Discrete event simulation (DES) model is based on individual data, by which discrete events over time are simulated to reflect disease progression. The effects of individual characteristics on disease progression could be considered in the DES model. Moreover, unlike state-transition models, DES model without setting of fixed cycle can contribute to more accurate estimation of event time, especially in the evaluation of the long-term effectiveness of screening strategies for complex diseases in which time dimension needs to be considered. This article introduces the general principles, construction steps, analytic methods and other relevant issues of the DES model. Based on a research case of estimating the cost-effectiveness of screening for abdominal aortic aneurysms in women aged 65 years and above in the United Kingdom, key points in applications of the DES model in analysis on effectiveness of complex disease screening are discussed in detail, including model construction and analysis and interpretation of the results. DES model can predict occurring time of discrete events accurately by establishing the distribution function of their occurring time and is increasingly used to evaluate the screening strategies for complex diseases in which time dimension needs to be considered. In the construction of DES model, it is necessary to pay close attention to the clear presentation of model structure and simulation process and follow the relevant reporting specification to conduct cost-effectiveness analysis to ensure the transparency and repeatability of the research.
Humans ; Female ; Cost-Benefit Analysis ; Cost-Effectiveness Analysis ; Disease Progression

OBJECTIVE: To evaluate the characteristics of severe periodontitis with various number of tooth loss during 4-year natural progression, and to analyze the factors related to higher rate of tooth loss. METHODS: A total of 217 patients aged 15 to 44 years with severe periodontitis were included, who participated in a 4-year natural progression research. Data obtained from questionnaire survey, clinical examination and radiographic measurement. Tooth loss during 4-year natural progression was evaluated. The baseline periodontal disease related and caries related factors were calculated, including number of teeth with bone loss > 50%, number of missing molars, number of teeth with widened periodontal ligament space (WPDL), number of teeth with periapical lesions and etc. Characteristics of populations with various number of tooth loss and the related factors that affected higher rate of tooth loss were analyzed. RESULTS: In 4 years of natural progression, 103 teeth were lost, and annual tooth loss per person was 0.12±0.38. Nine patients lost 3 or more teeth. Thirty-four patients lost 1 or 2 teeth, and 174 patients were absent of tooth loss. Molars were mostly frequent to lose, and canines presented a minimum loss. The number of teeth with WPDL, with periapical lesions, with intrabony defects, with probing depth (PD)≥7 mm, with PD≥5 mm, with clinical attachment loss≥5 mm, with bone loss > 50% and with bone loss > 65% were positively correlated to number of tooth loss. Results from orderly multivariate Logistic regression showd that the number of teeth with bone loss > 50% OR=1.550), baseline number of molars lost (OR=1.774), number of teeth with WPDL (1 to 2: OR=1.415; ≥3: OR=13.105), number of teeth with periapical lesions (1 to 2: OR=4.393; ≥3: OR=9.526) and number of teeth with caries/residual roots (OR=3.028) were significant risk factors related to higher likelihood of tooth loss and multiple tooth loss. CONCLUSION In 4 years of natural progression, the number of teeth with bone loss > 50%, baseline number of missing molars, number of teeth with WPDL, baseline number of teeth with periapical lesions and number of teeth with caries/residual roots were significantly related to higher risk of tooth loss and multiple tooth loss among Chinese young and middle-aged patients with severe periodontitis in rural areas.
Humans ; Tooth Loss/etiology* ; Periodontitis/complications* ; Tooth ; Periodontal Diseases ; Molar

OBJECTIVE: To assess changes of nutritional status by comprehensive nutrition assessment including nutritional risk screening, dietary assessment, blood biochemical index, and body composition in acute leukemia patients who had undergone chemotherapy. METHODS: A total of 169 patients with acute leukemia treated at The First Affiliated Hospital of Soochow University from June 2018 to August 2019 were recruited for this study. Before and after chemotherapy, the NRS-2002 and PG-SGA scales, dietary intake, blood biochemical index and body composition were evaluated to compare the changes of nutritional status. RESULTS: NRS-2002 score and PG-SGA score after chemotherapy were significantly increased than those before chemotherapy (P<0.001). Many patients had insufficient nutritional intake during chemotherapy, and the dietary intake score of patients with induction chemotherapy was significantly lower than that of patients with consolidation chemotherapy (P=0.043). The results of multivariate analysis showed that induction chemotherapy was the independent risk factor for the increase of PG-SGA scores and the decrease of dietary intake (all P<0.05). After chemotherapy, the white blood cell count, hemoglobin, and platelet count were significantly decreased (P<0.001), the prealbumin was significantly increased (P<0.001), and the blood glucose was increased (P=0.04), but albumin was not significantly changed. The weight, body mass index, fat-free mass, skeletal muscle mass and intracellular water were all significantly decreased (P<0.001), and visceral fat area was increased significantly after chemotherapy (P<0.05), especially in newly-diagnosed acute lymphoblastic leukemia patients after the induction of chemotherapy. CONCLUSION The nutritional status of patients with acute leukemia has undergone significant changes after chemotherapy. A single indicator has limited significance for nutritional status assessment. Comprehensive assessment of nutritional status by multiple tools is worthy of clinical application.
Acute Disease ; Humans ; Induction Chemotherapy/methods* ; Leukemia, Myeloid, Acute/drug therapy* ; Nutrition Assessment ; Nutritional Status ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

OBJECITVIE: To compare the liver protective activity of fresh/dried dandelion extracts against acetaminophen (APAP)-induced hepatotoxicity. METHODS: Totally 90 Kunming mice were randomly divided into 10 groups according to body weight (9 mice for each group). The mice in the normal control and model (vehicle control) groups were administered sodium carboxymethyl cellulose (CMC-Na, 0.5%) only. Administration groups were pretreated with high and low-dose dry dandelion extract (1,000 or 500 g fresh herb dried and then decocted into 120 mL solution, DDE-H and DDE-L); low-, medium- and high-dose dandelion juice (250, 500, 1,000 g/120 mL, DJ-L, DJ-M, and DJ-H); fresh dandelions evaporation juice water (120 mL, DEJW); dry dandelion extract dissolved by pure water (1 kg/120 mL, DDED-PW); dry dandelion extract dissolved by DEJW (120 g/120 mL, DDED-DEJW) by oral gavage for 7 days at the dosage of 0.5 mL solution/10 g body weight; after that, except normal control group, all other groups were intraperitonealy injected with 350 mg/kg APAP to induce liver injury. Twenty hours after APAP administration, serum and liver tissue were collected and serum alanine aminotransferase (AST), aspartate transaminase (ALT), alkaline phosphatase (AKP), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) activities were quantified by biochemical kits; tumor necrosis factor (TNF-α), interleukin (IL)-2, and IL-1 β contents in liver tissue were determined by enzyme linked immunosorbent assay kits. Histopathological changes in liver tissues were observed by hematoxylin and eosin staining; TUNEL Assay and Hoechst 33258 staining were applied for cell apoptosis evaluation. The expressions of heme oxygenase-1 (HO-1), nuclear factor erythroid-2-related factor 2 (Nrf-2), caspase-9, B-cell leukemia/lymphoma 2 (Bcl-2), Bax and p-JNK were determined by Western blot analysis. RESULTS: Pretreatment with fresh dandelion juice (FDJ, including DJ-L, DJ-M, DJ-H, DEJW and DDED-DEJW) significantly decreased the levels of serum ALT, AST, AKP, TNF-α and IL-1β compared with vehicle control group (P<0.05 or P<0.01). Additionally, compared with the vehicle control group, FDJ decreased the levels of hepatic MDA and restored GSH levels and SOD activity in livers (P<0.05 or P<0.01). FDJ inhibited the overexpression of pro-inflammatory factors including cyclooxygenase-2 and inducible nitric oxide synthase in the liver tissues (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that FDJ pretreatment inhibited activation of apoptotic signaling pathways via decreasing of Bax, and caspase-9 and JNK protein expression, and inhibited activation of JNK pathway (P<0.05 or P<0.01). Liver histopathological observation provided further evidence that FDJ pretreatment significantly inhibited APAP-induced hepatocyte necrosis, inflammatory cell infiltration and congestion. CONCLUSIONS FDJ pretreatment protects against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway, and the effect of fresh dandelion extracts was superior to dried dandelion extracts in APAP hepatotoxicity model mice.
Acetaminophen/toxicity* ; Alanine Transaminase ; Animals ; Apoptosis ; Body Weight ; Caspase 9/metabolism* ; Chemical and Drug Induced Liver Injury/prevention & control* ; Dichlorodiphenyl Dichloroethylene/pharmacology* ; Glutathione/metabolism* ; Liver ; Mice ; Oxidative Stress ; Plant Extracts/therapeutic use* ; Superoxide Dismutase/metabolism* ; Taraxacum/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Water/metabolism* ; bcl-2-Associated X Protein/metabolism*

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; Bendamustine Hydrochloride/therapeutic use* ; China ; Humans ; Lymphoma, Non-Hodgkin/drug therapy* ; Neoplasm Recurrence, Local/drug therapy* ; Prospective Studies ; Rituximab/therapeutic use*

Moslae Herba is a commonly used aromatic Chinese medicinal with volatile oil as the main effective component and exhibits broad-spectrum antibacterial and antiviral effects. However, the irritation and instability of Moslae Herba volatile oil necessitate the preparation into a specific dosage form. In this study, the steam distillation method was employed to extract the Moslae Herba volatile oil. The content of thymol and carvacrol in Moslae Herba volatile oil was determined by HPLC as(0.111 9±0.001 0) and(0.235 4±0.004 7) mg·mL~(-1), respectively. Pseudo-ternary phase diagrams and surfactants compounding were applied in the selection of the optimal excipients(surfactant and cosurfactant). On this basis, a nanoemulsion was prepared from the Moslae Herba volatile oil and then loaded into pressure vessels to get sprays, whose stability and antibacterial activity were evaluated afterward. With clarity, viscosity, smell and body feeling as comprehensive indexes, the optimal formulation of the Moslae Herba volatile oil nanoemulsion was determined as follows: Moslae Herba volatile oil∶peppermint oil∶cremophor EL∶absolute ethanol∶distilled water 7.78∶1.58∶19.26∶6.15∶65.23. The as-prepared nanoemulsion was a light yellow transparent liquid, with Tyndall effect shown under the irradiation of parallel light. It has the pH of 5.50, conductivity of 125.9 μS·cm~(-1), average particle size of 15.45 nm, polydispersity index(PDI) of 0.156, and Zeta potential of-17.9 mV. Under a transmission electron microscope, the Moslae Herba volatile oil nanoemulsion was presented as regular spheres without adhesion and agglomeration. Stability test revealed that the Moslae Herba volatile oil nanoemulsion was stable at 4-55 ℃, which was free from demulsification and stratification within 30 days. After the centrifugation at 12 000 r·min~(-1) for 30 min, there was no stratification either. The nanoemulsion had good inhibitory effects on Escherichia coli, Staphylococcus aureus and resistant S. aureus strains, with the minimum inhibitory concentrations of 0.39, 3.12 and 1.56 mg·mL~(-1), respectively. The above results demonstrated that the nanoemulsion was prepared feasibly and showed stable physical and chemical properties and good antibacterial effects. This study provides a practicable technical solution for the development of anti-epidemic and anti-infection products from Moslae Herba volatile oil.
Anti-Bacterial Agents/pharmacology* ; Emulsions ; Methicillin-Resistant Staphylococcus aureus ; Microbial Sensitivity Tests ; Oils, Volatile ; Particle Size

Objective To study the severe fever with thrombocytopenia syndrome bunyavirus (SFTSV)-related vector biological monitoring in Daishan County, Zhoushan Island of Zhejiang Province, and to explore the prevention and control strategies. Methods The monitoring was conducted as follows:squirrel-cage method was used for rodents from 2012 to 2014;the Buqi method for free tick density in villages and towns with confirmed cases in Daishan County from 2015 to 2018;and body surface comb method for parasitic ticks.RT-PCR method was used to detect SFTSV in ticks and rat specimens.Epidemiological survey followed by extensive health education was conducted from 2011 to 2015.Comprehensive health prevention and control measures, such as precision health education and chemical elimination of vectors were taken from 2016 to 2018. Results A total of 327 rodents were captured, including 172 stinking shrews, accounting for 52.60%, and 92 yellow mice, accounting for 28.13%.The main species of ticks was Haematopsus longicortus, accounting for 94.20%.Among them, there were 135 parasitic ticks in three species:Haematopsus longicorum, S.scallopus, and T.nigra. There were 382 free ticks in 6 species, including Haematopsichum longicorum, Sickle fan tick, Hemophilus fannicus, Ixodes ovaliformis, Ixodes granulata, and Ixodes sinensis.From May to October in 2015, the density of field ticks was ≥50 per cloth flag.From May 2016 to 2018, after the elimination application of chemical agents for elimination, the density of ticks was ≤50 per cloth flag.All ticks and rodent specimens tested by RT-PCR were negative for SFTSV.Since precision education in 2016, the awareness rate of SFTS in rural areas has increased from 32.05% to 83.33%.Approximately 70 early warning notices for the epidemic situation were issued in advance.Since 2017, the number of SFTS has been declining year by year, and only 8 cases occurred in 2018. Conclusion In the field environment, chlorothalonil is the dominant mouse species and long horn blood ticks are the dominant ticks.The government leadership, cooperation among departments, technical service provided by professional organization, health education, reduction of tick density in residential environment, timely risk early warning notice, and other comprehensive prevention and control hand strategy all contribute to the achieved result of prevention and control.

OBJECTIVE: To validate five-year risk prediction models for stroke in a contemporary rural Northern Chinese population. METHODS: Totally 6 483 rural adults aged 40 to 79 years without cardiovascular diseases were enrolled at baseline between June and August 2010, and followed up through January 2017. Expected prediction risk using the China-PAR (prediction for atherosclerotic cardiovascular disease risk in China) stroke risk equations were compared with the new Framingham stroke risk profile (FSRP). The recalibrated models were applied by adjusting the five-year baseline survival rate and the mean score to our rural northern Chinese population, while keeping other coefficient parameters the same as the original models. Kaplan-Meier analysis was used to obtain the observed event (nonfatal or fatal stroke) rate for the five years, and the expected-observed ratios were calculated to evaluate overestimation or underestimation in the cohort. The models were assessed by discrimination C statistic, calibration χ², and calibration charts and plots for illustration as well. RESULTS: Over an average of (5.83 ± 1.14) years of the follow-up in this validation cohort with 6 483 rural Chinese participants, 438 subjects deve-loped a first stroke event. Recalibrated China-PAR stroke risk equations and FSRP well-performed for predicting five-year stroke risk in men, and had C statistics of 0.709 (95%CI, 0.675 - 0.743) and 0.721 (95%CI, 0.688 - 0.754), with calibration χ² values being 5.7 (P = 0.770) and 13.6 (P = 0.137), respectively. However, both China-PAR and FSRP overestimated stroke events by 11.6% and 30.0% in women, and had C statistics of 0.713 (95%CI, 0.684-0.743) and 0.710 (95%CI, 0.679-0.740), respectively. Calibration χ² values in women were 12.5 (P = 0.188) for China-PAR and 24.0 (P = 0.004) for FSRP. In addition, the calibration charts and plots illustrated good agreement between the observations and the predictions only in the China-PAR stroke risk equations, especially for men. CONCLUSION In this validation cohort of rural northern Chinese adults, the China-PAR models had better performance of five-year stroke risk prediction than the FSRP, indicating that recalibrated China-PAR stroke risk equations might be appropriate tools for risk assessment and primary prevention of stroke in China.
Adult ; Aged ; Cardiovascular Diseases ; China ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Risk Assessment ; Risk Factors ; Stroke

A highly sensitive and selective bioluminescent probe for hydrazine (BPH) was designed, synthesized and evaluated for detection of hydrazine in vitro and in vivo. BPH was designed to include a specific recognition group (acetyl) of hydrazine at an appropriate modification site of the optical reporter hydroxyluciferin (D-luciferin), which showed excellent performance both in selectivity and sensitivity to hydrazine. The results showed that the bioluminescent probe BPH developed in this study is an innovative and widely applicable tool for detecting hydrazine in complex natural environment or in animals.

Objective The purpose of this study is to evaluate the in-hospital clinical outcome of patients with coronary artery disease who underwent transradial intervention (TRI) and analyze the predictors of chinical outcome. Methods From May 2004 to May 2009, there were 16 281 patients who underwent transradial intervention, as well as 5388 patients who underwent transfemoral intervention (TFI) at our institution. The clinical characteristics, procedural characteristics, and in-hospital clinical adverse events were compared between TRI and TFI groups. Multivariable logistic regression analysis was performed to determine predictors of in-hospital major adverse cardiac events ( composite of death, myocardial infarction,or target lesion revascularization) of TRI. Results The annulations time was significantly longer for TRIthan TFI (P ＜0. 01 ), fluoroscopy time, amount of contrast agent and procedural success rate (95.5% for TRI and 96. 2% for TFI) were similar between the two groups. However, the rates of vascular complications (0. 1% for TRI group and 1.3% for TFI group, P ＜0. 01 ), incidence of in-hospital major adverse cardiac events (1.6% vs. 3. 8%, P＜ 0.01) and in-hospital death (0.2% vs. 0.4%, P＜0.01) were all significantly lower in TRI group compared with TFI group. The following characteristics were identified as independent multivariate predictors of in-hospital major adverse cardiac events of TRI: age ≥65 ( OR: 1.98,95% CI: 1. 50 - 2. 61, P ＜ 0. 01 ), prior myocardial infarction ( OR:2. 14, 95% CI: 1.63 - 2. 82, P ＜0. 01 ), use of drug-eluting stent (DES) ( OR:0. 68, 95% CI:0. 47 - 0. 98, P = 0. 04 ), dissection during procedure (OR:4.08, 95%CI:2.28-7.33, P＜0.01), left main lesion (OR:2. 12, 95% CI:1.09-4. 13, P=0.03), number of implanted stents (OR:1.25, 95% CI:1.09 - 1.43, P ＜0.01), and total stented length (OR:1.01, 95% CI:1. 00 -1. 02 , P=0.03). Conclusions In this large single-centre patient cohort, the transradial intervention is superior to transfemoral intervention in terms of in-hospital safety and efficacy. Age ≥ 65, prior myocardial infarction, use of DES, dissection during procedure, left main lesion, number of implanted stents and total stented length were identified as independent multivariate predictors of in-hospital major adverse cardiac events of TRI.