[Treatment of ornithine transcarbamylase deficiency in a child with glyceryl phenylbutyrate]. / è‹¯ä¸é ¸ç”˜æ²¹é ¯æ²»ç–—å„¿ç«¥é¸Ÿæ°¨é ¸æ°¨ç”²é °åŸºè½¬ç§»é ¶ç¼ºä¹ç—‡1例.

Glyceryl phenylbutyrate (GPB) serves as a long-term management medication for Ornithine transcarbamylase deficiency (OTCD), effectively controlling hyperammonemia, but there is a lack of experience in using this medicine in China. This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, including a review of related literature. After diagnosis, the patient was treated with GPB, followed by efficacy follow-up and pharmacological monitoring. The 6-year and 6-month-old male patient exhibited poor speech development, disobedience, temper tantrums, and aggressive behavior. Blood ammonia levels peaked at 327 µmol/L; urine organic acid analysis indicated elevated uracil levels; cranial MRI showed extensive abnormal signals in both cerebral hemispheres. Genetic testing revealed de novo mutation in the OTC gene (c.241T>C, p.S81P). Blood ammonia levels were approximately 43, 80, and 56 µmol/L at 1, 2, and 3 months after starting GPB treatment, respectively. During treatment, blood ammonia was well-controlled without drug-related adverse effects. The patient showed improvement in developmental delays, obedience, temperament, and absence of aggressive behavior.

Deciphering the Hypoxia-immune interface in esophageal squamous carcinoma: a prognostic network model.

Introduction: The rapid progress and poor prognosis of the exercise of esophageal squamous cell carcinoma (ESCA) bring great challenges to the treatment. Hypoxia in the tumor microenvironment has become a key factor in the pathogenesis of tumors. However, due to the lack of clear therapeutic targets, hypoxia targeted therapy of ESCA is still in the exploratory stage. Methods: To bridge this critical gap, we mined a large number of gene expression profiles and clinical data on ESCA from public databases. First, weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis were performed. We next delved into the relationship between hypoxia and apoptotic cell interactions. Meanwhile, using LASAS-Cox regression, we designed a robust prognostic risk score, which was subsequently validated in the GSE53625 cohort. In addition, we performed a comprehensive analysis of immune cell infiltration and tumor microenvironment using cutting-edge computational tools. Results: Hypoxia-related genes were identified and classified by WGCNA. Functional enrichment analysis further elucidated the mechanism by which hypoxia affected the ESCA landscape. The results of the interaction analysis of hypoxia and apoptotic cells revealed their important roles in driving tumor progression. The validation results of the prognostic risk score model in the GSE53625 cohort obtained a good area under the receiver operating characteristic (ROC) curve, and the risk score was independently verified as a significant predictor of ESCA outcome. The results of immune cell infiltration and tumor microenvironment analysis reveal the profound impact of immune cell dynamics on tumor evolution. Conclusion: Overall, our study presents a pioneering hypoxiacentered gene signature for prognostication in ESCA, providing valuable prognostic insights that could potentially revolutionize patient stratification and therapeutic management in clinical practice.

Progress in research of long-term protective efficacy of human papillomavirus vaccine / 中华流行病学杂志

The efficacy of HPV vaccine in preventing cervical cancer has been demonstrated in numerous clinical trials and clinical uses. The follow-up after clinical trials usually last for 5-6 years to evaluate the long-term efficacy, and a series of long-term follow-up studies have been conducted in some regions. The literature retrieval of HPV vaccine long term efficiency research both at home and abroad indicated that the protective efficacy of the vaccine against vaccine-type-related cervical intraepithelial neoplasia grade 2 and above is higher than 90%.

[Evaluation of ecological conservation red line from the perspective of ecological security pattern: Taking Zhejiang Province, China as an example]. / ç”Ÿæ€å®‰å ¨æ ¼å±€è§†è§’ä¸‹çš„ç”Ÿæ€ä¿æŠ¤çº¢çº¿è¯„ä¼°­­ä»¥æµ™æ±Ÿçœä¸ºä¾‹.

To investigate the scientificity of the ecological conservation red line in Zhejiang Province, we evaluated the ecological effect based on the concept of ecosystem processes from the perspective of ecological security pattern. On the basis of clarifying the triple connotation of the ecological conservation red line, we constructed an evaluation index system to identify ecological sources and evaluate the importance of red line patches with InVEST model and net primary productivity quantitative analysis. Minimum resistance model and gravity model were used to construct the ecological corridors and evaluate the connectivity of red line. Moreover, landscape pattern index and overlay analysis were applied to evaluate the fragmentation and coordination of red line. The results showed that, from the perspective of ecological importance, the protection scale in Zhejiang Province was relatively large, but 13.5% of the red line areas were not of high importance. About 40% of the provincial ecological sources were not included in the ecological conservation red line. From the perspective of spatial structure, the connectivity of the ecological conservation red line was insufficient. The protection rate of the first-level ecological corridor was less than 15%. The red line patches in some counties and cities were relatively broken. From the perspective of natural-social system coordination, cross-administrative red line areas were well connected. However, it was still necessary to pay attention to the fact that the conflict between supply and demand in the plain area had led to spatial mismatch and fragmentation of red line. Using the ecological security pattern for reference, we put forward the relevant strategies of red line optimization and adjustment, which could provide scientific reference for ecological space management.

Evaluation of lipid metabolism imbalance in HIV-infected patients with metabolic disorders using high-performance liquid chromatography-tandem mass spectrometry.

Human immunodeficiency virus (HIV) infection and highly active antiretroviral therapy use are associated with the disruption of lipid and glucose metabolism. Herein, a sensitive and robust high-performance liquid chromatography-tandem mass spectrometry method for the quantitation of lysophosphatidylcholines (LPCs) and acylcarnitines (ACs) in human blood serum was developed and validated to investigate them as markers of metabolic disorders in HIV-infected patients. Under optimal extraction and detection conditions, the lower limits of quantification reached 5 ng/mL (LPCs) and 0.1 ng/mL (ACs), and precision and accuracy for both intra- and inter-day analyses were generally below 15%. Serum samples were stable for at least six months when stored at - 80 °C and for at least 12 h when stored at 4 °C or 25 °C. We investigated inter-group differences and associations between the biomarkers and observed a particular volatilitytrend of LPCs and ACs for HIV-infected patients with metabolic disorders. Thus, the developed method can be used for the rapid and sensitive quantitation of LPCs and ACs in vivo to further appraise the process of HIV infection, evaluate interveningmeasures, conduct mechanistic investigations, and further study the utility of LPCs and ACs as biomarkers of HIV infection coupled with metabolic disorders.

The overall action molecular mechanism of anti-hepatitis B active extracts in Flos chrysanthemi indici based on epigenetics and metabonomics / 药学学报

Using the concepts and methods of epigenetics and metabolomics, to investigate the overall action molecular mechanism of Chrysanthemi indici C (CIC), the anti-hepatitis B virus (HBV) active extracts from Flos chrysanthemi indici. The inhibitory effects of CIC on proliferation and hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg) and HBV-DNA of HepG2.2.15 cells were detected by CCK-8 and antigen kit. The DNA methyltransferases (DNMTs)/ten-eleven-translocation-2 (TET2) equilibrium was detected by ELISA. Illumina 850K methylation chip, pyrosequencing and qPCR were used to determine the action pathway and target of CIC by GO and KEGG analysis. Cell metabolites were extracted with 80% methanol, and the changes of differential metabolites, differential metabolic pathways and cell microenvironment were detected by LC-MS and other metabolomics methods. The results showed that CIC could inhibit the proliferation, HBsAg, HBeAg and HBV-DNA of HepG2.2.15 cells obviously, down-regulate DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3a (DNMT3a) and DNA methyltransferase 3b (DNMT3b), up-regulate TET2, and restore the balance of DNMTs/TET2. The action targets of CIC were phospholipase C gamma 2 (PLCG2), phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), 5-hydroxytryptamine receptor 2B (HTR2B), nerve growth factor (NGF), mainly involved in lipid metabolism, inflammation mediated regulation of transient receptor potential (TRP), phospholipase D signaling and advanced glycation end product-receptor for AGE (AGE-RAGE) signaling in diabetic complications pathways. CIC could significantly affect fatty acid metabolism and had great influence on phenolic acid, alkaloid and lipid metabolites in cell microenvironment. These results suggest that the action mechanism of CIC may be the synergistic action of multiple pathways and multiple targets, including related inflammatory pathways, immune pathways and lipid metabolism, through regulating epigenetic expression balance and restoring the balance of cell microenvironment.

Comparative study on the pharmacodynamic difference of oral administration of Xiaojin Pills accompanied with Chinese Baijiu and water.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaojin Pills is a classic prescription for the treatment of mammary glands hyperplasia with a history of nearly 300 years, and is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinic. Clinical and animal studies have shown that Xiaojin Pills has the effects of anti-mammary glands hyperplasia, promoting blood circulation, anti-inflammation and analgesia. However, its initial administration method was "taking orally after soaked with Chinese Baijiu", the modern method was changed to "taking orally with water" in recent 20 years. Whether there is any difference in the efficacy of the two administration methods is still unknown. AIM OF THE STUDY: To reveal the difference in efficacy and metabolic mechanism of anti-mammary gland hyperplasia between the oral administration of Xiaojin Pills accompanied with Chinese Baijiu (XJP&B) and water (XJP&W). MATERIALS AND METHODS: COX-2 inhibition rate test and anti-platelet aggregation activity test were used to investigate the efficacy difference between the 40 vol% Chinese Baijiu and water extracts of Xiaojin Pills on anti-inflammatory and blood-activating in vitro. Kunming male mice (20 ± 5 g) and SD female rats (200-220 g) were orally treated with XJP&B and XJP&W, respectively. Then the difference in anti-inflammatory and analgesic effects between XJP&B and XJP&W were evaluated via xylene-induced ear swelling test, formaldehyde-induced pain test, and acetic acid-induced writhing test in mice. Determination of nipple diameter, pathological examination of mammary gland tissue, determination of serum E2, P and FSH content and hemorheological parameters of rats with mammary gland hyperplasia were performed to explore the efficacy difference in anti-mammary gland hyperplasia between XJP&B and XJP&W. Metabolomics was used to study the difference of anti-mammary gland hyperplasia mechanism between XJP&B and XJP&W. RESULTS: The results showed that the effect of XJP&B was superior to that of XJP&W in anti-platelet aggregation, inhibition of inflammation and pain, and anti-mammary gland hyperplasia. Interestingly, the advantages were more significant under low-dose condition. In addition, the mechanism of the two combinations against mammary gland hyperplasia was indeed different. Their common metabolic pathways include tryptophan metabolism and alanine, aspartic acid and glutamic acid metabolism. However, Chinese Baijiu and XJP&B also have additional regulatory effects on linoleic acid metabolic pathway. CONCLUSION: In brief, this research demonstrated that the efficacy of XJP&B was better than that of XJP&W in activating the blood, anti-inflammation, analgesia and anti-mammary gland hyperplasia, which means that XJP&B has synergistic and superior effects. The special dose-effect relationship under the condition of XJP&B was also found, laying the foundation for clinical treatment to reduce the dosage and shorten the medication cycle, which is beneficial to reduce the economic burden of patients.

SEM analysis of sensilla on the mouthparts and antennae of Asian larch bark beetle Ips subelongatus.

The Asian larch bark beetle, Ips subelongatus, is a severe pest of larches in Northeastern China. The gustatory and olfactory systems of I. subelongatus play important roles in host location, mating, and feeding. In this study, we examined the types, distributions, and abundances of various sensilla associated with the mouthparts and antennae of I. subelongatus using scanning electron microscopy (SEM). On the mouthparts, five types of sensilla are present: sensilla trichodea (S.t.1-3), sensilla chaetica (S.c.1-3), sensilla basiconica (S.b.1-2), sensilla twig basiconica (S.tb.1-3), and sensilla placodea (S.p). S.t.3 are the most abundant sensilla subtype on the mouthparts in both sexes, while S.b.1 are the least abundant. Most sensilla on the mouthparts are located on the maxillae and labium, and the apex of each maxillary and labial palp carry the same sensilla subtypes (S.b.2 and S.tb.1-3). However, the total number of sensilla on the apex of each maxillary palp is higher than that on the labial palp. On the antennae, five types of sensilla are present: sensilla trichodea (S.t.1-3), sensilla chaetica (S.c.1-2), sensilla basiconica (S.b.1-3), Böhm bristles (B.b), and sensilla coeloconica (S.co). Antennal sensilla are mostly situated on the anterior surface of the antennal club, particularly on the two dense sensory bands. S.b.1 are the most abundant sensilla subtype on the antennae in both sexes, while S.t.1 are the least abundant. No sexual dimorphism in sensilla type or distribution on the mouthparts or antennae is observed between the sexes of I. subelongatus. However, S.t.3 (on mouthparts) and S.c.1 (on antennae) were significantly more abundant in males than in females, while more S.t.1 (on mouthparts) were observed in females than in males. Finally, the putative functions of each kind of sensilla with respect to their fine structures, distributions, and abundances on the mouthparts and antennae are discussed.

New progress in the pharmacology of protocatechuic acid: A compound ingested in daily foods and herbs frequently and heavily.

Protocatechuic acid is a natural phenolic acid, which widely exists in our daily diet and herbs. It is also one of the main metabolites of complex polyphenols, such as anthocyanins and proanthocyanins. In recent years, a large number of studies on the pharmacological activities of protocatechuic acid have emerged. Protocatechuic acid has a wide range of pharmacological activities including antioxidant, anti-inflammatory, neuroprotective, antibacterial, antiviral, anticancer, antiosteoporotic, analgesia, antiaging activties; protection from metabolic syndrome; and preservation of liver, kidneys, and reproductive functions. Pharmacokinetic studies showed that the absorption and elimination rate of protocatechuic acid are faster, with glucuronidation and sulfation being the major metabolic pathways. However, protocatechuic acid displays a dual-directional regulatory effect on some pharmacological activities. When the concentration is very high, it can inhibit cell proliferation and reduce survival rate. This review aims to comprehensively summarize the pharmacology, pharmacokinetics, and toxicity of protocatechuic acid with emphasis on its pharmacological activities discovered in recent 5 years, so as to provide more up-to-date and thorough information for the preclinical and clinical research of protocatechuic acid in the future. Moreover, it is hoped that the clinical application of protocatechuic acid can be broadened, giving full play to its characteristics of rich sources, low toxicity and wide pharmacological activites.

Neutralizing and binding antibody kinetics of COVID-19 patients during hospital and convalescent phases

Knowledge of the host immune response after natural SARS-CoV-2 infection is essential for informing directions of vaccination and epidemiological control strategies against COVID-19. In this study, thirty-four COVID-19 patients were enrolled with 244 serial blood specimens (38.1% after hospital discharge) collected to explore the chronological evolution of neutralizing (NAb), total (TAb), IgM, IgG and IgA antibody in parallel. IgG titers reached a peak later (approximately 35 days postonset) than those of Nab, Ab, IgM and IgA (20[~]25 days postonset). After peaking, IgM levels declined with an estimated average half-life of 10.36 days, which was more rapid than those of IgA (51.25 days) and IgG (177.39 days). Based on these half-life data, we estimate that the median times for IgM, IgA and IgG to become seronegative are 4.59 (IQR 4.12-5.03), 7.78 (IQR 6.71-9.16) and 42.72 (IQR 33.75-47.96) months post disease onset. The relative contribution of IgM to NAb was higher than that of IgG (standardized {beta} regression coefficient: 0.53 vs 0.48), so the rapid decline in NAb may be attributed to the rapid decay of IgM in acute phase. However, the relative contribution of IgG to NAb increased and that of IgM further decreased after 6 weeks postonset. Its assumed that the decline rate of NAb might slow down to the same level as that of IgG over time. This study suggests that SARS-CoV-2 infection induces robust neutralizing and binding antibody responses in patients and that humoral immunity against SARS-CoV-2 acquired by infection may persist for a relatively long time.

A Phase I dose-escalation, pharmacokinetics and food-effect study of oral donafenib in patients with advanced solid tumours.

PURPOSE: This Phase I study evaluated the safety, tolerability, food effects, pharmacodynamics, and pharmacokinetics of donafenib in patients with advanced solid tumours. METHODS: Eligible patients received a single dose of donafenib (50 mg, 100 mg, 200 mg, 300 mg, or 400 mg) and were then observed over a 7-day period; thereafter, each patient received the corresponding dose of donafenib twice daily for at least 4 weeks. Safety assessment and pharmacokinetic sampling were performed for all patients at the given time points; preliminary tumour response was also assessed. RESULTS: Twenty-five patients were enrolled in this study. Gastrointestinal reactions were the most common treatment-related adverse event, followed by skin toxicity. The maximum tolerated dose (MTD) was 300 mg bid. The dose-limiting toxicities (DLTs) were grade 3 diarrhoea and fatigue at 300 mg bid and grade 3 skin toxicity at 400 mg bid. In the dose range of 100 ~ 400 mg, T1/2 and AUC0-t after multiple doses were 26.9 ~ 30.2 h and 189 ~ 356 h*µg/mL, respectively. Food did not have a significant effect on the pharmacokinetics of donafenib. Twenty-one patients were assessed for efficacy, and two patients achieved a partial response according to Response Evaluation Criteria in Solid Tumors (RECIST), with a disease control rate of 57.1%. CONCLUSION: Oral donafenib was generally well tolerated and appeared to provide some clinical benefits; adverse events were manageable. Based on the results of this study, oral donafenib at 200 mg ~ 300 mg twice daily is recommended for further studies.

Research progress on application of epigenetics and metabolomics in traditional Chinese medicine / 中草药

Traditional Chinese medicine has multi-component, multi-target, and multi-path action characteristics and complexity, which makes the task of modernizing traditional Chinese medicine arduous, and many medical researchers have made unremitting efforts to this end. The development of systems biology and omics has ushered in an opportunity for the integration of traditional Chinese medicine and modern science. In particular, the characteristics integrity, dynamics, personalization, and interaction with the environment of epigenetics and metabolomics are consistent with function concept of traditional Chinese medicine. The application of popular DNA methylation, histone modifications, miRNA regulation of epigenetic research, and the application of metabolomics in the substance basis, quality control, pharmacodynamic action mechanism in traditional Chinese medicine research are reviewed in this paper. This paper also puts forward the idea that combining the two and innovative application can clarify the scientific connotation of the whole action mechanism of traditional Chinese medicine and the mechanism of multi-component, multi-channel, and multi-target synergistic action at the micro level, and explore a new research model for the scientific connotation of the core thought of traditional Chinese medicine.

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVES@#To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.@*METHODS@#A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.@*RESULTS@#An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).@*CONCLUSIONS@#Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

[Overview and prospects of traditional Chinese medicine blending technology oriented by quality consistency].

The consistency of drug quality is related to the clinical efficacy and safety,which is highly valued by the government and relevant industries. Compared with chemical medicine,traditional Chinese medicine originates from the nature,and is greatly influenced by natural factors,such as the place of origin,cultivation and processing technology,climate. The quality consistency of traditional Chinese medicine is poor. The quality consistency has become the pain point and difficulty of the development of the traditional Chinese medicine industry,which seriously affects the stability and controllability of clinical efficacy and the reproducibility or recognition of modern research results. It is also a bottleneck for Chinese patent medicine to enter the international market. Mixed batch blending technology is an effective method for the scientific guarantee of the quality consistency in other industries and disciplines,and widely applied in liquor making industry,tobacco industry and perfume industry. Overseas,mixed batch blending technology has been successfully applied in guaranteeing the quality consistency of Ginkgo biloba preparations Jinnado. It has been used in the production of Chinese formulations in Japan for more than 30 years. In recent years,mixed batch blending technology has been introduced into the pharmaceutical field to ensure the quality consistency of traditional Chinese medicine,and relevant research has gradually increased.This manuscript reviews the application of blending technology in other disciplines,summarizes the algorithm principles and software systems of mixed batch blending in traditional Chinese medicine or natural medicine,explains the specific implementation process of mixed batch blending technology,and looks forward to the application prospects of artificial intelligence and other new technologies,in the hope of providing new ideas and technologies for breaking through the problem of quality consistency,and boosting the high-quality and high-level development of Chinese medicine industry in the new era.

Exploration on the Approaches of Diverse Sedimentations in Polyphenol Solutions: An Integrated Chain of Evidence Based on the Physical Phase, Chemical Profile, and Sediment Elements.

Triphala is a famous herbal formula originated in Asia and is popular in America. Due to the high abundance of polyphenols, its oral liquid is unstable and easy to cause precipitate, which results in the loss of activities. However, complex composition and unclear precipitation mechanism hinders the improvement of stability. In this study, the accumulation of precipitation in the storage and its effect on activity were investigated. Then, an integrated chain of evidence was proposed based on the physical phase, chemical profile, and sediment elements. The results showed that antioxidant activity decreased from IC50 115 to 146 µl before and after 90 days of storage, and the anti-fatigue activity decreased from 30.54 to 28.47 min. Turbiscan Lab Expert observed that particle size increased from 106 to 122 nm, and the turbiscan stability index increased from 0 to 14, which indicated that its stability is continuously decreasing. High performance liquid chromatography (HPLC) fingerprint coupled with multivariate statistical analysis identified that these chemical markers changed significantly, such as gallic acid, catechins, and ellagic acid. Loss of catechins tends to be involved in the formation of phlobaphene precipitation. The fact that the new-born ellagic acid in precipitation (0.47 mg/ml) is significantly higher than that reduced in solution (0.25 mg/ml) indicates that it is not only derived from colloid aging. Microscopic observation combined with energy spectrum analysis further confirmed the existence of the multi-precipitates. The crystalline precipitate is ellagic acid, and the other is phlobaphene. In conclusion, based on the evidence chain analysis, this study revealed a systematic change of the whole polyphenol solution system. It provides a novel perspective to understand the sedimentation formation of polyphenol solution, which is an important theoretical contribution to the preparation of polyphenol solutions.

Seeing the Unseen of the Combination of Two Natural Resins, Frankincense and Myrrh: Changes in Chemical Constituents and Pharmacological Activities.

For the treatment of diseases, especially chronic diseases, traditional natural drugs have more effective therapeutic advantages because of their multi-target and multi-channel characteristics. Among many traditional natural medicines, resins frankincense and myrrh have been proven to be effective in the treatment of inflammation and cancer. In the West, frankincense and myrrh have been used as incense in religious and cultural ceremonies since ancient times; in traditional Chinese and Ayurvedic medicine, they are used mainly for the treatment of chronic diseases. The main chemical constituents of frankincense and myrrh are terpenoids and essential oils. Their common pharmacological effects are anti-inflammatory and anticancer. More interestingly, in traditional Chinese medicine, frankincense and myrrh have been combined as drug pairs in the same prescription for thousands of years, and their combination has a better therapeutic effect on diseases than a single drug. After the combination of frankincense and myrrh forms a blend, a series of changes take place in their chemical composition, such as the increase or decrease of the main active ingredients, the disappearance of native chemical components, and the emergence of new chemical components. At the same time, the pharmacological effects of the combination seem magically powerful, such as synergistic anti-inflammation, synergistic anticancer, synergistic analgesic, synergistic antibacterial, synergistic blood-activation, and so on. In this review, we summarize the latest research on the main chemical constituents and pharmacological activities of these two natural resins, along with chemical and pharmacological studies on the combination of the two.

ACOX1 destabilizes p73 to suppress intrinsic apoptosis pathway and regulates sensitivity to doxorubicin in lymphoma cells.

Lymphoma is one of the most curable types of cancer. However, drug resistance is the main challenge faced in lymphoma treatment. Peroxisomal acyl-CoA oxidase 1 (ACOX1) is the rate-limiting enzyme in fatty acid ß-oxidation. Deregulation of ACOX1 has been linked to peroxisomal disorders and carcinogenesis in the liver. Currently, there is no information about the function of ACOX1 in lymphoma. In this study, we found that upregulation of ACOX1 promoted proliferation in lymphoma cells, while downregulation of ACOX1 inhibited proliferation and induced apoptosis. Additionally, overexpression of ACOX1 increased resistance to doxorubicin, while suppression of ACOX1 expression markedly potentiated doxorubicin-induced apoptosis. Interestingly, downregulation of ACOX1 promoted mitochondrial location of Bad, reduced mitochondrial membrane potential and provoked apoptosis by activating caspase-9 and caspase-3 related apoptotic pathway. Overexpression of ACOX1 alleviated doxorubicin-induced activation of caspase-9 and caspase-3 and decrease of mitochondrial membrane potential. Importantly, downregulation of ACOX1 increased p73, but not p53, expression. p73 expression was critical for apoptosis induction induced by ACOX1 downregulation. Also, overexpression of ACOX1 significantly reduced stability of p73 protein thereby reducing p73 expression. Thus, our study indicated that suppression of ACOX1 could be a novel and effective approach for treatment of lymphoma. [BMB Reports 2019; 52(9): 566-571].

Comprehensive analysis of the aberrantly expressed profiles of lncRNAs, miRNAs and the regulation network of the associated ceRNAs in clear cell renal cell carcinoma / 生物医学工程学杂志

To evaluate the differential expression profiles of the lncRNAs, miRNAs, mRNAs and ceRNAs, and their implication in the prognosis in clear cell renal cell carcinoma (CCRCC), the large sample genomics analysis technologies were used in this study. The RNA and miRNA sequencing data of CCRCC were obtained from The Cancer Genome Atlas (TCGA) database, and R software was used for gene expression analysis and survival analysis. Cytoscape software was used to construct the ceRNA network. The results showed that a total of 1 570 lncRNAs, 54 miRNAs, and 17 mRNAs were differentially expressed in CCRCC, and most of their expression levels were up-regulated (false discovery rate 2). The ceRNA regulatory network showed the interaction between 89 differentially expressed lncRNAs and 9 differentially expressed miRNAs. Further survival analysis revealed that 38 lncRNAs (including COL18A1-AS1, TCL6, LINC00475, UCA1, WT1-AS, HOTTIP, PVT1, etc.) and 2 miRNAs (including miR-21 and miR-155) were correlated with the overall survival time of CCRCC ( < 0.05). Together, this study provided us several new evidences for the targeted therapy and prognosis assessment of CCRCC.

Clinical application of Apatinib in the treatment of malignancies / 国际肿瘤学杂志

Apatinib is a kind of antiangiogenesis drug of small molecular tyrosine kinase inhibitor, which can strongly against tumor angiogenesis by inhibiting vascular endothelial growth factor receptor 2 with highly selectivity. Apatinib can block cell cycle and reverse drug resistance. Clinical studies have shown that Apatinib is effective for many malignant tumors,including non-small cell lung cancer,breast cancer and gastric cancer,which has encouraging objective response rate and survival benefit. Apatinib also has good safety and tolerance.