Primary central nervous system T-cell lymphoma in children and adolescents: a clinicopathological analysis of five cases / 中华病理学杂志

Objective: To study the clinicopathological characteristics, and further understand primary central nervous system T-cell lymphoma (PCNSTCL) in children and adolescents. Methods: Five cases of PCNSTCL in children and adolescents were collected from December 2016 to December 2021 at the First Affiliated Hospital of Zhengzhou University. The clinicopathological characteristics, immunophenotypic, and molecular pathologic features were analyzed, and relevant literatures reviewed. Results: There were two male and three female patients with a median age of 14 years (range 11 to 18 years). There were two peripheral T-cell lymphomas, not otherwise specified, two anaplastic large cell lymphoma, ALK-positive and one NK/T cell lymphoma. Pathologically, the tumor cells showed a variable histomorphologic spectrum, including small, medium and large cells with diffuse growth pattern and perivascular accentuation. Immunohistochemistry and in situ hybridization showed CD3 expression in four cases, and CD3 was lost in one case. CD5 expression was lost in four cases and retained in one case. ALK and CD30 were expressed in two cases. One tumor expressed CD56 and Epstein-Barr virus-encoded RNA. All cases showed a cytotoxic phenotype with expression of TIA1 and granzyme B. Three cases had a high Ki-67 index (>50%). T-cell receptor (TCR) gene rearrangement was clonal in two cases. Conclusions: PCNSTCL is rare, especially in children and adolescents. The morphology of PCNSTCL is diverse. Immunohistochemistry and TCR gene rearrangement play important roles in the diagnosis.

Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China / 中西医结合学报

OBJECTIVE@#Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, is responsible for numerous infections in China. This study investigates the association between the use of Seven-Flavor Herb Tea (SFHT) and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019 (COVID-19).@*METHODS@#This case-control study was conducted at shelter hospitals and quarantine hotels in China. A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31, 2022, while 2190 uninfected individuals served as healthy controls. Structured questionnaires were used to collect data on demographics, underlying diseases, vaccination status, and use of SFHT. Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score. Subsequently, a conditional logistic regression model was used for data analysis.@*RESULTS@#Overall, 7538 eligible subjects were recruited, with an average age of [45.54 ± 16.94] years. The age of COVID-19 patients was significantly higher than that of uninfected individuals ([48.25 ± 17.48] years vs [38.92 ± 13.41] years; t = 22.437, P < 0.001). A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio. The use of SFHT (odds ratio = 0.753, 95% confidence interval: 0.692, 0.820) was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals.@*CONCLUSION@#Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection. This is a useful study in the larger picture of COVID-19 management, but data from large-sample multi-center, randomized clinical trial are warranted to confirm the finding. Please cite this article as: Zhang SX, Chen XX, Zheng Y, Cai BH, Shi W, Ru M, Li H, Zhang DD, Tian Y, Chen YL. Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China. J Integr Med. 2023; 21(4):369-376.

Analysis of incidence characteristics and trend of pneumoconiosis in Ningbo City from 1967 to 2019 / 中华劳动卫生职业病杂志

Objective: To understand the incidence of pneumoconiosis in Ningbo city from 1967 to 2019, and to analyze the distribution characteristics and change trend of pneumoconiosis. Methods: In February 2021, the data of pneumoconiosis patients in Ningbo city from 1967 to 2019 were sorted out. The data from 1967 to 1987 were from historical case files of Zhejiang Center for Disease Control and Prevention, the data from 1988 to 2005 were from the historical case files of Ningbo Center for Disease Control and Prevention, and the data from 2006 to 2019 were from the pneumoconiosis report card in China Disease Prevention and Control Information System; Followed up and supplement relevant information, including basic information, basic information of employers and information related to pneumoconiosis diagnosis, and comprehensively analyze the composition and development trend, population characteristics and industry characteristics of pneumoconiosis. Results: From 1967 to 2019, a total of 1715 cases of pneumoconiosis were reported in Ningbo City, including 1254 cases of stageⅠpneumoconiosis, 258 cases of stageⅡpneumoconiosis, 172 cases of stage Ⅲpneumoconiosis. 1202 cases of silicosis (70.09%) , 296 cases of asbestosis (17.26%) , 40 cases of welder's pneumoconiosis (2.33%) , 32 cases of graphite pneumoconiosis (1.87%) were reported. There were 1296 male cases (75.57%) and 419 female cases (24.43%) were reported. Silicosis (91.15%, 1102/1209) and welder's pneumoconiosis (100.00%, 40/40) were the most common pneumoconiosis in males, while asbestosis (90.24%, 268/297) and graphite pneumoconiosis (87.50%, 28/32) were the most common pneumoconiosis in females. The average age was (49.71±10.90) years old and the average length of service was (10.98±6.96) years. The top three reported pneumoconiosis cases were construction industry (336 cases, 19.59%) , ferrous metal smelting and rolling industry (317 cases, 18.48%) and non-metallic mineral products industry (315 cases, 18.37%) . The top three reported pneumoconiosis cases were 414 cases (24.14%) in Ninghai County, 294 cases (17.14%) in Yuyao City and 272 cases (15.86%) in Yinzhou District. Conclusion: With the development of industries in Ningbo City, government departments should strengthen supervision and management of enterprises involving silica dust and welding fume to curb the high incidence of pneumoconiosis.

Crosstalk between CpG Methylation and Polymorphisms (CpG-SNPs) in the Promotor Region of DIO2 in Kashin-Beck Disease / 中国医学科学杂志(英文版)

Objective This study was designed to determine the methylation profile of four CpGs and the genotypes of two CpG-SNPs located in promoter region of DIO2 in patients with Kashin-Beck disease (KBD). We also analyzed the interaction between the CpGs methylations and CpG-SNPs. Methods Whole blood specimens were collected from 16 KBD patients and 16 healthy subjects. Four CpGs and two CpG-SNPs in the promoter regions of DIO2 were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The CpGs methylation levels were compared between samples from KBD patients and healthy subjects. The methylation levels were also analyzed in KBD patients with different CpG-SNP genotypes. Results The mRNA expression of DIO2 in whole blood of KBD patients was significnatly lower than in healthy controls (P <0.05). The methylation levels of DIO2-1_CpG_3 in KBD patients were significantly higher than those in healthy controls (P <0.05). The methylation levels of four CpGs were not significantly different between KBD patients and healthy controls. The methylation level of DIO2-1_CpG_3 in the promoter region of DIO2 in KBD patients with GA/AA genotype was significantly higher than that of KBD patients with GG genotype (P <0.05). Conclusion The methylation level of DIO2 increases in KBD patients. Similar trends exist in KBD carriers of variant genotypes of CpG-SNPs DIO2 rs955849187.

Clinicopathological and molecular genetic features of cyclin D1-negative mantle cell lymphoma / 中华病理学杂志

Objective: To investigate the clinicopathological features and molecular genetics of cyclin D1-negative mantle cell lymphoma (MCL). Methods: The clinicopathological features and molecular genetics of CyclinD1-negative MCL diagnosed between January 2016 and July 2021 at the First Affiliated Hospital of Zhengzhou University were analyzed using immunohistochemistry and fluorescence in situ hybridization. Clinical information was collected and analyzed. Results: A total of five Cyclin D1-negative MCL cases from all 212 MCL patients (5/212, 2.4%)were included. There were three male and two female patients,age ranged from 59 to 70 years (median 64 years). All patients presented with nodal lesions. None of the patients had B symptoms but four had bone marrow involvement. Histopathologically, four cases were classic MCL and one case was pleomorphic variant type. All five cases were negative for Cyclin D1 but SOX-11 were positive in all cases. CD5 was positive in four cases and one case was weakly positive for CD23. CD10 and bcl-6 were negative in all cases. CCND1 translocation was identified in three cases and CCND2 translocation in one case by FISH analysis. However,CCND3 translocations were not found in the five cases. Conclusions: Cyclin D1-negative MCL are uncommon, its accurate diagnosis needs combined analysis with morphologic and immunophenotypic characteristics and genetic changes. It may be particularly difficult to distinguish from other small cell type B cell lymphomas. FISH analyses for CCND1/CCND2/CCND3 translocations and immunohistochemistry for SOX-11 are helpful to resolve such a difficult distinction.

Clinicopathological characteristics of natural killer cell enteropathy: report of two cases and review of literature / 中华病理学杂志

Objective: To study the clinicopathological and genetic features of natural killer (NK)-cell enteropathy for better understanding of this rare disease and prevention of its misdiagnosis. Methods: Two cases of NK-cell enteropathy were diagnosed in the First Affiliated Hospital of Zhengzhou University, China from October 2017 to February 2021. The clinical characteristics, morphology, immunohistochemistry, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization and T cell receptor gene rearrangement were analyzed. The patients were followed up by a telephone interview. Results: The patients were both male, aged 40 and 28 years, respectively. Both patients were admitted to the hospital for an annual checkup without obvious gastrointestinal symptoms. The endoscopy showed that the gastric body of case 1 had a mucosal bulge, small area of congestion and erosion, while the rectum of case 2 had congestion and erosion. Microscopically, the lesions of the 2 cases were relatively limited. Many lymphoid cells infiltrated within the lamina propria of the mucosa and into the muscularis mucosa in case 2. In case 1, the glands were reduced in the lesion, and the glandular cavity was slightly compressed and deformed. There was no infiltration or destruction of the glands in either case. Lymphoid cells were atypical, with medium-to-large cell sizes. Their cytoplasm was medium-to-slightly abundant and appeared eosinophilic or translucent. In case 2, characteristic eosinophilic granules were seen in the cytoplasm of a few cells. The nuclei in both cases were round, oval and irregular, with fine chromatin, inconspicuous nucleoli, and no mitotic figures were noted. Necrosis was seen in case 1 while both cases had no central growth or destruction of blood vessels. Immunophenotyping showed that CD56, granzyme B and TIA-1 were positive in both cases, part of the cells was CD3-positive, and some cells were weakly CD4-positive in case 2. The CD5, CD8, CD30, ALK and B-lineage markers (CD20, CD79α) were all negative. The Ki-67 proliferation index was about 60% and 30%, respectively. Both cases were EBER negative. TCR gene rearrangement was polyclonal. Follow-up showed that none of the 2 patients had any special treatments and stayed well. Conclusions: NK-cell enteropathy is rare, with biological behaviors similar to benign tumors, and occasional recurrence. Its histology and immunophenotype are easily confused with NK/T cell-derived lymphomas. Combination of its unique endoscopic features, EBER negativity, polyclonal TCR gene rearrangement and good prognosis can confirm the diagnosis and avoid misdiagnosis and overtreatment.

Association between socioeconomic status and chronic obstructive pulmonary disease in Jiangsu province, China: a population-based study / 中华医学杂志(英文版)

BACKGROUND@#Chronic obstructive pulmonary disease (COPD) is a common public health problem worldwide. Recent studies have reported that socioeconomic status (SES) is related to the incidence of COPD. This study aimed to investigate the association between SES and COPD among adults in Jiangsu province, China, and to determine the possible direct and indirect effects of SES on the morbidity of COPD.@*METHODS@#A cross-sectional study was conducted among adults aged 40 years and above between May and December of 2015 in Jiangsu province, China. Participants were selected using a multistage sampling approach. COPD, the outcome variable, was diagnosed by physicians based on spirometry, respiratory symptoms, and risk factors. Education, occupation, and monthly family average income (FAI) were used to separately indicate SES as the explanatory variable. Mixed-effects logistic regression models were introduced to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for examining the SES-COPD relationship. A pathway analysis was conducted to further explore the pulmonary function impairment of patients with different SES.@*RESULTS@#The mean age of the 2421 participants was 56.63 ± 9.62 years. The prevalence of COPD was 11.8% (95% CI: 10.5%-13.1%) among the overall sample population. After adjustment for age, gender, residence, outdoor and indoor air pollution, body weight status, cigarette smoking, and potential study area-level clustering effects, educational attainment was negatively associated with COPD prevalence in men; white collars were at lower risk (OR: 0.60, 95% CI: 0.43-0.83) of experiencing COPD than blue collars; compared with those within the lower FAI subgroup, participants in the upper (OR: 0.68, 95% CI: 0.49-0.97) tertiles were less likely to experience COPD. Such negative associations between all these three SES indicators and COPD were significant among men only. Education, FAI, and occupation had direct or indirect effects on pulmonary function including post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), FEV1, FVC, and FEV1 percentage of predicted. Education, FAI, and occupation had indirect effects on pulmonary function indices of all participants mainly through smoking status, indoor air pollution, and outdoor air pollution. We also found that occupation could affect post-bronchodilator FEV1/FVC through body mass index.@*CONCLUSIONS@#Education, occupation, and FAI had an adverse relationship with COPD prevalence in Jiangsu province, China. SES has both direct and indirect associations with pulmonary function impairment. SES is of great significance for COPD morbidity. It is important that population-based COPD prevention strategies should be tailored for people with different SES.

Xinglou Chengqi Decoction improves neurological function in experimental stroke mice as evidenced by gut microbiota analysis and network pharmacology / 中国天然药物

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction (XCD) based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion (MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke (IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis. We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis. Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids (SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.

Blood-retinal barrier as a converging pivot in understanding the initiation and development of retinal diseases / 中华医学杂志(英文版)

Clinical ophthalmologists consider each retinal disease as a completely unique entity. However, various retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, and primary open-angle glaucoma, share a number of common pathogenetic pathways. Whether a retinal disease initiates from direct injury to the blood-retinal barrier (BRB) or a defect/injury to retinal neurons or glia that impairs the BRB secondarily, the BRB is a pivotal point in determining the prognosis as self-limiting and recovering, or developing and progressing to a clinical phenotype. The present review summarizes our current knowledge on the physiology and cellular and molecular pathology of the BRB, which underlies its pivotal role in the initiation and development of common retinal diseases.

Spectrum-effect relationship between UPLC fingerprint of Smilax china and anti-pelvic inflammation in rats / 中国中药杂志

To study the correlation between ultra high performance liquid chromatography( UPLC) fingerprint of Smilax china and its anti-pelvic inflammatory effect,and to explore the pharmacodynamic material basis of S. china against pelvic inflammatory disease.UPLC fingerprints of 10 batches of S. china from different habitats were established,and the values of SOD,MDA,TNF-α,and IL-6 in rats with pelvic inflammation were measured. The weight of each single pharmacodynamics index to the total efficacy was determined by analytic hierarchy process,and the contribution of each peak in fingerprints to the each single pharmacodynamics index and total efficacy was analyzed by the grey relational analysis. Then the structures of chemical constituents at the identified peaks were confirmed by comparing with the reference substance. The 27 common characteristic peaks of UPLC fingerprints were all related to the anti-pelvic inflammation effect of S. china,of which 13 peaks were identified as peak 2( 3,5-dihydroxy-2-methylbenzoic acid-3-O-glucoside),peak 3( chlorogenic acid),peak 5( 2,7,4-trihydroxydihydroflavone-5-O-glucoside),peak 6( 7,4-dihydroxydihydroflavonol-5-O-glucoside),peak 7( taxifolin-7-O-glucoside),peak 9( taxifolin),peak 10( polydatin),peak 11( oxyresveratrol),peak 12( astilbin),peak15( resveratrol),peak 16( quercitrin),peak 18( engeletin) and peak 24( kaempferol). The correlation degree of 21 peaks and the total efficacy was greater than 0. 8,and the top 10 ranked by correlation degree were as follows: peak 1,3,7,19,18,17,4,11,16,and 21. The results showed that the anti-pelvic inflammation effect of S. china was achieved by the combined action of pharmacodynamic substances. In order to control the quality of S. china and its prepared slices more effectively,the index components of content detection should be selected reasonably.

Protective Effect and Mechanism of Extracts from Ginseng Radix et Rhizoma,Anemarrhenae Rhizoma and Paeoniae Radix Rubra on Hippocampal Neurons in Rats with Vascular Dementia / 中国实验方剂学杂志

Objective: To observe the effect of extracts from Ginseng Radix et Rhizoma,Anemarrhenae Rhizoma and Paeoniae Radix Rubra on N-methyl-D-aspartate receptors(NMDAR1) in hippocampal neurons in rats with vascular dementia and investigate its possible mechanism. Method: The 60 SPF male rats were randomly divided into normal group, sham-operated group,model group, traditional Chinese medicine group(0.20 g·kg-1)and memantine group(2.1 mg·kg-1),with 12 rats in each group. The model was established by repeated ischemia-reperfusion combined with intraperitoneal injection of sodium nitroprusside. After modelling, normal group, sham-operated group and model group were dosed the similar volume of normal saline once a day for 14 days. The learning and memory capacity was assessed by Morris water maze; pathologic change in the CA1 district of hippocampus was assessed by hematoxylin-eosin (HE) staining, and the expression level of NMDAR1 in hippocampal neuron membrane protein was detected by Western blot and immunohistochemistry(IHC),the NMDAR1 mRNA in hippocampal tissue was detected by Real-time PCR. Result:Compared with normal and sham-operated group, the latency period was prolonged in model group(PPPPPPPPConclusion:The extracts from Ginseng Radix et Rhizoma,Anemarrhenae Rhizoma and Paeoniae Radix Rubra can improve the learning and memory capacity of rats with vascular dementia, and alleviate the injury in CA1 district of hippocampus. The mechanism may be related to the down-regulation of NMDAR1 expression in hippocampal neurons.

Advance in milk fat globule membrane in infants and middle⁃aged and elderly population / 医学研究生学报

Milk fat globule membrane (MFGM) is a thin, dense membrane that packages outside the milk fat droplets during mammary gland lactating.MFGM is mainly composed of phospholipids, sphingolipids and a variety of specific membrane proteins. In recent years, due to the potential health benefits of MFGM, it has become a hot spot for research. In this paper, the structure and composition , the role of the main components and their applications in infants, middle⁃aged and elderly population of MFGM are reviewed.

Uterine leiomyoma and related issues of fertility and pregnancy safety / 中国实用妇科与产科杂志

Uterine leiomyoma is a common benign tumour in women of childbearing age,with an incidence of 25%-30%.Uterine myoma can cause infertility,as well as abortion,premature delivery,placental abruption and postpartum hemorrhage and other adverse pregnancy outcomes,which increases the cesarean section rate.The influence of uterine leiomyoma on fertility is closely related to its location and size.The treatment should be individualized,considering the size,location and fertility of the myoma.

Neural Respiratory Drive Measured Using Surface Electromyography of Diaphragm as a Physiological Biomarker to Predict Hospitalization of Acute Exacerbation of Chronic Obstructive Pulmonary Disease Patients / 中华医学杂志(英文版)

Background@#Neural respiratory drive (NRD) using diaphragm electromyography through an invasive transesophageal multi-electrode catheter can be used as a feasible clinical physiological parameter in patients with chronic obstructive pulmonary disease (COPD) to provide useful information on the treatment response. However, it remains unknown whether the surface diaphragm electromyogram (EMGdi) could be used to identify the deterioration of clinical symptoms and to predict the necessity of hospitalization in acute exacerbation of COPD (AECOPD) patients.@*Methods@#COPD patients visiting the outpatient department due to acute exacerbation were enrolled in this study. All patients who were subjected to EMGdi and classical parameters such as spirometry parameters, arterial blood gas analysis, COPD assessment test (CAT) score, and the modified early warning score (MEWS) in outpatient department, would be treated effectively in the outpatient or inpatient settings according to the Global Initiative for Chronic Obstructive Lung Disease guideline. When the acute exacerbation of the patients was managed, all the examination above would be repeated.@*Results@#We compared the relationships of admission-to-discharge changes (Δ) in the normalized value of the EMGdi, including the change of the percentage of maximal EMGdi (ΔEMGdi%max) and the change of the ratio of minute ventilation to the percentage of maximal EMGdi (ΔVE/EMGdi%max) with the changes of classical parameters. There was a significant positive association between ΔEMGdi%max and ΔCAT, ΔPaCO, and ΔpH. The change (Δ) of EMGdi%max was negatively correlated with ΔPaO/FiOin the course of the treatment of AECOPD. Compared with the classical parameters including forced expiratory volume in 1 s, MEWS, PaO/FiO, the EMGdi%max (odds ratio 1.143, 95% confidence interval 1.004-1.300) has a higher sensitivity when detecting the early exacerbation and enables to predict the admission of hospital in the whole cohort.@*Conclusions@#The changes of surface EMGdi parameters had a direct correlation with classical measures in the whole cohort of AECOPD. The measurement of NRD by surface EMGdi represents a practical physiological biomarker, which may be helpful in detecting patients who should be hospitalized timely.

Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry / 中国天然药物

Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from traditional Chinese medicine (TCM) powder for injection, since its use for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the same time, its allergic reactions have also emerged, which limits clinical applications. However, few scholars pay attention to the mechanism of allergic reactions. In this present study, metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction; we and analyzed the metabolites, metabolic pathway, and the mechanism which were closely related to the allergic reactions. The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the pattern recognition analysis, selected potential biomarkers associated with allergic reactions, and explored the pathological mechanism for SHLI induced allergic reaction, which laid the foundation for the safety research of SHLI. Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved, such as metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine and other metabolic pathways.

Metabonomics delineates allergic reactions induced by Shuang-huang-lian injection in rats using ultra performance liquid chromatography-mass spectrometry / 中国天然药物

Shuang-huang-lian Injection (SHLI) is the first successfully developed drug from traditional Chinese medicine (TCM) powder for injection, since its use for the treatment of acute respiratory tract infection, pneumonia, influenza, etc. At the same time, its allergic reactions have also emerged, which limits clinical applications. However, few scholars pay attention to the mechanism of allergic reactions. In this present study, metabonomics technology was used to explore the changes in endogenous metabolites in urine of the rat model of SHLI induced allergic reaction; we and analyzed the metabolites, metabolic pathway, and the mechanism which were closely related to the allergic reactions. The levels of serum histamine and tryptase were examined and changes in histomorphology were also observed. Based on the UPLC-Q-TOF/MS metabonomics, we carried out the pattern recognition analysis, selected potential biomarkers associated with allergic reactions, and explored the pathological mechanism for SHLI induced allergic reaction, which laid the foundation for the safety research of SHLI. Our results showed that SHLI increased the levels of serum histamine and tryptase in rats with allergic reaction; we determined 15 biomarkers in rat allergic reaction model induced by SHLI and found multiple metabolic pathways involved, such as metabolism of linolenic acid, phenylalanine, amino acid, 2-oxo acid, and purine and other metabolic pathways.

Regulatory effect and relevant mechanisms of fraction from heat-clearing and detoxifying herb couplet on macrophage M1/M2 phenotypes / 中国中药杂志

To explore the regulatory effect and relevant mechanisms of the fraction of Hedyotis diffusa and Scutellaria barbata herb couple(YDW11) on polarization of macrophage between M1/M2 phenotypes.RAW264.7 cells were induced with LPS/IFN- or IL-4/IL-13 to establish M1 or M2 macrophage cell model. MTT assay was used to measure the cell cytotoxicity of YDW11. Griess reaction was used to detect the changes of nitrite accumulation in the cell supernatant. Trans-well assay was used to measure the migration capability. QRT-PCR was used to assay mRNA expressions of iNOS, IL-1, Arg-1 and MR. Western blot was used to detect the effect of YDW11 on iNOS and Arg-1 protein expressions. Taqman MicroRNA RT-PCR was used to detect the effect of YDW11 on miR155 expression under M1 and M2 phenotype conditions. In addition, MS-UPLC assay was carried out to identify the constituents in YDW11. The results showed that the ethyl acetate of H. diffusa and S. barbata extracted in 1:1 ratio with water (YDW11) showed the activity in suppressing the nitrite content in M1 macrophages without cytotoxicity. YDW11 also inhibited the migration of breast cancer cells with the help of M2 macrophages by blocking their polarization towards M2. YDW11 decreased iNOS, IL-1, Arg-1and MR mRNA expressions and iNOS and Arg-1 protein expressions. YDW11 down-regulated miR155 expression in M1 phenotype, and up-regulated miR155 expression in M2 phenotype. Based on MS-UPLC,four compounds were identified in YDW11, including 4'-hydroxyacetophenone, scutellarin, luteolin and apigenin. YDW11 inhibited M1/M2 phenotypes of macrophages by regulating the expression of miR155.

Clinical Manifestations and Amplitude-integrated Encephalogram in Neonates with Early-onset Epileptic Encephalopathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The patients with early-onset epileptic encephalopathy (EOEE) suffer from neurodevelopmental delay. The aim of this study was to analyze the clinical manifestations and amplitude-integrated encephalogram (aEEG) characteristics of infants with EOEE with onset within the neonatal period, to make early diagnosis to improve the prognosis.</p><p><b>METHODS</b>One-hundred and twenty-eight patients with neonatal seizure were enrolled and followed up till 1 year old. Sixty-six neonates evolved into EOEE were as the EOEE group, the other 62 were as the non-EOEE (nEOEE) group. Then we compared the clinical and aEEG characteristics between the two groups to analyze the manifestations in neonates with EOEE.</p><p><b>RESULTS</b>Compared to the nEOEE group, the incidence of daily seizure attacks, more than two types of convulsions, more than two antiepileptic drugs (AEDs) application, severely abnormal aEEG background, absence of cyclicity, and more than two seizures detection were significantly higher in the EOEE group (P < 0.05) (97% vs. 54.8%; 30.3% vs. 14.5%; 97.0% vs. 25.4%; 39.4% vs. 3.2%; 57.6% vs. 9.7%; and 56% vs. 3.2%, respectively). Severely abnormal background pattern (odds ratio [OR] = 0.081, 95% confidence interval [CI]: 0.009-0.729, P = 0.025) and more than two seizures detection by aEEG (OR = 0.158, 95% CI: 0.043-0.576, P = 0.005) were the independent risk factors for the evolvement into EOEE. The upper and lower margins of active sleep (AS) and quiet sleep (QS) were significantly higher in EOEE group than those of the control group (P < 0.05) (34.3 ± 13.6 vs. 21.3 ± 6.4; 9.9 ± 3.7 vs. 6.7 ± 2.2; 41.2 ± 15.1 vs. 30.4 ± 11.4; and 11.9 ± 4.4 vs. 9.4 ± 4.0; unit: μV, respectively). AS upper margin was demonstrated a higher diagnostic specificity and sensitivity for EOEE than another three parameters according to the receiver operating characteristic curves; the area under the curve was 0.827.</p><p><b>CONCLUSIONS</b>The clinical characteristics of the neonatal seizure which will evolve into EOEE were more than two AEDs application, high seizure frequency (daily attack), and more than two types of the seizure. Significant high voltage, severely abnormal background, absence of cyclicity, and more than two seizures detected on aEEG were the meaningful indicators to the prediction of EOEE.</p>

Inhibitory mechanisms of timosaponin AⅢ on proliferation and growth of human glioblastoma cells / 中国中药杂志

To explore the inhibitory effect of timosaponin AⅢ on the proliferation of human glioblastoma cell line U87MG and investigate its related mechanism. As compared with the model group, the tumor weight was significantly reduced in timosaponin AⅢ-treated group. Timosaponin AⅢinhibited the proliferation of U87MG cell line in a dose-dependent manner. It up-regulated the gene and protein expression levels of p21, meanwhile inhibited the protein expression levels of β-Catenin, Cyclin D1 and Bcl-2. It also inhibited the translocation of β-Catenin into nucleus, suppressed the phosphorylation expression of ERK, but increased the phosphorylation expression of p38 and JNK. Combined use of JNK inhibitor SP600125 and p38 inhibitor SB203580 could decrease p21 and increase β-Catenin protein expressions. Timosaponin AⅢ inhibited the proliferation of human glioblastoma cell line U87MG partly by intervening MAPK and Wnt/β-Catenin signal pathways.

Treatment of Chronic Ulcer in Diabetic Rats with Asiaticosides / 中国药学杂志

OBJECTIVE: To investigate the treatment effects of chronic ulcer in diabetic rats with asiaticosides. METHODS: Totally 38 male CL grade SD rats were randomly divided into normal group and model group, and were feed in metabolic cage separately. The low (22.29 mg·cm-2), medium (111.45 mg·cm-2) and high (222.93 mg·cm-2) dose of centella triterpenes cream were characterized and tested on excision ulcer wounds of streptozotocin-induced diabetic rats. After treatment, the weight, blood glucose, water intake and total urine output were measured in 3, 7, 10 and 14 d respectively. The wound healing rate was evaluated by image processing software of Adobe Photoshop CS5. Histopathological studies were conducted on the healed wound tissues to observe for epithelisation, fibroblast proliferation and angiogenesis. RESULTS: It was found that at all time points the areas of wounds treated with asiaticosides were smaller compared with the controls. The expression of weight, water intake, total urine output and blood glucose increased statistically in the model group (P<0.05).Pathological results showed much better healing efficacy for the test samples compared with the control ones(P<0.05). The middle dose of centella triterpenes cream was the best (P<0.01). Histopathological studies had also shown that centella triterpenes cream treated wounds exhibited re-epithelisation, higher fibroblast proliferation, collagen synthesis, and angiogenesis. At 14 days post excision, the medium centella triterpenes cream treated group achieved complete repair. CONCLUSION: These findings suggest that asiaticosides may have a potential application in the treatment of diabetic ulcers and chronic wound healing.