Chronic obstructive pulmonary disease (COPD) is a chronic airway diseases,which leads to heavy social and economic burden to our country.We can use serum biomarkers to evaluate diagnosis,classification,treatment and prognosis of COPD.The change of biomarkers provides lots of valuable clinical information.A variety of biomarkers are associated with the severity of lung function,which can be used to judge disease severity.Some indicators are related to the diagnosis of acute exacerbation or hospitalization risk.Some serum markers would guide therapy and can be effectively applied to clinical work.Study of COPD serum biomarkers would provide more reference information for clinical physicians in diagnosis,treatment and prognosis of COPD.

Methods: This study established the MFSM method. To demonstrate its effectiveness, we applied this novel approach to analyze Danxi Granules (丹膝颗粒, DXG) and its constituent herbal materials. To begin with, the ultra-performance liquid chromatography (UPLC) was applied to obtain the chromatographic fingerprints of DXG and its constituent herbal materials. Next, the MFSM was leveraged to compress and integrate them into a new fingerprint with fewer analytical units. Then, we characterized the properties and variability of both the original and integrated fingerprints by calculating total quantum statistical moment (TQSM) parameters, information entropy and information amount, along with their relative standard deviation (RSD). Finally, we compared the TQSM parameters, information entropy and information amount, and their RSD between the traditional and novel fingerprints to validate the new analytical method. Results: The chromatographic peaks of DXG and its 12 raw herbal materials were divided and integrated into peak families by the MFSM method. Before integration, the ranges of the peak number, three TQSM parameters, information entropy and information amount for each peak or peak family of UPLC fingerprints of DXG and its 12 raw herbal materials were 95.07 − 209.73, 9390 − 183064 μv·s, 5.928 − 21.33 min, 22.62 − 106.69 min2, 4.230 − 6.539, and 50530 − 974186 μv·s, respectively. After integration, the ranges of these parameters were 10.00 − 88.00, 9390 − 183064 μv·s, 5.951 − 22.02 min, 22.27 − 104.73 min2, 2.223 − 5.277, and 38159 − 807200 μv·s, respectively. Correspondingly, the RSD of all the aforementioned parameters before integration were 2.12% − 9.15%, 6.04% − 49.78%, 1.15% − 23.10%, 3.97% − 25.79%, 1.49% − 19.86%, and 6.64% − 51.20%, respectively. However, after integration, they changed to 0.00%, 6.04% − 49.87%, 1.73% − 23.02%, 3.84% − 26.85%, 1.17% − 16.54%, and 6.40% − 48.59%, respectively. The results demonstrated that in the newly integrated fingerprint, the analytical units of constituent herbal materials, information entropy and information amount were significantly reduced (P < 0.05), while the TQSM parameters remained unchanged (P > 0.05). Additionally, the RSD of the TQSM parameters, information entropy, and information amount didn’t show significant difference before and after integration (P > 0.05), but the RSD of the number and area of the integrated analytical units significantly decreased (P < 0.05). Conclusion The MFSM method could reduce the analytical units of constituent herbal materials while maintain the properties and variability from their original fingerprint. Thus, it could serve as a feasible and reliable tool to reduce difficulties in analyzing multi-components within CMMs and facilitating the evaluation of their quality.

The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.
Biomarkers ; blood ; urine ; Chemical and Drug Induced Liver Injury ; diagnosis ; Humans ; Sensitivity and Specificity

BACKGROUND: In valerian-ligusticum extract (VLE), valeriana offici nalis extract (VOE) is γ aminobutyric acid (GABA) receptor kinetin, which can relax cerebral vascular spasm; ligusticum wallichii Fr. Extraxt (LWE)can pass through blood-brain barrier, enhance microcirculation of tissue and inhibit blood platelet aggregation and 5-Hydroxytryptamine (5-HT) release.OBJECTIVE: To probe into the effects of VLE prepared with effective components on prevention and treatment of cerebral ischemic injury.DESIGN:Complete randomized, negative and positive control experiment.SETTING: Institute of Senile Medicine and Pharmacology of Tongji Medical College of Huazhong University of Science and Technology.MATERIALS: The experiment was performed in Institute of Senile Medicine Pharmacology of Tongji Medical College of Huazhong University of ent blood perfusion in brain tissue: Fifty Kunming mice were employed,which was randomized into normal group, solvent control (model) group,ligustrazine 50 mg/kg group, VLE 170 mg/kg group and VLE 85 mg/kg Fifty Wistar rats were employed, which was randomized into solvent control (model) group, compound danshen (Radix Salviae Miltiorrhizae) 5 g/kg group,VLE 156 mg/kg group, VLE 94 mg/kg group and VLE 31.3 mg/kg group,Sixty Wistar rats were employed, which was randomized into sham-operation group, solvent control (model) group, ligustrazine 10 mg/kg group, VLE 156 mg/kg group, VLE 95 mg/kg group and VLE 31.3 mg/kg, 10 mice in each were employed, which was randomized into normal group, solvent control (model) group, ligustrazine 10 mg/kg group, VLE 200 mg/kg group and VLE 40 mg/kg, 10 mice in each one.sue, in advance, VLE (85, 170 mg/kg), ligustrazine (50 mg/kg) or solvent enhancer of equal volume (0.2 mL) were injected abdominally in each group. Twenty minutes later, pituitrin (2.5 u/kg) was injected intravenously; and 10 minutes later, isotope 99Tcm+ L, L-EthylCysteinate Dimer and Stannous Chloride (ECD) 3.7×1010Bq/ L(0.1 mL/per mouse) was injected in coccygeal nerve. Fifteen minutes later, radio-immunity counter was used periment of arteral-ovenous bypass method for thrombosis, before the opercal saline successively, continuously for 7 days, once per day. After 24 hours of medication pause, with abdominal anesthesia with pentobarbitol sodium, a catheter (with surgical thread inside) was used in vitro to connect common cervical vein and carotid artery. Thrombus mass was scaled 15 dominal anesthesia of chloral hydrate, intraluminal thread approach (ITA)was used to block unilateral MCA. Except that ITA was not used, the other management in sham-operation group was same as experimental groups.Gastric perfusion was done with VLE(156, 94, 31.3 mg/kg), ligustrazine operation and 3 hours and 12 hours after operation. 24 hours after modeling, the assessment was done for behavioral neurological damage and brain sive cerebral ischemia experiment, the model was prepared by coccygeal injection of collagen + adrenalin (AD). Respectively, 30 minutes before modeling injection and 1 hour after injection, gastric perfusion was done with VLE (200, 40 mg/kg), ligustrazine (10 mg/kg) or solvent enhancer of equal volume successively to observe the numbers of dead mice in 5 minutes after modeling and the numbers of hemiplegia mice in 15 minutes;and to determine brain mass index 8 hours later after sacrificed and lactic acid level of brain tissue homogenate with ultraviolet spectrophotometry.group.RESULTS: In the experiment of acute extensive brain ischemia in mice, in solvent control, during modeling, 3 mice were died and the rest 207 mice brain tissue in mice, the ratios of brain with and blood γ ray pulsating intensity in VLE 85 mg/kg group and VLE 170 mg/kg were higher than model group (0.53±0.09, 0.55±0.08, 0.45±0.08, t=2.234 6, 2.793 3, P method in rats, the thrombus masses in VLE 156 mg/kg group, 94 mg/kg group and 31.3 g/kg group were lower remarkably than the model group [(12.66±4.79), (13.31 ±3.97), (13.49±4.09), (19.21±5.76) g, (t=2.667 0,31.3 mg/kg group, 94 mg/kg group and 156 mg/kg group was lower remarkably than model group successively [(5.9±1.9), (6.0±2.0), (5.8±2.2),(8.7±0.9) score], and cerebral infarction index was lower than model group [(16.52±5.78)%,(16.54±3.00)%, (14.18±6.13)%, (24.03±4.85)%, (t=3.118 9-chemia in mice, brain mass indexes of VLE 40 mg/kg and 200 mg/kg groups were lower remarkably than model group [(0.91 ±0.20) and (0.82±0.24)%, (1.40±0.32)%], and lactic acid in brain tissue was lower than model group [(17.44±6.71),(14.43±2.81), (29.07±7.33) μmol/g (t=3.388 5-5.800 5, P＜ 0.01)].CONCLUSION: Valerian-liqusticum extract improves significantly cerebral ischemia in mice induced by pituitrin and the damage by medium cerebral artery embolism in rats, and it inhibits significantly blood platelet aggregation and thrombosis induced by AD+ collagen mixture or foreign objects. It is suggested that valerian-ligustrazine extract prevents and treats significantly the perfusion disturbance of cerebral microcirculation.

Objective To evaluate the feasibility of monitoring the gene expression of VEGF165 via the diglycylcysteine (GGC) reporter gene system by reporter probe of 99Tcm-GH. Methods DNA fragments encoding GGC binding motifs were prepared by PCR and positioned at the C end of VEGF165 gene after the linearization of pcDNA3-VEGF165 plasmid. A replication-defective adenovirus vector Ad5-VEGF165GGC motif-internal ribosomal entry site(IRES) -enhanced green fluorescent protein (EGFP) (Ad5-VIE)was constructed, with a cytomegalovirus (CMV) early promoter driving the expression of VEGF165 gene,GGC motif and EGFP, under the aid of an IRFS. A replication-defective adenovirus carrying the Ad5-EGFP was used as the control. Mensenchymal stem cells (MSC) were infected with the recombinant adenovirus at a multiplicity of infection (MOI) from 0 to 100 infectious units (0,10,25,50,100). The cellular uptake of 99Tcm-GH in infected MSC were then studied at 30, 60, 90 and 120 min. VEGF165 was detected by quantitative reverse transcriptase real-time PCR (RT-PCR), Western-blot, and immunohistochemisty. EGFP was observed by RT-PCR and fluorescence microscopy. The correlation analysis was studied between the cellular uptake of 99Tcm-GH and the expression of VEGF165. SPSS 13.0 was applied for statistical analysis. Independent samples t-test, q-test and Pearson correlation coefficient were used. Results After infected with different viral titer of Ad-VIE, the cellular uptake of 99Tcm-GH increased with the increasing virus titer(r2 =0.86, P ＜0.05), with the peak rate (7.94 ±0.75) % at MOI = 100. In time-dependent uptake study, the cellular uptake rates increased rapidly with the time extension, and the highest uptake occurred at 120 min with the peak uptake rate (7.72 ±0.22)%. The uptake rates of 99Tcm-GH in Ad5-VIE-infected cells were significantly higher than those of Ad5 -EGFP-transfected cells at all time points (t = 15.10- 54.92, all P ＜0.05). The VEGF165 and EGFP mRNA levels increased with increasing virus titer, and the VEGF165 mRNA correlated well with the EGFP mRNA(r2 = 0. 99, P ＜ 0.05). After infected with different MOI of Ad5-VIE, good relationship was found between the cellular uptake of 99Tcm-GH and the expression of VEGF165protein in MSC(r2 =0.90, P ＜0.05). Inmunohistochemisty showed VEGF165 protein expressed obviously at Ad5-VIE-infected MSC, and the EGFP was observed by fluorescence microscopy. Conclusions The cellular uptake of 99Tcm-GH in Ad5-VIE-infected MSC are well correlated with the expression of VEGF165 in vitro. The expression of therapeutic gene VEGF165 can be monitored by the GGC peptide expression.

OBJECTIVE ToexplorethepossiblemechanismoractiontargetsofT-2toxinembryo toxicity by observing the effect of T-2 toxin on mitochondrial function of differentiated murine e mbryonic stemcells(mESCs).METHODS Duringdifferentiationat24,72and120h,ESCswereexposedto T-2 toxin 0.5 μg·L-1 .Meanwhile,mESCs were pre-treated with antioxidant Trolox (200 μmol·L-1 )for 30 min and exposed to T-2 toxin (0.5 μg·L-1 )for 72 h.The mitochondrial ultrasture of differentiated mESCs was observed under a transi mission electrical microscope (TEM).The differentiated ESC mito-chondrial function,including respiratory control ratio (RCR),ATP synthase activity and mitochondrial membranepotential(MMP),wasmeasuredat144hafterdifferentiation.RESULTS Significant decrease of the mitochondrial number,deformation of mitochondrial structure,and lack of complete mito-chodrial crest were observed through TEM in the groups of T-2 toxin exposed for 72 and 1 20 h,respec-tively.Compared with the normal control group,RCR declined by 49.5% and 55.1%,ATP synthase activity decreased by 84.9% and 89.3%,and MMP decreased by 23.2% and 35.2% in T-2 toxin 0.5 μg·L-1 exposure 72 and 1 20 h group,respectively.However,the inhibition of mitochondrial function by T-2 toxin in differentiated mESCs recovered significantly in the presence of the antioxidant Trolox. CONCLUSION T-2toxininducesoxidativestressandinhibitsmESCsmitochondrialfunctionindifferenti-ated mESCs,and ROS-induced mitochondrial malfunction plays an i mportant role in T-2 toxin e mbryonic toxicity mechanis m.

Objective: To examine the expression of glucocorticoid receptor in human colon cancinoma tis-sues and call lines and to explore the survival of colon cancer cell lines treated with dexamethasone alone or in combination with 5-Fu and L-OHP in a way of dexamethasone pretreatment or co-administration in vitro.Methods: The expression of glucocorticoid receptor was detected in 61 cases of colon cancer tissue samples and 4 types of colon cancer cell lines by immunohistochemistry. Apoptosis was detected by Hoechst33342 staining and flow cytometry. MTT assay was employed to detect the chemosensitivity of colon carcinoma cells to L-OHP and 5-Fu with dexamethasone pretreatment for 24 hours or co-administretion. Results: Positive GR expression was found in 57.3% colon cancer tissue samples and in Lovo and HCT-116 cell lines, not in HT-29 and SW-480. Apoptosis was detected in GR-expressed Lovo and HCT-116 cells at 72 hours after 1×10~(-4)mol/L Dex treatment, and the rates of apoptosis were higher than those in the control groups without Dex (P<0.01),GR-negative cells, HT-29 and SW-480 even treated with 1 × 10~(-4)mol/L Dex for 72 hours. Pretreatment and co-administration for Lovo cells with 1×10~(-4)mol/L Dex could decrease the IC50 of L-OHP from 13.7±1:1.3μg/mL to 5.9±0.6μg/mL and 4.8±0.7μg/mL, respectively. IC50 of 5-Fu was decreased from 72.2±8.1 μg/mL to 21.1±4.1μg/mL and 18.6±4.0μg/mL, respectively. Conclusion: There is expression of glucocorticoid receptor in part of colon carcinoma tissue samples and cell lines. Apoptosis does occur in GR-expressed Lovo and HCT-116 cells induced by dexamethasone in vitro. Pretreatment for 24h and co-administration with Dex can increase the chemosensitivity of Lovo cells to L-OHP and 5-Fu.

Objective:To explore the risk factors of thyroid nodules in diabetic patients and its correlation with Traditional Chinese Medicine (TCM) constitution.Methods:A Total of 213 cases of diabetic patients in Guang’anmen Hospital and Tangshan Hospital from January 2019 to August 2020 were choosen to do the questionnaire, with containly symptom and constitution. The patients were divided into diabetes with thyroid nodules group and diabetes without thyroid nodules group according to whether thyroid nodules were combined. We compared the clinical data characteristics of 2 groups, and used multi-factor logistic regression model to analyze the risk factors of diabetic patients with thyroid nodules and their correlation with TCM constitutions. Results:Diabetes patients aged from 50-80 years old [ OR=2.949, 95% CI (1.266-6.714)], females [ OR=3.736, 95% CI (1.823-1.541)], diabetes duration≥15 years [ OR=1.558, 95% CI (1.623-1.585)], elevated HbA1c [ OR=5.862, 95% CI (1.418-23.629)], elevated VLDL [ OR=2.851, 95% CI (1.597-6.824)], frequent insomnia [ OR=1.970, 95% CI (1.315-3.395)], Qi stagnation [ OR=4.357, 95% CI (2.634-8.377)], blood stasis [ OR=4.420, 95% CI (1.874-15.258)] are more likely to suffer from thyroid nodules ( P<0.05). Conclusion:Diabetic patients aged from 50-80 years old, females, diabetes duration≥15 years, elevated HbA1c, family history of thyroid nodules, frequent insomnia, and mood swings are more likely to develop thyroid nodules; qi stagnation and blood stasis are dangerous constitutions for diabetic patients with thyroid nodules.

The specification of decoction pieces and quality uniformity are the important factors to influence the efficacy of clinical medicine. Considering the deficiency of diversity, poor quality uniformity and confusion of decoction pieces specifications, we first propose a new idea of precision decoction pieces (PDP) based on clinical demands and fresh-processed technology. In order to explain the idea, a study case of aconite SUP is provided, including the optimized specification design, processing technology, extraction effects, quality uniformity, and toxic and efficacy variation and so on. The results showed that preparing 5 mm PDP by fresh-cutting is rather simple and practicable, with high efficiency and large yield; then, this technology could significantly decrease the ingredients loss and increase the efficacy components; moreover, it was helpful for achieving the quality uniformity and best extraction effects. This work revealed the quality superiority of PDP, and provided a good strategy and example for the standard of decoction pieces specification and modernization of processing technology.
Aconitum ; chemistry ; Chemistry, Pharmaceutical ; methods ; Chromatography, High Pressure Liquid ; Particle Size ; Plant Extracts ; chemistry ; pharmacology ; Quality Control