42021292360. RESULTS: Sixteen RCTs that studied different types of vitamins and PUFAs were included. The meta-analysis revealed that vitamins affected global cognitive function (SMD = 0.58, 95% CI = [0.20, 0.96], P = 0.003), memory function (SMD = 2.55, 95% CI = [1.01, 4.09], P = 0.001), and attention (SMD = 3.14, 95% CI = [1.00, 5.28], P = 0.004) in patients with MCI, and PUFAs showed effects on memory function (SMD = 0.65, 95% CI = [0.32, 0.99], P < 0.001) and attention (SMD = 2.98, 95% CI = [2.11, 3.84], P < 0.001). Single vitamin B (folic acid [FA]: SMD = 1.21, 95% CI = [0.87, 1.55]) supplementation may be more effective than multiple nutrients (FA and vitamin B12: SMD = 0.71, 95% CI = [0.41, 1.01]; and FA combined with docosahexaenoic acid [DHA]: SMD = 0.58, 95% CI = [0.34, 0.83]) in global cognitive function. CONCLUSIONS: FA, vitamin B6, vitamin B12, and vitamin D may improve global cognitive function, memory function, and attention in patients with MCI. Eicosapentaenoic acid (EPA) and DHA may improve memory function and attention. We also noted that FA may exert a greater effect than a vitamin B combination (FA and vitamin B12) or the combination of FA and DHA. However, because of the low evidence-based intensity, further trials are necessary to confirm these findings.

Glycerol tributylate (Triacylglycerol tributanoate) promoted the liver lipid metabolism by cultivating the intestinal flora of grass carp (Ctenopharyngodon idellus).

To investigate the effects of glycerol tributyrin (TB) (Triacylglycerol tributanoate) on the regulation of liver lipid metabolism by intestinal flora of grass carp (Ctenopharyngodon idellus). The compound feed with soybean oil 2.8% + fish oil 1.8%, soybean oil 6.3% + fish oil 1.8%, and soybean oil 6.2% + fish oil 1.8% + TB 0.1% was added to the basal diet as a fat source and fed to the basal (control) group, high lipid (HL) group, and tributyrin (TB) group for 12 weeks. We tested the growth performance, fat content, diversity, and abundance of gut flora and other related indexes of grass carp by Soxhlet extraction, liver tissue enzyme activity, oil red O staining, and 16S rRNA high-throughput sequencing. The results showed that the liver fat number and liver fat content of grass carp in the TB group were lower than those in the HL group, while the fattening degree was significantly higher than those in the other two groups; according to the indices such as Shannon, Ace, and Coverage, it was found that the grass carp in the TB group had the highest abundance and diversity of intestinal microflora; at the portal level, Proteobacteria and Fusobacteria were the main dominant flora in the TB group, with the number of unique OUTs accounting for about 59. 9% of the total number measured; at the genus level, the relative abundance of lipase-producing, short-chain fatty acid-associated bacteria, such as Bacillus-Lactobacillus and Bifidobacterium, was significantly lower (p < 0.05). Thus, we conclude that the addition of TB to high-fat diets can alter the structure of the intestinal microbial community and promote hepatic lipid metabolism in grass carp. TB can alleviate fatty liver in grass carp by increasing the relative abundance of short-chain fatty acids in the intestine. Meanwhile, TB inhibits the conversion of primary bile acids to secondary bile acids in the host, which can block intestinal FXR signaling and the hepatic FXR-SHP pathway, thus slowing down fat synthesis and alleviating the accumulation of liver lipids in grass carp.

Global research trends and hotspots of Helicobacter pylori eradication based on clinical trial registration platforms: A cross-sectional analysis.

BACKGROUND: This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS: We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS: A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION: How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.

Impact of body size on efficacy of high-dose dual therapy for Helicobacter pylori eradication.

BACKGROUND: High-dose dual therapy (HDDT) is an emerging and promising therapeutic regime for Helicobacter pylori (H. pylori) eradication. However, the pharmacokinetics of the components of HDDT, amoxicillin and proton pump inhibitor, are likely to be affected by body size. In this study, we aimed to find out the impact of body size on the efficacy of HDDT. METHODS: We collected the medical data of 385 treatment-naive patients infected with H. pylori who received HDDT (esomeprazole 20 mg and amoxicillin 750 mg four times daily) for 14 days from July 2020 to December 2021. The associations among the eradication efficacy, adverse events, and variables (sex, age, height, body weight, body mass index (BMI), body surface area (BSA), smoking, drinking, etc.) were analyzed respectively in our study. Among these factors, continuous variables were classified into categorical variables using the cut-off values which were calculated by receiver operating characteristic analysis. RESULTS: The eradication rate of HDDT was 89.9%. There were 55 (14.3%) patients who occurred adverse events during the treatment. Patients with height <170.5 cm, body weight <60.5 kg, BMI <20.55 kg/m2 , BSA <1.69 m2 had a higher eradication rate (92.1% vs. 84.0%, 93.1% vs. 86.8%, 96.0% vs. 87.8%, 93.4% vs. 84.8%, all p < .05). The multivariate analysis showed that BSA ≥1.69 m2 (OR 2.53, 95% CI: 1.28-4.99, p = .007) was the only independent predictor of eradication failure. CONCLUSION: HDDT could achieve better eradication efficacy in patients with small BSA. Clinicians should be aware of the impact of BSA on the H. pylori eradication rate and pay more attention to patients with large BSA.

First report of jujube anthracnose caused by Colletotrichum siamense in China.

Jujube (Zizyphus jujuba Mill.), a native small deciduous tree of China, is widely cultivated in China, Korea, India, Japan, Europe, and the United States (Chen et al. 2020). The fruit have been commonly consumed as healthy food supplements and traditional Chinese medicine for over 2000 years (Li et al. 2007). In August 2019, anthracnose-like leaf spot symptoms were observed on jujube plants in Xiaomenya Village, Jinan City, Shandong Province, China (36°27'39″N, 117°3'13″E), with over 30% leaf disease incidence. The spots were circular, sunken, brown in the center and with dark brown edges. As the spots enlarged and coalesced, it resulted in leaf perforation and early defoliation. Sometimes acervuli were observed on the lesions (Fig. S1a, b). To identify the causal agent, 20 diseased leaves were sampled, the margins of the lesions were cut into pieces (5 × 5 mm), sterilized and cultured following the protocol described previously (Wan et al. 2020) at 25 ℃ for 5 days. Twelve monospore isolates showing identical colony morphology were obtained. Three representative isolates, JNZG11, JNZG311, JNZG313, were used for further study. When grown on PDA the colony color was initially white and then turned pale-gray to gray in 5-day-old cultures. On the reverse, colonies were brown-black with an orange pigmentation near the center. Aerial mycelium was cottony, dense, white to pale-gray. Conidia were hyaline, 1-celled, smooth-walled, subcylindrical, oblong, attenuated with slightly rounded ends, (11.1-) 12.7-13.3 (-17.8) ×(-4.4) 5.2-5.5 (-6.3) µm (n=50). Appressoria were dark-brown, oval or irregular, (7.3-) 8.6-9.2 (-9.8) ×(-5.1) 5.8-6.9 (-7.0) µm (n=50) (Fig. S1c-g). The morphology resembled those of Colletotrichum gloeosporioides species complex (Cannon et al. 2012). For accurate identification, the sequences of the ribosomal internal transcribed spacer (ITS), actin (ACT), ß-tub2 (TUB2), calmodulin (CAL), chitin synthase (CHS-1), and glyceraldehyde-3phosphate dehydrogenase (GAPDH) of the 3 isolates were sequenced (Weir et al. 2012), and deposited into GenBank (Accession Nos. see Table 1). The six loci (ITS, GAPDH, ACT, CHS-1, CAL, and TUB2) were concatenated and the aligned sequences (1904 bp) were 99.7% homologous to ex-type C. siamense ICMP18578. The sequences of 38 Colletotrichum species (44 isolates) were downloaded from GenBank for phylogenetic analyses. In the maximum likelihood phylogenetic tree generated, the highest log likelihood was -8798.90 and the three isolates were all in the C. siamense clade (bootstrap support 94 %) (Fig. S2). To complete Koch's postulates, 60 healthy, mature jujube leaves on 12 branches (5 leaves per branch) (variety 'Zhongqiuhong') were inoculated with 20 µL of spore suspension (106 conidia/mL) or sterile water as a control. The branches were placed in sterile beakers containing a small amount of sterile water sealed with plastic wrap and maintained at 28 °C, 12 h light/dark. Five days after inoculation, all treated leaves showed the typical anthracnose symptom, similar to that observed in the field (Fig. S1h). The same fungus was re-isolated from the margins of the lesions using the aforementioned methods. Whereas no fungus were isolated from the controls. Previously, C. siamense has been reported to infect Z. mauritiana in China (Shu et al. 2020). To our knowledge, this is the first report of C. siamense causing anthracnose on Z. jujuba in China. This finding provides crucial information for the effective management of this disease.

Standardization, objectification, and essence research of traditional Chinese medicine syndrome: A 15-year bibliometric and content analysis from 2006 to 2020 in Web of Science database.

The standardization, objectification, and essence research of traditional Chinese medicine (TCM) syndrome influence the modernization and international development of TCM syndrome. A total of 253 relevant publications collected from the Web of Science Core Collection database from 2006 to 2020 were analyzed by bibliometric and content methods. The co-occurrence analysis of countries, institutions, journals, authors, and keywords analysis were carried out by using Citespace software. The high-yield institutions and high-impact authors contributed to TCM syndrome publications were concentrated in China. Since 2012, driven by some groundbreaking publications, the number of TCM syndrome literatures has increased rapidly. According to the results of bibliometric and content analysis, research hotspots in TCM syndrome in the last 15 years can be summarized in six aspects: (a) objectification research of four TCM diagnostic methods, (b) omics technology for the essence research of TCM syndrome, (c) research on TCM syndrome evaluation scale, (d) metagenomic technology for the essence research of TCM syndrome, (e) data mining technology for TCM syndrome differentiation, and (f) systematic research on TCM syndromes of chronic hepatitis B. Emerging trends can be identified according to the most recent keywords bursts: (a) TCM syndrome diagnostic models with multiple indexes should be constructed to develop personalized medicine. (b) The connotation of TCM syndrome should be verified through "syndrome detecting from recipe used," and the screened potential markers of TCM syndrome need clinical verification. (c) The intervention and integration of multi-disciplines is expected to find a new breakthrough in the research of TCM syndrome.

Research and development of traditional medicines in low- and middle-income countries: A case study of artemisinin discovery in China.

Though traditional medicines have been developed through practice for thousands of years, limited research has discussed the research and development (R&D) pattern of traditional medicines. China's discovery of artemisinin accumulated valuable experiences to explore traditional medicine under low-resource settings. With limited R&D resources, China mobilized all domestic research units at different levels and departments to develop artemisinin collaboratively. The discovery of artemisinin not only based on valuable experiential wisdom of traditional medicine, but also relied on excellent synergy among all units. In this study, we reviewed the story of how artemisinin was discovered in China, summarized key factors for new drug development from traditional medicines under limited resources, and raised suggestions to utilize traditional medicines in low- and middle-income countries. This case suggested that the vitality of traditional medicine could be extended by promoting new drug development based on modern methods and collaboration.

Huangqin decoction ameliorates DSS-induced ulcerative colitis: Role of gut microbiota and amino acid metabolism, mTOR pathway and intestinal epithelial barrier.

BACKGROUND: The clinical treatment of ulcerative colitis (UC) is limited. A traditional Chinese medicinal formula, Huangqin decoction (HQD), is chronicled in Shang Han Lun and is widely used to ameliorate gastrointestinal disorders, such as UC; however, its mechanism is yet to be clarified. PURPOSE: The present study aimed to investigate the effect of HQD on 7-day colitis induced by 3% dextran sulfate sodium (DSS) in mice and further explore the inhibitory effect of metabolites on DSS-damaged FHC cells. METHODS: The therapeutic efficacy of HQD was evaluated in a well-established DSS-induced colitis mice model. The clinical symptoms were analyzed, and biological samples were collected for microscopic examination, metabolomics, metagenomics, and the evaluation of the epithelial barrier function. The mechanism of metabolites regulated by HQD was evaluated in the DSS-induced FHC cell damage model. The samples were collected to detect the physiological functions of the cells. RESULTS: HQD suppressed the inflammation of DSS-induced colitis in vivo, attenuated DSS-induced clinical manifestations, reversed colon length reduction, and reduced histological injury. After HQD treatment, the DSS-induced gut dysbiosis was modulated, and the gut microbiota achieved a new equilibrium state. In addition, HQD activated the mTOR signaling pathway by upregulating amino acid metabolism. Significant phosphorylation of S6 and 4E-BP1 ameliorated intestinal epithelial barrier dysfunction. Moreover, HQD-regulated metabolites protected the epithelial barrier integrity by inhibiting DSS-induced apoptosis of FHC cells and regulating the proteins affecting apoptosis and cell-cell junction. CONCLUSIONS: These findings indicated that the mechanism of HQD was related to regulating the gut microbiota and amino acid metabolism, activating the mTOR signaling pathway, and protecting the intestinal mucosal barrier integrity.

Antidiabetic potential of Catechu via assays for α-glucosidase, α-amylase, and glucose uptake in adipocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Catechu is the dry water extract of barked branches or stems from Senegalia catechu(L. F.)P. J. H. Hurter & Mabb, which is used as a hypoglycemic regulator in recent researches. Potential anti-hyperglycemic components and the putative mechanisms were evaluated in this investigation. AIM OF THE STUDY: Evaluated the hypoglycemic activity of Catechu via α-glucosidase, α-amylase inhibition assays, and glucose uptake in 3T3-L1 adipocytes. MATERIALS AND METHODS: The effects of Catechu on α-glucosidase, α-amylase inhibition assays and glucose uptake experiment were tested after the ethanol extract of Catechu (EE) was sequentially partitioned with petroleum ether (PEE), ethyl acetate (EAE), and n-butanol fractions (NBE). Next, HPLC-MS and traditional Chinese medicine (TCM) database were used to detect and analyze the primary active ingredients presented in hypoglycemic fraction. In addition, in silico molecular docking study was used to evaluate the candidates' inhibitory activity against α-glucosidase and α-amylase. RESULTS: The results of α-glucosidase and α-amylase inhibition assays indicated that all fractions, with the exception of PEE, presented significant inhibitory effects on α-glucosidase and α-amylase. The inhibitory effect of NBE on α-glucosidase was similar to the positive control (NBE IC50 = 0.3353 ± 0.1215 µg/mL; Acarbose IC50 = 0.1123 ± 0.0023 µg/mL). Furthermore, the inhibitory kinetics of α-glucosidase revealed that all fractions except for PEE belong to uncompetitive type. In silico molecular docking analysis showed that the main compositions of NBE ((-)-epicatechin, cyanidin, and delphinidin) possessed superior binding capacities with α-glucosidase (3WY1 AutoDock score: 4.82 kcal/mol; -5.59 kcal/mol; -5.63 kcal/mol) and α-amylase (4GQR AutoDock score: 4.80 kcal/mol; -5.89 kcal/mol; -4.26 kcal/mol), respectively. The results of glucose uptake experiment indicated that EE, PEE, EAE, and NBE without significant promotion effect on glucose uptake rate of 3T3-L1 adipocytes (P > 0.05). CONCLUSION: This study revealed that the hypoglycemic effect of Catechu might be related to the inhibitory effects of phenols on digestive enzymes (α-glucosidase and α-amylase), and the possible active phenols were (-)-epicatechin, cyanidin, delphinidin and their derivatives, which provided scientific evidences for Catechu's traditional use to treat T2DM.

[Moisture content measurement model of whole package of Chinese medicinal materials based on microwave transmission technology].

In view of the relatively low representativeness of manual sampling inspection, and long time-consuming in oven detection of moisture content, which delayed the subsequent production period, this paper proposed a scheme for rapid moisture quantitative detection for Chinese medicinal materials by microwave transmission technology, and took 8 different types of Chinese medicinal mate-rials as examples to analyze the feasibility and reliability of the scheme for the detection results of moisture content of the whole package of Chinese medicine. In the experiment, the least square method was used to establish the measurement model of microwave absorption rate-moisture content for each kind of medicinal material. The results showed that the microwave transmission measurement of moisture content achieved high-precision measurement of the moisture content of Schisandrae Chinensis Fructus, Ziziphi Spinosae Semen, Poria, Pheretima, Lilii Bulbus, Scutellariae Radix, and Galli Gigerii Endothelium Corneum. The measurement model of Ziziphi Spinosae Semen had the highest accuracy, and the R~2 and root mean square error of the validation set were 0.951 5 and 0.15%, respectively. At the same time, this study found that the microwave absorption intensity of animal medicines including Pheretima and Galli Gigerii Endothelium Corneum was much weaker than that of plant medicines such as Schisandrae Chinensis Fructus, but there was also a good linear relationship between microwave absorption and moisture content, which proved the universality of this method. However, this method was not suitable for Phellodendri Chinensis Cortex because its package contained iron wire. For the whole package of medicinal materials with uniform density and no metal inside, the microwave transmission technology for moisture content measurement can be used to detect the moisture content, which is an effective alternative method to detect the moisture content of medicinal materials.

[Purification and component identification of total proanthocyanidins in Choerospondias axillaris pericarp].

The present study determined the quantitative markers of total proanthocyanidins in the purification of the industrial waste Choerospondias axillaris pericarp based on the comparison results of high-performance liquid chromatography(HPLC) and mass spectrometry(MS) and optimized the purification process with two stable procyanidins as markers. The adsorption and desorption of five different macroporous adsorption resins, the static adsorption kinetics curve of NKA-Ⅱ resin, the maximum sample load, and the gradient elution were investigated. The UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the newly-prepared total proanthocyanidins of C. axillaris pericarp. As revealed by the results, NKA-Ⅱ resin displayed strong adsorption and desorption toward total proanthocyanidins. The sample solution(50 mg·mL~(-1)) was prepared from 70% ethanol crude extract of C. axillaris pericarp dissolved in water and 7-fold BV of the sample solution was loaded, followed by static adsorption for 12 h. After 8-fold BV of distilled water and 6-fold BV of 10% ethanol were employed to remove impurities, the solution was eluted with 8-fold BV of 50% ethanol, concentrated, and dried under reduced pressure, and purified total proanthocyanidin powder was therefore obtained. Measured by vanillin-hydrochloric acid method, the purity and transfer rate of total proanthocyanidins were 47.67% and 59.92%, respectively, indicating the feasibi-lity of the optimized process. UPLC-Q-TOF-MS/MS qualitative analysis identified 16 procyanidins in C. axillaris total proanthocyanidins. The optimized purification process is simple in operation and accurate in component identification, and it can be applied to the process investigation of a class of components that are difficult to be separated and purified. It can also provide technical support and research ideas for the comprehensive utilization of industrial waste.

Inflammation-nutritional markers of peripheral blood could predict survival in advanced non-small-cell lung cancer patients treated with PD-1 inhibitors.

BACKGROUND: Inflammation-nutritional markers of peripheral blood are easily assessed and can predict survival. The aim of this study was to investigate the association between inflammation-nutritional parameters and survival of anti-programmed death-1 (PD-1) therapy in non-small-cell lung cancer (NSCLC) patients. METHODS: We performed a retrospective study from March 2017 to April 2020 in advanced NSCLC patients treated with PD-1 inhibitors. Univariable and multivariable analyses were conducted to evaluate the relationship between peripheral blood parameters (absolute lymphocyte count [ALC], absolute neutrophil count [ANC], absolute monocyte count [AMC], absolute eosinocyte count [AEC], lactic dehydrogenase [LDH], plasma-albumin [ALB], neutrophil/lymphocyte ratio [NLR], and platelet/lymphocyte ratio [PLR]) measured before therapy initiation and prognosis. RESULTS: Among 184 evaluable patients, 134 (72.8%) were male and the median age was 58 years (range 33-87) with 31 (16.8%) ≥70 years. An elevated ANC (≥7500/ul), NLR (≥5), and PLR (≥200) was significantly associated with worse objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), while increased ALC (≥1000/ul) and ALB (≥3.5 g/dl) could significantly improve survival in terms of ORR, PFS, and OS. In multivariate analyses, higher AEC (≥150/ul) and AMC (≥650/ul) could significantly decrease the risk of death (hazard ratio [HR] 0.363, 95% confidence interval [CI] 0.141-0.931, p = 0.035; HR 0.370, 95% CI 0.203-0.675, p = 0.001). A higher NLR and PLR, and lower ALB were independent predictors of poor prognosis for OS (HR 1.964, 95% CI 1.027-3.755, p = 0.041; HR 4.255, 95% CI 2.364-7.658, p = 0.000; HR 1.962, 95% CI 1.213-3.174, p = 0.006, respectively). CONCLUSION: Our research illustrated that pretreatment AEC, AMC, ALB, NLR, and PLR are independent predictors for survival in advanced NSCLC patients treated with PD-1 inhibitors.

Efficacy of Sijunzi decoction on limb weakness in spleen Qi deficiency model rats through adenosine monophosphate-activated protein kinase/unc-51 like autophagy activating kinase 1 signaling.

OBJECTIVE: To investigate the efficacy of Sijunzi decoction () on limb weakness in a rat model of spleen Qi deficiency (SQD), and to study its effect on mitophagy in skeletal muscle through adenosine monophosphate-activated protein kinase (AMPK) / unc-51 like autophagy activating kinase 1 (ULK1) signaling. METHODS: SQD model rats were produced by fasting combined with forced swimming method for 15 d. After model assessment, rats were randomly divided into four groups of 10 [low/middle/high (L/M/H) Sijunzi decoction dose groups and a normal saline (S) group]. Limb holding power (HP) and body mass (BM) were measured after 2 weeks of treatment. Following euthanasia, quadriceps femoris were dissected and myofiber and mitochondrial morphology were observed by transmission electron microscopy (TEM). Mitochondrial membrane potential (MMP), adenosine triphosphatase (ATP) and reactive oxygen species (ROS) levels were determined using colorimetric methods, and immunoblot analysis of Microtubule-associated protein light chain 3 (LC3) and Sequestosome 1 (p62) was performed to monitor mitophagy and AMPK/ULK1 signaling. RESULTS: Compared with control (C) group rats, in the S group, HP was reduced, the myofiber Z line was disordered, mitochondria were scattered, and numerous vacuoles and mitophagy were observed. MMP and ATP levels were reduced, ROS levels were elevated, and LC3B expression, and p-AMPKα (Thr172)/AMPKα, p-ULK1 (Ser555)/ULK1, and p-Raptor (Ser792)/Raptor ratios were increased, while p62 expression and p-mTOR (Ser2448)/mTOR and p-ULK1 (Ser757)/ULK1 ratios were decreased. After treatment, compared with the S group, HP was improved in M and H groups but not in the L group. Mitophagy was reduced in M, H and L groups but the Z line was disordered and vacuolization remained in the L group. ATP levels were elevated in M, H and L groups, and MMPs were elevat-ed in M and H groups but not in the L group. ROS levels were decreased in M, H and L groups, as were LC3B expression and p-Raptor (Ser792)/Raptor ratios, while p62 expression and p-mTOR (Ser2448)/mTOR and p-ULK1 (Ser757)/ULK1 ratios were increased in M and H groups but not in the L group. p-AMPKα (Thr172)/AMPKα and p-ULK1 (Ser555)/ULK1 ratios were decreased in M, H and L groups. CONCLUSIONS: Sijunzi decoction improved HP, possibly by inhibiting mitophagy via suppression of AMPK/ULK1 signaling. This restored mitochondrial morphology and improved oxidative phosphorylation, which contributed to recovery of limb weakness in SQD model rats.

Purification and component identification of total proanthocyanidins in Choerospondias axillaris pericarp / 中国中药杂志

The present study determined the quantitative markers of total proanthocyanidins in the purification of the industrial waste Choerospondias axillaris pericarp based on the comparison results of high-performance liquid chromatography(HPLC) and mass spectrometry(MS) and optimized the purification process with two stable procyanidins as markers. The adsorption and desorption of five different macroporous adsorption resins, the static adsorption kinetics curve of NKA-Ⅱ resin, the maximum sample load, and the gradient elution were investigated. The UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the newly-prepared total proanthocyanidins of C. axillaris pericarp. As revealed by the results, NKA-Ⅱ resin displayed strong adsorption and desorption toward total proanthocyanidins. The sample solution(50 mg·mL~(-1)) was prepared from 70% ethanol crude extract of C. axillaris pericarp dissolved in water and 7-fold BV of the sample solution was loaded, followed by static adsorption for 12 h. After 8-fold BV of distilled water and 6-fold BV of 10% ethanol were employed to remove impurities, the solution was eluted with 8-fold BV of 50% ethanol, concentrated, and dried under reduced pressure, and purified total proanthocyanidin powder was therefore obtained. Measured by vanillin-hydrochloric acid method, the purity and transfer rate of total proanthocyanidins were 47.67% and 59.92%, respectively, indicating the feasibi-lity of the optimized process. UPLC-Q-TOF-MS/MS qualitative analysis identified 16 procyanidins in C. axillaris total proanthocyanidins. The optimized purification process is simple in operation and accurate in component identification, and it can be applied to the process investigation of a class of components that are difficult to be separated and purified. It can also provide technical support and research ideas for the comprehensive utilization of industrial waste.

Postnatal renin-angiotensin system inhibition prevents renal damage from prenatal inflammation in rats.

OBJECTIVE: To assess the protective role of benazepril, an angiotensin-converting enzyme inhibitor, in renal damage caused by prenatal inflammation. METHODS: Saline or lipopolysaccharide were administered intraperitoneally to pregnant Sprague- Dawley rats on gestation days 8, 10, and 12. After birth, offspring received either tap water or benazepril in water between 7 and 68 weeks. Blood pressure, blood urea nitrogen, creatinine, and 24-h urine volume were measured as indices of renal function. Hematoxylin, eosin, periodic acid-Schiff, and Sirius Red staining were used to evaluate renal damage. RESULTS: Postnatal benazepril treatment ameliorated hypertension and restored normal 24-h urine volume and blood urea nitrogen and serum creatinine levels. Benazepril treatment also reduced glycoprotein accumulation and fibrosis in the glomerulus and in tubular epithelial cells and inhibited nuclear factor-kappa B activation. CONCLUSION: Together with our previous findings that postnatal inhibition of nuclear factor-kappa B activation blocks intra-renal renin-angiotensin system activation, our current data demonstrate that intra-renal activation of the renin-angiotensin system interacts with nuclear factor-kappa B activation to cause renal damage in adulthood following prenatal inflammation.

Association of in-hospital intensive statins dosage and death in arteriosclerotic cardiovascular disease with percutaneous coronary intervention: insights of multicentre cohort from China.

PURPOSE: In-hospital statin dosage-related effect remains unknown for patients with arteriosclerotic cardiovascular disease (ASCVD). This study aimed to determine the associations of different in-hospital intensive statins dosages with the prognosis for patients in the era of percutaneous coronary intervention (PCI). METHODS: From January 2010 to December 2014, consecutive ASCVD patients receiving PCI were enrolled from five centres in China. All the enrolled patients were classified into high-dose (40 mg atorvastatin or 20 mg rosuvastatin) or low-dose (20 mg atorvastatin or 10 mg rosuvastatin) intensive statin group. In-hospital all-cause death was the primary outcome. RESULTS: Of the 7008 patients included in this study, 5248 received low-dose intensive statins (mean age, 64.28 ± 10.39; female, 25.2%), whereas 1760 received high-dose intensive statins (mean age, 63.68 ± 10.59; female, 23.1%). There was no significant difference in the in-hospital all-cause death between the two groups (adjusted OR, 1.27; 95% CI, 0.43-3.72; P = 0.665). All-cause death was similar between the two groups during the 30-day follow-up period (adjusted HR, 1.28; 95% CI, 0.55-2.97; P = 0.571). However, the high-dose intensive statins were tightly associated with the reduction in in-hospital dialysis (adjusted OR, 0.11; 95% CI, 0.01-0.81; P = 0.030). Besides, primary analyses were confirmed by subgroup analyses. CONCLUSIONS: The in-hospital high-dose intensive statins are not associated with the lower risk of in-hospital or 30-day all-cause death among ASCVD patients undergoing PCI. Given the robust beneficial effect of high-dose intensive statins with in-hospital dialysis, an individualized high-dose intensive statin therapy can be rational in specified populations.

Effect of melatonin for the management of endometriosis: A protocol of systematic review and meta-analysis.

BACKGROUND: This study aims to explore the effect of melatonin for the management of endometriosis. METHODS: We will search electronic databases (Cochrane Library, MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure) from their inceptions to the February 29, 2020 without language and publication time limitations. The study identification, study quality assessment, and data extraction will be undertaken by two separate researchers. We will also appraise evidence quality of main outcomes by Grading of Recommendations Assessment Development and Evaluation, and statistical analysis performance by RevMan 5.3 Software. RESULTS: This study will summarize up-to-date clinical evidence to investigate the effect of melatonin for the management of endometriosis. CONCLUSION: This study may provide helpful evidence of melatonin for the management of endometriosis. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040093.

Black mulberry ethanol extract attenuates atherosclerosis-related inflammatory factors and downregulates PPARγ and CD36 genes in experimental atherosclerotic rats.

Atherosclerosis (AS) is the pathological basis of various vascular diseases and currently is seriously affecting human health. Numerous studies have paid more attention to natural medicines with anti-AS properties. As a traditional Uygur folk medicine, black mulberry fruits are conventionally used in the prevention and treatment of cardiovascular diseases in southern Xinjiang of China, and their underlying mechanisms remain unknown. Our previous study revealed that the ethanol extract of black mulberry (EEBM) inhibited AS development by improving lipid metabolism abnormalities, enhancing anti-oxidative activities, and reducing atherosclerotic lesions of atherosclerotic rats. Based on this, our objective was to further investigate the effects of EEBM on the expression of AS-related inflammatory factors and the key genes PPARγ and CD36 of the ox-LDL-PPARγ-CD36 feed-forward cycle in experimental atherosclerotic rats. Black mulberry fruits were extracted with acid ethanol and chromatographed on an AB-8 macroporous resin to obtain EEBM. All experimental rats were randomly divided into five groups: normal, model, model plus simvastatin (5 mg/kg d·body weight), and model plus low-dose and high-dose EEBM groups (105 and 210 mg/kg d·body weight, respectively). Serum levels of the inflammatory factors were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA and protein expression of PPARγ and CD36 in atherosclerotic rats' liver tissue and thoracic aorta were determined by Q-PCR and western blot analysis, respectively. EEBM at high dose effectively attenuated the abnormally expressed AS-related inflammatory factors of TNF-α, IL-6, MMP-9, and CRP in atherosclerotic rats by 41.5%, 66.1%, 77.5%, and 79.5%, respectively. After treatment with high dose EEBM, the elevated-expressions of PPARγ and CD36 at the mRNA and protein levels in atherosclerotic rats were found to be obviously downregulated at both levels. These results demonstrate that EEBM might lessen the AS-related inflammatory reaction, and then inhibit the formation of ox-LDL, consequently downregulating the expression of PPARγ and CD36 at the mRNA and protein levels, thus reducing macrophage-foam-cell formation and prohibiting the development of atherosclerotic plaque through the ox-LDL-PPARγ-CD36 feed-forward cycle, which can effectively prevent the occurrence and development of AS in atherosclerotic rats.

[Comparative of functional components, antioxidant and α-glucosidase inhibition activities between Choerospondias axillaris fruit peel vinegar and apple vinegar].

Based on the idea of plant metabolomics, ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to compare the chemical composition between 6 batches of fruit vinegar brewed from Choerospondias axillaris fruit peel and 6 batches of apple vinegar purchased from 3 companies. Antioxidant and α-glucosidase inhibition activities were also tested in vitro. A total of 43 compounds were identified by reference substance, liquid chromatography-mass spectrometry(LC-MS/MS) fragmentation information or literature data. A total of 40 compounds were identified in the C. axillaris fruit peel vinegar. A total of 16 compounds were identified in apple vinegar. There were 13 common ingredients including organic acids and esters such as citric acid, 2-isopropyl malic acid, and triethyl citrate. The results of partial leastsquares-discriminant analysis(PLS-DA) indicated that they had 33 significantly different compounds such as proanthocyanidin oligomer, quercetin-3-O-rhamnoside and heptadecanoic acid. The proanthocyanidins and flavonoid glycosides in C. axillaris peel vinegar were more abundant than apple vinegar, so it had better health function than ordinary fruit vinegar. The results showed that C. axillaris fruit peel vinegar had stronger antioxidant and α-glucosidase inhibition activities in vitro. The vinegar brewed from waste C. axillaris fruit peel had more chemical ingredients than the apple vinegar. C. axillaris fruit peel vinegar had better biological activity and health function, so it had good development prospect. This study provided the scientific evidence for exploiting the C. axillaris fruit peel into high value-added products. It also provided ideas for the comprehensive development and utilization of similar Chinese medicine waste.

Epidemiological Features of NAFLD From 1999 to 2018 in China.

With dramatic changes in lifestyles over the last 20 years, nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disorder in China but has not received sufficient attention. NAFLD-related advanced liver disease and its mortality along with its overall disease burden are expected to increase substantially. There is thus an imperative need to clarify the epidemiological features of NAFLD to guide a holistic approach to management. We summarize eight epidemiological features of NAFLD in China over the past two decades using systematic review and meta-analysis methodology. Our data reveal a rapid growth in the NAFLD population, especially among younger individuals. Importantly, there is a strong ethnic difference in body mass index (BMI) and genetic risk of NAFLD compared with the US population. The etiology of advanced liver disease and its complications (e.g., hepatocellular carcinoma) has been altered because of a Westernized lifestyle and the implementation of effective vaccination strategies against viral hepatitis. Regional epidemiological patterns of NAFLD indicate that economics, environment, and lifestyle are critical factors in disease progression. The analysis also indicates that a large number of patients remain undiagnosed and untreated because of the inadequacy of diagnostic tools and the absence of effective pharmacologic therapies. Given the burden of NAFLD, future policy and research efforts need to address knowledge gaps to mitigate the risk burden.