Plasma circulating tumour DNA is a better source for diagnosis and mutational analysis of IVLBCL than tissue DNA.

Diagnosis of intravascular large B-cell lymphoma (IVLBCL) is a challenge due to its heterogeneous clinical presentation and lack of specific markers. This retrospective study investigated the utility of circulating tumour DNA (ctDNA) sequencing for diagnosing IVLBCL and analysing its mutation landscape. A cohort of 34 IVLBCL patients enrolled and underwent plasma ctDNA targeted sequencing. The median plasma ctDNA concentration was 135.0 ng/mL, significantly higher than that in diffuse large B-cell lymphoma (DLBCL) controls. Correlations were found between ctDNA concentration and disease severity indicators, LDH and SF. Mutation analysis revealed frequent mutations in B-cell receptor and NF-κB signalling pathways, including MYD88 (56%), CD79B (44%), TNFAIP3 (38%) and IRF4 (29%). CNS involvement was significantly related with BCL6 and CD58 mutation. Patients with complicated hemophagocytic lymphohistiocytosis had significantly higher mutation rates in B2M. Comparison with DLBCL subtypes showed distinctive mutation profiles in IVLBCL. Moreover, plasma ctDNA detected more mutations with higher variant allele fraction than tissue DNA, suggesting its superiority in sensitivity and accessibility. Dynamic monitoring of ctDNA during treatment correlated with therapeutic responses. This study revealed the role of ctDNA in IVLBCL diagnosis, mutation analysis, and treatment monitoring, offering a promising avenue for improving patient diagnosis in this rare lymphoma subtype.

Dual Channel H2O2 Photosynthesis in Pure Water over S-Scheme Heterojunction Cs3PMo12/CC Boosted by Proton and Electron Reservoirs.

Dual channel photo-driven H2O2 production in pure water on small-scale on-site setups is a promising strategy to provide low-concentrated H2O2 whenever needed. This process suffers, however, strongly from the fast recombination of photo-generated charge carriers and the sluggish oxidation process. Here, insoluble Keggin-type cesium phosphomolybdate Cs3PMo12O40 (abbreviated to Cs3PMo12) is introduced to carbonized cellulose (CC) to construct S-scheme heterojunction Cs3PMo12/CC. Dual channel H2O2 photosynthesis from both H2O oxidation and O2 reduction in pure water has been thus achieved with the production rate of 20.1 mmol L-1 gcat. -1 h-1, apparent quantum yield (AQY) of 2.1% and solar-to-chemical conversion (SCC) efficiency of 0.050%. H2O2 accumulative concentration reaches 4.9 mmol L-1. This high photocatalytic activity is guaranteed by unique features of Cs3PMo12/CC, namely, S-scheme heterojunction, electron reservoir, and proton reservoir. The former two enhance the separation of photo-generated charge carriers, while the latter speeds up the torpid oxidation process. In situ experiments reveal that H2O2 is formed via successive single-electron transfer in both channels. In real practice, exposing the reaction system under natural sunlight outdoors successfully results in 0.24 mmol L-1 H2O2. This work provides a key practical strategy for designing photocatalysts in modulating redox half-reactions in photosynthesis.

Distinct FDG PET/CT avidity among newly diagnosed intravascular large B-cell lymphoma patients: a descriptive observational study.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of aggressive B-cell non-Hodgkin lymphoma that poses a great diagnostic challenge due to its highly heterogenous clinical manifestations. Although 18F-fluorodeoxyglucose (FDG) is widely used as a diagnostic tool for patients suspected of having lymphoma, as it reveals FDG-avid lesions, the FDG avidity of IVLBCL has not been extensively characterized. Here, we present a comprehensive report of FDG avidity in IVLBCL and its association with clinicopathological features and survival. This descriptive observational study included consecutive patients aged at least 18 years diagnosed with IVLBCL in Peking Union Medical Hospital across 9 years. Among 50 screened IVLBCL patients, 42 had undergone 18F-FDG PET/CT to detect possible lesions for biopsy before pathological diagnosis; their FDG PET/CT (positron emission computed tomography, PET/CT) reports were retrospectively reviewed. The primary endpoint was the clinical description of FDG avidity of newly diagnosed intravascular large B-cell lymphoma and frequency. A total of 73.8% patients showed FDG-avid lesions, with a median SUVmax of 7.4 (range 1-27.7), which was lower than that for other aggressive lymphomas. Clinicopathological features were the same between the FDG-avid group and the non-FDG-avid group, except that the latter had a higher Ki-67 index (median 90% in the nonavid group vs. 80% in the avid group, P = 0.043). The overall survival rate was not different between the PET/CT groups. Our findings demonstrate that FDG PET/CT is a useful diagnostic tool for detecting FDG-avid lesions in IVLBCL patients. A random skin biopsy is essential for assisting in the diagnosis of IVLBCL, even for those with negative PET/CT.

Impact of homocysteine on acute ischemic stroke severity: possible role of aminothiols redox status.

BACKGROUND: Acute ischemic stroke (AIS) is one of the most common cerebrovascular diseases which accompanied by a disruption of aminothiols homeostasis. To explore the relationship of aminothiols with neurologic impairment severity, we investigated four aminothiols, homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CG) and glutathione (GSH) in plasma and its influence on ischemic stroke severity in AIS patients. METHODS: A total of 150 clinical samples from AIS patients were selected for our study. The concentrations of free reduced Hcy (Hcy), own oxidized Hcy (HHcy), free reduced Cys (Cys), own oxidized Cys (cysteine, Cyss), free reduced CG (CG) and free reduced GSH (GSH) were measured by our previously developed hollow fiber centrifugal ultrafiltration (HFCF-UF) method coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The concentration ratio of Hcy to HHcy (Hcy/HHcy), Cys to Cyss (Cys/Cyss) were also calculated. The neurologic impairment severity of AIS was evaluated using National Institutes of Health Stroke Scale (NIHSS). The Spearman correlation coefficient and logistic regression analysis was used to estimate and perform the correlation between Hcy, HHcy, Cys, Cyss, CG, GSH, Hcy/HHcy, Cys/Cyss and total Hcy with NIHSS score. RESULTS: The reduced Hcy and Hcy/HHcy was both negatively correlated with NIHSS score in AIS patients with P = 0.008, r=-0.215 and P = 0.002, r=-0.249, respectively. There was no significant correlation of Cys, CG, GSH, HHcy, Cyss, Cys/Cyss and total Hcy with NIHSS score in AIS patients with P value > 0.05. CONCLUSIONS: The reduced Hcy and Hcy/HHcy, not total Hcy concentration should be used to evaluate neurologic impairment severity of AIS patient.

Airborne atmospheric carbon dioxide measurement using 1.5 µm laser double-pulse IPDA lidar over a desert area.

An integrated path differential absorption (IPDA) lidar can accurately measure regional C O 2 weighted column average concentrations (X C O 2), which are crucial for understanding the carbon cycle in climate change studies. To verify the performance and data inversion methods of space-borne IPDA lidar, in July 2021, we conducted an airborne lidar validation experiment in Dunhuang, Gansu Province, China. An aircraft was equipped with a lidar system developed to measure X C O 2 and an in situ greenhouse gas analyzer (GGA). To minimize measurement errors, energy monitoring was optimized. The system bias error of the DAOD was determined by changing the laser output mode from the off/on to the on/on mode. The X C O 2 inversion results obtained through comparing the schemes of averaging signals before "log (logarithm)" and averaging after "log" indicate that the former performs better. The IPDA lidar measured X C O 2 over the validation site at 405.57 ppm, and both the IPDA lidar and GGA measured sudden changes in the C O 2 concentration. The assimilation data showed a similar trend according to the altitude to the data measured by the in situ instrument. A comparison of the mean X C O 2 derived from the GGA results and assimilation data with the IPDA lidar measurements showed biases of 0.80 and 1.12 ppm, respectively.

Mutation profiling, tumour burden assessment, outcome prediction and disease monitoring by circulating tumour DNA in peripheral T-cell lymphoma.

In this prospective study, we aimed to evaluate the utility of circulating tumour DNA (ctDNA) in peripheral T-cell lymphomas (PTCLs). Plasma cell-free DNA (cfDNA) was obtained, and the mutational profile was assessed in 47 patients with newly diagnosed mature T- and NK-cell lymphoma. To validate the mutations detected in cfDNA, paired tumour tissue samples were available for 36 patients. Targeted next-generation sequencing was performed. A total of 279 somatic mutations involving 149 genes were identified in the 47 cfDNA samples. The overall sensitivity of plasma cfDNA in discovering biopsy-confirmed mutations was 73.9% with a specificity of 99.6%. When we considered only mutations with variant allele frequency >5% in the tumour biopsy, the sensitivity increased to 81.9%. Pretreatment ctDNA concentration and the number of mutations were highly correlated with tumour burden indicators including lactate dehydrogenase, Ann Arbor stage and International Prognostic Index score. Patients with high ctDNA level (>1.9 log ng/mL) had significantly lower overall response rates, inferior 1-year progression-free survival and overall survival rates than those with low level. Longitudinal analysis of ctDNA showed a strong agreement between ctDNA dynamics and the radiographic response. In conclusion, our study demonstrates that ctDNA may serve as a promising tool for mutational profiling, tumour burden assessment, outcome prediction and disease monitoring in PTCLs.

Zinc finger protein 671 has a cancer-inhibiting function in colorectal carcinoma via the deactivation of Notch signaling.

Zinc finger protein 671 (ZNF671) has been described as a vital cancer inhibitor in multiple neoplasms, yet the functional roles of ZNF671 in colorectal carcinoma (CRC) remain unresolved. This project examined the possible link between ZNF671 and CRC. Lower levels of ZNF671 were observed in CRC tissue compared with noncancerous tissue, which were related to a worse survival rate in CRC patients. High methylation levels at the ZNF671 gene promoter region were shown in CRC tissue, which were inversely correlated with ZNF671 expression. Treatment with demethylation agents restored ZNF671 levels in CRC cell lines. Up-regulation of ZNF671 resulted in suppressive effects on the proliferative ability and metastatic potency of CRC cells. Moreover, the up-regulation of ZNF671 reinforced the chemosensitivity of CRC cells. A mechanism study determined ZNF671 to be a vital mediator of Notch signaling. The up-regulation of ZNF671 decreased the expression of Notch1 and lowered the levels of NICD, HES1, and HEY1. The overexpression of NICD1 diminished ZNF671-mediated antitumor effects. ZNF671 depletion reinforced Notch signaling, and Notch suppression reversed ZNF671-depletion-elicited protumor effects. Moreover, the overexpression of ZNF671 weakened the tumorigenicity of CRC cells in a xenograft model in vivo. In summary, ZNF671 exerts a cancer-inhibiting function in CRC via the deactivation of Notch signaling. Low ZNF671 levels caused by gene promoter hypermethylation contribute to the malignant transformation of CRC. This work underlines the interest of ZNF671 as a target candidate for exploiting novel anti-CRC therapies.

Insulin-like growth factor 1 receptor inhibits the proliferation of acute myeloid leukaemia cells via NK cell activation.

Acute myeloid leukaemia (AML) denotes a heterogeneous category of cancers occurring within the bone marrow that are initiated by the unrestricted proliferation of haematopoietic stem cells. Various factors effectuate the dysregulation of AML cell proliferation; for instance, the upregulation of insulin-like growth factor 1 receptor (IGF1R) within AML cells influences their proliferation. However, there is a current dearth of research assessing the association between IGF1R and prognostic risk as well as its potential as an AML immunotherapeutic. This study aims to elucidate the role of IGF1R in AML progression and evaluate its prognostic value. To this end, RNA-sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) database was analysed to compare IGF1R expression between AML and normal tissues. Moreover, a Kaplan-Meier survival analysis was performed to determine whether IGF1R expression correlates with patient overall survival (OS). TCGA data revealed upregulated IGF1R expression in the peripheral blood of AML patients compared to that in healthy individuals. Meanwhile, IGF1R expression positively correlates with patient OS. Additionally, elevated IGF1R expression promotes NK cell expansion and enhances its functional activation, thereby inhibiting AML cell proliferation. Collectively, these findings highlight the clinical potential of IGF1R in the effective treatment of AML through the activation of NK cell proliferation and function and suggest that it may represent a potential predictive marker of AML prognosis.

Activation-Assisted High-Concentration Phosphorus-Doping to Enhance the Electrochemical Performance of Cobalt Carbonate Hydroxide Hydrate.

P-doping into metal oxides has been demonstrated as a valid avenue to ameliorate electrochemical performance because it can tune the electronic structures and increase the active sites for an electrochemical reaction. However, it usually results in a low P-doping concentration via the commonly used gas phosphorization method. In this work, an activation-assisted P-doping strategy was explored to significantly raise the P-doping concentration in cobalt carbonate hydroxide hydrate (CCHH). The activation treatment increased active sites for electrochemical reaction and endowed the sample with a high P content in the subsequent gas phosphorization process, thereby greatly enhancing the conductivity of the sample. Therefore, the final CCHH-A-P electrode exhibited a high capacitance of 6.62 F cm-2 at 5 mA cm-2 and good cyclic stability. In addition, the CCHH-A-P//CC ASC with CCHH-A-P as the positive electrode and carbon cloth as the negative electrode provided a high energy density of 0.25 mWh cm-2 at 4 mW cm-2 as well as excellent cycling performance with capacitance retention of 91.2% after 20,000 cycles. Our work shows an effective strategy to acquire Co-based materials with high-concentration P-doping that holds great potential in boosting the electrochemical performance of electrode materials via P-doping technology.

Evaluation of progression-free survival as a surrogate end point in primary CNS lymphoma: a systematic review and meta-analysis.

Purpose: To evaluate progression-free survival (PFS) as early surrogate endpoints for overall survival (OS) in primary CNS lymphoma (PCNSL). Methods: PubMed, Embase and Cochrane Central Library were searched up to 7 June 2022. Trial-level analyses were performed by weighted linear regression of logarithmic hazard ratios for PFS and OS. Treatment arm-level analyses were performed between PFS rates and 3- or 5-year OS rates. Results: 1471 PCNSL patients in nine randomized control trials were included. PFS was associated with OS (r = 0.750; 95% CI: 0.228-0.937). Strong linear correlations existed between 1-, 2- and 3-year PFS and 3-year OS (r = 0.896-0.928), moderate or weak correlations existed between 3- to 6-month PFS and 3-year OS, 3-month to 5-year PFS and 5-year OS. Conclusion: Short-term PFS can validly substitute for long-term OS in PCNSL.

Numerical modeling of the impacts of acoustic stimulus on fish otoliths from two directions.

Previous experiments have shown (1) evidence that exposure to high-intensity sounds (e.g., air-gun signals) may cause damage to the sensory hair cells of the fish ears and impair fish hearing and (2) evidence that in some circumstances such exposures cause minimal structural damage. The contradictory results regarding the damage accrued suggested that the angle of sound energy arrivals at the fish ears may play a part in the propensity of the sound to cause damage to sensory hair cells. To further study this and gain insight into specific details of the differential motion of the otolith relative to the sensory macula when incident sounds arrive from different directions, three-dimensional finite element models were constructed based on the micro-computed tomography imaging of the sagittal otoliths of the bight redfish (Centroberyx gerrardi). We used the models to study the response of fish sagittal otoliths to sounds arriving from horizontal and vertical directions. Sound pressure levels, relative displacement, acceleration, and shear stress of the otoliths and/or otolith-water boundary were calculated and compared. The results suggest that the angle of sound energy arrivals at the otoliths and the geometry of the otolith lead to different magnitudes of the differential motion between the macula and otoliths, with sound arriving in the vertical potentially creating more damage than the same sound arriving from the horizontal.

Historical trend and drivers of China's CO2 emissions from 2000 to 2020.

China is the largest CO2 emitter in the world and announced that carbon peak and neutral targets will be achieved before 2030 and 2060, respectively. A retrospective analysis of past CO2 emissions and their drivers is important for the actions of peaking CO2 emissions before 2030 in China. CO2 emissions from energy use (coal, oil, and natural gas) and cement production from 2000 to 2020 were calculated first, and their drivers were decomposed into economic and population growth, energy intensity, and emission coefficient by logarithmic mean Divisa index (LMDI) analysis in this study. China's CO2 emissions increased nearly threefold from 3385 in 2000 to 10,788 million tonnes (Mt) in 2020, with a decline from 2013 to 2016. Coal was the major emission sector contributing more than 70% in most years, while natural gas emissions increased nearly 13 times from 53 to 723 Mt in the two decades, although its contribution only accounted for 6.7% in 2020. Economic growth was the major positive driver, while energy intensity reduction was the major negative driver of the emission increments by year and by the Five Year Plan (FYP). Emission coefficient reduction gradually became important due to its negative effect, especially in the 13th FYP, which offset ~ 30% of the emissions induced by economic growth. The projections of CO2 emissions in 2025, 2030, and 2035 could be 11,596 ± 582, 11,774 ± 621, and 11,401 ± 672 Mt, respectively, suggesting that China's carbon emissions could peak around 2030 with an increment of ~ 1000 Mt on the 2020 levels. Under the sustainable growth of the economy and population, it is possible to reduce the carbon peak value or achieve peak time earlier through the additional reduction of energy intensity and emission coefficient by technological progress and energy alternatives such as non-fossil fuels. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-022-02811-8.

A Direct Injection Technique to Improve Biosafety to Analyze Levetiracetam Concentrations in Human Serum and Its Application in Therapeutic Drug Monitoring.

BACKGROUND: With the outbreak of COVID-19, it has become very important to improve biosafety measures taken by medical staff. Fewer pretreatment steps correspond to lower chances of infection. The authors established a direct injection technique to analyze levetiracetam (LEV) concentrations in human serum and studied its application in therapeutic drug monitoring. METHODS: Serum samples were prepared by hollow fiber centrifugal ultrafiltration and the filtrate was directly injected into a ultra-high performance liquid chromatography apparatus (Waters UPLC BEH C18 column: 50 × 2.1 mm, 1.7 µm) for analysis. The mobile phase consisted of acetonitrile and water (8:92) at a flow rate of 1.0 mL/min. The column temperature was maintained at 30°C. The detected wavelength was 210 nm. RESULTS: A linear relationship was obtained for LEV from 0.625 to 80 mcg/mL (r2 = 0.999). The limit of detection for the analysis of LEV was 0.125 mcg/mL. The analysis time was shortened to 4 minutes. The recovery rate of LEV based on the current method was 96.6%-100.1%, whereas the absolute recovery rate was 93.2%-96.8%. The relative SD of intraday and interday precision was <7.3%. Stability was achieved at room temperature for 24 hours after 3 freeze-thaw cycles and at -80°C for 21 days. The method was successfully applied to determine LEV concentrations in the serum of 19 patients. CONCLUSIONS: The present method is simple, accurate, and sensitive, and can improve biosafety with the direct injection technique. It is suitable for the analysis of LEV concentrations in therapeutic drug monitoring.

A simple and accurate HFCF-UF method for the analysis of homocysteine, cysteine, cysteinyl-glycine, and glutathione in human blood.

The presence of reduced aminothiols, including homocysteine (Hcy), cysteine (Cys), cysteinyl-glycine (CG), and glutathione (GSH), is significantly increased in the pathological state. However, there have been no reports on the relationship between reduced aminothiols (Hcy, Cys, CG, and GSH) and different genders, ages, and drug combinations in human blood. The accurate quantification of these reduced thiols in biological fluids is important for monitoring some special pathological conditions of humans. However, the published methods typically not only require cumbersome and technically challenging processing procedures to ensure reliable measurements, but are also laborious and time-consuming, which may disturb the initial physiological balance and lead to inaccurate results. We developed a hollow fiber centrifugal ultrafiltration (HFCF-UF) method for sample preparation coupled with a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method and used it to determine four reduced aminothiols (Hcy, Cys, CG, and GSH) in human blood for the first time. A total of 96 clinical patients were enrolled in our study. The influence of different genders, ages, and drug combinations on the levels of four reduced thiols in human blood was also discussed by SPSS 24.0. The sample preparation was simplified to a single 5 min centrifugation step in a sealed system that did not disturb the physiological environment. The validation parameters for the methodological results were excellent. The procedure was successfully applied to monitoring the concentrations of four reduced aminothiols (Hcy, Cys, CG, and GSH) in 96 clinical blood samples. There were no significant differences in Hcy, Cys, CG, or GSH for the different genders, ages, or combinations with methotrexate or vancomycin (P > 0.05). However, there was a significant increase in Hcy concentration in patients treated with valproic acid who were diagnosed with epilepsy (p=0.0007). It is advisable to measure reduced Hcy level in patients taking valproic acid. The developed HFCF-UF method was simple and accurate. It can be easily applied in clinical research to evaluate oxidative stress in further study.

Combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase (GDP-ML) for patients with newly diagnosed extranodal natural killer/T cell lymphoma, nasal type: a single arm, single center, prospective phase 2 study.

Extranodal natural killer/T cell lymphoma, nasal type (ENKL) is a highly aggressive tumor with relatively poor prognosis. In this prospective study, we investigated the efficacy and toxicity of a novel GDP-ML regimen (combined gemcitabine, cisplatin, dexamethasone, methotrexate, and pegaspargase) as front-line treatment in newly diagnosed ENKL. Eligible newly diagnosed stage I/II ENKL patients received sandwich chemoradiation therapy. Patients with stage III/IV disease received an initial 4 cycles of GDP-ML regimen. After 4 cycles, responding patients continued to receive either autologous transplantation or additional two courses of GDP-ML. A total of 44 patients were enrolled with a median follow-up of 26 months. The overall response rate (ORR) were 78.6% for the whole cohort, 84.6% for stage I/II, and 66.7% for stage III/IV, and corresponding complete remission (CR) rates were 61.9%, 76.9%, and 33.3%. The 1- year and 2- year progression-free survival (PFS) rates were 69.3% and 62.9%, and 1- year and 2-year overall survival (OS) rates were 76.5% and 67.4%, respectively. Patients with stage I/II disease showed better 2-year OS rate compared with stage III/IV patients (88.1% vs. 33.2%, p < 0.001). Patients who achieved CR had significantly better 2-year OS rate compared with non-CR patients (90.8% vs. 24.5%, p < 0.001). The main adverse event was hematologic toxicity. Grade 3/4 neutropenia occurred in 59.1% of patients. These results indicate that GDP-ML is an effective and well-tolerated induction regimen with newly diagnosed ENKL patients. This clinical trial was registered on www.chictr.org.cn (ChiCTR-ONC-12002055).

Modeling of the near to far acoustic fields of an echolocating bottlenose dolphin and harbor porpoise.

Echolocation signals emitted by odontocetes can be roughly classified into three broad categories: broadband echolocation signals, narrowband high-frequency echolocation signals, and frequency modulated clicks. Previous measurements of broadband echolocation signal propagation in the bottlenose dolphin (Tursiops truncatus) did not find any evidence of focusing as the signals travel from the near-field to far-field. Finite element analysis (FEA) of high-resolution computed tomography scan data was used to examine signal propagation of broadband echolocation signals of dolphins and narrowband echolocation signals of porpoises. The FEA results were used to simulate the propagation of clicks from phonic lips, traveling through the forehead, and finally transmission into the water. Biosonar beam formation in the near-field and far-field, including the amplitude contours for the two species, was determined. The finite element model result for the simulated amplitude contour in the horizontal plane was consistent with prior direct measurement results for Tursiops, validating the model. Furthermore, the simulated far-field transmission beam patterns in both the vertical and horizontal planes were also qualitatively consistent with results measured from live animals. This study indicates that there is no evidence of convergence for either Tursiops or Phocoena as the sound propagates from the near-field to the far-field.

[Analysis of adverse events and influencing factors in randomized controlled trials of oral Chinese medicine published in English].

In order to analyze the incidence of adverse events(AE) and evaluate the related influencing factors in randomized controlled trials(RCTs) of oral Chinese medicine which published in English, Medline, EMbase, and the Cochrane Central Register of Controlled Trials(CENTRAL) database were searched. Oral Chinese medicine RCTs published in English from January 2009 to July 2018 were collected to extract the basic characteristics, subjects, intervention characteristics and AE information. The AE incidence of each study was merged by using Meta analysis. Finally, 218 RCTs were included, of which 28.4% did not report any AE. A total of 1 634 AE occurred in 103 oral Chinese medicine groups, and the total incidence of AE was 11.2%(95%CI[10.7%, 11.7%]). The highest incidence of AE came to blood routine laboratory abnormalities, 8.0%(95%CI[6.6%, 9.7%]), followed by neurological and psychiatric systems 7.9%(95%CI[6.6%, 9.5%]), digestive system 7.8%(95%CI[6.8%, 8.9%]) and liver function abnormalities 7.6%(95%CI[6.4%, 8.9%]). Among the oral dosage forms, tablets and granules had the highest incidence of AEs, while decoction and oral liquids had the lowest incidence. The combination of oral Chinese medicine and Western medicine had the highest incidence of AE. As the medication course increased, the incidence of AE increased accordingly. The incidence of AE in children was higher than that in adults. Based on the analysis results, the higher AE incidence of oral Chinese medicine was in the neuropsychiatric system, gastrointestinal system and liver function abnormalities. The incidence of AE was related to the dosage form, drug combination, medication duration, and patient age. We should pay attention to the AE in children due to modern dosage forms of traditional Chinese medicine, combination of Chinese and Western medicine, and long course of medication.

A biosonar model of finless porpoise (Neophocaena phocaenoides) for material composition discrimination of cylinders.

Research into the physical mechanism of odontocetes biosonar has made great progress in the past several decades, especially on wave propagation and biosonar beam formation in the foreheads of odontocetes. Although a number of experimental studies have been performed, the physical mechanism of odontocetes underwater target discrimination has not yet been fully understood. Previous research has experimentally studied the finless porpoise's target discrimination using cylinders different in material [Nakahara, Takemura, Koido, and Hiruda (1997). Mar. Mamm. Sci. 13(4), 639-649]. The authors proposed a computed tomography based finite element biosonar model to simulate the detailed process of a finless porpoise click emission and target detection in order to gain a further understanding of the underlying physical mechanism. The numerical solutions of resonance features of both steel and acrylic cylinders in this study are very consistent with the analytic solutions. Furthermore, the simulated outgoing clicks and echoes match the experiment results measured by Nakahara et al. The beam patterns of the scattered field were extracted and the resonance features of cylinders in different materials were analyzed. This method in this study could be used to study some other odontocetes that are inaccessible for experimental work and could also provide physical information for intelligent biomimetic underwater signal processors design.

A study on the asymmetric cylinder wall thickness difference discrimination by dolphins.

Atlantic bottlenose dolphins (Tursiops truncatus) can effectively discriminate between water-filled cylinders with different wall thicknesses. The dolphins' performance may be particularly good when the cylinders are thinner. The dolphins' performance is also asymmetric, in that the discrimination accuracy is not equal when the target thickness increases and decreases by the same amount. Inspired by this, a finite element model is proposed here to mimic a dolphin actively transmitting sound to discriminate between targets using acoustic echoes. The waveforms and frequency spectra of acoustic echoes from a standard cylinder and comparison cylinders with wall thickness differences of ±0.3 mm were compared. The employed model simulations show good agreement with previous experimental measurements by Au and Pawloski [(1992). J. Compar. Physiol. A 170(1), 41-47]. Asymmetric arrival time shifts were found for the echo peaks and troughs with the same sequence numbers when the wall thicknesses were increased and decreased by the same amount. This asymmetry became more significant for echo peaks and troughs with higher sequence numbers. Apart from these asymmetric arrival time shifts of the acoustic echoes, the patterns of echo waveforms, the spatial distributions of sound pressures in the water, and the particle vibratory displacements in the cylinders were also found to vary with cylinder thickness. The physical origin of this asymmetric discrimination by the dolphins was explored using both geometric acoustics and wave acoustics. The asymmetry observed might be caused by the circumferential surface (Lamb) wave in the cylinder wall, which is a wave acoustics phenomenon that cannot be derived from geometric acoustics. The findings in this paper might be valuable not just for understanding the mechanism of the effect described, but also for helping the development of biomimetic intelligence for robust signal processing in underwater target discrimination.