Study on the relationship between secondhand smoke exposure and dyslipidemia in adult residents in Beijing / 中华流行病学杂志

Objective: To understand the relationship between secondhand smoke exposure and dyslipidemia among adults in Beijing and to provide a scientific basis for relevant intervention. Methods: Data were from Beijing Adult Non-communicable and Chronic Diseases and Risk Factors Surveillance Program in 2017. A total of 13 240 respondents were selected by multistage cluster stratified sampling method. The monitoring contents include a questionnaire survey, physical measurement, collection of fasting venous blood, and determination of related biochemical indicators. SPSS 20.0 software was used for the chi-square test and multivariate logistic regression analysis. Results: The prevalence of total dyslipidemia (39.27%), hypertriglyceridemia (22.61%), and high LDL-C (6.03%) were the highest among those exposed to daily secondhand smoke. Among the male respondents, the prevalence of total dyslipidemia (44.42%) and hypertriglyceridemia (26.12%) were the highest among those exposed to secondhand smoke daily. Multivariate logistic regression analysis after adjustment for confounding factors showed that compared with no exposure to secondhand smoke, the population with an average exposure frequency of 1-3 days per week had the highest risk of total dyslipidemia (OR=1.276, 95%CI: 1.023-1.591). Among the patients with hypertriglyceridemia, those exposed to secondhand smoke daily had the highest risk (OR=1.356, 95%CI: 1.107-1.661). Among the male respondents, those exposed to secondhand smoke for 1-3 days per week had a higher risk of total dyslipidemia (OR=1.366, 95%CI: 1.019-1.831), and the highest risk of hypertriglyceridemia (OR=1.377, 95%CI: 1.058-1.793). There was no significant correlation between the frequency of secondhand smoke exposure and the risk of dyslipidemia among female respondents. Conclusions: Secondhand smoke exposure in Beijing adults, especially men, will increase the risk of total dyslipidemia, especially hyperlipidemia. Improving personal health awareness and minimizing or avoiding exposure to secondhand smoke is necessary.

Clinical and genetic characteristics of 9 rare cases with coexistence of dual genetic diagnoses / 中华儿科杂志

Objective: To analyze the clinical and genetic characteristics of pediatric patients with dual genetic diagnoses (DGD). Methods: Clinical and genetic data of pediatric patients with DGD from January 2021 to February 2022 in Peking University First Hospital were collected and analyzed retrospectively. Results: Among the 9 children, 6 were boys and 3 were girls. The age of last visit or follow-up was 5.0 (2.7,6.8) years. The main clinical manifestations included motor retardation, mental retardation, multiple malformations, and skeletal deformity. Cases 1-4 were all all boys, showed myopathic gait, poor running and jumping, and significantly increased level of serum creatine kinase. Disease-causing variations in Duchenne muscular dystrophy (DMD) gene were confirmed by genetic testing. The 4 children were diagnosed with DMD or Becker muscular dystrophy combined with a second genetic disease, including hypertrophic osteoarthropathy, spinal muscular atrophy, fragile X syndrome, and cerebral cavernous malformations type 3, respectively. Cases 5-9 were clinically and genetically diagnosed as COL9A1 gene-related multiple epiphyseal dysplasia type 6 combined with NF1 gene-related neurofibromatosis type 1, COL6A3 gene-related Bethlem myopathy with WNT1 gene-related osteogenesis imperfecta type XV, Turner syndrome (45, X0/46, XX chimera) with TH gene-related Segawa syndrome, Chromosome 22q11.2 microduplication syndrome with DYNC1H1 gene-related autosomal dominant lower extremity-predominant spinal muscular atrophy-1, and ANKRD11 gene-related KBG syndrome combined with IRF2BPL gene-related neurodevelopmental disorder with regression, abnormal movement, language loss and epilepsy. DMD was the most common, and there were 6 autosomal dominant diseases caused by de novo heterozygous pathogenic variations. Conclusions: Pediatric patients with coexistence of double genetic diagnoses show complex phenotypes. When the clinical manifestations and progression are not fully consistent with the diagnosed rare genetic disease, a second rare genetic disease should be considered, and autosomal dominant diseases caused by de novo heterozygous pathogenic variation should be paid attention to. Trio-based whole-exome sequencing combining a variety of molecular genetic tests would be helpful for precise diagnosis.

Analysis of Effect of Characteristic Processing with Rice-washed Water on Volatile Components in Raw and Bran-fried Products of Atractylodis Macrocephalae Rhizoma by HS-GC-MS / 中国实验方剂学杂志

ObjectiveBy comparing the differences in composition and content of volatile components between Atractylodis Macrocephalae Rhizoma（AMR）and bleaching AMR， bran-fried AMR and bran-fried bleaching AMR， the effect of processing with rice-washed water on the volatile components in AMR and bran-fried AMR were investigated. MethodHeadspace gas chromatography-mass spectrometry（HS-GC-MS）was used to determine the volatile components in raw products， bran-fried products and their processed products with rice-washed water. GC conditions were programmed temperature（starting temperature of 50 ℃， rising to 140 ℃ at 10 ℃·min-1， maintained for 5 min， then rising to 210 ℃ at 4 ℃·min-1）， splitting ratio of 10∶1， high purity helium as the carrier gas and a solvent delay time of 3 min. MS conditions were an electron bombardment ion source（EI） with an electron collision energy of 70 eV， ion source temperature of 230 ℃， and the detection range of m/z 20-650. The relative contents of the components were determined by the peak area normalization method， the obtained sample data were subjected to principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） by SIMCA 14.1 software， and the differential components of AMR and bleaching AMR， and bran-fried AMR and bran-fried bleaching AMR were screened according to variable importance in the projection（VIP） value>1 and P<0.05. ResultA total of 71 volatile components were identified， including 53 in AMR， 50 in bleaching AMR， 51 in bran-fried AMR， and 44 in bran-fried bleaching AMR. OPLS-DA results showed that there were significant differences between AMR and bleaching AMR， bran-fried AMR and bran-fried bleaching AMR， but not between AMR samples from different origins. The compound composition of AMR and bleaching AMR， bran-fried AMR and bran-fried bleaching AMR did not change， but the contents of monoterpenes and sesquiterpenes changed significantly. ConclusionSignificant changes in the contents of volatile components were observed in AMR and bleaching AMR， bran-fried AMR and bran-fried bleaching AMR， among them， 1，2-dimethyl-4-methylidenecyclopentene， 9，10-dehydro-isolongifolene， γ-elemene， zingiberene， atractylone， silphinene， modhephene and （1S，4S，4aS）-1-isopropyl-4，7-dimethyl-1，2，3，4，4a，5-hexahydronaphthalene can be used as candidate differential markers of volatile components of AMR before and after processing with rice-washed water.

Optimal processing technology of Zhangbang vinegar-processed Olibanum with multi-indicator-response surface methodology and anticoagulant effect evaluation / 中国中药杂志

This study first optimized the processing technology for Zhangbang vinegar-processed Olibanum and investigated its in vitro anticoagulant activity. A multi-index-response surface methodology was used, with yield, powder yield, and the relative percentage of the content of six non-volatile components [11-keto-boswellic acid(KBA), 3-acetyl-11-keto-boswellic acid(AKBA), β-elemonic acid, α-boswellic acid(α-BA), β-boswellic acid(β-BA), and α-acetyl-boswellic acid(α-BA)] and three volatile components(octyl acetate, incensole, and incensole acetate) as evaluation indicators. Analytical hierarchy process(AHP) combined with coefficient of variation method was used to calculate the weight of each indicator and calculate the comprehensive score(OD). Furthermore, response surface methodology was used to investigate the effects of frying temperature(A), burning time(B), rice vinegar dosage(C), and steaming time(D) on the processing technology of vinegar-processed Olibanum. Vinegar-steamed Olibanum was prepared according to the optimal processing technology for in vitro anticoagulant experiments. The results showed that the weights of octyl acetate, incensole, incensole acetate, KBA, AKBA, β-elemonic acid, α-BA, β-BA, α-ABA, yield, and powder yield were 0.358 2, 0.104 5, 0.146 4, 0.032 9, 0.123 7, 0.044 4, 0.022 1, 0.042 2, 0.110 1, 0.012 2, and 0.0032, respectively. The optimal processing technology for Zhangbang vinegar-processed Olibanum was as follows. Olibanum(50 g) with a particle size of 1-5 mm was continuously stir-fried at a low heat of 150-180 ℃ until in a gel-like state, ignited for burning for 15 s, sprayed with 7.5 g of rice vinegar(15%), and steamed for 3 min without fire. Subsequently, the cover was removed, and the product was continuously stir-fried at 150-180 ℃ until in a soft lump shape, removed, cooled, and crushed. The results of the in vitro anticoagulant experiments showed that compared with the blank group, both Olibanum and vinegar-processed Olibanum significantly prolonged the activated partial thromboplastin time(APTT), thrombin time(TT), and prothrombin time(PT) of rat platelet-poor plasma(PPP), and the effect of vinegar-processed Olibanum was significantly better than that of Olibanum(P<0.05). The optimized processing technology for Zhangbang vinegar-processed Olibanum is stable, feasible, and beneficial for the further development and utilization of Olibanum slices. At the same time, using the content of volatile and non-volatile components, yield, and powder yield as indicators, and verifying through pharmacological experiments, the obtained results are more reasonable and credible, and have positive guiding significance for the clinical application of characteristic processed Olibanum products.

Progress in the diagnosis and treatment of immunoglobulin G4-related ophthalmic diseases / 国际眼科杂志(Guoji Yanke Zazhi)

Immunoglobulin G4-related diseases(IgG4-RD)are chronic, systemic diseases that have received much attention in recent years. IgG4-RD can affect almost all tissues of the body, mainly manifested by swelling and space-occupying changes in the involved sites. It is called IgG4-related ophthalmic disease(IgG4-ROD)when the lesions invade the ocular area. The disease mainly invades the lacrimal glands, orbital fat, infraorbital nerve, extraocular muscles, and eyelids. At present, the main treatment modalities for IgG4-ROD include medication, surgery, and radiation therapy, etc. With the enhanced understanding of the disease and the increasing cure rate in recent years, this article reviews the latest progress in the epidemiological characteristics, clinical manifestations, imaging features, diagnosis and treatment of IgG4-ROD.

Effect of γ-ray on metabolic enzyme CYP3A1 in rat liver on multiple levels / 中国药理学通报

Aim To explore the effect of γ-ray on the mRNA,protein expression levels and metabolic activity level of the key drug metabolic enzyme CYP3A1 in rat liver. Methods Wistar rats were randomly divided into control group, 24 h post-radiation group and 72 h post-radiation group. The experimental group was exposed to total body irradiation of single 6 Gy γ-ray. Blood was collected from the orbital venous plexus for blood routine examination and biochemical analysis 24 h and 72 h after irradiation, and liver tissue was prepared for quantifying expression of CYP3A1 mRNA and liver-specific microRNA (miR-122-5p) through RT-PCR. The expression level of CYP3A1 protein was analyzed by Western blot, and the metabolic activity level of CYP3A1 detected by the specific substrate midazolam combined with LC-MS method. Results Com¬pared with the control group, the weights of the rats in the radiation group significantly decreased, and the number of white blood cells was markedly reduced. Simultaneously, the activities of alanine aminotrans-ferase and alkaline phosphatase continuously descended, as well as the levels of total bilirubin and bile acid significantly increased, which indicated that the liver may be damaged after radiation. The relative expression of CYP3A1 mRNA continued to increase significantly 24 h and 72 h after irradiation. CYP3A1 protein expression and metabolic activity levels showed an obvious increasing trend 24 h after irradiation, and rose significantly 72 h after irradiation compared with the control group. At the same time, the expression of miR-122-5p in liver of rats in the 24 h and 72 h post-radiation group continued to decrease rapidly compared with the control group. Conclusions γ-ray radiation may arouse damage effect on liver, which leads to the continuous up-regulation of the mRNA and protein expression levels of the capital metabolic enzyme CYP3A1 in liver tissue, as well as the elevation of the metabolic activity level. The regulatory mechanism might be related to miR-122-5p.

Predictive Value of Complete Blood Count and Inflammation Marker on Risk of Recurrence in Children with Henoch-Schönlein Purpura / 中国实验血液学杂志

OBJECTIVE@#To investigate the predictive value of complete blood count (CBC) and inflammation marker on the recurrence risk in children with Henoch-Schönlein purpura (HSP).@*METHODS@#One hundred and thirty-three children with HSP admitted to Cangzhou Central Hospital from February 2017 to March 2019 were enrolled. The clinical data of the children were collected, at the time of admission CBC and C-reactive protein (CRP) were detected. After discharge, the children were followed up for 1 year, the clinical data of children with and without recurrence were compared, and multivariate logistic regression was used to analyze the risk factors affecting HSP recurrence. Receiver operating characteristic (ROC) curve should be drawn and the predictive value of CBC and CRP on HSP recurrence should be analyzed.@*RESULTS@#In the follow-up of 133 children, 8 cases were lost and 39 cases recurred, with a recurrence rate of 31.20% (39/125). The age, skin rash duration, proportion of renal damage at the initial onset, percentage of neutrophils, percentage of lymphocytes, platelet count (PLT), mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), MPV/PLT ratio (MPR), and CRP level of patients with recurrence were statistically different from those without recurrence (P <0.05). Multivariate logistic regression analysis showed that long skin rash duration, renal damage at the initial onset, increased PLR, high PLT, increased MPV and elevated CRP level were independent risk factors for recurrence in children with HSP (P <0.05). The ROC curve analysis showed that the area under the curve (AUC) of the combination of the four blood and inflammation marker (PLT, MPV, PLR and CPR) in the early prediction of HSP recurrence was 0.898, which was higher than the initial renal damage (AUC=0.687) and persistent skin rash time (AUC=0.708), with a sensitivity of 84.62% and a specificity of 83.72%.@*CONCLUSION@#Observation of CBC and CPR can predict the risk of HSP recurrence early and guide early clinical intervention.

Study on dynamic changes of volatile components during the bleaching process of Atractylodis macrocephala with the water of washing rice / 中国药房

OBJECTIV E To study composition an d content changes of volatile components during the bleaching process of Atractylodis macrocephala with the water of washing rice. METHODS The raw products of A. macrocephala and bleached products of 5 different bleaching stages were prepared （in the first and second stages ，raw products were bleached with 9-fold volumn of the water of washing rice for 12 h and 24 h，respectively；in the third ，fourth and fifth stages ，the raw products were firstly bleached with 9-fold volumn of the water of washing rice for 24 h，and then bleached with 9-fold volumn of clean water for 12，24 and 48 h，respectively）；the bleaching temperature was set at 26 ℃. The volatile components of raw products of A. macrocephala and its bleached products of 5 different bleaching stages were qualitatively analyzed by using headspace gas chromatography-mass spectrometry. The relative percentage of each component was calculated by peak area normalization method. RESULTS A total of 49 volatile components were identified from raw products of A. macrocephala and its bleached products of 5 different bleaching stages，including 20 common volatile components such as terpinolene ，cyperene and atractylon ，etc. Among them ，33，31，28， 30，28 and 29 volatile components were identified from the raw products of A. macrocephala and the bleached products of the first to fifth stages ，the relative percentages of which were 66.218％ ，64.711％ ，79.410％ ，65.419％ ，67.101％ ，66.818％ ， respectively；among them ，the relative percentage of atractylon in bleached products was the highest in the fourth stage （41.206％），but was the lowest in the third stage （35.926％）. Compared with the raw product ，16 volatile components such as pethylbrene and β-vetivenen were added in the bleaching process ，while 8 volatile components such as ethyl palmitate and β-maaliene were not detected. However ，5 volatile components including 11-rotundene and （－）-valeranone in the bleaching process showed a trend of disappearance-emergence and disappearance-emergence-disappearance. CONCLUSIONS In the third stage，the total relative percentage of each volatile component and the relative percentage of representative dry component as ， atractylone are the lowest in bleached products of A. ； macrocephala，i.e. the bleaching technology of relieving the dry property of A. macrocephala e with the water of washing rice is bleaching with 9-fold volumn of the water of washing rice for 24 h，and then bleaching with 9-fold volumn of clean water for 12 h.

IRE1α deficiency impairs autophagy in chondrocytes by upregulating calcium homeostasis endoplasmic reticulum protein / 南方医科大学学报

OBJECTIVE@#To explore the mechanism by which inositol-requiring enzyme-1α (IRE1α) regulates autophagy function of chondrocytes through calcium homeostasis endoplasmic reticulum protein (CHERP).@*METHODS@#Cultured human chondrocytes (C28/I2 cells) were treated with tunicamycin, 4μ8c, rapamycin, or both 4μ8c and rapamycin, and the expressions of endoplasmic reticulum (ER) stress- and autophagy-related proteins were detected with Western blotting. Primary chondrocytes from ERN1 knockout (ERN1 CKO) mice and wild-type mice were examined for ATG5 and ATG7 mRNA expressions, IRE1α and p-IRE1α protein expressions, and intracellular calcium ion content using qPCR, Western blotting and flow cytometry. The effect of bafilomycin A1 treatment on LC3 Ⅱ/LC3 Ⅰ ratio in the isolated chondrocytes was assessed with Western blotting. Changes in autophagic flux of the chondrocytes in response to rapamycin treatment were detected using autophagy dual fluorescent virus. The changes in autophagy level in C28/I2 cells overexpressing CHERP and IRE1α were detected using immunofluorescence assay.@*RESULTS@#Tunicamycin treatment significantly up-regulated ER stress-related proteins and LC3 Ⅱ/LC3 Ⅰ ratio and down-regulated the expression of p62 in C28/I2 cells (P < 0.05). Rapamycin obviously up-regulated LC3 Ⅱ/LC3 Ⅰ ratio (P < 0.001) in C28/I2 cells, but this effect was significantly attenuated by co-treatment with 4μ8c (P < 0.05). Compared with the cells from the wild-type mice, the primary chondrocytes from ERN1 knockout mice showed significantly down-regulated mRNA levels of ERN1 (P < 0.01), ATG5 (P < 0.001) and ATG7 (P < 0.001), lowered or even lost expressions of IRE1α and p-IRE1α proteins (PP < 0.01), and increased expression of CHERP (P < 0.05) and intracellular calcium ion content (P < 0.001). Bafilomycin A1 treatment obviously increased LC3 Ⅱ/ LC3 Ⅰ ratio in the chondrocytes from both wild-type and ERN1 knockout mice (P < 0.01 or 0.05), but the increment was more obvious in the wild-type chondrocytes (P < 0.05). Treatment with autophagy dual-fluorescence virus resulted in a significantly greater fluorescence intensity of LC3-GFP in rapamycin-treated ERN1 CKO chondrocytes than in wild-type chondrocytes (P < 0.05). In C28/I2 cells, overexpression of CHERP obviously decreased the fluorescence intensity of LC3, and overexpression of IRE1α enhanced the fluorescence intensity and partially rescued the fluorescence reduction of LC3 caused by CHERP.@*CONCLUSION@#IRE1α deficiency impairs autophagy in chondrocytes by upregulating CHERP and increasing intracellular calcium ion content.

Analysis of Terpenoids in Alismatis Rhizoma Before and After Processing with Salt-water Based on UPLC-Q-TOF-MS / 中国实验方剂学杂志

ObjectiveTo identify the chemical constituents of Alismatis Rhizoma before and after processing with salt-water by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and to investigate the changes of terpenoids in Alismatis Rhizoma before and after processing with salt-water. MethodUPLC-Q-TOF-MS was used to detect with 0.1% formic acid aqueous solution （A）-acetonitrile （B）as mobile phase for gradient elution （0-0.01 min， 20%B； 0.01-5 min， 20%-40%B； 5-40 min， 40%-95%B； 40-42 min， 95%B； 42-42.1 min， 95%-20%B； 42.1-45 min， 20%B）， electrospray ionization （ESI） was selected for collection and detection in positive ion mode with the scanning range of m/z 100-1 250 and ion source temperature at 500 ℃. The data were analyzed by PeakView 1.2.0.3， the components were identified according to the primary and secondary MS data， and combined with the reference substance and literature. After normalized treatment by MarkerView 1.2.1， the MS data were analyzed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， and then the differential components before and after processing were screened. The content changes of differential components were analyzed according to the relative peak area. ResultA total of 30 components were identified under positive ion mode， including 28 prototerpene triterpenes and 2 sesquiterpenes. The results of PCA and OPLS-DA showed that there were significant differences in components from Alismatis Rhizoma before and after processing with salt-water， and 10 differential components （alisol B 23-acetate， alisol I， alismol， 11-deoxy-alisol B 23-acetate， alisol B， alisol C， 11-deoxy-alisol B， alisol G， 11-deoxy-alisol C and alisol A） were screened， and the contents of alisol G and alisol A decreased significantly after processing. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents in raw and salt-processed products of Alismatis Rhizoma. It takes a great difference in the contents of chemical constituents before and after processing， and the difference of substituents is the main reason for this differences， which can provide reference for determining the material basis of efficacy changes of Alismatis Rhizoma before and after processing with salt-water.

Analysis of Terpenoids in Alismatis Rhizoma Before and After Processing with Salt-water Based on UPLC-Q-TOF-MS / 中国实验方剂学杂志

ObjectiveTo identify the chemical constituents of Alismatis Rhizoma before and after processing with salt-water by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， and to investigate the changes of terpenoids in Alismatis Rhizoma before and after processing with salt-water. MethodUPLC-Q-TOF-MS was used to detect with 0.1% formic acid aqueous solution （A）-acetonitrile （B）as mobile phase for gradient elution （0-0.01 min， 20%B； 0.01-5 min， 20%-40%B； 5-40 min， 40%-95%B； 40-42 min， 95%B； 42-42.1 min， 95%-20%B； 42.1-45 min， 20%B）， electrospray ionization （ESI） was selected for collection and detection in positive ion mode with the scanning range of m/z 100-1 250 and ion source temperature at 500 ℃. The data were analyzed by PeakView 1.2.0.3， the components were identified according to the primary and secondary MS data， and combined with the reference substance and literature. After normalized treatment by MarkerView 1.2.1， the MS data were analyzed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， and then the differential components before and after processing were screened. The content changes of differential components were analyzed according to the relative peak area. ResultA total of 30 components were identified under positive ion mode， including 28 prototerpene triterpenes and 2 sesquiterpenes. The results of PCA and OPLS-DA showed that there were significant differences in components from Alismatis Rhizoma before and after processing with salt-water， and 10 differential components （alisol B 23-acetate， alisol I， alismol， 11-deoxy-alisol B 23-acetate， alisol B， alisol C， 11-deoxy-alisol B， alisol G， 11-deoxy-alisol C and alisol A） were screened， and the contents of alisol G and alisol A decreased significantly after processing. ConclusionUPLC-Q-TOF-MS can comprehensively and accurately identify the chemical constituents in raw and salt-processed products of Alismatis Rhizoma. It takes a great difference in the contents of chemical constituents before and after processing， and the difference of substituents is the main reason for this differences， which can provide reference for determining the material basis of efficacy changes of Alismatis Rhizoma before and after processing with salt-water.

Visual Detection of Vibrio parahaemolyticus using Combined CRISPR/Cas12a and Recombinase Polymerase Amplification / 生物医学与环境科学（英文）

Objective@#To establish an ultra-sensitive, ultra-fast, visible detection method for Vibrio parahaemolyticus (VP) .@*Methods@#We established a new method for detecting the tdh and trh genes of VP using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 12a (CRISPR/Cas12a) combined with recombinase polymerase amplification and visual detection (CRISPR/Cas12a-VD).@*Results@#CRISPR/Cas12a-VD accurately detected target DNA at concentrations as low as 10 -18 M (single molecule detection) within 30 min without cross-reactivity against other bacteria. When detecting pure cultures of VP, the consistency of results reached 100% compared with real-time PCR. The method accurately analysed pure cultures and spiked shrimp samples at concentrations as low as 10 2 CFU/g.@*Conclusion@#The novel CRISPR/Cas12a-VD method for detecting VP performed better than traditional detection methods, such as real-time PCR, and has great potential for preventing the spread of pathogens.

LXYL-P1-2 immobilized on magnetic nanoparticles and its potential application in paclitaxel production

BACKGROUND: LXYL-P1-2 is the first reported glycoside hydrolase that can catalyze the transformation of 7-b-xylosyl-10-deacetyltaxol (XDT) to 10-deacetyltaxol (DT) by removing the D-xylosyl group at the C7 position. Successful synthesis of paclitaxel by one-pot method combining the LXYL-P1-2 and 10- deacetylbaccatin III-10-b-O-acetyltransferase (DBAT) using XDT as a precursor, making LXYL-P1-2 a highly promising enzyme for the industrial production of paclitaxel. The aim of this study was to investigate the catalytic potential of LXYL-P1-2 stabilized on magnetic nanoparticles, the surface of which was modified by Ni2+-immobilized cross-linked Fe3O4@Histidine. RESULTS: The diameter of matrix was 20­40 nm. The Km value of the immobilized LXYL-P1-2 catalyzing XDT (0.145 mM) was lower than that of the free enzyme (0.452 mM), and the kcat/Km value of immobilized enzyme (12.952 mM s 1 ) was higher than the free form (8.622 mM s 1 ). The immobilized form maintained 50% of its original activity after 15 cycles of reuse. In addition, the stability of immobilized LXYL-P1-2, maintained 84.67% of its initial activity, improved in comparison with free form after 30 d storage at 4 C. CONCLUSIONS: This investigation not only provides an effective procedure for biocatalytic production of DT, but also gives an insight into the application of magnetic material immobilization technology.

Targeting PAK2 Reverses Gefitinib Resistance in Non-small Cell Lung Cancer Cells / 中国生物化学与分子生物学报

EGFR tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy has been playing an important role in the treatment of non-small cell lung cancer (NSCLC). However, unavoidable therapeutic resistance significantly limits the clinical efficacy of TKI. As an important member of the PAK family of serine/threonine kinases, p21-activated protein kinase 2 (PAK2) plays a critical role in tumorigenesis and tumor development. The aim of this work is to investigate the effect and molecular mechanism of inhibition of PAK2 on the reversal of gefitinib resistance in NSCLC. Firstly, Western blotting was used to detect the expression and phosphorylation level of PAK2 in gefitinib-resistant HCC827/GR cells. The results showed that the phosphorylation level of PAK2 was significantly increased in HCC827/GR cells compared with HCC827 cells (P < 0. 01), while the total protein level of PAK2 did not change. Then, HCC827/GR cells were treated with PAK2 inhibitors FRAX597 or G5555. The MTS assay and clone formation assay results showed that FRAX597 or G5555 significantly increased the sensitivity of HCC827/GR cells to gefitinib (P < 0. 01). Flow cytometry analysis showed that treatment of FRAX597 could induce cell cycle arrest in G

Identification of Function and Mechanism of Apolipoprotein H Gene in Liver Failure Based on Bioinformatics Analysis / 中山大学学报(医学科学版)

@#【Objective】To explore the function and mechanism of differentially expressed Apolipoprotein H（APOH） gene in liver failure by bioinformatics. 【Methods】Multiple chip datasets（GSE14688，GSE38941 and GSE96851） were downloaded from the Gene Expression Omnibus （CEO）database. The differentially expressed genes were screened out based on P value < 0.05 and |log2FC| > 5. Biological function enrichment and KEGG pathway analysis of APOH gene， which was among the top ten key genes screened，was analyzed by Cytoscape and R，for further validation of expression of APOH in chronic hepatitis B virus-related liver failure.【Results】A total of 2 438 differentially expressed genes were screened，among which 1 162 were significantly up-regulated and 1 276 were significantly down-regulated. According to Protein-protein Interaction Network（PPIN）analysis，the top ten key genes were KNG1，IGF1，SPARC，APOH，CLU， SERPING1，TGFB2，CDC37L1，PCYOX1L and APOOL. High expression of APOH was found in chronic hepatitis B virus- related liver failure tissues and GeneMANIA predicted that APOH was associated with inflammation. GO analysis and KEGG analysis showed that APO，which was closely related to complement/coagulation cascade pathway and carbon metabolism pathway，positively correlated with C3（complement C3）.【Conclusion】APOH is involved in the occurrence and development of liver failure by C3 regulating complement/coagulation cascade pathway and carbon metabolism pathway.

Observation on Choroidal Thickness of School-aged Children and Relevant Factors / 中山大学学报(医学科学版)

@#【Objective】To observe macular choroidal thickness and topographical variation in Chinese healthy and myopic children and to investigate the correlated factors. 【Methods】 A total of 196 myopic children treated at Hainan Province Eye Hospital were selected and divided into hyperopia ，emmetropia，low，moderate and severe myopia groups according to their spherical equivalents（SE）. Axial length（AXL），subfoveal choroidal thickness（SFCT）and 1 mm ，3 mm nasal，temporal，superior，and inferior to the foveal choroidal thickness were recorded. Forty- five students from Tung Wah Group of Hospital′s MA Kam Chan Memorial Primary School in Hong Kong were also recruited in this 1-year longitudinal study. Children were grouped to myopic group and emmetropic or hyperopic group according to SE ，thickness changes of choroid were compared among children with or without myopic shift. The correlation among choroidal SE，and AXL variations were also investigated.【Results】Mean SFCT was 250（204~314）μm. The choroid was thinner at the nasal and inferior sectors ，the thinnest being at 3mm nasal to the fovea ，and the thickest at 1mm temporal to the fovea. Choroidal thickness in all orientations became thinner with progressively descending refractive degree. SFCT and 1 mm around fovea decreased most compared with other surrounding directions in all groups（Kruskal- Wallis test，P < 0.05）. The choroidal thickness in subfovea and other sectors got thinned after 1 year follow-up time（Pair t test，P < 0.05）.The variation of the choroidal thickness in fovea and surrounding positions was positively correlated with the change of SE and negatively related to the change of the AXL. The myopic group had a faster descent of SE and a faster growth of AXL than the emmetropic or hyperopic group. SFCT and surrounding choroidal thickness showed a progressive descent in the myopic group，but a slight decrease in the emmetropic or hyperopic groups.【Conclusions】There is significant topographic variation of choroidal at different regions of the macular. The choroidal thickness decreases faster in myopes. SFCT is more sensitive to myopic progression compared with surrounding regions.

Curative efficacy and influencing factors of 131I treatment for pulmonary metastases from differentiated thyroid carcinoma / 上海交通大学学报（医学版）

Objective · To investigate the curative efficacy and influential factors of 131I treatment for pulmonary metastases from differentiated thyroid carcinoma (DTC). Methods · A total of 95 DTC patients (33 males and 62 females) with pulmonary metastasis who underwent 131I treatment in Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, from April 2012 to May 2016 were retrospectively analyzed. The efficacy of 131I treatment was assessed using determination of serum thyroglobulin level and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (～ (18) F-FDG PET/CT). The possible factors affecting efficacy included gender, age, pathological classification, wheteer pulmonary metastasis diagnosed before treatment, the iodine and 18F-FDG uptake of pulmonary lesions, the size and number of lung lesions, extrapulmonary distant metastasis.Univariate analysis was performed using Rank test and χ2 test, the critical value was obtained through receiver operating characteristic (ROC) curve and Logistic regression was also performed. Results · The rates of efficacy and inefficacy of 131I treatment were 53.68％ and 46.32％, respectively. Univariate analyses showed that maximum standardized uptake value (SUVmax) evaluated by 18F-FDG PET/CT (P=0.004), the size of lung metastases (P=0.000), age＜45 years (P=0.004), 131I uptake (P=0.022), whether pulmonary metastasis diagnosed before treatment (P=0.000), extrapulmonary distant metastasis (P=0.014) were the factors influencing outcome of 131I treatment. The critical value of 18F-FDG uptake for patients obtained by ROC curve was 1.45 (sensitivity of 56.8％ and specificity of 76.5％) and the critical value of lung lesion diameter was 9.63 mm (sensitivity of 43.2％ and specificity of 88.2％). Multivariate Logistic regression analysis showed that the influential factors included the age of patients, the size and 18F-FDG SUVmax of lung metastases and whether pulmonary metastasis diagnosed before treatment. Conclusion · 131I treatment is an effective method for pulmonary metastases from DTC. The patients aged less than 45 years, with the lung lesion size less than 9.63 cm, low 18F-FDG SUVmax and diagnosed before treatment may have good response to 131I treatment.

Study on Improvement Effect of Selenium-enriched Ganoderma lucidum Crude Extract on Lipid Metabolism ，Liver Function and Inflammatory Response in Type 2 Diabetic Model Rats and Its Mechanism / 中国药房

OBJECTIVE： To study the effects of selenium-enriched Ganoderma lucidum crude extract on lipid metabolism， liver function and inflammatory response in type 2 diabetic model rats. METHODS： Totally 120 rats were randomly divided into normal control group （n＝20， normal saline） and model group （n＝100）. Normal control group was fed with normal diet， and model group was fed with high-fat diet. 4 weeks later， model group was given intraperitoneal injection of Streptozotocin solution （30 mg/kg） to induce T2DM model. After modeling， 90 rats were randomly subdivided into model control group （normal saline）， positive control group （metformin， 200 mg/kg） and selenium-enriched G. lucidum crude extract low-dose， medium-dose and high-dose groups （300， 600， 1 200 mg/kg， calculated by extract）， with 18 rats in each group. They were given medicine intragastrically， once a day， from Monday to Saturday. Half of rats in each group were selected 4， 8 weeks after medication； the serum levels of glucose and insulin were detected， and islet resistance index were calculated. The serum levels of liver function indexes （AST， ALT， AKP）， blood lipid indexes （FFA， TC， TG， LDL-C） and inflammatory factors （TNF-α， IL-6， IL-1β） were detected by ELISA. After HE staining， the histopathological changes of liver tissue were observed by microscopy. mRNA and protein expressions of peroxisome proliferator activated receptor α （PPARα） and peroxidase acyl coenzyme A oxidase 1 （ACOX1） in liver tissue were detected by RT-qPCR and Western blot assay. RESULTS： Compared with normal control group， glucose， insulin serum levels and islet resistance index were significantly increased （P＜0.01）； serum liver function indexes， blood lipid indexes and inflammatory factor levels of model control group were increased significantly in model control group after 4 and 8 weeks medication （P＜0.05 or P＜0.01）. The hepatocyte swelling of model control group was round and the volume was significantly larger than that of blank control group.  The liver had different degrees of steatosis and vacuolization， accompanied by a small amount of inflammatory cell infiltration. mRNA and protein expressions of PPARα and ACOX1 in liver tissue were decreased significantly （P＜0.05 or P＜0.01）. Compared with model control group， except that there was no significant decreased in islet resistunce index and AST， ALT， IL-6， IL-1β serum levels after 4 weeks of medication， and glucose， insulin， ALT serum levels after 8 weeks of medication and the levels of 4 blood lipid indexes after 4 and 8 weeks of medication in selenium-enriched G. lucidum crude extract low-dose group （P＞0.05）， above serum indexes of other groups were decreased significantly after 4 and 8 weeks of medication （P＜0.05 or P＜0.01）. After 4 and 8 weeks of medication， the pathological changes of liver tissue in rats were alleviated in varying degrees. protein and mRNA expressions of PPARα and ACOX1 in liver tissue were increased significantly after 4 and 8 weeks of medication （P＜0.05 or P＜0.01）. CONCLUSIONS： Selenium-enriched G. lucidum crude extract can up-regulate protein and mRNA expressions of PPARα and ACOX1 in liver tissue， promote the excretion of accumulated fatty acid and significantly improve fatty acid metabolism， inflammatory response and liver function in T2DM model rats.

Advances in the use of single-point lasers and multi-point scanning lasers to treat diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#Diabetic retinopathy(DR)is the most common retinal vascular disease, seriously compromising visual function and quality-of-life. Retinal laser photocoagulation is one of the safest, most effective, and economical methods used to treat DR, but is associated with certain side-effects developing at the time of treatment. Given the continuous developments in diagnostic and treatment modalities, the complications associated with the use of traditional single-point lasers are becoming better understood. Today, the clinical demand for multi-point scanning lasers is increasing, but the effectiveness and safety of both treatments require further exploration. Here, we review the effects of laser treatment on vision, fundus fluorescein angiography, the visual field, visual function, macular edema, and the corneal nerve.

Amplified cardiorespiratory activity by hypoxia in conscious spontaneously hypertensive rats / 生理学报

Activation of peripheral respiratory chemoreceptors provokes respiratory and cardiovascular reflexes, providing a novel understanding of pathogenic mechanism of hypertension. Here we hypothesize that activation of peripheral respiratory chemoreceptors by hypoxia causes enhanced cardiorespiratory activity in conscious spontaneously hypertensive rats (SHRs). Using whole body plethysmography in combination with radio telemetry, pulmonary ventilation, arterial blood pressure and heart rate were examined in SHRs and Wistar-Kyoto (WKY) rats. We found that exposure to hypoxia induced greater increases in tidal volume and minute ventilation volume in SHRs compared to WKY rats. In addition, hypoxia caused a robust increase in arterial blood pressure and heart rate in SHRs relative to WKY counterparts. After carotid body denervation, the hypoxic ventilatory response was significantly decreased in both SHRs and WKY rats, but without significant difference between the two strains; moreover, the differences of arterial blood pressure and heart rate changes during hypoxic exposure were statistically insignificant between SHRs and WKY rats. It is concluded that hypoxia remarkably potentiates cardiorespiratory activity in the SHRs, suggesting an enhanced sensitivity of carotid bodies to hypoxia.