Industrial Distillation Fractions of Garlic Essential Oil, Design, Synthesis, and Antifungal Activity Evaluation of Aliphatic Substituted Trisulfide Derivatives.

Garlic oil has a wide range of biological activities, and its broad-spectrum activity against phytopathogenic fungi still has the potential to be explored. In this study, enzymatic treatment of garlic resulted in an increase of approximately 50 % in the yield of essential oil, a feasible GC-MS analytical program for garlic oil was provided. Vacuum fractionation of the volatile oil and determination of its inhibitory activity against 10 fungi demonstrated that garlic oil has good antifungal activity. The antifungal activity levels were ranked as diallyl trisulfide (S-3)>diallyl disulfide (S-2)>diallyl monosulfide (S-1), with an EC50 value of S-3 against Botrytis cinerea reached 8.16 mg/L. Following the structural modification of compound S-3, a series of derivatives, including compounds S-4~7, were synthesized and screened for their antifungal activity. The findings unequivocally demonstrated that the compound dimethyl trisulfide (S-4) exhibited exceptional antifungal activity. The EC50 of S-4 against Sclerotinia sclerotiorum reached 6.83 mg/L. SEM, In vivo experiments, and changes in mycelial nucleic acids, soluble proteins and soluble sugar leakage further confirmed its antifungal activity. The study indicated that the trisulfide bond structure was the key to good antifungal activity, which can be developed into a new type of green plant-derived fungicide for plant protection.

Evaluation of anticholinergic burden in elderly outpatients and the risk factors. / è€å¹´é—¨è¯Šæ‚£è€ æŠ—èƒ†ç¢±èƒ½å¤„æ–¹è´Ÿæ‹ è¯„ä»·åŠå ¶å±é™©å› ç´ .

OBJECTIVES: The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs. METHODS: A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia. RESULTS: A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine). CONCLUSIONS: There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.

Maritime accidents in the Yangtze River: A time series analysis for 2011-2020.

The theoretical analysis of maritime accidents is a hot topic, but the time characteristics and dynamics of maritime accidents time series are still unclear. It is difficult to draw a clear conclusion from the cause analysis, so the accident is difficult to be predicted. To bridge this gap, this research analyzes the characteristics and evolution mechanism of maritime accidents time series from the perspective of complex network theory. The visual graph algorithm is used to model the complex network of maritime accidents data in 22 jurisdictions of the Yangtze River, map the time series into a complex network, and reveal the time characteristics and dynamics of maritime accidents time series based on the complex system theory. In the empirical analysis, degree distribution, clustering coefficient and network diameter are used to analyze the characteristics of time series. The results show that the degree distribution of maritime accidents time series network presents power-law characteristics in the macro and micro levels, which shows that the maritime accidents time series is scale-free. In addition, according to the clustering coefficient and network diameter, maritime accidents time series in the Yangtze River has the characteristics of small-world and hierarchical structure. The research of this manuscript shows that the occurrence of maritime accidents is not random events and does not follow specific patterns but presents the characteristics of complex systems, and this phenomenon is common. The analysis of maritime accidents time series by complex network theory can provide theoretical support for maritime traffic safety management.

Development of the Practice of Pharmaceutical Care for Cancer Pain Management in Outpatient Clinics Using the Delphi Method.

Background: There exists no broad agreement of experts on the practice of pharmaceutical care for cancer pain management in outpatient clinics. Objectives: This study aimed to use the Delphi consensus process to provide expert recommendations on the practice of cancer pain management in outpatient clinics from the point of view of pharmaceutical care in clinical practice and future clinical trials. Methods: A comprehensive literature review was conducted to draft the initial practice. In this process, 30-40 senior experts from various provinces in China were invited to rank the items of practice during the two Delphi consultations. The definitions of consensus included a combination with an average score of ≥4, the percentage of experts rating the scores at >4 points, and the coefficient of variation of the scores. Results: The expert panel comprised 18 pharmacists, 3 anesthesiologists, 6 oncologists, and 9 nurses. As a result of a comprehensive review, 33 items were initially formed. Among them, the consensus was reached for 27 items after the first Delphi round. The other six items and a total of five items for supplementation entered the second round, among which consensus was reached for eight items and three items were excluded. Expert consensus was achieved on 35 items after two rounds of consultation, which involved the collection of patient basic information, comprehensive pain assessment, breakthrough or neuropathic pain assessment, analgesic treatment evaluation, out-of-hospital follow-up, medical records, and evidence-based documents for reference. Conclusion: The final list of 35 items could be used to develop the practice of pharmaceutical care for cancer pain management in outpatient clinics in China. The practice may aid in the standardization of pharmaceutical care for pain, relieve pain to the greatest extent possible, and enhance the level of pain management in China.

The effect of low molecular weight-polycyclic aromatic hydrocarbons responsive hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 circuit on inflammatory response of A549 cells via the PI3K/AKT pathway and epithelial-mesenchymal transition process.

Inflammation is widely recognized as an essential inducer of epithelial-mesenchymal transition (EMT). Meanwhile, competitive endogenous RNA (ceRNA) has been involved in a variety of disease processes. Therefore, the aim of the current study is to explore the regulation of ceRNA in the PI3K/AKT pathway and EMT mechanism in inflammatory response caused by low molecular weight-polycyclic aromatic hydrocarbons (LMW-PAHs). The A549 cells were treated with an equal mixture of phenanthrene (Phe) and fluorene (Flu), and total RNA was extracted for transcriptome sequencing. The target regulation of ceRNA hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 was further determined for mechanism study. The mixture of Phe and Flu significantly upregulated the expressions of hsa_circ_0039929 and FGF2, down-regulated hsa-miR-15b-3p_R-1, activated the PI3K/AKT pathway and promoted EMT. Mechanically, the overexpression of hsa-miR-15b-3p_R-1 inhibited the expressions of hsa_circ_0039929 and FGF2, reversed the activation of PI3K/AKT signaling pathway by LMW-PAHs, and blocked the occurrence of EMT progression. Furthermore, knockdown of hsa_circ_0039929 could promote the levels of hsa-miR-15b-3p_R-1, while inhibit the expression of FGF2. The effects of hsa_circ_0039929 knockdowns on PI3K/AKT pathways and EMT progress resembled the hsa-miR-15b-3p_R-1 overexpression. All above suggested that ceRNA hsa_circ_0039929/hsa-miR-15b-3p_R-1/FGF2 played an important role in the inflammation and EMT caused by LMW-PAHs.

Based on the Beers Criteria 2019 Edition Over-the-Counter Drugs Risk Confirmation of Elderly Chinese.

OBJECTIVE: To explore OTC (over-the-counter drugs) in Chinese community pharmacies often causes ADE (adverse drug event) in elderly patients. METHODS: Use the drugs in the Beers Criteria 2019 potentially inappropriate medication use (PIM) list as search terms. Search for drugs registered on the National Medical Products Administration of China website before December 2019 to determine the drugs containing PIM active ingredients and, then, search the Chinese OTC selection and conversion catalog database to determine it as OTC. Two databases are considered to be the same drug if they have the same drug composition. RESULTS: The incidence of PIM in elderly patients in our community is relatively high, and the management of OTC may be related to risk factors. Statistics found that 71 OTC contained the Beers Criteria ingredients, including 65 chemicals and six Chinese patent medicines. Varieties of compound preparations accounted for 78.9% and cold medicines accounted for 47.9%. CONCLUSIONS: The high detection rate of the Beers Criteria in Chinese OTC suggests that medical practitioners in China, especially community pharmacists, should pay attention to the rational use of OTC in the elderly.

Correction: Effect of Physician-Pharmacist Participation in the Management of Ambulatory Cancer Pain Through a Digital Health Platform: Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/24555.].

Effect of Physician-Pharmacist Participation in the Management of Ambulatory Cancer Pain Through a Digital Health Platform: Randomized Controlled Trial.

BACKGROUND: Self-management of ambulatory cancer pain is full of challenges. Motivated by the need for better pain management, we developed a WeChat-supported platform, Medication Housekeeper (MediHK), to enhance communication, optimize outcomes, and promote self-management in the home setting. OBJECTIVE: We conducted a randomized controlled trial to assess whether the joint physician-pharmacist team through MediHK would provide better self-management of ambulatory patients with cancer pain. METHODS: Patients were randomly assigned to either an intervention group or control group. During the 4-week study period, the pharmacist would send 24-hour pain diaries daily, adverse drug reaction (ADR) forms every 3 days, and the Brief Pain Inventory form every 15 days to patients in the intervention group via MediHK. If a patient needed a change in drug/dosage or treatment of an ADR after the comprehensive review, the pharmacist would propose pharmacological interventions to the attending physician, who was then responsible for prescribing or adjusting pain medications. If no adjustments were needed, the pharmacist provided appropriate targeted education based on knowledge deficits. Patients in the control group received conventional care and did not receive reminders to fill out the forms. However, if the control group patients filled out a form via MediHK, the pain management team would review and respond in the same way as for the intervention group. The primary outcomes included pain intensity and pain interference in daily life. Secondary outcomes included patient-reported outcome measures, medication adherence, ADRs, and rehospitalization rates. RESULTS: A total of 100 patients were included, with 51 (51%) in the intervention group and 49 (49%) in the control group. The worst pain scores, least pain scores, and average pain scores in the intervention group and the control group were statistically different, with median values of 4 (IQR 3-7) vs 7 (IQR 6-8; P=.001), 1 (IQR 0-2) vs 2 (IQR 1-3; P=.02), and 2 (IQR 2-4) vs 4 (IQR 3-5; P=.001), respectively, at the end of the study. The pain interference on patients' general activity, mood, relationships with others, and interests was reduced, but the difference was not statistically significant compared with the control group (Ps=.10-.76). The medication adherence rate increased from 43% to 63% in the intervention group, compared with an increase of 33% to 51% in the control group (P<.001). The overall number of ADRs increased at 4 weeks, and more ADRs were monitored in the intervention group (P=.003). Rehospitalization rates were similar between the 2 groups. CONCLUSIONS: The joint physician-pharmacist team operating through MediHK improved pain management. This study supports the feasibility of integrating the internet into the self-management of cancer pain. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900023075; https://www.chictr.org.cn/showproj.aspx?proj=36901.

Germanium Nanosheets with Dirac Characteristics as a Saturable Absorber for Ultrafast Pulse Generation.

Bulk germanium as a group-IV photonic material has been widely studied due to its relatively large refractive index and broadband and low propagation loss from near-infrared to mid-infrared. Inspired by the research of graphene, the 2D counterpart of bulk germanium, germanene, has been discovered and the characteristics of Dirac electrons have been observed. However, the optical properties of germanene still remain elusive. In this work, several layers of germanene are prepared with Dirac electronic characteristics and its morphology, band structure, carrier dynamics, and nonlinear optical properties are systematically investigated. It is surprisingly found that germanene has a fast carrier-relaxation time comparable to that of graphene and a relatively large nonlinear absorption coefficient, which is an order of magnitude higher than that of graphene in the near-infrared wavelength range. Based on these findings, germanene is applied as a new saturable absorber to construct an ultrafast mode-locked laser, and sub-picosecond pulse generation in the telecommunication band is realized. The results suggest that germanene can be used as a new type of group-IV material for various nonlinear optics and photonic applications.

Effects of a physician- and pharmacist-managed clinic on pain management in cancer patients in China.

In China, pharmacists have started to manage cancer pain at outpatient clinics. This retrospective study performed at a tertiary teaching hospital was aimed to evaluate the effects of a physician-pharmacist joint clinic for cancer pain management. The study was performed between December 2016 and August 2019 and included 113 outpatients with moderate to severe cancer-related pain. Patients were divided into two groups according to the clinic each patient visited: the physician-pharmacist joint clinic (joint group, n = 59) or physician-only clinic (usual group, n = 54). Brief Pain Inventory (BPI) and Morisky Medication Adherence Measure (MMAM) were used to collect data on pain intensity, interference and medication adherence. Pain Management Index (PMI) was also calculated. BPI, MMAM and PMI were assessed at baseline (patients' first visit, week 0) and week 4 follow-up. The Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was used to assess patients' health-related quality of life (HRQoL) at week 4. The primary outcomes were the improvement in pain intensity, adequacy of pain management and medication adherence. The secondary outcome was the improvement in HRQoL. At week 4, compared to the usual group, the BPI pain intensity categories except the pain right now were significantly lower in the joint group: worst pain, 4 (3-7) vs 6 (4-8), P = .020; least pain, 1 (0-2) vs 2 (1-3), P = .010; average pain, 3 (2-4) vs 4 (2-5), P = .023; pain right now, 2 (1-3) vs 2 (0-4), P = .796. For the seven pain interference categories, there were no significant improvements in the joint group (P > .05). Significantly more patients achieved adequate pain control in the joint group than the usual group ((P = .002). There was also a significant difference in medication adherence between the two groups (P = .001). There were no significant differences in HRQoL between the two groups. The study suggests that pharmacist participation in outpatient cancer pain management is associated with improvement of patients' pain control and medication adherence.

Influencing factors of end-of-dose failure in patients with cancer pain after oral oxycodone sustained-release tablets: a retrospective, case-control study.

OBJECTIVE: Comparing the characteristics of end-of-dose failure patients and non-end-of-dose failure patients in the Chinese population and exploring the factors that may affect the occurrence of end-of-dose failure in cancer pain patients. METHODS: The outpatient with cancer pain from 2016 to 2019 were collected through hospital information system, and patients were included who met the following criteria: patients with the average numerical rating scale  ≥4 points within 3 days after taking the oxycodone sustained-release preparation, titrated to an effective therapeutic dose suitable for patients, had at least two clinical visits information of the patient with a minimum of ≥3 days between visits, the average numerical rating scale of the next visit after the treatment of occasional pain is ≥4, and were divided into end-of-dose failure group and non-end-of-dose failure group. RESULTS: Age (P < 0.05, odds ratio 0.933), diagnosis of nasopharyngeal carcinoma (P < 0.05, odds ratio 0.009), pain site is the head and neck (P < 0.05, odds ratio 0.005) and the abdomen (P < 0.01, odds ratio 0.021), and the metastatic site is the liver (P < 0.05, odds ratio 0.001) are related to the occurrence of end-of-dose failure. CONCLUSIONS: Younger patients are more likely to develop end-of-dose failure. Patients diagnosed with nasopharyngeal cancer, with pain in the head and neck and abdomen, and with liver metastases have a lower incidence of end-of-dose failure.

Catalyst-Free Growth of Two-Dimensional BCxN Materials on Dielectrics by Temperature-Dependent Plasma-Enhanced Chemical Vapor Deposition.

Traditional methods to prepare two-dimensional (2D) B-C-N ternary materials (BCxN), such as chemical vapor deposition (CVD), require sophisticated experimental conditions such as high temperature, delicate control of precursors, and postgrowth transfer from catalytic substrates, and the products are generally thick or bulky films without the atomically mixed phase of B-C-N, hampering practical applications of these materials. Here, for the first time, we develop a temperature-dependent plasma-enhanced chemical vapor deposition (PECVD) method to grow 2D BCxN materials directly on noncatalytic dielectrics at low temperature with high controllability. The C, N, and B compositions can be tuned by simply changing the growth temperature. Thus, the properties of the as-made materials including band gap and conductivity are modulated, which is hardly achieved by other methods. A 2D hybridized BC2N film with a mixed BC2N phase is produced, for the first time, with a band gap of about 2.3 eV. The growth temperature is 580-620 °C, much lower than that of traditional catalytic CVD for growing BCxN. The product has a p-type conducting property and can be directly applied in field-effect transistors and sensors without postgrowth transfer, showing great promise for this method in future applications.

Ambulatory care pharmacy practice in China: status and future efforts.

In recent years, as the era of deepening healthcare reform in China progresses, there is a gradual development of ambulatory care pharmacy practice. This commentary reviews the current state of ambulatory care pharmacy practice in China and discusses future efforts to advance the practice. Areas of focus include practice standardization, transitions of care, and reimbursements of ambulatory care pharmacy practice.

Potentially inappropriate medications in Chinese community-dwelling older adults.

Background There is a lack of data on the prevalence of potentially inappropriate medications (PIMs) in community-dwelling older adults in China. Objective To assess the prevalence of potentially inappropriate medication in community dwelling older adults in China and to investigate risk factors associated with the use of such medication. Setting Ambulatory Care Clinic of Xiangya Hospital, Central South University. Method A cross-sectional retrospective review of prescriptions for older patients (aged ≥ 65 years) was performed using the 2019 American Geriatrics Society (AGS) Beers Criteria and the 2017 Chinese Criteria. We only assessed potentialli inappropriate medications independently from diagnosis and drug-drug interactions. Each patient was classified as PIM-user or non-PIM-user, according to whether a patient took at least one potentially inappropriate medication. Main outcome measure Prevalence of potentially inappropriate medication based on the two criteria. Results A total of 8477 medications among 1874 elderly patients were examined over the study period from January 1 to December 31, 2018. The Chinese Criteria detected significantly more PIM-users than the AGS Beers Criteria (50.6% vs 35.0%, P < 0.001), and also a higher percentage of inappropriate medication in prescribed medications (14.7% vs 8.5%, P < 0.001). Benzodiazepines, anticholinergics, antipsychotics, and insulin were the most frequently prescribed classes by both criteria. Alprazolam (47.7%) was the most frequently found inappropriate medicine based on the 2019 AGS Beers Criteria compared to clopidogrel (42.2%) based on the Chinese Criteria. The number of medications was a significant risk factor to the use of potentially inappropriate medication in both criteria. Conclusion The prevalence of the use of potentially inappropriate medication in Chinese community-dwelling older adults is high, and explicit criteria are a useful tool to evaluate the prescription of such medication in the elderly.

Time-Varying Risk Measurement for Ship Collision Prevention.

We propose an innovative time-varying collision risk (TCR) measurement for ship collision prevention in this article. The proposed measurement considers the level of danger of the approaching ships and the capability of a ship to prevent collisions. We define the TCR as the probability of the overlap of ships' positions in the future, given the uncertainty of maneuvers. Two sets are identified: (1) the velocity obstacle set as the maneuvers of the own ship that lead to collisions with target ships, and (2) the reachable velocity set as the maneuvers that the own ship can reach regarding its maneuverability. We then measure the TCR as the time-dependent percentage of overlap between these two sets. Several scenarios are presented to illustrate how the proposed measurement identifies the time-varying risk levels, and how the approach can be used as an intuitively understandable tool for collision avoidance.

Flexible, Printable Soft-X-Ray Detectors Based on All-Inorganic Perovskite Quantum Dots.

Metal halide perovskites represent a family of the most promising materials for fascinating photovoltaic and photodetector applications due to their unique optoelectronic properties and much needed simple and low-cost fabrication process. The high atomic number (Z) of their constituents and significantly higher carrier mobility also make perovskite semiconductors suitable for the detection of ionizing radiation. By taking advantage of that, the direct detection of soft-X-ray-induced photocurrent is demonstrated in both rigid and flexible detectors based on all-inorganic halide perovskite quantum dots (QDs) synthesized via a solution process. Utilizing a synchrotron soft-X-ray beamline, high sensitivities of up to 1450 µC Gyair -1 cm-2 are achieved under an X-ray dose rate of 0.0172 mGyair s-1 with only 0.1 V bias voltage, which is about 70-fold more sensitive than conventional α-Se devices. Furthermore, the perovskite film is printed homogeneously on various substrates by the inexpensive inkjet printing method to demonstrate large-scale fabrication of arrays of multichannel detectors. These results suggest that the perovskite QDs are ideal candidates for the detection of soft X-rays and for large-area flat or flexible panels with tremendous application potential in multidimensional and different architectures imaging technologies.

Flexible photodetectors based on reticulated SWNT/perovskite quantum dot heterostructures with ultrahigh durability.

Recently, single-walled carbon nanotube (SWNT) films have been regarded as a promising channel material for flexible photodetectors due to their high intrinsic carrier mobility, conductivity, and mechanical flexibility. However, the application of SWNTs in photonic devices is limited due to their weak light absorption and the absence of a gain mechanism. Here, we demonstrate a high-performance flexible photodetector that consists of a reticulated SWNT film covered with a thin film of CsPbI3 perovskite colloidal quantum dots. The unique hierarchical reticulated structure of the SWNTs provides such films with extremely high tensile strength and great extensibility, which can ensure the appropriate toughness for achieving flexible photodetectors. Meanwhile, the perovskite quantum dots enhance light absorption, thereby sensitizing the creation of free electrical carriers within the SWNTs. This hybrid photodetector exhibits an extended photonic response and gain compared with the original pure SWNT devices. In addition, the device exhibits good robustness against repetitive bending and stretching, suggesting its applicability as a large-area wearable flexible photodetector.

The prognostic value of preoperative inflammatory indexes in gallbladder carcinoma with hepatic involvement.

BACKGROUND: Neutrophil-Lymphocyte Ratio (NLR) and Platelet-Lymphocyte Ratio (PLR) have been considered as indicators for prognosis in various cancers. However, the prognostic values of NLR and PLR have never been tested in gallbladder carcinoma (GBC) with hepatic involvement. OBJECTIVE: The aim of the current study was to assess the prognostic significance of NLR, PLR, and other candidate biomarkers in GBC with liver involvement. METHODS: Receiver operating characteristic (ROC) curve analyses were utilized to pinpoint the cut-off values for NLR, PLR, and Monocyte-Lymphocyte Ratio (MLR). Univariate analyses were employed to estimate the impact of NLR, PLR, MLR, and other inflammatory indexes on median survival. Multivariate analyses were used to verify the independent prognostic predictors. RESULTS: Eighty four patients were enrolled from 2009 to 2017. The cut-off values for NLR, PLR, and MLR were 3.20, 117.75, and 0.25, respectively. Univariate analyses revealed that TNM stage, NLR, PLR, MLR, lactate dehydrogenase, alkaline phosphatase, and carcinoembryonic antigen were significantly associated with decreased survival in GBC with hepatic involvement. Advanced TNM stage (P< 0.001) and elevated preoperative NLR (P= 0.002) were significantly associated with lower median survival periods, as revealed by multivariate analyses. CONCLUSIONS: These findings suggest that preoperative NLR may be an independent prognostic factor in evaluating prognosis in GBC with liver involvement.

Safety assessment of saponins extract in Dolichos falcatus Klein: Subchronic study in Sprague-Dawley rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dolichos falcatus Klein (DF), a Chinese Dai ethnic medicine popularly known as "Tuoyeteng" in Yunnan province of China, has been widely used in China to treat fracture, rheumatoid arthritis and soft tissue injuries for a long time. Our previous study showed that saponins in DF (DFS) ameliorated the gouty arthritis induced by MSU crystals in vivo and in vitro. The present study was carried out to evaluate the no-observed-adverse-effect level (NOAEL) of DFS. MATERIALS AND METHODS: Sprague-Dawley rats (10/sex/group) were gavaged with DFS at dose level of 0, 50, 100 and 200 mg/kg body weight /day for 90-days. RESULTS: DFS administration did not result in mortality or show treatment-related changes in clinical signs of toxicity, body weights gain or feed consumption. Similarly, in addition to slightly hemolytic anemia and gastrointestinal tract lesion in males of high-dose treatment group, no toxicologically significant treatment-related changes in hematological, clinical chemistry, urine analysis parameters, organ weights, and macroscopic and microscopic abnormalities were noted during the testing period. CONCLUSION: The results of subchronic toxicity study support the NOAEL for DFS as 200 mg/kg/d in females and as 100mg/kg/d in males. These results provide an important reference for further DFS-related clinical trials or new drug exploration.

[Application of space-time scan statistics in the analysis of spatial and temporal distribution of Oncomelania hupensis snails in Gaoyou County, Jiangsu Province].

OBJECTIVE: To investigate the distribution features of Oncomelania hupensis infested areas in Gaoyou County so as to formulate surveillance and intervention strategies. METHODS: A database was established through collecting data of the snail infested areas during 1970-2009 in the County. The data were input into SaTScan 9.2 software for spatial-temporal cluster analysis to determine the spatial and temporal cluster of the snail habitats. The results were displayed by ArcGIS 10.1 software. RESULTS: There were historically 720 snail habitats in the County in 1970-2009 including 521 in plain region with water networks and 199 in lake & marshland region. Those in water networks covered an area of 456.62 ha distributing mainly in the northern towns/townships of the County, and the latters distributed in the Xinmin Beach between Gaoyou Lake and Shaobo Lake, and Qiaojian Beach close to Tianchang County of Anhui Province with an area of 4 495.75 ha. The spatial-temporal cluster analysis revealed that among all the historical snail habitats, there were two prominent spatial-temporal clusters with a relative risk of >3. One cluster appeared in Xinmin Beach in 1983-2002 and another one located in the north of Gaoyou in 1970-1973. Separate analysis was performed by the regions of water network or lake & marshland, indicating 2 clusters in each of the regions. During 1970-2009, 244 snail habitats were newly found in the County with 130 in water network region and 114 in lake & marshland region. Again, the spatial-temporal cluster analysis displayed 2 prominent clusters. By separate analysis, 2 clusters existed in each of the regions. CONCLUSION: The space-time scan statistics can be applied in detecting the cluster of snail infested areas in two dimensions, which will provide information for guiding specific measures of surveillance and control.