Clinical features and prognostic factors of elderly patients with mantle cell lymphoma / 中华血液学杂志

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.

Comparison and improvement of palatability for multisourced oral azithromycin suspension / 药学学报

Azithromycin dry suspension is one of the most commonly used drugs in pediatric clinic, but its taste masking has been difficult to achieve. 5 representative products of azithromycin dry suspension were chose to compare their tastes both using electronic tongue and human sensory evaluation methods, and there existed the differences of bitterness, later bitterness, graininess, and adhesion among these products. Raman micro-imaging was used to determine the difference in taste mainly due to different prescription ingredients and manufacturing techniques. Through mixing the dry suspensions with alkaline mixing solvent, the bad taste of each product was masked after evenly dispersing in the solvent, and their tastes were all close to the taste of the solvent. In the future, it is planned to investigate the stability and bioavailability of the solvent preparations, and then to give the medication suggestion of solvent preparation after ensuring their efficacy.

Study on formulation screening of chloral hydrate oral solution / 药学学报

Chloral hydrate is a commonly used central sedative drug before pediatric clinical examination, but its clinical safety and medication adherence are needed to focus on normally because of its poor stability and palatability. Under the premise of investigating the stability of different formulations, their palatability were also screened by using both human sensory and electronic tongue evaluation techniques. Human sensory evaluation has been conducted with the informed consent of all participants in accordance with the ethical requirements of the Good Clinical Practice for Drug Trials. The results showed that the addition of sorbitol and sucralose could effectively ensure the stability of the oral solution. Sorbitol is the main taste-masking component, and the ratio of 40% sorbitol and 0.5% sucralose can effectively mask the bitterness, astringency and spicy taste of 10% chloral hydrate oral solution. The results detected by human sensory and electronic tongue have good correlation and complementarity, and the combination of these two methods is more conducive to getting objective and reasonable conclusions.

Comparative study on the methods to determine disintegration time of oral soluble films / 药学学报

Disintegration time is a key parameter that affects the palatability and compliance of oral soluble films. At present, there is no standard method to determine the disintegration time of oral soluble films. In this study, we compared the six methods (pharmacopoeial disintegration method, petri dish method, sponge surface method, slide frame and ball method, partially immersed into liquid (without weight attached) and partially immersed into liquid (with weight attached)) to determine the in vitro disintegration time of oral soluble films with different thickness, and evaluated the correlation with the in vivo disintegration time. The results showed that the repeatability and correlation of pharmacopoeial disintegration method and the partially immersed into liquid method (with weight attached) were excellent, with the endpoint of disintegration testing easy to determine. Partially immersed into liquid method (with weight attached), properly simulating the physiological condition in oral cavity, showed strong operability, good repeatability and in vitro-in vivo correlation, and was suitable for in vitro disintegration evaluation of oral soluble film dosage form. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.

Technical status and development trends of electronic tongue / 药学学报

Electronic tongue is one kind of bionic detection technologies, which can objectively reflect the taste of drugs based on electrochemical principle. In this paper, the development histories of electronic tongue both of potential type and voltammetry type were introduced, including their detection principles and key innovation technologies. In order to comprehensively improve the understanding of electronic tongue, its technological progresses, such as the study of dedicated sensors or biosensors for specific tastes, and the development of miniaturized or hybrid devices, were also discussed in detail. And the challenges and countermeasures in the application of electronic tongue were analyzed to provide some suggestions for its further technology promotion.

Formulation optimization and analysis of taste-masking effect of licorzine granules based on sensory evaluation and electronic tongue method / 药学学报

Licorzine granules are common preparations for children zinc deficiency. Considering the long course of treatment, the taste of licorzine granules may become a main factor affecting medication adherence. To date there have been no taste evaluation research into licorzine granules yet. In this study, both sensory evaluation and electronic tongue method were utilized to optimize licorzine granules formulations, evaluate the tastes of licorzine, excipients, optimized formulation in vivo and in vitro. As the results show, bitterness and astringency are the main unpleasant tastes generating from licorzine. Xanthan gum is the main taste-masking excipient, lowering down the bitterness and astringency of licorzine by at least one grade. Good correlation exists between the results of sensory evaluation and electronic tongue method, and an integrated combination of the two helps to obtain objective and rational research conclusions. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.

Application progress of electronic tongue on taste evaluation for drug products / 药学学报

The taste of oral dosage forms has become a critical factor affecting the drug compliance and adherence to the treatment, and clinical application of the drug product may seriously restricted due to its bad taste. On the basis of the statement for the basic principle and specific performance of existing instruments, the application progress of electronic tongue on drug taste evaluation is addressed in detail. In view of its objective, fatigue-free, less harmful and accurate advantages, electronic tongue has been widely and meaningfully applied in the aspects of bitterness masking, and quality assessment and assurance of drug products. In addition, the reasons limiting the popularization of electronic tongue are mentioned in the paper, and some suggestions might be useful to enlarge the further application in the future.

Effects of Huangpu Tongqiao Capsules on EGFR-PLCγ signal pathway of hippocampus in rats with Alzheimer's disease / 中国中药杂志

Huangpu Tongqiao Capsules(HPTQC), with the functions of invigorating Qi and kidney, eliminating phlegm and removing blood stasis, have the effect of treating Alzheimer's disease(AD), but its mechanism needs further exploration. To explore the relationship between the therapeutic mechanism of HPTQC on Alzheimer's disease and EGFR-PLCγ signal pathway, 40 healthy male SD rats were selected and divided into 4 groups randomly: sham operation group(sham), model group(model), HPTQC group(HPTQC), and nimodipine group(NMP). AD rat model was established by intraperitoneal injection of D-galactose combined with an intracerebral injection of amyloid-β peptide(25-35). After 28 days of administration, Morris water maze test and HE staining showed that the learning and memory ability of AD rats were significantly decreased(P<0.01), and hippocampal neurons were obviously da-maged. However, HPTQC could improve the learning and memory ability of AD rats(P<0.05) and reduce the damage of hippocampal neurons. Immunofluorescence test results showed that the expression levels of EGFR and p-Tau in hippocampal CA1 region of AD rats were significantly increased(P<0.01), and HPTQC could reduce the expression of EGFR and p-Tau in hippocampus of AD rats(P<0.01). Western blot results showed that the protein expression levels of EGFR, PLCγ, IP3 R and p-Tau in hippocampus of AD rats were significantly increased(P<0.01), and HPTQC could reduce the protein expression of EGFR, PLCγ, IP3 R and p-Tau in AD rats(P<0.05). RT-PCR results showed that the mRNA levels of EGFR, PLCγ, IP3 R and Tau in hippocampus of AD rats were significantly increased(P<0.01), and HPTQC could reduce the mRNA levels of EGFR, PLCγ, IP3 R and Tau in AD rats(P<0.05). The results indicate that HPTQC can improve the learning and memory ability of AD rats, and its mechanism of action may be related to regulating EGFR-PLCγ signal pathway.

Therapeutic effect of heat-clearing and dampness-eliminating method combined with 5-aminolevulinic acid photodynamic therapy on moderate and severe acne and its influence on MMP-1, MMP-9, IL-1β and TNF-α / 中国基层医药

Objective:To investigate the effect of heat-clearing and dampness-eliminating therapy combined with 5-aminolevulinic acid photodynamic therapy on moderate and severe acne and its influence on matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-9 (MMP-9), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α).Methods:From March 2017 to March 2019, 106 patients with moderate to severe acne admitted to the Traditional Chinese Medicine Hospital of Ningbo were divided into observation group ( n=53) and control group ( n=53) according to the random digital table method.The control group was treated with 5-aminolevulinic acid photodynamic therapy, while the observation group was treated with heat-clearing and dampness-eliminating therapy on the basis of the control group.Both two groups were treated for 6 weeks.The therapeutic effects, skin lesions, dermatological quality of life index (DLQI), MMP-1, MMP-9, IL-1β and TNF-α levels, and adverse reactions were compared between the two groups before and after treatment. Results:The total effective rate of the observation group (94.34%) was higher than that of the control group (73.58%) (χ 2=8.477, P<0.05). The scores of acne[(19.32±2.37)points], inflammatory papules [(25.42±4.17)points] and pustules[(14.32±3.29)points] in the observation group after treatment were lower than those in the control group [(28.74±3.46)points, (32.87±3.78)points, (23.78±4.76)points]( t=16.352, 9.637, 11.902, all P<0.05). After treatment, the scores of DLQI scale in the observation group[(0.65±0.13)points, (0.63±0.15)points, (1.23±0.16)points, (1.18±0.19)points, (1.39±0.23)points, (1.45±0.28)points] were lower than those in the control group [, (1.20±0.17)points, (1.14±0.18)points, (1.92±0.23)points, (1.79±0.13)points, (1.81±0.27)points, (1.87±0.21)points] ( t=18.710, 15.846, 17.929, 19.290, 8.621, 8.736, all P<0.05). After treatment, the serum levels of MMP-1[(34.25±7.48)μg/L], MMP-9 [(108.98±14.25)μg/L], IL-1β [(137.98±10.23)μg/L] and TNF-α[(103.24±10.18)μg/L] in the observation group were lower than those in the control group [(59.37±4.56)μg/L, (164.32±18.48)μg/L, (156.37±13.10)μg/L and (137.91±8.29)μg/L]( t=20.875, 17.264, 8.055, 19.226, all P<0.05). There were no serious adverse reactions in both two groups. Conclusion:The method of heat-clearing and dampness-eliminating combined with 5-aminolevulinic acid photodynamic therapy is effective in treating moderate and severe acne, and can reduce the serum levels of MMP-1, MMP-9, IL-1β and TNF-α.

Effect of Vibration Training with Different Frequencies on Lower Limb Muscle Strength and Symptoms of Knee Osteoarthritis in Old Adults / 中国康复理论与实践

Objective:To explore the effect of vibration training with different frequencies on muscle strength and symptoms of lower limb joints in the elderly suffering from knee osteoarthritis (KOA). Methods:From July to October, 2019, 82 KOA elderly were randomly divided into control group (n = 20), low frequency group (n = 20), medium frequency group (n = 21) and high frequency group (n = 21). The latter three groups received 15 Hz, 30 Hz and 45 Hz vibration training, respectively, with the same amplitude (3 mm), 15 minutes a time, three times a week, for 16 weeks. The flexion and extension isokinetic muscle strength (60°/s and 180°/s) of lower limb joints were tested, and they were assessed with Western Ontario and McMaster Universities Osteoarthritis Index before and after training. Results:After training, the peak torques of knee extensor under 60°/s and 180°/s increased in the medium frequency group (|t| > 2.162, P <0.05), the peak torques of knee and ankle extensors under 60°/s and 180°/s increased in the high frequency group (|t| > 2.227, P <0.05), the endurance of hip and knee extensors increased (|t| > 1.997, P < 0.05), and the score of pain significantly decreased (t = 16.901, P < 0.001) in the high frequency group. After training, the peak torques of knee and ankle extensors under 60°/s, the endurance of hip and knee extensors were higher in the high frequency group than in the low frequency group and the medium frequency group (P < 0.05); the peak torques of hip, knee and ankle extensors under 180°/s were higher in the high frequency group than in the low frequency group (P < 0.05); the score of pain was lower in the high frequency group than in other groups (P < 0.05). Conclusion:45 Hz vibration training could improve the absolute force and explosive force of knee and ankle extensors, and the endurance of hip and knee extensors; and relieve pain in KOA elderly.

Protective effects of genistein on Aβ₂₅₋₃₅-induced PC12 cell injury via regulating CaM-CaMKIV signaling pathway / 中国中药杂志

Genistein is a kind of isoflavone compounds， also called phytoestrogens， with clinical effects on cardiovascular disease， cancer and postmenopausal-related gynecological diseases， and also has the potentiality in the prevention and treatment of Alzheimer's disease(AD). In this study， the protective effect of genistein on Aβ₂₅₋₃₅-induced PC12 cell injury and effect on CaM-CaMKIV signaling pathway were observed to investigate its mechanism for AD. PC12 cells were cultured and then the safe concentration of genistein and the modeling concentration and optimal time point of administration of Aβ₂₅₋₃₅ were screened by MTT assay. After being pretreated with different concentrations of genistein(25， 50， 100 μmol·L⁻¹) on PC12 cells， the AD model of PC12 cells was induced by Aβ₂₅₋₃₅. Then the survival rate of cells was detected by MTT assay; morphological change of cells was observed under the inverted microscope， and apoptosis of cells was assessed by AO/EB fluorescence staining; the neuroprotective effects of genistein on AD cell model were observed and the optimal concentration of genistein was determined. Expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau were detected by qRT-PCR and Western blot assay， respectively. The results showed that as compared with the blank group， the cell survival rate was decreased; the cell damage and apoptosis were increased; and the expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau were increased in AD model group. Genistein could significantly improve the cell survival rate， reduce the cell damage and apoptosis of AD cell model， and significantly down-regulate the expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau of AD cell model. These results indicated that genistein has obviously neuroprotective effect on the AD cell model induced by Aβ₂₅₋₃₅， and the mechanism may be related to the down-regulation of CaM-CaMKIV signaling pathway and Tau protein expression.

The effects of electroacupuncture at and points of stomach on gastric motility, the NMDA of vagus nerve dorsal nucleus and serum NO expression in functional dyspepsia rats / 中国针灸

<p><b>OBJECTIVE</b>To research the central molecular mechanism of gastric motility in functional dyspepsia (FD) rats treated with electroacupuncture (EA) at and points of stomach.</p><p><b>METHODS</b>A total of 30 SD rats were randomized into a blank group, a model group, a Zhongwan+Weishu group, a Weishu group and a Zhongwan group, 6 rats in each group. FD rats were established by moderate clipping tail infuriation and irregular feeding except in the blank group. EA was used at "Zhongwan"(CV 12),"Weishu"(BL 21), and"Zhongwan"(CV 12) +"Weishu"(BL 21) in the corresponding groups for 7 days, once a day, and 20 min a time. No intervention was used in the blank and model groups. Grabbing and fixation were applied in the model group. Gastric antrum motion range and frequency were recorded by gastrointestinal pressure transducer. The expression of subunit NR1 of N-methyl-D-aspartate recepter (NMDAR) in dorsal motor nucleus of the vagus (DMV) was determined by Western blotting. The content of serum nitric oxide (NO) was measured by ELISA.</p><p><b>RESULTS</b>Compared with the blank group, the gastric antrum motion range and NR1 in the DMV decreased and the serum NO content increased in the model group (all <0.05). Compared with the model group, the gastric antrum motion range and NR1 in the DMV increased and the serum NO content decreased in the three EA groups (all <0.05). Compared with the Zhongwan and Weishu groups, the gastric antrum motion range and NR1 in the DMV increased in the Zhongwan + Weishu group (all <0.05). Compared with Zhongwan + Weishu and Zhongwan groups, the expression of NO in the Weishu group decreased (both <0.05). The gastric antrum motion frequency among the 5 groups had no statistical significance (all >0.05).</p><p><b>CONCLUSION</b>EA at the and points can regulate the gastric motility in FD rats which may be by modulating the activity of NMDAR in the central DMV region, thus regulating the serum NO content.</p>

Effects of Huangpu Tongqiao capsule on apoptosis of Alzheimer's disease cell model / 中国中药杂志

The loss of hippocampal neurons is one of the main pathological features of Alzheimer's disease (AD), which is related to the apoptosis of hippocampal neurons. Huangpu Tongqiao capsule is used for the treatment of AD, but the underlying mechanism is still unclear. This study is to investigate the mechanism of neuroprotective effect of Huangpu Tongqiao capsule in the treatment of AD, through observing the effect of Huangpu Tongqiao capsule containing serum on cell injury of primary cultured hippocampal neurons induced by Aβ₂₅₋₃₅ via inhibiting the cell apoptosis. Primary cultured hippocampal neurons were cultured and identified by MAP-2 immunofluorescence staining, and cell growth state was observed by inverted microscope. The Huangpu Tongqiao capsule containing serum was prepared using the method of serum pharmacology. MTT assays were used to measure the optimum concentration range of Huangpu Tongqiao capsule containing serum, and optimum Aβ concentration for establishing the AD model. After primary cultured hippocampal neurons AD cell model was induced by Aβ₂₅₋₃₅, cell survival rate was detected by MTT, cell apoptosis rate was assayed by flow cytometry, and protein expressions of Bax, Cyt C and caspase-3 were determined by Western blot analysis. The results showed that the primary cultured hippocampal neurons were cultured successfully, and cells grew mature at seventh days; Compared with normal group, the survival rate of hippocampal neurons in AD cell model group was decreased, the apoptosis rate of hippocampal neurons was increased, and the protein expressions of Bax, Cyt C and caspase-3 were increased (<0.05, <0.01); Compared with AD cell model group, the survival rate of hippocampal neurons in Huangpu Tongqiao capsule containing serum group was increased, the apoptosis rate of hippocampal neurons was decreased, and the protein expressions of Bax, Cyt C and caspase-3 were decreased (<0.05, <0.01). These findings suggest that Huangpu Tongqiao capsule containing serum has a neuroprotective effect on cell injury of the primary cultured hippocampal neurons induced by Aβ₂₅₋₃₅, and its effect on the treatment of AD is associated with the inhibition the apoptosis of hippocampal neurons.

Three-dimensional printing-assisted atlantoaxial pedicle screw placement for type II C odontoid fracture / 中国组织工程研究

BACKGROUND: Three-dimensional (3D) printing has been widely applied in pelvic fracture and joint surgeries, but its feasibility in atlantoaxial pedicle screw placement needs to be studied further.OBJECTIVE: To explore the feasibility and accuracy of 3D printing-assisted atlantoaxial pedicle screw placement in the treatment of type II C odontoid fracture.METHODS: Clinical data of 20 patients with type II C odontoid fracture admitted in the Ganzhou Hospital Affiliated to Nanchang University from June 2014 to December 2015 were analyzed retrospectively. The patients were randomized into two groups, and then received 3D printing-assisted atlantoaxial pedicle screw placement (experimental group), or conventional atlantoaxial pedicle screw placemen (control group). The placement was observed through X-ray and CT scanning. All patients were followed up for 12 months, and the clinical efficacy was assessed by Visual Analogue Scale and cervical Japanese Orthopaedic Association scores.RESULTS AND CONCLUSION: (1) The operation time, blood loss and radiation exposure time in the experimental group were significantly less than in the control group (P < 0.05). (2) The accuracy of placement in the experimental group was significantly higher than that in the control group (P < 0.05). No spinal cord, vertebral artery or nerve injuries occurred in the two groups. (3) The postoperative clinical efficacy was assessed by Visual Analogue Scale and cervical Japanese Orthopaedic Association scores in the two groups were significantly improved (P < 0.05). (4) These findings manifest that 3D printing-assisted trans-atlantoaxial pediele screw placement is a safe and effective method for type Ⅱ C odontoid fracture.

Quantitation of Circulating Cell-free DNA in Patients with Lymphoma and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate the value of circulating cell-free DNA (CFDNA) quantification for screening lymphoma, to analyse the relationship of circulating CFDNA with curative effect under standard therapeutic schedule, and to determine whether circulating CFDNA could be applied to monitor and prognosticate lymphoma.</p><p><b>METHODS</b>The peripheral blood samples from 32 patients(21 cases of lymphoma and 11 cases of lymphadenitis) with superficial lymph node enlargement were collected, 9 healthy volunteers were as the normal control. Fluorescent quantitative PCR was used to detect the circulating CFDNA in 3 groups. Then, the relationship of circulating CFDNA with common characteristics of lymphoma was analysed, so as to evaluate the importance of circulating CFDNA to the curative effect and prognosis.</p><p><b>RESULTS</b>The circulating CFDNA level in patients with lymphoma was higher than that in patients with lymphadenitis and healthy volunteers (56.71±50.61) ng/ml vs (19.21±15.52) ng/ml and (8.26±7.06) ng/ml (P<0.05), but the difference between the latter 2 was not statistically significant (P=0.118). The circulating CFDNA level in lymphoma significantly correlated with the level of lactate dehydrogenase(LDH) (P<0.05). ROC analyses revealed that the detection of plasma DNA could discriminate the lymphoma from normal controls with 75% sensitivity, 85% specificity and with a cut-off value of 24.67 ng/ml. The higher circulating CFDNA clearance rate after standard therapy, the higher the rate of complete remission(CR) (P<0.05) and the longer overall survival(P<0.001).</p><p><b>CONCLUSION</b>Elevated circulating cell-free DNA levels may be useful as a screening tool for lymphoma. Circulating CFDNA level may serve as a potential indicator for evaluation of the curative effect and prognosis.</p>

Plasma Metabolic Profile Determination in Young ST-segment Elevation Myocardial Infarction Patients with Ischemia and Reperfusion: Ultra-performance Liquid Chromatography and Mass Spectrometry for Pathway Analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>This study was to establish a disease differentiation model for ST-segment elevation myocardial infarction (STEMI) youth patients experiencing ischemia and reperfusion via ultra-performance liquid chromatography and mass spectrometry (UPLC/MS) platform, which searches for closely related characteristic metabolites and metabolic pathways to evaluate their predictive value in the prognosis after discharge.</p><p><b>METHODS</b>Forty-seven consecutive STEMI patients (23 patients under 45 years of age, referred to here as "youth," and 24 "elderly" patients) and 48 healthy control group members (24 youth, 24 elderly) were registered prospectively. The youth patients were required to provide a second blood draw during a follow-up visit one year after morbidity (n = 22, one lost). Characteristic metabolites and relative metabolic pathways were screened via UPLC/MS platform base on the Kyoto encyclopedia of genes and genomes (KEGG) and Human Metabolome Database. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of characteristic metabolites in the prognosis after discharge.</p><p><b>RESULTS</b>We successfully established an orthogonal partial least squares discriminated analysis model (R2X = 71.2%, R2Y = 79.6%, and Q2 = 55.9%) and screened out 24 ions; the sphingolipid metabolism pathway showed the most drastic change. The ROC curve analysis showed that ceramide [Cer(d18:0/16:0), Cer(t18:0/12:0)] and sphinganine in the sphingolipid pathway have high sensitivity and specificity on the prognosis related to major adverse cardiovascular events after youth patients were discharged. The area under curve (AUC) was 0.671, 0.750, and 0.711, respectively. A follow-up validation one year after morbidity showed corresponding AUC of 0.778, 0.833, and 0.806.</p><p><b>CONCLUSIONS</b>By analyzing the plasma metabolism of myocardial infarction patients, we successfully established a model that can distinguish two different factors simultaneously: pathological conditions and age. Sphingolipid metabolism is the top most altered pathway in young STEMI patients and as such may represent a valuable prognostic factor and potential therapeutic target.</p>

Analysis of serum metabolic profile by ultra-performance liquid chromatography-mass spectrometry for biomarkers discovery: application in a pilot study to discriminate patients with tuberculosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tuberculosis (TB) is a chronic wasting inflammatory disease characterized by multisystem involvement, which can cause metabolic derangements in afflicted patients. Metabolic signatures have been exploited in the study of several diseases. However, the serum that is successfully used in TB diagnosis on the basis of metabolic profiling is not by much.</p><p><b>METHODS</b>Orthogonal partial least-squares discriminant analysis was capable of distinguishing TB patients from both healthy subjects and patients with conditions other than TB. Therefore, TB-specific metabolic profiling was established. Clusters of potential biomarkers for differentiating TB active from non-TB diseases were identified using Mann-Whitney U-test. Multiple logistic regression analysis of metabolites was calculated to determine the suitable biomarker group that allows the efficient differentiation of patients with TB active from the control subjects.</p><p><b>RESULTS</b>From among 271 participants, 12 metabolites were found to contribute to the distinction between the TB active group and the control groups. These metabolites were mainly involved in the metabolic pathways of the following three biomolecules: Fatty acids, amino acids, and lipids. The receiver operating characteristic curves of 3D, 7D, and 11D-phytanic acid, behenic acid, and threoninyl-γ-glutamate exhibited excellent efficiency with area under the curve (AUC) values of 0.904 (95% confidence interval [CI]: 0863-0.944), 0.93 (95% CI: 0.893-0.966), and 0.964 (95% CI: 00.941-0.988), respectively. The largest and smallest resulting AUCs were 0.964 and 0.720, indicating that these biomarkers may be involved in the disease mechanisms. The combination of lysophosphatidylcholine (18:0), behenic acid, threoninyl-γ-glutamate, and presqualene diphosphate was used to represent the most suitable biomarker group for the differentiation of patients with TB active from the control subjects, with an AUC value of 0.991.</p><p><b>CONCLUSION</b>The metabolic analysis results identified new serum biomarkers that can distinguish TB from non-TB diseases. The metabolomics-based analysis provides specific insights into the biology of TB and may offer new avenues for TB diagnosis.</p>

Relation of intermediate-conductance Ca(2+)-activated K(+) channels with ability of proliferation, migration, invasion and IgE secretion of multiple myeloma cells / 中国实验血液学杂志

This study was aimed to investigate the effects of the intermediate-conductance Ca(2+)-activated K(+) (IKCa1) channels on the proliferation, migration, invasion ability and monoclonal immunoglobulin (IgE) secretion of multiple myeloma (MM) cells. Trypan blue exclusion was used to evaluate the impact of clotrimazole (CLO, an inhibitor of the KCa1) on the survival ability of MM cell line U266; transwell chamber and matrigel experiments were used to evaluate the impact of CLO on the ability of the migration and invasion of U266 cells; the influence of CLO on IgE secretion in U266 cells was detected by ELISA. The results showed that small dose of CLO ( ≤ 1.0 µmol/L) could not inhibit the viability of U266 cells. The Transwell and Matrigel invading tests displayed that the cell number moving into lower chamber of transwell decreased after U266 cells treated with small dose of CLO ( ≤ 1.0 µmol/L). After treating the cells with 1.00 µmol/L CLO for 24 h and 48 h, the concentration of IgE in cell supernatant was (4.98 ± 0.39) and (4.38 ± 0.32) ng/ml, while those in control group were (15.41 ± 1.88) and (19.73 ± 2.01) ng/ml, respectively, suggesting significant difference between them(P < 0.05). It is concluded that CLO can decrease the ability of migration and monoclonal immunoglobulin secretion of multiple myeloma cells by blocking the IKCa1, thus this study provides a new think for the targeted therapy of MM.

Preventive effects of sevoflurane treatment on lung inflammation in rats

OBJECTIVE@#To observe the effects of sevoflurane treatment on lung inflammation in rats with lipopoIysaccharide-induced acute lung injury (ALI).@*METHODS@#The rat model of ALI was established by intratracheal instillation of lipopolysaccharide (LPS). 45 infantile SD rats [body weight (272±15) g] were randomly divided into 3 groups (n=15): control group, LPS group, sevoflurane group. NS (1 mL/kg) was instillated in rats' airways of control group; LPS (5 mg/kg) was instillated in rats' airways of LPS group. Sevoflurane group rats received sevoflurane (2.4%) inhalation for a hour after LPS was instillated in rats' airways. Six hours after NS or LPS instillation, all rats were exsanguinated. Lung tissues were examined by HE staining. Expressions of TNF-α and ICAM1 mRNA were detected by semiquantitative RT-PCR techniques. The protein level of TNF-α and ICAM1 were assessed by western blot techniques.@*RESULTS@#In LPS group the permeability of lung tissues increased, organizational structure severely damaged and the alveolar wall tumed thick, with interstitial edema and Europhiles infiltrated increasingly. The LPS group had higher mRNA expressions of TNF-α and ICAM1 than control group and sevoflurane group (P<0.05), and LPS group had higher protein level of TNF-α and ICAM1 than control group and sevoflurane group (P<0.05).@*CONCLUSIONS@#Sevoflurane treatment can attenuate lung inflammation in rats with lipopolysaccharide-induced acute lung injury.

Association analysis of cytokine polymorphisms and plasma level in Northern Chinese Han patients with paroxysmal nocturnal hemoglobinuria / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>While the incidence of paroxysmal nocturnal hemoglobinuria (PNH) is relatively high in Northern China, the exact mechanism of the disease remains unknown. Immunoregulatory cytokine polymorphisms can directly regulate the expression levels of cytokines, which play a crucial role in many diseases. The purpose of this study was to study cytokine gene single nucleotide polymorphisms (SNPs) and the correlated cytokine expression levels in relationship to the PNH pathogenesis.</p><p><b>METHODS</b>Peripheral blood samples were collected from 30 PNH patients and 40 healthy donors; all of the samples were collected from the Han people of Northern China. Eight SNP loci in five cytokine genes, including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-β), interleukin-6 (IL-6), and IL-10, and aplastic anemia (AA) were assessed. TNF-a, TGF-b, IFN-g, IL-6, and IL-10 were analyzed by sequence-specific primer polymerase chain reaction (PCR-SSP). The plasma protein levels of TNF-a, TGF-b, and IFN-g were assessed by an ELISA.</p><p><b>RESULTS</b>The PNH patients had a lower frequency of the TC/GG genotype of the TGF-b gene (P < 0.01) and a higher frequency of the C allele in the TGF-b gene (+10) compared to the controls (P < 0.05). The predominant genotype of the +874 locus of the IFN-g gene was TA in the PNH patients, while that in the predominant genotype was AA in the control group and was statistically significant (P < 0.001). The frequency of the T allele in the IFN-g gene was dramatically higher in the PNH patients than in the controls (P < 0.05). The PNH patients had a reduced frequency of the GC and CC genotypes, as well as the C allele at locus -174 of the IL-6 gene compared to the controls (P < 0.01). In addition, the plasma concentrations of TNF-a, TGF-b, and IFN-g were significantly higher in the PNH group compared to the control group (P < 0.01).</p><p><b>CONCLUSIONS</b>Expression levels of the TNF-a, TGF-b, and IFN-g cytokines play an important role in PNH. The GC and CC genotypes, as well as the C allele of the IL-6 gene may protect the Han people of Northern China against PNH. Additionally, the TC/GG genotype of the TGF-b gene may be the protective allele. In contrast, the TA genotype and the T allele for the IFN-g gene, as well as the C allele of TGF-b may be susceptible to PNH. However, SNPs in the TNF-a and IL-10 genes did not correlate with PNH development. Alternatively, the increased plasma concentrations of TNF-a, TGF-b, and IFN-g in PNH patients may also be related to PNH development.</p>