Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type associated with diffuse large B-cell lymphoma: a clinicopathological study / 中华病理学杂志

Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.

Experimental research progress in traditional Chinese medicine prevention and treatment of diabetic peripheral neuropathy based on autophagy / 中国中药杂志

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.

Research progress on chemical constituents and biological activities of Arisaematis Rhizoma / 中国中药杂志

Arisaematis Rhizoma included in the Chinese Pharmacopoeia is the dried tuber of Arisaema erubescens, A. heterophyllum or A. amurense in the family Araceae. This paper mainly focuses on the classification and summary of the chemical components and structures reported in recent years in the above three varieties of this medicinal material included in the pharmacopoeia, including alkaloids, flavonoids, phenylpropanoids, lignans and benzene ring derivatives, steroids and terpenes, glycosides and esters, etc. Then we reviewed the reported biological activities of these chemical components, including cytotoxicity, antitumor activity, antibacterial activity, nematicidal activity, etc. Although there have been reports on the review of the chemical composition of the medicinal material, the structure and classification of the chemical composition in these reviews are not clear enough. This review provides a basis for the later study of the chemical composition of this medicinal material, especially the identification of the chemical structures. And most of the current reviews on the biological activity of this medicinal material are mainly for the crude extract. This paper mainly summarized the biological activity of related monomer compounds and expected to lay a foundation for the development of novel high-efficiency and low-toxicity active leading compounds from Arisaematis Rhizoma.

Generation and phenotypic analysis of TD02 knockout mice / 中国药理学通报

Aim To construct TD02 gene knockout C57BL/6 mice, and meanwhile to study their phenotypes preliminarily. Methods The sgRNA plasmids were designed and constructed according to the principle of CRISPR-Cas9 technology, and were microinjected into mouse zygotes after transcription in vitro with Cas9 plasmids. FO generation mice with multiple genotypes were obtained by embryo transplantation. The PCR method was used to determine the genotype, and the positive F0 generation mice were obtained. F1 generation heterozygous mice were obtained by backcrossing the positive F0 generation mice and the wild type mice. The positive F1 generation heterozygous mice were matched to each other to obtain F2 generation homozygous mice. And their growth characteristics, reproductive ability, and progeny survival rate were observed and analyzed respectively. TDO2 protein expression in liver tissues of homozygous TDO2 gene knockout mice was detected by Western blot. Results TDO2 gene knockout mice were successfully bred and identified, and the genotypes of offspring mice were successfully identified by PCR. The results showed that TDO2 gene knockout was successfully conducted and TDO2 protein expression was not detected in liver tissues of TDO2 gene knockout mice. No abnormal changes were observed in diet, body weight, breeding ability of TDO2 knockout mice. Conclusions TDO2 gene knockout mice have been initially established, which would provide experimental means for studying the biological function of TDO2 gene and its regulatory role in diseases.

Paeoniflorin-6'-O-benzene sulfonate ameliorates progression of adjuvant-induced arthritis by inhibiting interaction between Ahr and GRK2 of fibroblast-like synoviocytes / 中国药理学与毒理学杂志

OBJECTIVE Aryl hydrocarbon receptor (Ahr) is thought to be a crucial factor that regulates immune responses, which may be involved in the pathogenesis of autoimmune inflammation including rheumatoid arthritis (RA). The results of our group in recent years have shown that CP-25, a novel ester derivative of paeoniflorin, has a good effect on improving RA animal models. However, whether the anti-arthritis effect of CP-25 is related to Ahr remains unclear. METHODS CP-25 treatment ameliorated adjuvant-induced arthritis (AA), a mouse model of RA, by inhibiting Ahr-related activities in fibroblasts like synoviocytes (FLS). AA rats were treated with CP-25 or paroxetine from day 17 to 33 after immunization. RESULTS CP-25 alleviated arthritis symptoms and the pathological changes, decreased the expression of Ahr in the synovium and FLS of AA rats. Besides, treatment with CP-25 reduced the proliferation and migration of MH7A caused by Ahr activation. In addition, we also demonstrated that CP-25 down-regulated the co-expres?sion and co-localization of Ahr and G protein-coupled receptor kinase 2 (GRK2) in MH7A. CONCLUSION The data pre?sented here demonstrated that CP-25 suppressed FLS dysfunction in rats with AA, which were associated with reduced Ahr activation and the interaction between Ahr and GRK2.

Application of DrugAbacus Method in Pricing Antitumor Drugs / 中国药学杂志

OBJECTIVE: China is still in its infancy in assessing the value of anti-tumor drugs, lacking a mature drug value assessment system. To provide reference for the establishment of a pharmacoeconomic model based on value assessment in China, and provide valuable reference for clinicians and patients to choose treatment options, Through the analysis and discussion of the DrugAbacus interactive calculator. METHODS: The value components and data sources of the DrugAbacus interactive calculator were analyzed by literature search, data query, etc., and the price of the anti-tumor drugs was evaluated according to the baseline values. RESULTS: The actual price of anti-cancer drug afinitor is higher than the recommended price when used to treat kidney cancer, pancreatic cancer and breast cancer. When the anti-tumor drug avastin is used in the treatment of colon cancer, the actual price is not much different from the recommended price. Halaven's suggested price is always higher than the actual price, that is, the price of the drug is at least reasonable or even low, and Ixempra's price is high, so using the drug Halaven can save more money than using the drug Ixempra. CONCLUSION: The DrugAbacus method provides a complex analysis of the factors that should be considered in drug pricing. Although there are limitations, this method reflects to a large extent the evaluation of the value of innovative drugs in society, which can provide reference for drug pricing in China.

Dr.He Guanqing, an unforgettable master for epidemiology and public health in new China / 中华疾病控制杂志

The article is a brief biography of Prof. and Dr. Guangqing He (Dr. Eutrope A. Ho or Dr. Kuan-Ching Ho), in particular, focusing on his contributions to education and research in epidemiology and medicine after foundation of the People’s Republic of China. It also introduces the history of Peking Union Medical College and its influence on development of epidemiology and public health in China.

Diagnostic Utility of Interferon-Gamma Release Assay in Tuberculous Lymphadenitis / 中国医学科学杂志(英文版)

Objective The aim of this study was to evaluate the diagnostic performance of T-SPOT.TB for tuberculous lymphadenitis. Methods Suspected tuberculous lymphadenitis patients between September 2010 and September 2018 who had both peripheral blood T-SPOT.TB test and lymph node biopsy were retrospectively enrolled in this study. The cutoff value of T-SPOT.TB test for peripheral blood was set as 24 spot forming cell (SFC)/10 6 periphreral blood monocyte cell (PBMC) according to the instruction of testing kits. The gold standard for diagnosis of TBL was the combination of microbiology results, histopathology results and patient's response to anti-TB treatment. Diagnostic efficacy of T-SPOT.TB was evaluated, including sensitivity, specificity, accuracy, predictive values, and likelihood ratio. Results Among 91 patients who met the inclusion criteria, we excluded 8 cases with incomplete clinical information and 6 cases who lost to follow-up. According to the gold standard, there were 37 cases of true TBL (9 confirmed TBL and 28 probable TBL), 30 cases of non-TBL, and 10 cases of clinically indeterminate diagnosis who were excluded from the final analyses. The T-SPOT.TB tests yielded 43 cases of positive response and 24 cases of negative response. The sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of peripheral blood T-SPOT.TB for diagnosing TBL were 89.2%, 66.7%, 79.1%, 76.7%, 83.3%, 2.68 and 0.16, respectively. The number of SFCs of T-SPOT.TB in TBL patients [432(134-1264)/10 6 PBMCs] was higher than that in non-TBL patients [0 (0-30) /10 6PBMCs] with a significant difference (Z=-5.306, P <0.001). Conclusion T-SPOT.TB is a rapid and simple diagnostic test for TBL with a high sensitivity and negative predictive value.

Clinical and Laboratory Characteristics of Disseminated Non-tuberculous Mycobacterial Disease / 中国医学科学院学报

Objective To explore the clinical and laboratory characteristics and the prognosis of disseminated non-tuberculous mycobacteria(NTM)diseases in human immunodeficiency virus(HIV)negative patients. Methods Cases of disseminated NTM disease were retrospectively collected in Peking Union Medical College Hospital from January 2012 to October 2018.Clinical manifestations,laboratory findings,treatment,and prognosis of these cases were retrieved from the electronic medical record system. Results Among the 23 HIV negative patients with disseminated NTM disease,21 had underlying diseases,with rheumatoid immune disease(n=7)as the most common one.The main clinical manifestation was fever(n=23).Laboratory tests showed anemia [hemoglobin(85.78±25.47)g/L],hypoalbuminemia [albumin 29(27-32)g/L],elevated erythrocyte sedimentation rate [(85.73±43.78)mm/h] and hypersensitive C-reactive protein [(112.00±70.90)mg/L],and reduction of lymphocyte count [0.69(0.29-2.10)×10 /L].Lymphocyte subset analysis indicated reduction in CD4 T cells [213(113-775)/μl],CD8 T cells [267(99-457)/μl],B cells [39(4-165)/μl],and NK cells [88(32-279)/μl] and elevation of human leukocyte antigen-D related(HLA-DR),and CD38 expression in CD8 T cells [HLA-DR CD8 /CD8 ,60(40-68)%;CD38 CD8 /CD8 ,81(65-90)%].The most common species of NTM was Mycobacterium intracellular(n=6).Lymphocyte,CD8 T cell,B cell,and NK cell counts were significantly lower in dead patients than surviving patients(P =0.045,P=0.045,P=0.032,and P=0.010,respectively). Conclusions Disseminated NTM disease in HIV negative patients is mainly manifested as fever,anemia,hypoalbuminemia,and elevated inflammatory indicators.It is more likely to occur in immunocompromised patients.Patients with decreased lymphocytes,CD8 T cells,B cells and NK cells tend to have a poor prognosis.

Determination of Donepezil and Rivastigmine in Human Serum by High-performance Liquid Chromatogra-phy Combined with Mass Spectrum / 中国药师

Objective: To develop an LC-MS/MS method for the determination of donepezil and rivastigmine in human serum. Methods: After protein precipitation with 600μl acetonitrile, the serum samples were analyzed by LC-MS/MS. Using loratadine as the internal standard, a Waters Xselect CSH C18(150 mm×3 mm, 2. 5 μm) column was used with the mobile phase consisting of water (containing 10 mmol·L-1ammonium acetate)-acetonitrile(20 ∶ 80)at a flow rate of 0. 4 ml·min-1with the column temperature at 40 ℃. The ion transitions were performed in a positive electrospray ionization multiple reaction-monitoring mode regarding [M+H] +as the molecular ion peak of donepezil and rivastigmine monitored with m/z 380. 1→m/z 91. 1 and m/z 251→m/z 206. 5, respectively. The internal standard was monitored with m/z 383. 1→m/z 337. 1. Results: The linear range of donepezil and rivastigmine was 0. 5-400 ng·ml-1(r>0. 99) and the lowest quantification limit was 0. 5 ng·ml-1. For donepezil, the intra-day and inter-day RSD was 2. 06% to 12. 51% , the relative error was -6. 60% to 4. 20% , and the relative recovery was ranged from 80. 76% to 96. 17% (RSD<15% ). For rivastigmine, the intra-day and inter-day RSD was 1. 69% to 9. 31% , the relative error was -5. 58% to 5. 20% , and the mean relative recovery was ranged from 96. 69% to 100. 15% (RSD<15% ). For the two compounds, the serum samples were stable at -40℃ for 75 d and kept stable after three repeated freeze-thaw cycles. The prepared samples were stable in the automatic sample injector (4℃) for 5 h (RSD<15% ). Conclusion: The developed assay method can be applied in the therapeutic monitoring and pharmacokinetic study of donepezil and rivastigmine in human serum.

Regional comparison and implications of China's long-term care insurance system / 中国卫生政策研究

This paper attempts to review the long-term care insurance policies which have been issued in 13 national pilot cities such as Qingdao and Haidian district,Beijing. The paper investigates the problems and challen-ges China's long-term care insurance system faces with,and put forward the construction of long-term care insurance system. The preliminary thinking on some issues, such as the relationship between welfare and marketization when the long-term care insurance has been put into practice on a trial basis,the relationship between long-term care insur-ance and medical insurance,and the specific implementation plan of the long-term insurance. According to the issued documents issued by pilot regions,it was found that there are not only differences but also similarities among the pilot cities in who are insured,who pays the insurance fee,what might be covered,what the levels of insurance are,and what kind of service will be provided. Although the long term care insurance system has been initially established in these cities, the specific implementation remains to be demonstrated, e. g. supervision and management, nursing service provision. In addition,local governments need to continuously expand the benefit range of long-term care in-surance to ensure long-term success,do good coordination and connection of long-term care insurance and pension in-surance,and reasonably allocate the medical insurance,pension,and health care resources.

Demonstration of field prevention and control equipment system / 医疗卫生装备

Objective To establish an infectious disease field prevention and control equipment system to facilitate equipment efficacy evaluation. Methods The equipment system was determined by analyses on the main procedure of infectious disease field prevention and control,researches on the missions and equipment requirements of grades of facilities for disease prevention and control,references to related equipment allocation standards as well as expert consulting.Results The first-grade system consisted of six classes and 136 subclasses of equipment,the second-grade system was made up of six classes and 114 subclasses of equipment and the third-grade system included six classes and 58 subclasses of equipment. Conclusion The three-grade infectious disease field prevention and control equipment system contributes to equipment efficacy evaluation.

Dynamic monitoring of γδT cells in murine cornea in vivo using two-photon laser scanning microscopy / 眼科新进展

Objective To compare the removal efficiency of γδT cells between cornea and ear skin and develop an alternative method for dynamic monitoring of γδT cells in mouse cornea in vivo using 2-photon laser scanning microscopy.Methods The γδT cells in mouse ear skin were monitored before and after antibody neutralization,and the mice corneas were excised and stained for counting γδT cells at 6 h,12 h,24 h after antibody neutralization by using 2-photon laser scanning microscopy,followed by comparison of the removal efficiency of γδT cells between the cornea and ear skin.Results The γδT cells in normal mouse cornea were often distributed in the limbal epithelium and superficial stromal layer.The irregular morphology of γδT cells in the epithelial layer was often accompanied by protuberances,while the stromal γδT cells were mostly round or oval and the number of cells was approximately 27 ± 4.After antibody neutralization,the number of γδT cells in the cornea of mice gradually decreased,and the number of cells at 6 h,12 h and 24 h was significantly lower than that of before depletion (P =0.03,0.00,0.00),and the removal efficiencies were 48％,78％,and 96％,respectively.The γδT cells in ear skin of the normal mice were ellipse or stellate with cell processes and they were located in epidermal layer,and the cell number was about 60 ± 9.After antibody neutralization,the number of γδT cells were significantly reduced at 6 h,12 h and 24 h compared with before depletion (P =0.000,0.000,0.000) and the removal efficiency were 43％,72％ and 95％,respectively.Conclusion The number of γδT cells in the cornea and ear skin is gradually decreased after antibody neutralization,and their removal efficiency is consistent with time.Therefore,monitoring the γδT cells in the mouse ear skin is an ideal alternative to dynamically monitoring the changes in the number of γδT cells in the cornea in vivo.

Synthesis of trifluoromethyl-substituted mono-carbonyl curcumin analogs and evaluation of their anti-proliferation activity on lung cancer cells / 国际药学研究杂志

Objective To synthesize trifluoromethyl-substituted mono-carbonyl curcumin analogs and investigate their effects on the proliferation of human lung cancer cells A549 and NCI-H460. Methods Six mono-carbonyl curcumin analogs 1a-1f were synthesized via Aldol condensation using commercially available 2-trifluoromethyl benzadehyde and different ketones (actone, cyclopentanone, cyclohexanone, piperid-4-one, and 1-methylpiperid-4-one). MTT method was used to test the effect of 1a-1f on the proliferation of A549 and NCI-H460 cells. Results Compared with curcumin, most of the mono-carbonyl curcumin analogs 1a-1f exhibited anti-proliferation activity on the A549 cells. The values of IC50 were lower than that of curcumin (P＜0.01), and 1a and 1f showed much better activities both on the A549 and NCI-H460 cells, with their IC50 values were much lower than that of curcumin (P＜0.01).Among them, 1f showed better medicinal chemical properties, with the relative molecular mass less than 500, cLogP 5.25, and the polar surface area (PSA) 37.38, which was more better accorded with the Lipinski′s five rules. Conclusion Six mono-carbonyl curcumin analogs 1a-1f were synthesized, and 1f showed much better anti-proliferation activity on A549 and NCI-H460 cells.

Effects of doxorubicin on neuropathic pain in chronic sciatic nerve constriction injury rats and its underlying mechanism / 中国药理学通报

Aim To observe the analgesic effect of doxorubicin ( DOX) on chronic sciatic nerve constric-tion injury (CCI) rat model, and analyze the underly-ing mechanism from the ultrastructure of sciatic nerve ganglion and the expressions of some apoptotic pro-teins.Methods A total of 60 SD rats were randomly divided into four groups: sham operation group ( Sham ) , CCI model group ( Model ) , sham operation+DOX 5 mg· kg -1 group ( Sham+DOX) , CCI mod-el +DOX 5 mg· kg -1 group (Model+DOX).DOX was given by caudal vein injection after model estab-lishment .Sham group and model group were given the same amount of saline . The mechanical withdrawal threshold and thermal withdrawal latency were deter-mined by behavioral test .The ultrastructural changes of L4-5 DRG were examined by light microscopy and scanning electron microscopy , respectively .The pro-tein expression levels of Bax , Bcl-2 , PKCɑ, PKCδand PKCε in DRG tissues were determined by Western blot.Results The fluorescence of DOX was found in DRG after DOX was given intravenously .In compari-son with sham group , the thermal and mechanical pain thresholds had no obvious changes in sham +DOX group, while the thresholds were decreased obviously seven days after surgery in model group .In comparison with model group , the pain thresholds in model +DOX group increased significantly , which lasted for the en-tire observation time of six days .The ultra-structure of tissues was damaged obviously in both sham +DOX group and model+DOX group.The protein expression of Bax/Bcl-2 increased, while the expressions of PKCδand PKCεdecreased with DOX injection .Conclusions DOX can retrograde and reach the DRG tissues after intravenous administration . The attenuation effect of DOX on neuropathic pain is related to the apoptosis in-duced by the down-regulation of PKCδ and PKCε in DRG cells.

Effects of lithium chloride on transforming growth factor beta and connective tissue growth factor in cultured human Tenon's capsule fibroblasts / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To research the effects of lithium chloride on transforming growth factor beta (TGF-β) and connective tissue growth factor (CTGF) in cultured human Tenon capsule fibroblasts (HTFs) and explore its mechanism.METHODS:HTFs were cultured and identified by vimentin staining with immunofluorescence and the morphological characteristics.The experimental group was processed 48h with LiCl in concentration of 80mmol/L, the control group without LiCl.The mRNA expression of TGF-β and CTGF in two groups were analyzed with real-time fluorescent quantitative polymerase chain reaction (real time-qPCR) and the protein expression was detected with Western blot.RESULTS:The cultured HTFs expressed TGF-β and CTGF.The mRNA expression of TGF-β and CTGF significantly decreased compared with the control group(t=20.042, 14.995, P<0.05).the protein expression of TGF-β and CTGF also decreased significantly compared with the control group(t=46.058、12.452, P<0.05)CONCLUSION:The cultured HTFs can express TGF-β and CTGF in mRNA and proteins' level.LiCl can reduce the expression of TGF-β and CTGF both in gene and proteins' level.LiCl has the potential to modulate wound healing for glaucoma filtration surgery.

Clinical observation of tiotropium combined with large dose salmeterol/fluticasone in the treatment of severe bronchial asthma with COPD stabilization / 中国生化药物杂志

Objective To evaluate the clinical efficacy of tiotropium combined with large dose salmeterol/fluticasone in the treatment of severe bronchial asthma with chronic obstructive pulmonary disease (COPD). Methods 60 patients with severe bronchial asthma with COPD stabilization in Taizhou hospital of Zhejiang province from January 2015 to December 2016 were selected and divided into the control and the study group according to the time of visiting hospital,30 cases in each group. The control group were given large dose Salmeterol/fluticasone on the basis of conventional treatment, the study group were treated with tiotropium bromide on the basis of control group. Results FEV1、FVC、FEV1/FVC、PEF and pulmonary function index were compared before the treatment between two groups. After treatment,FEV1,FVC,FEV1/FVC、PEF and pulmonary function index in the study group were better than the control group (P<0.05). Conclusion The combination of tiotropium and large dose salmeterol/fluticasone can significantly improve the clinical efficacy in the treatment of severe bronchial asthma and chronic obstructive pulmonary disease.

Clinical observation of tiotropium combined with large dose salmeterol/fluticasone in the treatment of severe bronchial asthma with COPD stabilization / 中国生化药物杂志

Objective To evaluate the clinical efficacy of tiotropium combined with large dose salmeterol/fluticasone in the treatment of severe bronchial asthma with chronic obstructive pulmonary disease (COPD). Methods 60 patients with severe bronchial asthma with COPD stabilization in Taizhou hospital of Zhejiang province from January 2015 to December 2016 were selected and divided into the control and the study group according to the time of visiting hospital,30 cases in each group. The control group were given large dose Salmeterol/fluticasone on the basis of conventional treatment, the study group were treated with tiotropium bromide on the basis of control group. Results FEV1、FVC、FEV1/FVC、PEF and pulmonary function index were compared before the treatment between two groups. After treatment,FEV1,FVC,FEV1/FVC、PEF and pulmonary function index in the study group were better than the control group (P<0.05). Conclusion The combination of tiotropium and large dose salmeterol/fluticasone can significantly improve the clinical efficacy in the treatment of severe bronchial asthma and chronic obstructive pulmonary disease.

Methodological Studies of the Determination of Lacidipine in Human Plasma by HPLC-MS/MS / 中国药师

Objective: To develop a method for the determination of lacidipine (LAC) in human plasma.Methods: After liquid-liquid extraction with tert-butyl methyl ether, the plasma samples were analyzed by LC-MS/MS.Using lacidipine-13C8 as the internal standard, a Agilent ZORBAX Eclipse XDB C18 column (150 mm×2.1 mm, 5 μm) was used with the mobile phase consisting of water(containing 5 mmol·L-1 ammonium formate)-acetonitrile(15∶85,v/v)at a flow rate of 0.3 ml·min-1 and with the column temperature at 40 ℃.The ion transitions were performed in a positive electrospray ionization multiple reaction-monitoring mode regarding + as the molecular ion peak of lacidipine and monitoring with m/z 473.5→m/z 410.3, m/z 473.5→m/z 400.1 and m/z 473.5→m/z 354.3.The internal standard was monitored with m/z 481.4→m/z 362.3.Results: The linear range of lacidipine was 0.1-10 ng·ml-1 (r＞0.99) and the lower quantification limit was 0.1 ng·ml-1.The intra-and inter-day RSDs were 3.15%-7.04% and the relative error was from-8.58% to 12.71%.The mean relative recovery of lacidipine was from 107% to 118% (RSD＜15%).The plasma samples were stable at-20℃ for 40 d and kept stable after three repeated freeze-thaw cycles.The prepared samples were stable at room temperature for 24 h and in the automatic sample injector (4℃) for 24 h(RSD＜15%).Conclusion: The developed assay method can be applied in the bioequivalence evaluation and pharmacokinetic studies of lacidipine in human.

Relationship between Fractional Exhaled Nitric Oxide Level and Efficacy of Inhaled Corticosteroid in Asthma-COPD Overlap Syndrome Patients with Different Disease Severity

This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity. A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study. Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups. We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO₂) and arterial partial pressure of carbon dioxide (PaCO₂), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores. Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO₂, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO₂, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment. This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients.