Anti-obesity and Gut Microbiota Modulation Effect of Astragalus Polysaccharides Combined with Berberine on High-Fat Diet-Fed Obese Mice / 中国结合医学杂志

OBJECTIVE@#To investigate whether astragalus polysaccharides (APS) combined with berberine (BBR) can reduce high-fat diet (HFD)-induced obesity in mice.@*METHODS@#Except for normal mice, 32 HFD-induced obese mice were randomized into HFD, APS (1,000 mg/kg APS), BBR (200 mg/kg BBR), and APS plus BBR (1,000 mg/kg APS plus 200 mg/kg BBR) groups, respectively. After 6-week treatment (once daily by gavage), the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat, liver, and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer. The feces were collected at the 12 th week, and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid (16S rRNA) sequencing.@*RESULTS@#Compared with HFD group, the average body weight of APS plus BBR group was decreased (P<0.01), accompanied with the reduced fat accumulation, enhanced colonic integrity, insulin sensitivity and glucose homeostasis (P<0.05 or P<0.01). Importantly, APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance (P<0.05 or P<0.01). 16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis, exclusively via the enriched abundances of Bacteroides, which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism.@*CONCLUSION@#APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.

Egg white protein hydrolysate ameliorated sepsis-induced inflammatory injuries in kidney and liver based on metabolomics analysis.

Sepsis caused by infection could induce systemic inflammation and various organ damages. Bioactivities of peptides derived from eggs were proved by lots of researchers; hence they might be further developed for therapeutic use. In this study, the hydrolysate named "PEP" was obtained by enzymatic hydrolysis and purification. Rats were divided into control, LPS, PEP1 and PEP2 groups. The rat model was established using lipopolysaccharide (LPS) at 10 mg/kg by intraperitoneal injection. The results of blood counts, pro-inflammatory cytokines (TNF-α and IL-6), BUN and Cr levels and pathological damage in tissue or serum suggested that PEP alleviated LPS-induced injuries. Plasma metabolites of PEP were analyzed and identified using UPLC-MS/MS, which revealed that seven pathways might play critical roles in the protection process, involved in oxidative stress, energy and amino acid metabolism. Our data suggest that PEP ameliorated LPS-induced acute liver and kidney injuries, which is helpful for further development and research.

Content determination ，fingerprint establishment and differential markers screening of Rougui renshen granules / 中国药房

OBJECTIVE To determine the conte nts of 4 main components in Rougui renshen granules ，and to establish the fingerprint and to screen differential markers affecting its quality. METHODS HPLC method was employed to determine the contents of ammonium glycyrrhizinate ，glycyrrhizin，cinnamic acid and cinnamaldehyde. HPLC fingerprints of 10 batches of Rougui renshen granules were established simultaneously. Similarity Evaluation System of Chromatographic Fingerprint of TCM （2012 edition）was used to evaluate the similarity and determine the common peak ；SPSS 25.0 and SIMCA 14.1 software were applied for cluster analysis （CA），principal component analysis （PCA）and partial least square-discriminant analysis （OPLS-DA）. The differential markers affecting sample quality were screened by using the variable importance in projection （VIP）value＞ 1 as standard. RESULTS The methodology of content determination met the relevant requirements. The contents of ammonium glycyrrhizinate，glycyrrhizin，cinnamic acid and cinnamaldehyde were 1.808 4-2.770 0，1.137 2-1.481 4，0.076 5-0.091 8 and 0.130 9-0.478 4 mg/g，respectively. A total of 16 common peaks were found in the fingerprints of 10 batches of Rougui renshen granules. Four chromatographic peaks were identified ，i.e. glycyrrhizin （peak 6），cinnamic acid （peak 10），cinnamaldehyde（peak 11）and ammonium glycyrrhizinate （peak 15）. The similarities of samples were ＞0.95. Results of CA showed that 10 batches of samples could be classified into three categories ：S3 was grouped into one category ；S1-S2，S4-S5 and S 10 were grouped into one category；S6-S9 were grouped into one category. The results of PCA showed that the cumulative contribution rate of the first three principal components was 91.918％，and the classification results were consistent with CA. The results of OPLS-DA showed that the four peaks with VIP value ＞1 were peak 11（cinnamaldehyde），peak 15（ammonium glycyrrhizinate ），peak 6（glycyrrhizin） and peak 9. CONCLUSIONS Established methods of content determination and fingerprint are accurate and reproducible ，and can be used for the quality evaluation of Rougui renshen granules. The components as ammonium glycyrrhizinate ，cinnamaldehyde， glycyrrhizin may be differential markers affecting the quality of Rougui renshen granules.

Analysis of Crucial Transcription Factors of Berberine Against Cerebral Ischemia Based on Transcriptomics and Proteomics / 中国实验方剂学杂志

ObjectiveOn the basis of determining the protective effect of berberine （BBR） on cerebral ischemia， crucial transcription factors （TFs） of BBR against cerebral ischemia was identified by using transcriptome and proteome sequencing. MethodThe model of middle cerebral artery occlusion （MCAO） was established by thread embolization. The sham operation group， model group， low-dose group of BBR （dose of 37.5 mg·kg-1·d-1） and high-dose group of BBR （75 mg·kg-1·d-1） were set up. The rats were killed after continuous intragastric administration for 7 days. The pharmacodynamics was evaluated by Longa score and cerebral infarction rate， and the expressions of inflammatory cytokines， such as interleukin （IL）-1β， tumor necrosis factor （TNF）-α and monocyte chemotactic protein-1 （MCP-1） were measured by enzyme-linked immunosorbent assay （ELISA）. Then， RNA-Seq technique was used to detect the differentially expressed genes （DEGs） before and after BBR intervention， and DAVID 6.8 was used for enrichment analysis of DEGs. CatTFREs technique was used to detect differential TFs before and after BBR intervention， and DAVID 6.8 and STRING 11.0 were used for enrichment analysis and TFs association analysis. Finally， by integrating the activity of TFs and the changes of downstream target genes， crucial TFs were identified and the related regulatory network was constructed by Cytoscape 3.7.1. ResultCompared with the sham operation group， the neurological impairment was significant in the model group （P<0.01）， and compared with the model group， the low and high dose BBR groups could significantly reduce the neurological function damage （P<0.01） and decrease the rate of cerebral infarction （P<0.01）. Transcriptome data analysis showed that BBR was involved in the recovery process after cerebral ischemia mainly by affecting cell adhesion， brain development， neuron migration， calcium signaling pathway， cyclic adenosine monophosphate （cAMP） signaling pathway， inflammatory response and other related functions and signaling pathways. Proteomic data analysis showed that the differentially expressed TFs after BBR intervention interfered with cerebral ischemia mainly by regulating cell differentiation， immune system process， cell proliferation and other biological processes. In addition， integration analysis of TFs and DEGs revealed that transcription factor CP2-like 1 （TFCP2L1）， nuclear factor erythroid-2 like 1 （NFE2L1）， neurogenic differentiation protein 6 （NeuroD6） and POU domain， class 2， transcription factor 1 （POU2F1） were crucial TFs against cerebral ischemia-reperfusion injury mediated by BBR. ConclusionBBR has obvious protective effect on cerebral ischemia-reperfusion injury and its crucial TFs include TFCP2L1， NFE2L1， NeuroD6 and POU2F1.

Progress on the left-right asymmetry patterning in amphioxus.

The mechanisms underlying the establishment of left-right (L-R) asymmetry in bilaterians is one of the central enigmas in developmental biology. Amphioxus is an important model in studying the mechanisms of animal asymmetry specification due to its particular phylogenetic position, vertebrate-like embryogenesis and body plan. Recently, with the establishments of artificial breeding technology, high-efficiency microinjection method and gene knockout technology, researchers have successfully dissected the mechanisms of amphioxus L-R asymmetry development. In this review, we summarize the major progress in understanding L-R asymmetry specification in amphioxus and propose a model of regulation of L-R asymmetry in this species. Hh protein is transported dominantly to the right side by cilia movement, leading to R>L Hh signaling andCerexpression. Cer inhibits expression of Nodal, leading to the asymmetric expression of Nodal-dependent genes. The L-R differences in the propagation of the Nodal pathway result in the correct morphological L-R asymmetry development in amphioxus embryo. BMP signaling probably does not provide the asymmetric cue, but is necessary for correct expression ofCer andNodal.

Suppression of OCT2/MRP2 decreases kidney injury and enhances the chemosensitivity of co-administration of cisplatin and astragaloside IV / 药学学报

Kidney injury and decreased chemosensitivity of tumor cells are obstacles with cisplatin (CDDP) chemotherapy. Down-regulation of the organic cation transporter 2 (OCT2) and multidrug resistance-associated protein 2 (MRP2) is a key means to alleviate CDDP-induced kidney injury and increase chemosensitivity. Astragaloside IV (AS IV) is obtained from the well-known traditional Chinese herb Astragalus membranaceus. This study explored the role of AS IV in preventing kidney injury and enhancing the antitumor effect of CDDP by suppressing OCT2 expression in kidney and MRP2 in tumors. This project was reviewed and approved by the Animal Ethics Committee of the First Hospital of Jilin University. The effects of AS IV on CDDP inhibition of tumor growth and promotion of apoptosis were assessed in Lewis lung tumor (LLC)-bearing mice by H&E and TUNEL staining. Kidney injury was assessed by serum biochemical parameters and H&E staining. We used Western blotting and immunohistochemistry assays to detect OCT2 and MRP2 expression in kidney and tumor. The concentration of CDDP in kidney and tumor was measured by HPLC-MS/MS. AS IV enhanced CDDP chemosensitivity by increasing tumor cell apoptosis and slowing tumor growth, and decreased kidney injury as evidenced by lower blood creatinine (Cr) and blood urea nitrogen (BUN). Co-administration of AS IV suppressed MRP2 overexpression induced by CDDP in tumor tissues and may be an important mechanism for enhancing CDDP chemosensitivity. Moreover, AS IV reduced CDDP-induced kidney injury in mice along with suppression of OCT2 expression in kidney. The concentration of CDDP was increased in tumor but decreased in kidney. In total, AS IV not only enhanced the antitumor effect of CDDP by suppressing MRP2 expression in tumor cells, but also decreased kidney injury induced by CDDP. The results provide new insight into the combined use of a chemotherapy drug and natural ingredients to treat cancer.

Chemical constituents from roots of Arctium lappa / 中草药

Objective: To research the chemical constituents from the roots of Arctium lappa. Methods: The compounds were isolated and purified by column chromatography over normal phase silical gel, reverse phase silical gel, ODS column chromatography and semi-preparative HPLC. Their structures were identified by various spectroscopic analysis, including NMR. Results: Fourteen compounds were isolated from the 55% EtOH extract of the roots of A. lappa. And their structure were identified as 1,5-di-O-caffeoyl-3-O-maloyl quinic acid (1), 3,5-di-O-caffeoyl-1-O-(2-O-caffeoyl-4-maloyl)-quinic acid (2), 3,5-di-O- caffeoyl-1-(2-O-caffeoyl-4-maloyl methyl ester)-quinic acid (3), 3,5-di-O-caffeoyl-1-O-succinyl methyl ester quinic acid (4), 3,4-di-O-caffeoyl-1-O-succinyl methyl ester quinic acid (5), 1,3,5-tri-O-caffeoyl-4-O-succinyl quinic acid (6), 1,5-di-O- caffeoyl-3-O-succinyl quinic acid (7), 1,5-di-O-caffeoyl-4-O-succinyl quinic acid (8), 1,5-di-O-caffeoyl-4-O-succinyl methyl ester quinic acid (9), 1,5-di-O-caffeoyl-3-O-succinyl methyl ester quinic acid (10), 1,3,4-tri-O-caffeoyl quinic acid (11), 1,4,5-tri-O-caffeoyl quinic acid methyl ester (12), 3-O-caffeoyl quinic acid (13), and 4-hydroxy-phenylacetic acid (14). Conclusion: Compounds 3-5, 9, 11, 12 are obtained from Arctium genus for the first time, and compound 14 is isolated from A. lappa for the first time.

Mechanism of Guhong Injection Against Cerebral Ischemia Based on Transcriptome Analysis / 中国实验方剂学杂志

Objective::Based on the protective effect of Guhong injection (GH) on cerebral ischemia, mechanism of GH against cerebral ischemia was identified using RNA-seq transcriptome and bioinformation analysis. Method::The model of middle cerebral artery occlusion (MCAO) was established through thread embolization. Sham group, model group, low-dose GH group (0.625 mL·kg-1·d-1), high-dose GH group (2.5 mL·kg-1·d-1), positive group (Ginaton, 8 mL·kg-1·d-1) were set up. Ludmila Belayev 12-point scoring method was applied to assess the protective effect of GH against MCAO-induced cerebral ischemia. And the differentially expressed genes after treatment with GH were identified by RNA-Seq technology. Enrichment analysis, cluster analysis and association analysis on disease targets of cerebral ischemia were carried out through such databases as DAVID, String and The Human Phenotype Ontology. Finally, the regulatory network was constructed by Cytoscape3.4.0. Result::Compared with the sham group, the neurological impairment was obvious in the model group (P<0.01), and the neurological impairment was alleviated in the GH group compared with the model group (P<0.05). RNA-Seq technology analysis showed that GH regulated genes involving such biological processes as cell apoptosis, inflammation, oxidative stress, toll-like signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway. Twenty disease targets and 64 MAPK signaling pathway genes were associated with differentially expressed genes after GH treatment, in which 23 genes were involved in apoptosis and inflammation. Conclusion::GH protected against cerebral ischemia in many ways, among which MAPK signaling pathway is an important way to exert its effect in inhibiting apoptosis and inflammation.

XingNaoJing injections protect against cerebral ischemia/reperfusion injury and alleviate blood-brain barrier disruption in rats, through an underlying mechanism of NLRP3 inflammasomes suppression / 中国天然药物

The aim of this study was to explore the neuroprotective effect and mechanism of XingNaoJing injections (XNJ) on cerebral ischemia injury and blood-brain barrier (BBB) disruption. Middle cerebral artery occlusion (MCAO) method was applicated to establish the model of cerebral ischemia/reperfusion (I/R) injury in rats. BBB permeability after I/R injury was assessed with the leaking amount of Evans Blue and the expression of occludin and ZO-1. The expression of NOD-like receptor family, pyrin domain containing (NLRP3) was checked to explore the inhibition of inflammation by XNJ. The results showed that XNJ could significantly increase the survival percent, decrease the infarct area and ameliorate neurological deficits and brain damage after I/R injury. Leaking amount of Evans Blue was reduced by XNJ, and the expression of tight junction protein, occludin and ZO-1 was also up-regulated by XNJ, which showed a role of protection on BBB disruption. The expression of NLRP3 was inhibited after exposure of XNJ, which was associated with inhibition of the inflammatory response. In summary, XNJ could suppress NLRP3 inflammasomes and improve BBB disruption and brain damage in rats after cerebral I/R injury, which provided a beneficial insight to further explore XNJ.

A survey of the ten-year implementation of WHO surgical safety checklist in China / 中华麻醉学杂志

Objective@#To investigate the current status of the ten-year implementation of the World Health Organization (WHO) surgical safety checklist (SSC) in China.@*Methods@#A questionnaire was designed based on the three phases described by the checklist — the period before induction of anaesthesia, the period before skin incision, and the period before patient leaves operating room, taking into account some hotspots and disputes.The questionnaire was sent to the members of the Chinese-based online New Youth Anesthesia Forum through the WeChat platform.Answers were completed by mobile phones or desktop computers.Each WeChat ID number allowed only one answer for each individual participant.@*Results@#A total of 3 943 members red the questionnaire invitation, of which 2 121 members completed the questionnaire with an overall completion rate of 53.79%.For checks completed before induction of anesthesia, the percentage of members who routinely practiced checks before induction of anesthesia was 93.35%, the percentage of members who completed each and every element of the checklist was 60.16%, and the percentage of members who selected the element of the checklist the surgeon was not involved in the check was 14.05%.For checks practiced before skin incision, the percentage of members who routinely completed checks before skin incision was 78.22%, the percentage of members who completed each and every element of the checklist was 51.91%, and the percentage of members who selected the element of the checklist surgeons and anesthesiologists routinely stated their own professional key information was 18.24% and 18.81%, respectively.For checks practiced before the patient leaved the operating room, the percentage of members who routinely completed checks before removing the patient from the operating room was 64.26%, and the percentage of members who completed each and every element of the checklist was 44.18%.The percentage of members who was really serious about practicing the checklist was 56.20%.The percentage of members who believed that surgeons should participated in checks practiced before induction of anesthesia was 81.47%.If the member himself or a member of his family needed a surgery, the percentage of members who hoped to implement the checklist was 98.35%.The percentage of members who believed that practicing WHO SSC could reduce the complications of surgery and improve the anesthetic safety of patients was 94.34%.@*Conclusion@#The implementing rate of checks practiced before induction of anesthesia is high, while the implementing rates of checks completed before skin incision and before patient leaves operating room are sequentially reduced in China.Although there are some problems with the implementation of WHO SSC, most respondents believe that implementing SSC can improve the anesthetic safety of patients undergoing surgery.

A survey of the ten-year implementation of WHO surgical safety checklist in China / 中华麻醉学杂志

Objective To investigate the current status of the ten-year implementation of the World Health Organization (WHO) surgical safety checklist (SSC) in China.Methods A questionnaire was designed based on the three phases described by the checklist — the period before induction of anaesthesia,the period before skin incision,and the period before patient leaves operating room,taking into account some hotspots and disputes.The questionnaire was sent to the members of the Chinese-based online New Youth Anesthesia Forum through the WeChat platform.Answers were completed by mobile phones or desktop computers.Each WeChat ID number allowed only one answer for each individual participant.Results A total of 3 943 members red the questionnaire invitation,of which 2 121 members completed the questionnaire with an overall completion rate of 53.79％.For checks completed before induction of anesthesia,the percentage of members who routinely practiced checks before induction of anesthesia was 93.35％,the percentage of members who completed each and every element of the checklist was 60.16％,and the percentage of members who selected the element of the checklist the surgeon was not involved in the check was 14.05％.For checks practiced before skin incision,the percentage of members who routinely completed checks before skin incision was 78.22％,the percentage of members who completed each and every element of the checklist was 51.91％,and the percentage of members who selected the element of the checklist surgeons and anesthesiologists routinely stated their own professional key information was 18.24％ and 18.81％,respectively.For checks practiced before the patient leaved the operating room,the percentage of members who routinely completed checks before removing the patient from the operating room was 64.26％,and the percentage of members who completed each and every element of the checklist was 44.18％.The percentage of members who was really serious about practicing the checklist was 56.20％.The percentage of members who believed that surgeons should participated in checks practiced before induction of anesthesia was 81.47％.If the member himself or a member of his family needed a surgery,the percentage of members who hoped to implement the checklist was 98.35％.The percentage of members who believed that practicing WHO SSC could reduce the complications of surgery and improve the anesthetic safety of patients was 94.34％.Conclusion The implementing rate of checks practiced before induction of anesthesia is high,while the implementing rates of checks completed before skin incision and before patient leaves operating room are sequentially reduced in China.Although there are some problems with the implementation of WHO SSC,most respondents believe that implementing SSC can improve the anesthetic safety of patients undergoing surgery.

Antineutrophil cytoplasmic antibodies in Chinese patients with tuberculosis.

INTRODUCTION: Based on reports, infection with Mycobacterium tuberculosis is believed to induce the development of antibodies that are considered to be biological indicators for the diagnosis of some other diseases. However, conflicting results have been published regarding the presence of antineutrophil cytoplasmic antibodies (ANCAs) in patients with tuberculosis. We aim to study the seroprevalence of ANCA in a population of Chinese patients with tuberculosis, which may lead to the misdiagnosis of vasculitic disorders. METHODS: The study was conducted from January 2016 to May 2017 to evaluate the presence of ANCA in 103 Chinese patients using indirect immunofluorescent assay. An enzyme-linked immunosorbent assay was performed for anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3) detection. RESULTS: Perinuclear ANCA (p-ANCA) was detected in 4.8% (5/103) of patients, whereas cytoplasmic ANCA (c-ANCA) was not detected; 1.9% (2/103) of patients with tuberculosis was positive for anti-MPO antibodies, and none had anti-PR3 antibodies. Both anti-MPO-positive patients were diagnosed with ANCA-associated vasculitides. CONCLUSIONS: ANCA positivity may be more related to vasculitis and immunological disorders than to a M. tuberculosis infection. Therefore, to improve diagnostic accuracy, patients with M. tuberculosis who are ANCA positive should be investigated for concurrent diseases, including the effects of drugs. Therefore, even in tuberculosis epidemic area, ANCA seropositivity, detected by ELISA, is still more suggestive of ANCA-associated vasculitides.

Antineutrophil cytoplasmic antibodies in Chinese patients with tuberculosis

Abstract INTRODUCTION: Based on reports, infection with Mycobacterium tuberculosis is believed to induce the development of antibodies that are considered to be biological indicators for the diagnosis of some other diseases. However, conflicting results have been published regarding the presence of antineutrophil cytoplasmic antibodies (ANCAs) in patients with tuberculosis. We aim to study the seroprevalence of ANCA in a population of Chinese patients with tuberculosis, which may lead to the misdiagnosis of vasculitic disorders. METHODS: The study was conducted from January 2016 to May 2017 to evaluate the presence of ANCA in 103 Chinese patients using indirect immunofluorescent assay. An enzyme-linked immunosorbent assay was performed for anti-myeloperoxidase (MPO) and anti-proteinase 3 (PR3) detection. RESULTS: Perinuclear ANCA (p-ANCA) was detected in 4.8% (5/103) of patients, whereas cytoplasmic ANCA (c-ANCA) was not detected; 1.9% (2/103) of patients with tuberculosis was positive for anti-MPO antibodies, and none had anti-PR3 antibodies. Both anti-MPO-positive patients were diagnosed with ANCA-associated vasculitides. CONCLUSIONS: ANCA positivity may be more related to vasculitis and immunological disorders than to a M. tuberculosis infection. Therefore, to improve diagnostic accuracy, patients with M. tuberculosis who are ANCA positive should be investigated for concurrent diseases, including the effects of drugs. Therefore, even in tuberculosis epidemic area, ANCA seropositivity, detected by ELISA, is still more suggestive of ANCA-associated vasculitides.

Efficacy of low-protein diet for diabetic nephropathy: a systematic review of randomized controlled trials.

BACKGROUND: A low-protein diet (LPD) is believed to be beneficial in slowing the progression of kidney disease. It is reported that low protein diet can improve protein, sugar and lipid metabolism, and reduce the symptoms and complications of renal insufficiency. However, there has been controversial regarding the effects of protein restriction on diabetic nephropathy (DN). OBJECTIVE: To investigate the efficacy of LPD on renal function in patients with type 1 or 2 DN by meta-analysis of randomized controlled trials (RCTs). DESIGN: PubMed, MEDLINE, EMBASE and China National Knowledge Infrastructure databases were searched. Eleven randomized controlled trials met the inclusion criteria, of which 10 were English and 1 was Chinese. The primary outcome was a change in glomerular filtration rate (GFR). The secondary outcome was a change in proteinuria. Random-effects models were used to calculate the standardized mean difference (SMD) and the corresponding 95% confidence intervals (CI). Subgroup analyses were also performed. RESULTS: Our research indicated that LPD was not associated with a significant improvement in GFR (1.59 ml · min-1 · 1.73 m-2, 95% CI -0.57, 3.75, I2 = 76%; p = 0.15). This effect was consistent across the subgroups regardless of type of diabetes, course of diabetes and intervention period. Our results also showed that there was no significant difference on improvement of proteinuria in patients of LPD and those in normal-protein diet groups (- 0.48, 95%CI-1.70, 0.74, I2 = 94%, p = 0.44). Subgroup analysis revealed that LPD resulted in increased excretion of proteinuria in patients with type 2 diabetes (1.32, 95% CI 0.17, 2.47, I2 = 86%, p = 0.02). CONCLUSION: The present research showed that LPD was not significantly associated with improvement of renal function in patients with either type 1 or 2 diabetic nephropathy. Although these results do not completely eliminate the possibility that LPD is beneficial for patients with diabetic nephropathy, it does not seem to be significant benefit to renal function.

Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study / 中华医学杂志(英文版)

Background@#Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.@*Methods@#A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation.@*Results@#In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively.@*Conclusions@#R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.@*Trial Registration@#ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.

Development of Two-Dimensional Liquid Chromatography Coupled with Tandem Mass Spectrometry for Identification of Extracted Proteins of Rice Leaves: Hydrophilic Interaction-Reversed-phase Approach / 分析化学

A two-dimensional liquid chromatography method was developed for the analysis of rice leaves proteomics based on the coupling of hydrophilic interaction liquid chromatography-reversed-phase liquid chromatography with online tandem mass spectrometry. The influence of pH value of chromatographic mobile phase on the orthogonality of the hydrophilic interaction-reversed-phase two-dimensional liquid chromatography was evaluated by the changes of standard peptide retention. The results indicated that the better orthogonality (R2=0.34113) was achieved from the system with hydrophilic interaction columns(pH 9.3) in the first and C18columns(pH 3.3) in the second LC dimension. Coupled with multiple fraction concatenation strategy,the orthogonality of two-dimensional liquid chromatography was further evaluated in the analysis of complex rice leaf proteins. The results showed that more than 50% of the total peptides were identified less than two times, and the peptides obtained from first-dimension were well distributed across the elution window,indicating that the method showed significant orthogonality in the identification of complex rice leaf proteins. Based on the proteome discoverer software,207345 peptides belonged to 2930 protein clusters were identified.

Metabolic Profiling Analysis of Rice Leaf Based on Hydrophilic Interaction Chromatography Combined with Reversed Phase Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry / 分析化学

A metabolic profiling analysis method for metabolomic studies of rice leaf was established based on HSS T3 combined with XBridge Amide Q-TOF LC/MS by comparing the influences of different extraction methods in rice leaves of metabolites. The extraction and separation of rice leaf metabolites using three different methods including methanol-chloroform-water,methanol-chloroform-ammonia,methanol-methyl tert-butyl ether -water and different chromatographic systems were compared by the numbers of peaks, identified metabolites and the metabolic pathways. The results showed that the method of methanol-chloroform-water reached the highest coverage rate of metabolites in rice leaves,and the maximum number of unique metabolites including prephenic acid, luteolin, α-linolenic acid, aconitic acid, gibberellin A12 aldehyde, isovitexin, L-Glutamate were detected. Metabolites with different polarity in rice leaf could be detected by HSS T3 and XBridge Amide. A total of 16 kinds of organic acids, 17 kinds of nucleotides, 21 kinds of amino acids, 66 kinds of fatty acids,11 kinds of phospholipids and 7 kinds of sphingolipids were identified. XBridge Amide had an absolute advantage in detecting phospholipids and sphingolipids. The metabolic pathways involved purine metabolism, pyrimidine metabolism, tricarboxylic acid cycle, arginine metabolism, fatty acid metabolism, phospholipid metabolism, sphingolipid metabolism, phenylalanine metabolism and vitamin B2 synthesis. It showed certain complementarity between the two columns in identifying metabolites and involved the metabolic pathways. The established method is expected to be useful for the metabolomic studies of rice.

Recurrent or refractory childhood B cell lymphoblastic lymphoma:A case report and literature review / 吉林大学学报(医学版)

Objective:To explore the clinical characteristics,the diagnostic framework,and the treatment methods of B cell lymphoblastic lymphoma(B-LBL),and to clarify the progress of diagnosis and treatment of B-LBL to improve the clinician's understanding of the disease and provide the guidance for prognostic evaluation and therapeutic options.Methods:The clinical data including symptoms,physical signs,ancillary testings,diagnosis, treatment and disease prognosis of a child suffered from B-LBL were retrospectively analyzed;in the meantime,the relative literatures were reviewed.Results:The patient was definitly diagnosed as B-LBL according to the clinical characteristics and received combination therapy with vincristine,daunorubicin,L-asparaginase,and prednisone as the first course,along with the intrathecal injection of methotrexate and dexamethasone to prevent central nervous system leukemia(CNS-L).The patient achieved complete remission(CR)25 d after the first circle chemotherapy but was diagnosed as degree 4 myelosuppression.Therefore,the second cycle combination therapy was adjusted with cyclophosphamide,cytarabine and 6-MP,and the intrathecal injection to prevent CNS concomitantly.DegreeⅣ myelosuppression appeared repeatedly after 2 cycles and the combination chemotherapy was reajdusted. So mercaptopurine and high dose of methotrexate were given as the 4th cycle,and CNS was prevented continously. The patient kept CR until the second cycle finished but get recurrence after the third chemotherapy(prolymphocytes 10%).Then remission and recurrence were found in the disease counrse during which mary chemotherapy methods were attempted until the patient got stable CR after treatment for 31 months.Then the patient was treated with oral mercaptopurine(50 g·d-1)and methotrexate(25 mg per week)and kept disease-free survival for more than 3 years.Conclusion:B-LBL is a rapidly developed disease with the bone marrow involvement occurring in the short term and easy to relapse during treatment.However,it is extremely easy to transform to recurrent and refractory B-LBL after the first remission.It is of great importance to estimate the risk stratification and to evaluate the prognosis of LBL patients in order to treat as soon as possible for the improvement of one's life quality and the prolongation of survival.

Recurrent or refractory childhood B cell lymphoblastc lymphoma: A case report and literature review / 吉林大学学报(医学版)

Objective: To explore the clinical characteristics, the diagnostic framework, and the treatment methods of B cell lymphoblastic lymphoma (B-LBL), and to clarify the progress of diagnosis and treatment of B-LBL to improve the clinician's understanding of the disease and provide the guidance for prognostic evaluation and therapeutic options. Methods: The clinical data including symptoms, physical signs, ancillary testings, diagnosis, treatment and disease prognosis of a child suffered from B-LBL were retrospectively analyzed; in the meantime, the relative literatures were reviewed. Results: The patient was definitly diagnosed as B-LBL according to the clinical characteristics and received combination therapy with vincristine, daunorubicin, L-asparaginase, and prednisone as the first course, along with the intrathecal injection of methotrexate and dexamethasone to prevent central nervous system leukemia (CNS-L). The patient achieved complete remission (CR) 25 d after the first circle chemotherapy but was diagnosed as degree 4 myelosuppression. Therefore, the second cycle combination therapy was adjusted with cyclophosphamide, cytarabine and 6-MP, and the intrathecal injection to prevent CNS concomitantly. Degree IV myelosuppression appeared repeatedly after 2 cycles and the combination chemotherapy was reajdusted. So mercaptopurine and high dose of methotrexate were given as the 4th cycle, and CNS was prevented continously. The patient kept CR until the second cycle finished but get recurrence after the third chemotherapy (prolymphocytes 10%). Then remission and recurrence were found in the disease counrse during which Mary chemotherapy methods were attempted until the patient got stable CR after treatment for 31 months. Then the patient was treated with oral mercaptopurine (50 g · d-1) and methotrexate 25 mg per week) and kept disease-free survival for more than 3 years. Conclusion: B-LBL is a rapidly developed disease with the bone marrow involvement occurring in the short term and easy to relapse during treatment. However, it is extremely easy to transform to recurrent and refractory B-LBL after the first remission. It is of great importance to estimate the risk stratification and to evaluate the prognosis of LBL patients in order to treat as soon as possible for the improvement of one's life quality and the prolongation of survival.

Preventive and therapeutic effect of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage

Objective To investigate the preventive and therapeutic effect and mechanism of simvastatin on secondary inflammatory damage of rats with cerebral hemorrhage. Methods Sixty SD rat aged 9–12 weeks were chosen and divided into the control group, model group and simvastatin-treated group randomly with 20 rats in each group. Rats in the model group and simvastatin-treated group were infused with autologous fresh uncoagulated blood to the right brain tissue of the basal ganglia to build the cerebral hemorrhage model, while rats in the control group were treated with the same amount of normal saline. Then, rats in the simvastatin-treated group were given a gavage of 3 mg/kg of simvastatin once a day after modeling. Rats in the three groups were given nerve dysfunction score (NDS) and wet-dry weighting method was used to detect the brain water content (BWC) of brain tissues around the lesion of the rats. Then Nissl staining was conducted and the undamaged neurons were counted. Immunohistochemical SP method was applied to count the number of NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions, and the immuno fluorescence method was employed to determine the expression levels of NF-κB, TLR4 and IL-1β proteins. Results The NDS results of the simvastatin-treated group at all time points were all significantly higher than those of the model group (P < 0.05); the BWC values of the simvastatin-treated group at all time points were all significantly lower than those of the model group at the same periods (P < 0.05); the number of the undamaged neurons around the lesions of the simvastatin-treated group at all time points were all significantly higher than those of the model group (P < 0.05); seven days after treatment, the number of the NF-κB, TLR4 and IL-1β positive cells in brain tissues around the lesions of the simvastatin-treated group were all significantly lower than those of the model group (P < 0.05), and its expression levels of NF-κB, TLR4 and IL-1β protein were also significantly lower than those of the model group (P < 0.05). Conclusions Simvastatin can inhibit the expressions of NF-κB, TLR4 and IL-1β proteins in rats with cerebral hemorrhage, and protect neurons and reduce secondary inflammatory damages by down-regulating the above protein-mediated inflammatory responses.