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ABSTRACT Objective: To analyze the compliance with the commercialization of children's products included in the Brazilian Code of Marketing of Infant and Toddlers Food and Childcare-Related Products (NBCAL) in drugstores in Uberlândia/MG. Methods: A cross-sectional study was carried out in 143 drugstores that sold infant products: infant formula (IF), follow-up IF, nipples, teats, pacifiers and nipple shields; FI for young children, transition foods and cereal-based foods, fluid or powdered milk, modified/similar milks of plant origin and dairy compounds. The location of drugstores in the five geographic sectors was performed by geoprocessing. The data collected were: types of promotion and types of drugstore administration (drugstore chains/drugstores with independent administration). Irregular commercial promotion was expressed as absolute and relative frequencies. Results: Irregular commercial promotion was found in 11.7% of nipples, pacifiers and bottles, in 10.0% of IF and follow-up formula, in 9.5% of IF for young children, in 11.1% fluid or powdered milk, in 25.0% of transition foods and cereal-based foods and in 59.1% of dairy compounds. In commercial drugstore chains, the presence of promotion for dairy (81.8 vs. 28.6%, respectively) was higher than in drugstores with independent administration. The opposite ocurred for fluid or powdered milk, modified and similar milks of plant origin. The downtown and eastern sectors had the highest percentages of promotions (26%). Conclusions: NBCAL violations still occur in drugstores, mainly in the sale of young children's foods and in the commercial network drugstores.
RESUMO Objetivo: Analisar a conformidade da comercialização dos produtos infantis incluídos na Norma Brasileira de Comercialização de Alimentos para Lactentes e Crianças de Primeira Infância, Bicos, Chupetas e Mamadeira (NBCAL) e de compostos lácteos em drogarias de Uberlândia/MG. Métodos: Estudo transversal realizado em 143 drogarias que vendiam produtos infantis: fórmulas infantis (FI) para lactentes, FI de seguimento para lactentes, mamadeiras, bicos, chupetas e protetores de mamilo; FI para crianças de primeira infância, alimentos de transição e alimentos à base de cereais, leites fluidos/em pó, leites modificados/similares de origem vegetal e composto lácteo. A localização das drogarias nos cinco setores geográficos foi realizada por geoprocessamento. Os dados coletados foram: tipos de promoção comercial irregular e tipo de administração da drogaria (rede/independente). As promoções comerciais irregulares foram expressas em frequências absoluta e relativa. Resultados: Verificamos a presença de promoção comercial irregular em 11,7% dos bicos, chupetas e mamadeiras, em 10,0% das FI lactentes/seguimento de lactentes, em 9,5% das FI para crianças de primeira infância, em 11,1% dos leites, em 25,0% de alimentos de transição e em 59,1% dos compostos lácteos. Nas drogarias de rede, a presença de promoção comercial irregular foi maior para compostos lácteos (81,8 vs. 28,6%, respectivamente) e, para leites, foi maior nas drogarias independentes (30,8 vs. 6,0%). Os setores central e leste apresentaram os maiores percentuais de promoção comercial irregular (26%). Conclusões: As violações à NBCAL ainda ocorrem nas drogarias, principalmente para os produtos destinados às crianças de primeira infância, e nas drogarias de rede.
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Danggui Sinitang is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Han dynasty. It is composed of Angelicae Sinensis Radix， Cinnamomi Ramulus， Paeoniae Radix Alba， Asari Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Tetrapanacis Medulla， and Jujubae Fructus and serves as a classic formula for treating the syndrome of blood deficiency and cold reversal. This study systematically reviews the records of Danggui Sinitang in ancient Chinese medicine books of various dynasties and the modern clinical applications to probe into the composition， plant species， processing， dosage， decocting method， and indications of Danggui Sinitang， aiming to provide a reference for the development and clinical application of this classic formula. The review of the records showed that there were a variety of records of Danggui Sinitang with different composition， and the composition of this formula listed in the Treatise on Cold Damage has a significant impact on later generations and has been used by medical practitioners throughout history. Although the dosage of some drugs decreased during the Ming and Qing dynasties， the medical practitioners continued to use the original formula. In terms of processing， although there were slight changes in the processing of Angelicae Sinensis Radix， Paeoniae Radix Alba， Glycyrrhizae Radix et Rhizoma， and Tetrapanacis Medulla， the original processing method was inherited. In terms of indications， Danggui Sinitang was designed to treat cold reversal due to blood deficiency and dysentery. Furthermore， it was used to treat headache， convulsive disease， infantile convulsion， and private part adduction in the Ming and Qing dynasties. Nowadays， this formula is mostly used to treat diabetes peripheral neuropathy， rheumatoid arthritis， dysmenorrhea， Raynaud's disease and other diseases. In terms of precautions， ancient physicians believed that Danggui Sinitang should not be taken by pregnant women and should only be used for limb chills caused by blood deficiency and cold coagulation. For limb chills caused by other reasons， this formula should not be used indiscriminately. Modern research has not reported any serious adverse reactions related to this formula. Danggui Sinitang has a definite therapeutic effect. In subsequent research and development， quality control standards of Danggui Sinitang should be established while its safety is ensured， and the related preparations should be developed and applied.
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ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.
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ObjectiveTo observe the clinical effectiveness and safety of She medicine （畲药） Diren Zishen Formula（地稔滋肾方） combined with acupuncture as adjunctive treatment for primary biliary cholangitis with liver and kidney yin deficiency syndrome. MethodsSeventy patients of primary biliary cholangitis with liver and kidney yin deficiency syndrome were randomly divided into a control group and a treatment group， with 35 patients in each group. The control group received oral ursodeoxycholic acid capsules （250 mg per dose， three times daily）. The treatment group received She medicine Diren Zishen Formula oral decoction （one dose daily， 200 ml per dose in the morning and evening， served warm） and acupuncture ［bilateral Sanyingjiao （SP6）， Taichong （LR3）， Ganshu （BL18）， Zusanli （ST36）， Fenglong （ST17）， once daily， 5 consecutive days per week］ in addition to the same treatment as the control group. The treatment duration was three months for both groups. Comparisons were made between the two groups before and after treatment for the following parameters， which were four traditional Chinese medicine （TCM） symptoms scores （skin itching， fatigue， jaundice， and flank pain）， TCM syndrome scores， liver function indicators including aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， gamma-glutamyl transferase （GGT） and total bilirubin （TBiL）， liver fibrosis markers including serum laminin （LN）， serum hyaluronic acid （HA）， serum type Ⅳ collagen （Ⅳ-C） and serum type Ⅲ procollagen （PC-Ⅲ）， and inflammatory factor indicators including serum interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α）. The effectiveness of TCM syndrome between the two groups was compared and safety evaluations were also conducted after treatment. ResultsA total of 32 cases were finally analyzed in the treatment group， while the control group had 31 cases. The total effective rate of TCM syndrome in the treatment group （87.50%， 28/32） was higher than that in the control group （67.74%， 20/31） （P＜0.05）. After treatment， the TCM symptom scores， syndrome scores， liver function， and liver fibrosis markers in both groups signi-ficantly decreased， while in the treatment group， the inflammatory factor indicators decreased after treatment， and more decreases were found than those in the control group （P＜0.05 or P＜0.01）. Both groups had good safety， and no adverse reactions were observed. ConclusionThe combination of She medicine Diren Zishen Formula and acupuncture as an adjunctive treatment for primary biliary cholangitis can significantly improve the clinical effectiveness， improve liver function， reduce inflammatory response， and alleviate liver fibrosis， with good safety.
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In recent years， data mining algorithms have been widely employed in scientific research within the field of traditional Chinese medicine （TCM）. The data mining algorithms are used to effectively handle and analyze the complex data in TCM formulas， providing a rational explanation for the mechanism of action. This method has proven particularly useful in uncovering patterns of compatibility and frequent combinations of herbs in TCM， thereby enhancing the reliability and accuracy of clinical diagnosis， target screening， and the study of new drugs. This paper reviews and analyzes 147 papers on TCM formula research that utilize data mining algorithms. The results indicate that data mining algorithms play a unique advantage in six sub- areas， including the study on the mechanism of action in TCM formula， the dose-efficacy of TCM formulas， the identification of core drugs pairs/groups， mining the relationships among “formulas-drug-symptom”， the discovery of new formulas， and mining the compatibility law. Notably， association rules and clustering algorithms are the most representative.
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ObjectiveTo investigate the possible mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of pyroptosis. MethodsFifty-two rats were randomly divided into sham operation group （n=8） and modeling group （n=44）. In the modeling group， the anterior descending branch of the left coronary artery was ligated to construct CHF rat model. Forty successfully-modelled rats were randomly divided into model group， Entresto group， Shenqi Jianxin Formula group， MCC950 group and the combination group （Shenqi Jianxin Formula plus MCC950）， with 8 rats in each group. In Shenqi Jianxin Formula group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， while in Entresto group， 68 mg/（kg·d） of Entresto suspension was given by gavage； in MCC950 group， MCC950 was injected intraperitoneally with 10 mg/kg once every other day， and in the combination group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， and MCC950 was injected intraperitoneally with 10 mg/kg once every other day； 10 ml/（kg·d） of saline was given by gavage in the sham operation group and the model group. After 3 weeks of continuous intervention， serum brain B-type natriuretic peptide （BNP）， creatine kinase isoenzyme MB （CK-MB）， interleukin 1β （IL-1β）， and interleukin 18 （IL-18） levels were detected by ELISA； HE staining and MASSON staining were used to observe pathological changes in rat myocardium. Except for the Entresto group， western blot technique was used to detect the expression of NOD-like receptor protein 3 （NLRP3）， caspase-1， and apoptosis-associated speck-like protein possessing a caspase-recruiting domain （ASC）； RT-PCR was used to detect the expression of NLRP3 and caspase-1 mRNA. ResultsCompared with the sham operation group， HE staining of rats in the model group showed obvious myocardial injury， while MASSON staining showed increased area of collagen fibrosis， and serum BNP， CK-MB， IL-1β， IL-18， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were all elevated （P＜0.05）. Compared with those in the model group， cardiomyocyte injury of rats and collagen fibrosis area were reduced， and serum BNP， CK-MB， IL-1β， and IL-18 contents were all reduced in Shenqi Jianxin Formula group， Entresto group， MCC950 group， and the combination group； except for Entresto group， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were reduced in the remaining three medication group （P＜0.05）. Compared with Shenqi Jianxin Formula group， the MCC950 group and the combination group showed decreased serum IL-1β and IL-18 content， collagen fibrosis area， myocardial tissue NLPR3， caspase-1 protein expression， and caspase-1 mRNA expression， and decreased ASC and NLRP3 mRNA expression was shown in the combination group （P＜0.05）. Compared with MCC950 group， collagen fibrosis area was reduced， and serum IL-18 content， NLRP3， caspase-1 mRNA expression were reduced in the combination group （P＜0.05）. ConclusionShenqi Jianxin Formula can effectively improve the myocardial injury and heart failure in rats with CHF， and its mechanism may be related to the inhibition of cardiomyocyte pyroptosis through NLPR3/Caspase-1 pathway to reduce the level of intramyocardial inflammation. The combined use of MCC950 with Shenqi Jianxin Formula could more effectively inhibite myocardial pyroptosis， with better therapeutic result than single use of each part.
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ObjectiveTo qualitatively analyze the chemical constituents and their tissue distribution in Lujiao formula based on ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Orbitrap-MS）. MethodThe separation was performed on an ACQUITY UPLC® BEH C18 column（2.1 mm×100 mm， 1.7 μm） with the mobile phase of 0.1% formic acid aqueous solution（A）-methanol（B） in a gradient elution（0-2 min， 4%B； 2-6 min 4%-12%B； 6-38 min， 12%-70%B； 38-38.5 min， 70%B； 38.5-39 min， 70%-95%B； 39-43 min， 95%B； 43-43.1 min， 95%-4%B； 43.1-45 min， 4%B）， the flow rate was 0.3 mL·min-1 with the column temperature of 40 ℃ and the injection volume of 5 µL. The data were acquired by an electrospray ionization（ESI） in the full scanning mode of positive and negative ions， the scanning rang was set at m/z 100-1 500， the collision energies were 10， 20， 40 eV. Retention time， precise relative molecular mass and secondary mass spectrometry fragment ions were used to identify the compounds in Lujiao formula and analyze their tissue distribution， combing with self-established database and comparing with standard substances and published literature data. ResultA total of 260 compounds， including 156 flavonoids， 43 terpenoids， 18 coumarins， 13 organic acids， 7 phenylethanoids， 7 alkaloids and 16 others， were identified or hypothesized from Lujiao formula， 68 of which were identified by comparison with standard substances. And the results of tissue distribution showed that 100， 143， 129 and 126 prototype components were detected in blood， heart， liver and kidney， respectively. ConclusionThe chemical composition of Lujiao formula and their tissue distribution were systematic analyzed， which can provide reference for the quality control， clinical application， pharmacokinetics and pharmacodynamic material basis of Lujiao formula and its medicinal materials.
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@#COVID-19 infection in pregnant mothers is associated with higher risk of intrauterine growth retardation and premature births. Very low birth weight infants are more susceptible to neurodevelopmental and chronic respiratory problems. An infant delivered at 33 weeks via caesarean section to a COVID-19 Stage 5A positive mother, weighing 1.43kg at birth. She was kept nil by mouth with parenteral nutrition (PN) support since day five of life until referred to dietitian on day 22 of life for enteral nutrition (EN) establishment. Feeding was administered intermittently via oro-gastric Ryles tube. She was kept under non-invasive ventilation (NIV) mode and had difficulty in weaning from ventilation, leading to slow feeding progress. Initially, enteral trophic feeding was administered using premature infant formula fortified with modular products. In the later stage of feeding, modular products were tapered off and the formula was concentrated. Frequency of bowel output when using fortified formula is lesser compared to when using concentrated and supplemented formula. There is no significant difference in renal profile observed in both stages of feeding. Increasing energy intake using easily digestible sources is preferable as opposed to concentrating feeds even further due to concerns about osmolality and excess administration of other solutes. Intermittent bolus feeding mode may have an effect on dependency on oxygen since intermittent feeds can decrease tidal volume, minute ventilation and dynamic compliance. Additional research is necessary to establish optimal caloric density and nutritional compositions of feedings, feeding mechanisms and its’ effect on feeding tolerance.
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El tratamiento del defecto epitelial refractario es un reto y está sujeto al desarrollo de estudios preclínicos y clínicos con el objetivo de obtener tratamientos eficaces, entre los que emerge la insulina tópica. El objetivo del presente artículo fue describir la respuesta cicatrizal del epitelio corneal bajo tratamiento con colirio de insulina. Se presentan dos pacientes con diagnóstico de defecto epitelial persistente posúlcera corneal. Se indicó insulina tópica una gota cada 6 horas, con evolución hacia la epitelización corneal total a los 10 días de iniciado el tratamiento. Se sugiere el mecanismo por el cual la insulina promueve la cicatrización corneal al lograr la restauración de los nervios corneales y favorecer la migración de células epiteliales. En ambos casos el colirio de insulina logró la promover la cicatrización epitelial total de la córnea por lo que se es útil en el tratamiento de defecto epitelial persistente.
The treatment of refractory epithelial defect is a challenge and depends upon the development of preclinical or clinical studies aimed at obtaining effective treatments, among which topical insulin emerges. The objective of this article was to describe the healing response of the corneal epithelium under treatment with insulin eye drops. The cases are presented of two patients with a diagnosis of persistent post-corneal ulcer epithelial defect. Topical insulin was prescribed at one drop every six hours, with evolution towards total corneal epithelialization ten days after the treatment started. The mechanism is suggested by which insulin promotes corneal healing, thus restoring corneal nerves and favoring epithelial cell migration. In both cases, the insulin eye drops were able to promote total epithelial healing of the cornea, making it useful in the treatment of persistent epithelial defect.
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Purpose: The ideal formula for intraocular lens (IOL) power calculation following cataract surgery in pediatric eyes till date has no answer. We compared the predictability of the Sanders–Retzlaff–Kraff (SRK) II and the Barrett Universal (BU) II formula and the effect of axial length, keratometry, and age. Methods: This was a retrospective analysis of children who were under eight years of age and who underwent cataract surgery with IOL implantation under general anesthesia between September 2018 and July 2019. The prediction error of SRK II formula was calculated by subtracting the target refraction and the actual postoperative spherical equivalent. Preoperative biometry values were used to calculate the IOL power using the BU II formula with the same target refraction that was used in SRK II. The predicted spherical equivalent of the BU II formula was then back?calculated using the SRK II formula with the IOL power obtained with the BU II formula. The prediction errors of the two formulae were compared for statistical significance. Results: Seventy?two eyes of 39 patients were included in the study. The mean age at surgery was 3.8 ± 2 years. The mean axial length was 22.1 ± 1.5 mm, and the mean keratometry was 44.7 ± 1.7 D. The group with an axial length >24 mm showed a significant and strong positive correlation (r = 0.93, P = 0) on comparison mean absolute prediction errors using the SRK II formula. There was a strong negative correlation between the mean prediction error in the overall keratometry group using the BU II formula (r = ?0.72, P < 0.000). There was no significant correlation between age and refractive accuracy using the two formulae in any of the subgroups of age. Conclusion: There is no perfect answer to an ideal formula for IOL calculation in children. IOL formulae need to be chosen keeping in mind the varying ocular parameters.
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Osteoporosis is an important cause of bone weakness and susceptibility to fractures. Anti-osteoporosis drugs of Western medicine cannot reverse its progression， and can only reduce the loss of bone density； long-term use of them is accompanied by certain adverse reactions. Traditional Chinese medicine focuses on syndrome differentiation and holistic approach， which can make up for the shortcomings of Western medicine’s treatment. The mammalian target of rapamycin （mTOR） signaling pathway is involved in the growth， proliferation， and differentiation of bone cells， and is closely related to the occurrence and development of osteoporosis. In recent years， various traditional Chinese medicine monomers （such as flavonoids， polysaccharides， alkaloids， etc.） and traditional Chinese medicine formulas （such as Bushen huoxue decoction， Liuwei dihuang pills， Erzhi pills， etc.） have been proven to promote bone formation， inhibit bone resorption， enhance bone cell autophagy， and delay the progression of osteoporosis by regulating the mTOR signaling pathway. Therefore， the article summarizes the traditional Chinese medicine monomer and formula that intervene in the mTOR signaling pathway for the treatment of osteoporosis， in order to provide medication ideas for the traditional Chinese medicine treatment of osteoporosis.
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OBJECTIVE To explore the mechanism of Yishen tongluo formula （YSTLF） in improving abnormal lipid metabolism based on the sterol regulatory element binding proteins （SREBPs） pathway. METHODS Using C57BLKS/J （db/db） mice as model and C57BLKS/J （db/m） mice as normal control， the mechanism of 1， 2.5 and 5 g/kg YSTLF improving abnormal lipid metabolism of db/db mice was investigated by determining the liver coefficient， the contents of serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL） and high-density lipoprotein （HDL）， observing steatosis and lipid accumulation in liver tissue of mice， detecting the protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription levels of Srebp- 1c， Srebp-2 and their downstream lipid metabolism-related target genes （Fasn， Acc1， Scd5， Fads1， Hmgcr， Dhcr24， Insig-1， Fdps） in liver tissue of mice. Using low-fat cultured human liver cancer cell HepG2 as an in vitro cell model for abnormal lipid metabolism， and 25-HC （SREBPs inhibitor， 10 μmol/L） as the control， the effects of 125， 250 and 500 μg/mL YSTLF on protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription of SREBP-1c， SREBP-2 and their downstream lipid metabolism-related target genes were investigated to verify the mechanism in vitro. RESULTS 1， 2.5， 5 g/kg YSTLF significantly reduced the levels of TC， TG and LDL， the percentage of lipid droplet-positive region in liver tissue and liver coefficient， significantly down-regulated protein expressions of Pre-SREBP-1， n-SREBP-1， Pre-SREBP-2 and n-SREBP-2， and mRNA transcription of Srebp-1c， Srebp-2 and their downstream target genes in liver tissue， while significantly increased HDL level， with statistical significance （P＜0.05 or P＜0.01）. In the cell experiment in vitro， the expressions of the above-mentioned proteins and genes in the cells treated with YSTLF at 125， 250 and 500 μg/mL for 24 hours were consistent with those in the animal experiment； there was no significant difference in the expressions of the above-mentioned proteins and genes between inhibitor control group and 250， 500 μg/mL YSTLF groups （P＞0.05）. CONCLUSIONS YSTLF can regulate the expression of transcription factor SREBPs， so as to inhibit the high expression of fatty acid and cholesterol synthesis-related genes， promote the degradation of TC and TG， improve the abnormality of lipid metabolism and inhibit lipid accumulation， thus playing the role of lipid-lowering.
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In this study, the mechanism of Xiaoyan Lidan formula (XYLDF) against 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-collidine (DDC)-induced chronic intrahepatic cholestasis (CIHC) in mice was investigated based on metabolomics, molecular docking and pharmacological methods. In the pharmacodynamics study, a dosage of 5 g·kg-1 (clinical equivalent) XYLDF was administered in DDC-induced mice, then the effect of XYLDF against CIHC was evaluated by measuring the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP) as well as total bilirubin (TBIL) in serum and observing liver histopathological changes. All experiments were approved by the Ethical Committee Experimental Animal Center of Guangzhou University of Chinese Medicine (ZYD-2021-001). The serum metabolites of mice in each group were detected and identified based on ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, and the relevant biological pathways and molecular key targets were further enriched. Molecular docking technology was used to further evaluate the binding activity of the main active ingredients of XYLDF with potential targets. Subsequently, the in vitro experiment was conducted for the validation of the vital target. The results showed that compared with the model group, XYLDF significantly decreased the levels of ALT, AST, AKP and TBIL in the serum of CIHC mice, as well as alleviated inflammatory infiltration and hepatocyte necrosis in liver tissue. According to the metabonomic study, a total of 35 differential metabolites was identified as biomarkers associated with cholestasis, 12 of which were significantly recovered by XYLDF treatment. These biomarkers were involved in the pathways of primary bile acid biosynthesis and linoleic metabolism, which are closely related to the mechanism of XYLDF against CIHC. Protein-protein interaction network indicated that cytochrome P450 3A4 (CYP3A4) and cytochrome P450 1A1 (CYP1A1) are significant potential targets with good binding properties with six major active ingredients of XYLDF. Furthermore, it was found that 4-methoxy-5-hydroxycanthin-6-one, dehydroandrographolide and isodocarpin, three of the main active components in XYLDF, markedly induced the expression of CYP3A4 mRNA in vitro. This study revealed that XYLDF mainly mediates the biosynthesis of bile acids in CIHC mice to improve liver tissue lesions and bile efflux disorders, among which, CYP3A4 is the key target in the protection of XYLDF against CIHC. This research provides a reference for further elucidation of the pharmacological mechanism of XYLDF.
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In this study, we investigated the effect of Cigu Xiaozhi formula on HSC-T6 activity in hypoxic microenvironment based on network pharmacology and computer-aided drug design, and predicted and verified its possible targets and related signaling pathways. The potential active components and targets of Cigu Xiaozhi formula were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Encyclopaedia of Traditional Chinese Medicine (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases, and the liver fibrosis related targets retrieved from Gene Cards and Pharm GK database were integrated to obtain the potential targets of Cigu Xiaozhi formula in the treatment of liver fibrosis. GO enrichment analysis and KEGG signaling pathway enrichment analysis were performed on Omic Share platform, and Cytoscape software was used to construct the "potential active ingredient-key target-pathway" network. The active components and target proteins were subjected to molecular docking analysis by Auto Dock software. According to the results of molecular dynamics simulation and binding free energy calculation, the top 5 active components with degree were scored. The active components stigmasterol and β-sitosterol were subjected to molecular docking. CoCl2 was used to induce HSC-T6 cells to construct hypoxia model in vitro. The cell viability was detected by CCK-8 assay, and the optimal time and concentration of hypoxia model of HSC-T6 cells was determined to be 100 µmol·L-1 CoCl2 for 24 h. Under hypoxia condition, HSC-T6 cells were activated, the wound healing rate was significantly increased, and the fluorescence signal of activation marker protein α-smooth muscle actin (α-SMA) was significantly enhanced. However, 6% drug-containing serum could inhibit the activation of HSC-T6 cells, and the wound healing rate was significantly decreased, and the fluorescence signal of α-SMA was significantly weakened. Further studies showed that the expressions of hypoxia-inducible factor-1α (HIF-1α), α-SMA and key proteins of Hedgehog (Hh) signaling pathway in HSC-T6 cells were up-regulated under hypoxia, while the expressions of HIF-1α, α-SMA, Patched-1 (Ptch-1) and glioma related oncogene homology-1 (Gli-1) were down-regulated in 6% drug-containing serum group, the YC-1 group and the cyclopamine group. These results indicated that HIF-1α and Hh signaling pathways were involved in the activation of HSC-T6 cells, and the traditional Chinese medicine Cigu Xiaozhi formula could inhibit the activation of HSC-T6 cells, and the mechanism may be related to the inhibition of HIF-1α expression and the blocking of Hh signaling pathway. In conclusion, Cigu Xiaozhi formula can inhibit the activation of HSC-T6 cells by directly acting on HIF-1α and Hh signaling pathway, and exert an anti-hepatic fibrosis effect. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Gansu University of Chinese Medicine, in compliance with the Institutional Animal Care Guidelines.
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ObjectiveTo explore the effects and possible mechanism of Wenshen Tongdu Formula （温肾通督方， WTF） on spinal cord injury. MethodsThirty-six C57BL/6 female mice were randomly divided into sham operation group， model group and WTF group， with 12 mice in each group. The spinal cord injury model was established in the model group and the WTF group using the modified Allen's method， while in the sham operation group the spinal cord was only exposed. Since the 1st day after surgery， 50 g/（kg·d） of WTF solution was given to the WTF group by gavage， while 20 ml/（kg·d） of normal saline was given to the sham operation and model group by gavage， all for 14 days. Before surgery and on the 1st， 7th， and 14th days after surgery， the motor function of the mice was evaluated using the inclined plane test and hind limb motor function score （by BMS）. On the 3rd day after surgery， the nerve electrophy-siology was detected through electromyography and motor evoked potential； the spleen length was measured， and B cells in the spleen were sorted by magnetic beads； the differential expression of proteins were detected through proteomics technology； and the protein expression of mitochondrial outer membrane transport porin 20 （Tom20） and downstream cleaved caspase-3 in spleen B cells were measured using Western blotting. On the 14th day after surgery， MRI was used to observe the recovery of the spinal cord. ResultsCompared to those in the sham operation group at the same time， the BMS scores and subscores and the inclined plane test angle in the model group were reduced on the 1st， 7th and 14th days after surgery； the peak value of electromyogram and motor evoked potential were reduced， and the spleen length was shortened， while the expression of Tom20 and cleaved caspase-3 increased in splenic B cells increased （P＜0.05）. Compared to those in the model group at the same time， the BMS subscores on the 14th day and the angle of the inclined plane test on the 7th and 14th days after surgery increased in the WTF group； the peak value of electromyography and motor evoked potential， as well as the length of spleen increased， and the expression of Tom20 and cleaved caspase-3 decreased （P＜0.05）. The proteomics results showed that there were 100 differential proteins in the WTF group versus the model group， of which 37 were up-regulated and 63 were down-regulated. GO enrichment analysis showed that differential proteins mainly played their roles in oxygen binding， exogenous apoptosis negative feedback， zinc ion response， and oxygen transport. KEGG enrichment analysis showed that differential proteins were mainly concentrated in metabolic pathways， Huntington's disease， oxidative phosphorylation and other pathways. Subcellular localization showed that differential proteins were associated with mitochondria. Magnetic resonance imaging on the 14th day after surgery showed that the spinal cord structure of the mice in the sham operation group was intact， and the segments were clear， with normal spinal cord signal； the low signal area in the spinal cord injury area increased in the model group， and the spinal cord became significantly thinner； the injured segment had obvious depression in the WTF group， but the structure was more complete than that in the model group. ConclusionWTF may promote spinal cord injury repair by regulating immune function， and its mechanism may be related to inhibiting pyroptosis of spleen B cells.
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ObjectiveTo observe the clinical effect of Yiqi Liangxue Shengji Formula （益气凉血生肌方， YLSF） on recurrence of angina pectoris and quality of life at eight weeks after perecutaneous coronary intervention （PCI）. MethodsEighty-two coronary artery disease （CAD） patients with qi deficiency and blood stasis and binding of stasis and heat syndrome who had underwent PCI were randomly divided into two groups with 41 patients each in the treatment group and the control group. Based on conventional western medicine after PCI， patients in the treatment group orally took YLSF granules while those in the control group were administered with placebo， one dose daily for 8 weeks. The recurrence rate of angina pectoris and readmission rate within eight weeks after PCI were recorded. Before and after treatment， total traditional Chinese medicine （TCM） syndrome score， Seattle Angina Questionnaire （SAQ） scores （physical limitation， angina stability， angina frequency， treatment satisfaction and disease perception）， and the SF-36 scores for quality of life （physical and mental health） were evaluated. The adverse reactions during medication in both groups were recorded. ResultsWithin eight weeks after PCI， the recurrence rate of angina pectoris in the treatment group （4/41， 9.76%） was significantly lower than that in the control group （11/41， 26.83%， P＜0.05）. The readmission rate in the treatment group was 2.44% （1/41）， while that in the control group was 12.20% （5/41）， with no significantly statistical difference （P＞0.05）. After treatment， total TCM syndrome score significantly decreased in both groups， while in terms of quality of life， the SAQ scores on domains of angina stability， angina frequency and disease perception as well as SF-36 total scores， physical health and mental health scores significantly increased （P＜0.05 or P＜0.01）. Compared between the two groups， total TCM syndrome score was significantly lower in the treatment group than the control group （P＜0.01）， while no significant differences were found in SAQ scores and SF-36 total， physical and mental health scores （P＞0.05）. No adverse reactions occurred in both groups during the treatment period. ConclusionYLSF can reduce the recurrence rate of angina pectoris within eight weeks after PCI for coronary artery disease， and can improve the TCM syndrome score， and have sound safety， with comparable effect to that of placebo in improving postoperative short-term quality of life.
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OBJECTIVE In order to analyze the current situation of policy tool allocation in China’s TCM formula granule industry， and provide a theoretical basis for the high-quality development of the industry. METHODS Based on the perspective of policy tools，“ TCM formula granules” was used as the keyword to retrieve the official websites of departments directly under the State Council such as the National Medical Products Administration and the National Administration of Traditional Chinese Medicine， as well as provincial governments. The relevant clauses in the policy documents related to TCM formula granules in China from 1993 to 2022 were encoded， and then the application of policy tools was summarized and classified. RESULTS & CONCLUSIONS A total of 12 national documents and 77 provincial documents were ultimately selected， involving 556 relevant policy clauses. It was found that among the relevant policy tools， environmental policy tools had the highest degree of attention， accounting for 62.6%； the proportions of demand-oriented policy tools and supply-oriented policy tools were less， accounting for 17.8% and 19.6%， respectively. From the perspective of policy tools， the use of demand-oriented policy tools in current policy texts was relatively simple， and various policy tools were given low attention； from the perspective of policy objectives， the proportion of use of environmental， demand-oriented and supply-oriented policy tools were not balanced enough. It is suggested to increase the proportion of demand- oriented policy tools to meet international competition； emphasize the use of supply-oriented policy tools to strictly control product quality； consolidate the use of environmental policy tools to standardize quality standards. On this basis， we will coordinate the overall situation， balance the use of various policy tools and promote the development of TCM formula granule industry.
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Objective To observe the protective effect of Shenmajing formula on brain tissue of mice with cerebral ischemic injury and explore the possible mechanism. Methods Thirty SPF-grade C57 BL/6 male mice were randomly divided into model control group, Shenmajing group and nimodipine group, and the animal models of cerebral ischemic injury in mice were prepared by electrocoagulation. The protein expression level in endothelial progenitor cells were detected by Western blot. Results Compared with the model control group, the infarct volume of mice in the Shenmajing group was significantly reduced, and the migration, adhesion and tubule formation ability of endothelial progenitor cells were significantly improved, and the expression level of BDNF protein in endothelial progenitor cells was significantly increased. Conclusion The protective effect of Shenmajing granules on brain tissue of mice with cerebral ischemic injury could be closely related to the regulation of BDNF expression in endothelial progenitor cells and improvement of endothelial progenitor cell function of bone marrow origin.
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@#【Objective】 To investigate the correlations between intestinal flora, plasma metabolites, and blood stasis syndrome in coronary heart disease (CHD), and the mechanisms of Yangxin Tongmai Formula (养心通脉方, YXTMF) for blood stasis syndrome in CHD rats. 【Methods】 A total of 18 specific pathogen free (SPF) male Sqrague-Dawley (SD) rats were used to establish CHD rat models with blood stasis syndrome, which were then randomized into model, YXTMF, and atorvastatin calcium (AVT) groups, with six rats in each group, and were intervened through gavage for two weeks. Subsequently, additional six rats that received normal diet were included as normal group. The pathological changes in the CHD rat models were identified by hematoxylin-eosin (HE) staining. The electrocardiogram, hemodynamics, and lipid profiles of the rats were detected as well. The untargeted plasma metabolomics of rats were analyzed by liquid chromotography-tandem mass spectrometry (LC-MS/MS), their ileal mucosal flora by 16S rRNA sequencing, and the correlation between the two results were also analyzed. 【Results】 The whole blood viscosity, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of rats in the model group increased compared with those in the control group (P < 0.05). In the model group, the proliferation of endothelial cells in the coronary artery of rats was damaged, with quite a few vacuolated pathological changes observed. However, the endothelial lesions in the coronary artery of rats were alleviated in the intervention groups (YXTMF and AVT groups). With the use of LC-MS/MS, a total of 33 potential endogenous metabolites were identified in plasma, among which 1-methylhistidine, N-acetylhistamine, progesterone, and deoxycorticosterone were expected to be the differential metabolites in CHD rats with blood stasis syndrome. The 16S rRNA sequencing results showed that improved diversity and abundance of intestinal flora were observed in the YXTMF group. The correlation analysis suggested that Hydrogenophaga, Limnohabitans, and Polaromonas, which were highly related to the formation of blood stasis syndrome in CHD patients, were positively correlated with plasma metabolites such as 5-hydroxyindole, N-acetylhistamine, and progesterone (P < 0.01), but were negatively correlated with plasma metabolites such as L-arginine, homoarginine, and Boc-beta-cyano-L-alanine (P < 0.01). After YXTMF intervention, Lactobacillus, Corynebacterium, and Candidatus Nitrososphaera were positively correlated with plasma metabolites such as Boc-β-cyano-L-alanine, stachydrine, and naringenin (P < 0.05), while negatively correlated with 5-hydroxyindole, N-acetylhistamine, and oleoylethanolamide (P < 0.05). 【Conclusion】 YXTMF could alleviate blood stasis syndrome in CHD rats through improving their plasma metabolisms achieved by regulating the intestinal flora.
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ObjectiveTo explore the possible mechanism of reducing cholecystitis and preventing cholelithiasis by Dahuang Lingxian Formula（大黄灵仙方， DLF）. MethodsFifty SD rats were randomly divided into blank group， model group， DLF group， DLF + blank inhibitor group， and DLF + inhibitor group， with 10 rats in each group. The rat model of cholecystitis was established by lipopolysaccharide （LPS） induction in all the groups except for the blank group. Rats in DLF group， DLF + blank inhibitor group and DLF + inhibitor group received intragastric administration of 320 mg/ （kg·d） of DLF 3 days before the preparation of cholecystitis model， while those in blank group and model group were given 2 ml/100 g of distilled water by gastric， twice a day， for 6 consecutive days. Hematoxylin-eosin （HE） staining was used to observe the histopathologic changes of bile duct tissues in each group. The expression of nuclear factor κB （NF-κB） protein in bile duct tissues was detected by immunohistochemistry. The expression levels of interleukin1β （IL-1β） and tumor necrosis factor α （TNF-α） in serum of rats were detected by enzym-linked immunosorbent assay （ELISA）. The mRNA expression levels of miRNA-30b， transforming growth factor β1 （TGF-β1）， nucleotide-binding oligomerization domain-like receptor protein 3 （NLRP3） and bone morphogenetic protein 2 （BMP2） in bile duct tissues were detected by real-time PCR， and the protein expression levels of TGF-β1， NLRP3 and BMP2 were detected by Western blot. ResultsCompared to those in the blank group， the structure of the bile duct in the model group was abnormal， and a large number of lymphocytes， plasma cell infiltration and bile canaliculi dilation were seen in the portal area； the positive expression of NF-κB protein increased； there was nuclear infiltration； the expressions of serum inflammatory factors IL-1β and TNF-α， as well as the mRNA and protein expressions of TGF-β1， NLRP3 and BMP2 in bile duct tissue significantly increased， while the expression level of miRNA-30b significantly decreased （P＜0.01）. Compared to those in the model group， the pathological morphology of the bile ducts in the DLF group and DLF + blank inhibitor group was improved， and the infiltration of inflammatory cells was reduced， with decreased positive expression of NF-κB and nuclear infiltration； expression levels of serum inflammatory factors IL-1β and TNF-α， and the mRNA and protein expressions of TGF-β1， NLRP3 and BMP2 in bile duct tissue decreased， while the expression level of miRNA-30b significantly increased （P＜0.05 or P＜0.01）. Compared to the model group， those indicators in the DLF + inhibitor group was not significantly improved （P＞0.05）. There was no significant difference in the indicators between the DLF group and the DLF + blank inhibitor group （P＞0.05）. ConclusionDLF may play a role in delaying the progression of cholelithiasis by regulating the expression of miRNA-30b and inflammation-fibrosis related factors.