abstract Cell metabolite analysis is of great interest to analytical chemists and physiologists, with some meta-bolites having been identified as important indicators of major diseases such as cancer. A high-throughput and sensitive method for drug metabolite analysis will largely promote the drug discovery industry. The basic barrier of metabolite analysis comes from the interference of complex components in cell biological system and low abundance of target substances. As a powerful tool in biosample analysis, microfluidic chip enhances the sensitivity and throughput by integrating multiple functional units into one chip. In this review, we discussed three critical steps of establishing functional microfluidic platform for cellular metabolism study. Cell in vitro culture model, on chip sample pretreatment, and microchip combined detectors were described in details and demonstrated by works in five years. And a brief summary was given to discuss the advantages as well as challenges of applying microchip method in cell metabolite and biosample analysis.

Objective:To investigate the correlation of serum testosterone level with severity and characteristics of coronary plaque, stent implantation rate and major cardiovascular adverse events(MACE)in elderly male patients with coronary heart disease(CHD).Methods:In this retrospective study, a total of 63 elderly male patients of the Third People's Hospital of Hangzhou with coronary angiography(CAG)-confirmed CHD and to undergo percutaneous coronary intervention(PCI)were selected.According to serum testosterone level, they were divided into the low testosterone(low T)group and the normal testosterone(normal T)group.Optical coherence tomography(OCT)was performed in both groups to define the characteristics of coronary artery lesions and guide stent implantation.The correlation of serum testosterone level with blood lipids, glycated hemoglobin(HbA1c), degree of coronary artery lesions, plaque characteristics, stent implantation and MACE in two groups were analyzed.The in-stent restenosis rate after stent implantation and the variation of minimum lumen diameter of stent were determined during 12 months follow up in both groups.Results:Total cholesterol(TC), low-density lipoprotein(LDL-C)and HbA1c were higher in the low T group than in the normal T group( t=7.808、-5.871、6.611, all P<0.05). When taking testosterone as the independent variable, and TC, triglycerides(TG), LDL-C, high density lipoprotein cholesterol(HDL-C)and HbA1c as the dependent variables, linear regression analysis showed that TC, LDL-C and HbA1c were negatively correlated with testosterone level( β=-0.733, -0.716, -0.581, P<0.05). More than 2 vascular lesions were more common in low testosterone group versus the control group( χ2=8.66, P<0.05). Mixed plaques, lipid plaques, and calcified plaques were more commonly found in low testosterone group versus the control group( χ2=7.87, P<0.05). Unstable plaques were more common in the low T group( χ2=6.14, P<0.05). The low T group vs the normal T group, coronary stent implantation rate were 93.3%(28/30 cases) vs.66.7%(22/33 cases), the difference was statistically significant( χ2=6.82, P<0.05). When testosterone, TC, TG, LDL-C, HDL-C, HbA1c were taken as the independent variables, and the stent implantation rate was the dependent variable, logistic regression analysis results showed that only testosterone, TC and HbA1c were independently correlated with stent implantation rate( OR=0.971、425.523、0.004, P<0.05). There was no statistically significant difference in minimum stent lumen diameters between the two groups under OCT-guided coronary stent implantation( t=-1.064, P>0.05). During 12 months follow up, the MACE0 incidence was 26.7%(8/30 cases, in low T group)than 6.1%(2/33 cases, in normal T group), with statistically significant difference( χ2=5.00, P<0.05). When taking testosterone, TC, TG, LDL-C, HDL-C and HbA1c as the independent variables, and MACE as the dependent variable, logistic regression analysis results showed that only testosterone and LDL-C were independently correlated with MACE( OR=0.968, 0.008, P<0.05). Conclusions:Serum testosterone level is negatively correlated with TC, LDL-C and HbA1c, and may be correlated with the degree of coronary artery lesions, plaque properties, MACE and stent implantation rate of CHD patients.Serum testosterone can be used to evaluate the characteristics and conditions of CHD, and help to predict the prognosis of CHD.The OCT is a good guide tool for coronary stent implantation.

Objective To investigate the value of renal CT volumetric texture analysis with machine learning radiomics in assessment of pathological grade of clear cell renal cell carcinoma(ccRCC). Methods Thirty-four biopsy-confirmed ccRCC subjects who had four-phase CT scanning (NC:non-contrast, CM: Corticomedullary, N: Nephrographic, E: Excretory) were collected retrospectively from June 2013 to October 2017 for the study.Non-rigid registration was performed on multi-phase CT images in reference to CM-phase.Each lesion was segmented on CM-phase CT images using our in-house volumetric image analysis platform,"3DQI".A set of fifty-nine volumetric textures,including histogram,gradient,gray level co-occurrence matrix(GLCM),run-length(RL),moments,and shape,was calculated for each segment lesion in each phase as parameters for the training/testing of Random Forest (RF) classifier. Four groups according to pathological Fuhrman grade on a scaleⅠtoⅣ,these tumors were then divided into low(Ⅰ+Ⅱ) and high grade ( Ⅲ + Ⅳ) groups. Feature selection was performed by Boruta algorithm. A 10-fold cross-validation method was applied to validate the RF performance by receiver operating characteristic (ROC) curves analysis to determine the diagnostic accuracy of the model. Results Subjects were divided into four groups by Fuhrman grade on a scaleⅠtoⅣ:3 cases gradeⅠ,19 cases gradeⅡ,8 cases gradeⅢand 4 cases gradeⅣ.In CM-phase,kurtosis and long-run-emphasis(RLE)were selected the most important textures for ccRCC staging among 59 features. The area under curve (AUC) of ROC was 0.88 (79% sensitivity and 82% specificity)by using kurtosis and RLE textures.The mean values of kurtosis and RLE were(-20.00±22.00)×10-2and(3.00±0.40)×10-2for low group,whereas(31.00±32.00)×10-2and(5.00± 0.02)×10-2for high group.Within the mean±SD range of statistics,radiomics can distinguish between low and high grade tumors.In multi-phase analysis,three most important features were selected among 236(59× 4) textures: kurtosis (CM-phase), GLCM homogeneity I (HOMO 1) (E-phase), and GLCM homogeneity 2 (HOMO2)(E-phase).The mean values of HOMO 1(E-phase)and HOMO 2(E-phase)were(19.00±0.03)× 10-2and(11.00±0.02)×10-2for low group,whereas(22.00±0.03)×10-2and(14.00±0.02)×10-2for high group. The AUC was 0.92(93% sensitivity and 87% specificity)by using these three textures. Conclusion This study has demonstrated that renal CT volumetric texture analysis with machine learning radiomics could preoperative accurately perform cancer staging for ccRCC.

Chronic heart failure(CHF) is the end stage of various cardiovascular diseases and is one of the common diseases among the elderly in China. Sarcopenia is a geriatric syndrome characterized by the age-related loss of skeletal muscle quantity and/or mass and the decline in muscle strength and/or physical performance. There is a common pathophysiological mechanism of CHF and sarcopenia, and they interact with each other and influence each other′s prognosis. There are few confirmed effective treatments for sarcopenia, and even fewer measures that can help slow the progression of both syndromes. However, on the basis of heart failure treatment hormone therapy, exercise training and nutritional support may slow the progression of sacopenia. This article reviews the recent advances in the relationship between elderly CHF patients with sarcopenia and related treatment.

Livestock husbandry is vital to economy of the Tarim Basin, Xinjiang Autonomous Region, China. However, there have been few surveys of the distribution of ixodid ticks (Acari: Ixodidae) and tick-borne pathogens affecting domestic animals at these locations. In this study, 3,916 adult ixodid ticks infesting domestic animals were collected from 23 sampling sites during 2012-2016. Ticks were identified to species based on morphology, and the identification was confirmed based on mitochondrial 16S and 12S rRNA sequences. Ten tick species belonging to 4 genera were identified, including Rhipicephalus turanicus, Hyalomma anatolicum, Rh. bursa, H. asiaticum asiaticum, and Rh. sanguineus. DNA sequences of Rickettsia spp. (spotted fever group) and Anaplasma spp. were detected in these ticks. Phylogenetic analyses revealed possible existence of undescribed Babesia spp. and Borrelia spp. This study illustrates potential threat to domestic animals and humans from tick-borne pathogens.

Objective To investigate the ultrasonography discrepancy of hepatic neuroendocrine neoplasm ( hNEN ) derived from different primary locations and pathological grades . Methods From August 2010 to April 2016 ,50 consecutive patients with 54 hNENs confirmed by pathology and imaging diagnosis underwent baseline ultrasound ( BUS ) and contrast-enhanced ultrasound ( CEUS ) in the First Affiliated Hospital of Sun Yat-sen University were enrolled in the retrospective study . On the basis of primary sites ,all hNENs were divided into three groups :pancreas ,gastrointestinal tract and other location groups . According to the pathological grading ,the hNENs were divided into hNET ( hepatic neuroendocrine tumor) group and hNEC ( hepatic neuroendocrine carcinoma) group . The imaging features of BUS and CEUS were retrospectively investigated and the ultrasonography discrepancy of hNEN derived from different primary focus and pathological grades were compared . Results ① Comparison of hNEN derived from different primary sites :hNEN derived from pancreas and gastrointestinal tract were smaller than hNEN derived from other sites[ ( 3 .8 ± 2 .6) cm vs ( 8 .7 ± 7 .0) cm , P = 0 .037 ;( 2 .9 ± 2 .1) cm vs ( 8 .7 ± 7 .0) cm , P = 0 .005] ,but the difference between the pancreas and gastrointestinal tract was not statistically significant ( P = 1 .0 ) . As for the pattern of CEUS enhancement ,hNEN derived from pancreas and gastrointestinal tract usually showed homogenous enhancement ( 13/19 ,15/23) while hNEN derived from other primary sites usually showed heterogeneous enhancement ( 10/13) ,and the difference was statistically significant ( P = 0 .025) . ② Comparison of hNET and hNEC :the distinction of enhancement level in the portal phase of contrast-enhanced ultrasound was statistically significant ( P = 0 .033) . All hNEC appeared hypo-enhancement ,while a small part of hNET ( 7/31 ) appeared iso-enhancement .More hNEC lesions showed heterogenous enhancemnt than hNET in the arterial phase ( 14/21 vs 9/31 , P = 0 .007) ,and there were less hNEC lesions presented tumor bleeding vessels than hNET ( 8/21 vs 22/31 , P = 0 .019 ) . Conclusions hNEN derived from pancreas and gastrointestinal tract are in a manner similar to hNEN derived from other primary sites on ultrasonography , so it' s difficult to identify in ultrasound . The ultrasonographic features of hNEC are more resemble to malignancy and it can be distinguished from hNET .

Objective:The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.
Adult ; Humans ; Cross-Sectional Studies ; Nasal Cavity/surgery* ; Allergens ; Pollen ; Artemisia ; Hydrodynamics

Tuberculosis (TB) is one of the deadly diseases caused by Mycobacterium tuberculosis (Mtb), which presents a significant public health challenge. Treatment of TB relies on the combination of several anti-TB drugs to create shorter and safer regimens. Therefore, new anti-TB agents working by different mechanisms are urgently needed. FtsZ, a tubulin-like protein with GTPase activity, forms a dynamic Z-ring in cell division. Most of FtsZ inhibitors are designed to inhibit GTPase activity. In Mtb, the function of Z-ring is modulated by SepF, a FtsZ binding protein. The FtsZ/SepF interaction is essential for FtsZ bundling and localization at the site of division. Here, we established a yeast two-hybrid based screening system to identify inhibitors of FtsZ/SepF interaction in M. tuberculosis. Using this system, we found compound T0349 showing strong anti-Mtb activity but with low toxicity to other bacteria strains and mice. Moreover, we have demonstrated that T0349 binds specifically to SepF to block FtsZ/SepF interaction by GST pull-down, fluorescence polarization (FP), surface plasmon resonance (SPR) and CRISPRi knockdown assays. Furthermore, T0349 can inhibit bacterial cell division by inducing filamentation and abnormal septum. Our data demonstrated that FtsZ/SepF interaction is a promising anti-TB drug target for identifying agents with novel mechanisms.

[This corrects the article DOI: 10.1016/j.apsb.2023.01.022.].