Multi-omics analysis reveals that linoleic acid metabolism is associated with variations of trained immunity induced by distinct BCG strains.

Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.

Effectiveness and Safety of Chinese Herbal Injections Combined with SOX Chemotherapy Regimens for Advanced Gastric Cancer: a Bayesian Network Meta-Analysis.

Background: Randomized controlled trials (RCTs) have demonstrated that combining Chinese herbal injections (CHIs) with oxaliplatin plus tegafur (SOX) chemotherapy regimens improves clinical effectiveness and reduces adverse reactions in patients with advanced gastric cancer (AGC). These RCTs highlight the potential applications of CHIs and their impact on AGC patient prognosis. However, there is insufficient comparative evidence on the clinical effectiveness and safety of different CHIs when combined with SOX. Therefore, we performed a network meta-analysis to rank the clinical effectiveness and safety of different CHIs when combined with SOX chemotherapy regimens. This study aimed to provide evidence for selecting appropriate CHIs in the treatment of patients with AGC. Methods: We searched eight databases from their inception until March 2023. Surface Under the Cumulative Ranking Curve (SUCRA) probability values were used to rank the treatment measures, and the Confidence in Network Meta-Analysis (CINeMA) software assessed the grading of evidence. Results: A total of 51 RCTs involving 3,703 AGC patients were identified. Huachansu injections + SOX demonstrated the highest clinical effectiveness (SUCRA: 78.17%), significantly reducing the incidence of leukopenia (93.35%), thrombocytopenia (80.19%), and nausea and vomiting (95.15%). Shenfu injections + SOX improved Karnofsky's Performance Status (75.59%) and showed a significant reduction in peripheral neurotoxicity incidence (88.26%). Aidi injections + SOX were most effective in reducing the incidence of liver function damage (75.16%). According to CINeMA, most confidence rating results were classified as "low". Conclusion: The combination of CHIs and SOX shows promising effects in the treatment of AGC compared to SOX alone. Huachansu and Shenfu injections offer the greatest overall advantage among the CHIs, while Aidi injections are optimal for reducing the incidence of liver damage. However, further rigorous RCTs with larger sample sizes and additional pharmacological studies are necessary to reinforce these findings.

Determinants affecting the blood mercury levels of preschool children in Shanghai, China: A cross-sectional study.

Infants and children are vulnerable to mercury (Hg)-induced toxicity, which has detrimental effects on their neurological development. This study measured blood Hg levels (BMLs) and identified potential factors influencing BMLs, including demographic and socioeconomic factors, lifestyle, and daily dietary habits, among 0 to 7-year-old children in Shanghai. Our study recruited 1474 participants, comprising 784 boys and 690 girls. Basic demographic and lifestyle information were obtained and blood Hg were analyzed using the Direct Mercury Analyzer 80. The blood Hg concentrations of children in Shanghai ranged from 0.01 to 17.20 µg/L, with a median concentration of 1.34 µg/L. Older age, higher familial socioeconomic status, higher residential floors, and a higher frequency of consuming aquatic products, rice, vegetables, and formula milk were identified as risk factors. Other potential influencing factors including the mother's reproductive history (gravidity and parity), smoking (passive smoking), supplementation of fish oil and calcium need to be further investigated. These findings can be useful in establishing appropriate interventions to prevent children's high blood Hg concentrations in Shanghai and other similar metropolitan cities.

The effect of oropharyngeal colostrum administration on the clinical outcomes of premature infants: A meta-analysis.

BACKGROUND: Preterm complications are now the second leading cause of death in children under five years of age. Colostrum is essential to prevent infection and promote maturation in preterm infants. Guidelines recommend that preterm infants be fed colostrum by the oral and pharyngeal routes as early as possible after birth to provide immune protection; however, due to disease and an uncoordinated sucking and swallowing function, it is challenging to provide colostrum through the oropharyngeal route, which limits the immune protection it provides. OBJECTIVE: To update the existing meta-analysis, evaluate the effect of oropharyngeal colostrum administration on related outcomes in preterm infants and explore the optimal frequency and duration of oropharyngeal colostrum administration through subgroup analysis. METHODS: The Cochrane Library, PubMed, Web of Science, ScienceDirect, and Ovid databases were searched for randomized control trials (RCTs) of oropharyngeal colostrum administration for preterm infants. Two researchers screened the literature strictly according to the inclusion and exclusion criteria and evaluated the quality. Primary data and data from the included literature were extracted. Finally, the data were statistically analyzed by the Review Manager 5.3 software. RESULTS: A total of 1736 preterm infants were included in 16 RCTs. The meta-analysis showed that the incidence of necrotizing enterocolitis, late-onset sepsis, feeding intolerance, and death was lower, the time to full enteral feeding was shorter, and the day of recovery to birth weight was earlier in the intervention group (oropharyngeal colostrum administration group) than in the control group, and this difference was statistically significant. Subgroup analysis: Frequency of oropharyngeal colostrum administration: The incidence of necrotizing enterocolitis and late-onset sepsis in the once every 4 h group was lower than that in the control group, and the time to complete enteral feeding was shorter. Duration of oropharyngeal colostrum administration: In the 1-3 days group and 4-7 days group, the time to full enteral feeding in the intervention group was shorter. In the 8-10 days group, the incidence of necrotizing enterocolitis and late-onset sepsis was lower in the intervention group. CONCLUSIONS: Oropharyngeal colostrum administration can reduce the incidence of necrotizing enterocolitis, late-onset sepsis, feeding intolerance and mortality, shorten the time to full enteral feeding, and lead to a faster recovery to birth weight in preterm infants. The appropriate oropharyngeal colostrum administration frequency may be 4 h, and the optimal duration may be 8-10 days. Therefore, it is recommended that clinical medical staff implement oropharyngeal colostrum administration for premature infants based on existing evidence. TWEETABLE ABSTRACT: Oropharyngeal colostrum administration can reduce the incidence of complications in preterm infants and shorten the time to full enteral feeding.

Effects of food-borne cholesterol supplementation on lead-induced neurodevelopmental impairments of rats based on BDNF signaling pathway and cholesterol metabolism.

Despite the ubiquity and prevalence of lead (Pb) in the environment and industry, the mechanism of lead-induced neurotoxicity in the brain remains unclear, let alone its prevention and treatment. In this study, we hypothesized that exogenous cholesterol supplementation acts as an effective remedy for lead-induced neurodevelopmental impairments caused by lead. Forty 21-day-old male rats were randomly divided into four groups and administered 0.1 % lead water and/or 2 % cholesterol-containing feed for 30 d. Ultimately, rats in the lead group lost weight, accompanied by spatial learning and memory impairments as verified by the Morris water maze test, in which the escape latency of rats was prolonged, and the number of crossings in the target platform and the residence time in the target quadrant were significantly diminished compared to the control group. Hematoxylin-Eosin (H&E) staining and Nissl staining illustrated that typical pathological morphology occurred in the brain tissue of the lead group, where the tissue structure was loose, the number of hippocampal neurons and granulosa cells decreased significantly and were arranged loosely, along with enlarged intercellular space, light matrix staining, and decline in Nissl bodies. In addition, inflammatory response and oxidative stress were significantly induced by lead. Immunofluorescence experiments showed apparent activation of astrocytes and microglia, followed by the enhancement of TNF-α and IL-ß levels. Moreover, the MDA content in the lead group was elevated dramatically, whereas the activities of SOD and GSH were significantly inhibited. As for the mechanism, western blot and qRT-PCR experiments were performed, where lead could significantly inhibit the BDNF-TrkB signaling pathway, lowering the protein expression of BDNF and TrkB. Cholesterol metabolism was also affected by lead exposure, in which cholesterol metabolism-related protein expression and gene transcription, including SREBP2, HMGCR, and LDLR, were downregulated. However, cholesterol supplementation efficiently detoxified the negative effects of lead-induced neurotoxicity, reversing the inflammatory response, oxidative stress, inactivation of the BDNF signaling pathway, and imbalance of cholesterol metabolism, thus improving the learning and memory ability of rats. In brief, our study demonstrated that cholesterol supplementation could ameliorate the deficiency of learning and memory induced by lead, which is closely associated with the initiation of the BDNF/TrkB signaling pathway and regulation of cholesterol metabolism.

[Effect on Danggui Shaoyao Powder on mitophagy in rat model of Alzheimer's disease based on PINK1-Parkin pathway].

This study investigated the mechanism of Danggui Shaoyao Powder(DSP) against mitophagy in rat model of Alzheimer's disease(AD) induced by streptozotocin(STZ) based on PTEN induced putative kinase 1(PINK1)-Parkin signaling pathway. The AD rat model was established by injecting STZ into the lateral ventricle, and the rats were divided into normal group, model group, DSP low-dose group(12 g·kg~(-1)·d~(-1)), DSP medium-dose group(24 g·kg~(-1)·d~(-1)), and DSP high-dose group(36 g·kg~(-1)·d~(-1)). Morris water maze test was used to detect the learning and memory function of the rats, and transmission electron microscopy and immunofluorescence were employed to detect mitophagy. The protein expression levels of PINK1, Parkin, LC3BⅠ/LC3BⅡ, and p62 were assayed by Western blot. Compared with the normal group, the model group showed a significant decrease in the learning and memory function(P<0.01), reduced protein expression of PINK1 and Parkin(P<0.05), increased protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05), and decreased occurrence of mitophagy(P<0.01). Compared with the model group, the DSP medium-and high-dose groups notably improved the learning and memory ability of AD rats, which mainly manifested as shortened escape latency, leng-thened time in target quadrants and elevated number of crossing the platform(P<0.05 or P<0.01), remarkably activated mitophagy(P<0.05), up-regulated the protein expression of PINK1 and Parkin, and down-regulated the protein expression of LC3BⅠ/LC3BⅡ and p62(P<0.05 or P<0.01). These results demonstrated that DSP might promote mitophagy mediated by PINK1-Parkin pathway to remove damaged mitochondria and improve mitochondrial function, thereby exerting a neuroprotective effect.

Polyphenol-Rich Liupao Tea Extract Prevents High-Fat Diet-Induced MAFLD by Modulating the Gut Microbiota.

The modulation of gut microbiota dysbiosis might regulate the progression of metabolic-associated fatty liver disease (MAFLD). Here, we found that polyphenol-rich Liupao tea extract (PLE) prevents high-fat diet (HFD)-induced MAFLD in ApoE-/- male mice accompanied by protection of the intestinal barrier and downregulation of lipopolysaccharide (LPS)-related Toll-like receptor 4 (TLR4)-myeloid differentiation primary response 88 (MyD88) signaling in the liver. Fecal microbiome transplantation (FMT) from PLE-and-HFD-treated mice delayed MAFLD development significantly compared with FMT from HFD-treated mice. In this case, 16S rRNA gene sequencing revealed that Rikenellaceae and Odoribacter were significantly enriched and that Helicobacter was significantly decreased in not only the HFD+PLE group but also the HFD+PLE-FMT group. Furthermore, the level of 3-sulfodeoxycholic acid was significantly decreased in the HFD+PLE-FMT group compared with the HFD-FMT group. In conclusion, our data demonstrate that PLE could modulate the MAFLD phenotype in mice and that this effect is partly mediated through modulation of the gut microbiota.

Synergistic effect and mechanisms of ultrasound and AlOOH suspension on Al hydrolysis for hydrogen production.

Ultrasound can accelerate and change the reaction process and is widely used in the field of hydrogen production and storage. In this study, ultrasound (US) and AlOOH suspension (AH) are used to promote hydrogen production from Al hydrolysis. The results indicate that both US and AH greatly shorten the induction time and enhance the hydrogen production rate and yield. The promoting effect of US and AH on Al hydrolysis originates from the acoustic cavitation effect and catalytic effect, respectively. When AH is used in combination with US, Al hydrolysis has the best hydrogen production performance and the hydrogen yield can reach 96.6 % within 1.2 h, because there is a synergistic effect on Al hydrolysis between AH and US. Mechanism analyses reveal that the micro-jets and local high temperature environment arising from acoustic cavitation improve the catalytic activity of AlOOH, while the suspended AlOOH particles enhance the cavitation effect of US. This work provides a novel and feasible method to promote hydrogen production from Al hydrolysis.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

[Baicalin inhibits LPS/IFN-γ-induced inflammation via TREM2/TLR4/NF-κB pathway in BV2 cells].

This study investigated the mechanism of baicalin on lipopolysaccharide(LPS)/interferon γ(IFN-γ)-induced inflammatory microglia based on the triggering receptor expressed on myeloid cells 2(TREM2)/Toll-like receptor 4(TLR4)/nuclear factor kappaB(NF-κB) pathway. Specifically, LPS and IFN-γ were used to induce inflammation in mouse microglia BV2 cells. Then the normal group, model group, low-dose(5 µmol·L~(-1)) baicalin group, medium-dose(10 µmol·L~(-1)) baicalin group, high-dose(20 µmol·L~(-1)) baicalin group, and minocycline(10 µmol·L~(-1)) group were designed. Cell viability was detected by CCK-8 assay and cell morphology was observed under bright field. The expression of interleukin-1ß(IL-1ß), interleukin-4(IL-4), inducible nitric oxide synthase(iNOS), interleukin-6(IL-6), interleukin-10(IL-10), and arginase-1(Arg-1) mRNA was detected by real-time quantitative PCR, the protein expression of tumor necrosis factor-α(TNF-α), IL-1ß, TREM2, TLR4, inhibitor kappaB-alpha(IκBα), p-IκBα, NF-κB p65 and p-NF-κB p65 by Western blot, and transfer of NF-κB p65 from cytoplasm to nucleus by cellular immunofluorescence. Compared with the normal group, most of the BV2 cells in the model group tended to demonstrate the pro-inflammatory M1 amoeba morphology, and the model group showed significant increase in the mRNA levels of IL-1ß, IL-6, and iNOS, decrease in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), rise of the protein expression of TNF-α, IL-1ß, TLR4, p-IκBα, and p-NF-κB p65(P<0.01), reduction in TREM2 protein expression, and increase in the expression of NF-κB p65 in nucleus. Compared with the model group, baicalin groups and minocycline group showed the recovery of BV2 cell morphology, significant decrease in the mRNA levels of IL-1ß, IL-6 and iNOS, increase in the mRNA levels of IL-4, IL-10, and Arg-1(P<0.01), reduction in the protein expression of TNF-α, IL-1ß, TLR4, p-IκBα, and p-NF-κB p65(P<0.05), rise of TREM2 protein expression, and decrease in the expression of NF-κB p65 in nucleus. In summary, these results suggest that baicalin can regulate the imbalance between TREM2 and TLR4 of microglia and inhibit the activation of downstream NF-κB, thus promoting the polarization of microglia from pro-inflammatory phenotype to anti-inflammatory phenotype.

Immune Mechanism, Gene Module, and Molecular Subtype Identification of Astragalus Membranaceus in the Treatment of Dilated Cardiomyopathy: An Integrated Bioinformatics Study.

Astragalus membranaceus has complex components as a natural drug and has multilevel, multitarget, and multichannel effects on dilated cardiomyopathy (DCM). However, the immune mechanism, gene module, and molecular subtype of astragalus membranaceus in the treatment of DCM are still not revealed. Microarray information of GSE84796 was downloaded from the GEO database, including RNA sequencing data of seven normal cardiac tissues and ten DCM cardiac tissues. A total of 4029 DCM differentially expressed genes were obtained, including 1855 upregulated genes and 2174 downregulated genes. GO/KEGG/GSEA analysis suggested that the activation of T cells and B cells was the primary cause of DCM. WGCNA was used to obtain blue module genes. The blue module genes are primarily ADCY7, BANK1, CD1E, CD19, CD38, CD300LF, CLEC4E, FLT3, GPR18, HCAR3, IRF4, LAMP3, MRC1, SYK, and TLR8, which successfully divided DCM into three molecular subtypes. Based on the CIBERSORT algorithm, the immune infiltration profile of DCM was analyzed. Many immune cell subtypes, including the abovementioned immune cells, showed different levels of increased infiltration in the myocardial tissue of DCM. However, this infiltration pattern was not obviously correlated with clinical characteristics, such as age, EF, and sex. Based on network pharmacology and ClueGO, 20 active components of Astragalus membranaceus and 40 components of DMCTGS were obtained from TCMSP. Through analysis of the immune regulatory network, we found that Astragalus membranaceus effectively regulates the activation of immune cells, such as B cells and T cells, cytokine secretion, and other processes and can intervene in DCM at multiple components, targets, and levels. The above mechanisms were verified by molecular docking results, which confirmed that AKT1, VEGFA, MMP9, and RELA are promising potential targets of DCM.

Study on fragmentation patterns of coumarins in Notopterygium inchum with ultrahigh performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry / 中国中药杂志

To demonstrate the fragmentation patterns of simple coumarins furanocourmarin(C_7-C_8), furanocourmarin(C_6-C_7) and dihydrofuran coumarin by mass spectrometry, with fraxin, scopoletin, isopsoralen, pimpinellin, isoimperatorin, notopterol and noda-kenin as study subjects, so as to provide a basis for rapid identification of compounds in different subtypes of coumarins. Ultrahigh performance liquid chromatography combined with quardrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was implemented in both positive and negative ion modes. Masslynx software was employed to provide the elemental constituents of each detected ion based on its accurate molecular weight. Chemdraw 2014 was used to cultivate mass number of each inferred structure. The fragment pattern of each compound was determined based on the structures inferred from all the relevant ions. And the patterns were drawn by Chemdraw 2014. The deviation between the calculated molecular weight of the inferred structure and the detected value of the ions was used to assess the correctness of the inferred structures in the fragmentation patterns. The results showed that with UPLC-Q-TOF, neutral loss of CO_2 and CO was reflected in lactone and furan skeletons from the courmarin structure. An even mass was attributed to the loss of an odd number of methyl radicals from compounds with a methoxy substituent. Furanocourmarin(C_7-C_8) produced a protonated molecular ion([M+H]~+), while the other courmarin subtypes produced either a sodium adduct of the molecular ion([M+Na]~+) or a sodium adduct of the molecular ion([M+Na]~+) with a protonated molecular ion([M+H]~+). The m/z 203.03 was a diagnostic ion for furanocourmarin(C_6-C_7), and the m/z 147.04 was supplementary evidence for furanocourmarin(C_6-C_7) identification. The characteristic ion of furanocourmarin(C_7-C_8) was m/z 131.05, while m/z 187.04 was the characteristic ion of dihydrofuran coumarin. The m/z 203.03 ion for furanocourmarin(C_7-C_8) was pretty weak. In negative ion mode, furanocourmarin(C_7-C_8) did not have any signals that were different from the other subtypes of courmarins. The fragmentation patterns in negative ion mode for the other subtypes of courmarins were similar to those in positive ion mode. Four types of fragmentation patterns were identified as forcourmarins from Notopterygium inchum. This study provides the basis for the rapid identification of courmarin subtypes by mass spectrometry.

[Discussion on historical evolution and modern research progress of Sesami Semen Nigrum processing based on visual thinking].

Sesami Semen Nigrum has a long history of dual use(medicine and food). The research of its processing technology is related to the development and utilization of its own "medicine-food balance" feature, which is the basis for Sesami Semen Nigrum to realize the modernization of technology and standardization of quality. Due to its various processing methods and the long history span, the traditional medical classics(from the end of Han Dynasty to the Republic of China), modern standard specification and researches on processing were sorted out with the help of database and document mining technology, and the visual thinking was adopted to analyze the evolution trend of Sesami Semen Nigrum processing methods. In addition, the processing characteristics of Sesami Semen Nigrum in various periods and effect of processing on its chemical compositions and pharmacological effect were briefly described to explore the differences and their reasons in the processing of Sesami Semen Nigrum from ancient times to the present time, aiming to provide an idea and documentary basis for the study of traditional processing technology.

[Textual research on traditional application of Moringa].

Moringa has a long history of edible and medicinal use in foreign countries, this paper collected and sorted out the traditional application of Moringa recorded in the ancient medical books and historical materials of countries and regions along the ancient Silk Road. According to preliminary research, the earliest record of Moringa in China can be traced back to The Bower Manuscript(volume Ⅱ)(about the 4 th-6 th century A.D.) unearthed in Kuqa, Xinjiang. Around the 8 th century, with the communication between countries along the ancient Silk Road becoming prosperous, more and more medical books containing Moringa and its prescriptions were introduced to Tibet, Xinjiang and other places in today's China. The leaves, root bark, seeds and stem bark of Moringa all can be used for medicinal purposes and are recorded in The Ayurvedic Pharmacopoeia of India(API). Among them, Moringa leaves have been approved as a new resource food in China. According to the API, it is of cold property and sweet taste, its post-digestive effect is sweet and has the functions of removing wind, bile and fat, relieving pain, killing abdominal worms, moistening skin, brightening eyes and clearing brain. It can be used to treat edema, parasitic diseases, spleen diseases, abscess, tumor, pharyngeal swelling and other diseases. This study explored and organized the historical evidence of communication through the Silk Road and traditional application records of Moringa, in order to provide the evidence of traditional medicine basis, medicine property and efficacy application reference for the realization of the introduction of Moringa as a new resource of traditional Chinese medicine.

Shengui Sansheng Pulvis maintains blood-brain barrier integrity by vasoactive intestinal peptide after ischemic stroke.

Background Shengui Sansheng Pulvis (SSP) has about 300 years history used for stroke treatment, and evidences suggest it has beneficial effects on neuro-angiogenesis and cerebral energy metabolic amelioration post-stroke. However, its protective action and mechanisms on blood-brain barrier (BBB) is still unknown. Purpose Based on multiple neuroprotective properties of vasoactive intestinal peptide (VIP) in neurological disorders, we investigate if SSP maintaining BBB integrity is associated with VIP pathway in rat permanent middle cerebral artery occlusion (MCAo) model. Methods Three doses of SSP extraction were administered orally. Evaluations of motor and balance abilities and detection of brain edema were performed, and BBB permeability were assessed by Evans blue (EB) staining. Primary brain microvascular endothelial cells (BMECs) were subjected to oxygen-glucose deprivation, and incubated with high dose SSP drug-containing serum and VIP-antagonist respectively. Transendothelial electrical resistance (TEER) assay and Tetramethylrhodamine isothiocyanate (TRITC)-dextran (4.4 kDa) and fluorescein isothiocyanate (FITC)-dextran (70 kDa) were used to evaluate the features of paracellular junction. Western blot detected the expressions of Claudin-5, ZO-1, Occludin and VE-cadherin, matrix metalloproteinase (MMP) 2/9 and VIP receptors 1/2, and immunofluorescence staining tested VIP and Claudin-5 expressions. Results Our results show that SSP significantly reduces EB infiltration in dose-dependent manner in vivo and attenuates TRITC- dextran and FITC-dextran diffusion in vitro, and strengthens endothelial junctional complexes as represented by decreasing Claudin-5, ZO-1, Occludin and VE-cadherin degradations and MMP 2/9 expression, as well as promoting TEER in BMECs after ischemia. Moreover, it suggests that SSP notably enhances VIP and its receptors 1/2 expressions. VIP-antagonist exacerbates paracellular barrier of BMECs, while the result is reversed after incubation with high dose SSP drug-containing serum. Additionally, SSP also improve brain edema and motor and balance abilities after ischemic stroke. Conclusions we firstly demonstrate that the ameliorated efficacy of SSP on BBB permeability is related to the enhancements of VIP and its receptors, suggesting SSP might be an effective therapeutic agent on maintaining BBB integrity post-stroke.

Interventional effect of Chinese herbal preparation Xi Fu Pai Chen in rats with silicosis / 中国职业医学

OBJECTIVE: To investigate the interventional effect of the Chinese herbal preparation Xi Fu Pai Chen(XFPC) on pulmonary inflammation and fibrosis in rats with silicosis. METHODS: A total of 144 adult specific pathogen free male SD rats were randomly divided into 6 groups: blank control group, silicosis model group, drug administration control group and groups of low-dose,medium-dose and high-dose XFPC, with 24 rats in each group. Lung silicosis model was established by single inhalation tracheal instillation method, which was treated with 50.0 g/L silica suspension, in groups except in the blank control group. On the 7 th day of modeling, the rats in the drug administration control group were orally given tetrandrine(5 mg/kg body weight), while those in the low-, medium-and high-dose groups were given 43, 86 and 192 g/L of XFPC by atomization inhalation once a day for 20 minutes, 5 days a week for 4 weeks. At the end of drug administration, the histopathological changes of the lung were observed. The number and classification of cells in bronchoalveolar lavage fluid(BALF)were examined, and the levels of malondialdehyde(MDA) and interferon-gamma(IFN-γ) in BALF were measured by enzyme-linked immunosorbent assay. RESULTS: On the 7 th day after modeling, the body weight in the drug administration control group and XFPC high-dose group decreased compared with the blank control group(P<0.05). On the 35 th day after modeling, the body weights of rats in the other 5 groups were lower than that in the blank control group(P<0.05). The pathological changes of lung tissue(infiltration of inflammatory cells, fibrosis and size of silicon nodule) in drug administration control group and XFPC low-dose group were better than those in silicosis model group by naked eyes and under light microscope. The lung coefficient, the proportion of neutrophils and the level of MDA and IFN-γ in BALF of the drug administration control group and XFPC low-dose group decreased(P<0.05), and the proportion of macrophages in BALF increased(P<0.05) compared with the silicosis model group. There was no significant difference in lung coefficients and the relevant indices of BALF between XFPC medium-, high-dose groups and silicosis model group(P>0.05). CONCLUSION: Low dosage XFPC can improve pulmonary fibrosis and inflammation in rats with silicosis, and its mechanism of action may be related to reducing the levels of IFN-γ and MDA in BALF.

Comparative Studies of Two Major Sets of Tibetan Medical Paintings: A Historical Perspective.

Tibetan medicine, one of the time-honored medical systems in the world, has increasingly been receiving attention the world over. Tibetan medical paintings (TMP, tib. Sman thang) has become one of the focal points in the studies of this medical system. To date, there are many atlases and publications on TMP, which are principally based on the two major sets of TMP series existing today in the world, the Lhasa set and the Buryat set. It has been found that the Buryat set is based on the Lhasa set, which was brought in late 19th to the first half of the 20th century from Tibet to Buryatia, Russia. A careful investigation on the basic structure of the two sets reveals that there are many differences between the two sets of paintings, including the total number of the paintings involved, of which some are missing in one set, the details of the captions of some of the paintings, the existence of the 80th painting and its supervisor, and the overall order of the entire set, etc. The details of the differences are elaborated and discussed, and the prospective of developing the research to arrive at a standard and perfect TMP set in the future is also analyzed and anticipated.

Antipruritic effects of electroacupuncture on morphine-induced pruritus model mice through the TLR2/4-MyD88-NF-κB pathway.

Pruritus is one of the common side effects of intrathecal or epidural injection of opioids. The aim of this study was to test the antipruritic effect of acupuncture and its possible mechanism. We used electroacupuncture (EA), toll-like receptor (TLR)2/4 antagonist sparstolonin B (SsnB), and TLR2/4 agonist peptidoglycan (PGN) to precondition female wild-type BALB/c mice, and then prepared a morphine-induced pruritus model. The mRNA and protein expression levels of TLR2, TLR4, MyD88, and NF-κB were detected by RT-PCR and western blotting. The contents of interleukin (IL)-1, IL-6, IL-12, IL-10, and tumor necrosis factor-α in serum were measured by ELISA assays. Flow cytometry was performed to analyze the ratio of M1-phenotype to M2-phenotype macrophages. Our results showed that EA preconditioning improved pruritus; reduced the expressions of TLR2, TLR4, MyD88, and NF-κB both at the mRNA and protein levels (P<0.05); reduced the expression of proinflammatory cytokines IL-1, IL-6, IL-12, and tumor necrosis factor-α; and increased the expression of anti-inflammatory cytokine IL-10 (P<0.05). EA promoted M2-phenotype macrophage differentiation. Moreover, these results showed no significant difference between the SsnB group and the EA+SsnB group (P>0.05), but showed a significant difference between the PGN group and the EA+PGN group (P<0.05). Therefore, we propose that EA may be involved in the remission of pruritus in morphine-induced pruritus model mice through the TLR2/4-MyD88-NF-κB pathway. EA is a potential therapeutic treatment for pruritus.

Transformation and attribution of drug properties in Galla Chinesis fermented Baiyaojian based on cold and heat syndrome rats / 中国中药杂志

To reveal the transformation and attribution of drug properties in Galla Chinesis fermented Baiyaojian by studying the effect of Galla Chinesis and Baiyaojian on cold and heat syndrome rats. Euthyrox was used to induce the hyperthyrosis model,ice water stimulation was used to induce the cold syndrome model,and different concentrations of Galla Chinesis and Baiyaojian water decoction were administrated by gavage for 15 d continuously. Symptom indexes were evaluated,content of pyruvic acid( PA),ATPase activity in liver and contents of DA,T4,cAMP,5-HT,NE,17-OHCS,TRH and TSH in serum were assayed by enzyme linked immunosorbent assay and spectrophotometry. The rectal temperature,water consumption and body weight of heat syndrome rats in model group were increased,cAMP,NE,17-OHCS,TRH and PA were increased,TSH,Na-K ATPase and Ca-Mg ATPase were increased significantly( P<0. 01),while 5-HT was decreased,compared with those of the blank group( P< 0. 05),the contents of T4,DA,NE,TSH,TRH,cAMP and 17-OHCS were decreased significantly( P<0. 01),PA and Ca-Mg ATPase in WG and BG groups were decreased compared with those of the model group( P<0. 05),and the Galla Chinesis content of WG group was lower than that of BG group,while the contents of 5-HT in WG and BG groups were increased,and the Galla Chinesis content of WG group was higher than that of BG group,with no significant difference of viscera index between heat syndrome rats in blank group,model group and drug groups. The rectal temperature,water consumption and body weight of cold syndrome rats in model group were decreased,DA,T4,cAMP,NE,17-OHCS,TRH,TSH,PA,Na-K ATPase and Ca-Mg ATPase of rats in model group were decreased,whereas 5-HT was increased compared with those of the blank group( P<0. 05),the indexes of heart,lung and kidney were significantly higher than those in the blank group( P<0. 05). Both Galla Chinesis and Baiyaojian can significantly alleviate the symptoms of heat syndrome rats caused by levothyroxine sodium. Galla Chinesis has a better effect than Baiyaojian,but cannot alleviate the symptoms of cold syndrome caused by ice water stimulation,suggestting that the decoction of Galla Chinesis and Baiyaojian are both cold,but Galla Chinesis is colder than Baiyaojian. Cold property in Galla Chinesis fermented Baiyaojian can be relieved. In clinical application,the property of " slight cold" is more accurate than " neutral property" for Baiyaojian.

Establishment of a spectral database for classification of edible oils using matrix-assisted laser desorption/ionization mass spectrometry.

In this study, we aim to establish a comprehensive spectral database for analysis of edible oils using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). More than 900 edible oil samples, including 30 types of edible oils, were analyzed and compared, and the characteristic peaks and spectral features of each edible oil were obtained. Edible oils were divided into eight groups based on their characteristic spectral patterns and principal component analysis results. An overall correct rate of 97.2% (98.1% for testing set) was obtained for classification of 435 edible oil products using partial least square-discriminant analysis, with nearly 100% correct rate for commonly used edible oils. Differentiation of counterfeit edible oils, repeatedly cooked edible oils and gutter oils from normal edible oils could also be achieved based on the MALDI-MS spectra. The establishment of this spectral database provides reference spectra for spectral comparison and allows rapid classification of edible oils by MALDI-MS.