Aim To discover the potential active compounds and possible mechanisms in rheumatoid arthritis (RA) treatment with Zhi-Huang-Zhi-Tong powder (ZHZTP) by using network pharmacology and in vitro study. Methods The active ingredient targets and disease targets of Zhihuang Zhitong Powder were searched and screened by database; they intersected to get a common target; and the "drug-component-target" relationship network diagram was constructed for GO and KEGG enrichment analysis of the overlapping genes; then the core components were docked with the core targets. Finally, based on the inflammation model of HUVECs in vitro, the efficacy and mechanism of Zhihuang Zhitong powder were verified by MTT method, plate scratch test and Western blot. Results Active compounds involved in RA treatment were screened in the present study, and the top two were ursolic acid and emodin, all playing crucial roles in RA treatment with ZHZTP. Additionally, the key target was AKTA, TNF and IL-6. GO and KEGG enrichment analysis revealed that ZHZTP regulated BP, MF and CC, and also focused on regulating AKTA, TNF and IL-6 signaling pathway. Molecular docking showed that interactions between key active compounds and key targets were stable. In vitro ZHZTP significantly inhibited cell viability and migration of TNF-a-stimulated HUVECs, and the involved mechanism may be associated with PI3K/AKT/m-TOR signaling. Conclusions The present study reveals that the potential active compounds of ZHZTP are ursolic acid and emodin, and moreover, the involved mechanisms of ZHZTP for RA treatment are associated with PI3 K/AKT/m-TOR signaling.

Aim To investigate the mechanism by which formononetin (FN) inhibits mitochondrial dynamic-related protein 1 (DRP1) -NLRP3 axis via intervening the generation of ROS to reduce allergic airway inflammation. Methods In order to establish allergic asthma mouse model, 50 BALB/c mice aged 8 weeks were divided into the control group, model group, FN treatment group and dexamethasone group after ovalbumin (OVA) induction. Airway inflammation and collagen deposition were detected by HampE and Masson staining. Th2 cytokines and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and IgE levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA, ROS in BEAS-2B cells was assessed by DCFH-DA staining, DRP1 expression in lung tissue and BEAS-2B cells was detected by immunohistochemistry and immunofluorescence, and the DRP1-NLRP3 pathway was analyzed by immunoblotting. Results FN treatment could effectively ameliorate the symptoms of asthmatic mouse model, including reducing eosinophil accumulation, airway collagen deposition, decreasing Th2 cytokine and IgE levels, reducing ROS and MDA production, increasing SOD and CAT activities, and regulating DRP1-NLRP3 pathway-related protein expression, thereby relieving inflammation. Conclusion FN ameliorates airway inflammation in asthma by regulating DRP1-NLRP3 pathway.

Field effect transistor(FET)biochemical sensors show great potential in the fields of environmental monitoring,food safety,disease diagnosis and clinical treatment due to their low noise,low power consumption,label-free,easy integration and miniaturization characteristics.Two-dimensional(2D)materials,as a new generation of channel materials for FET biochemical sensors,have atomic-level thickness,high carrier mobility,high specific surface area and tunable bandgap,which can further improve the performance of FET biochemical sensors,extend their application areas,and promote the rapid development of FET biochemical sensors.This review focused on the development and latest progress of 2D material-based FET biochemical sensors,along with the challenges and prospects of 2D material-based FET biochemical sensors,which aimed to provide new device design conceptions and promote the further development of biochemical sensing technology.

Objective To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS).Methods The pretreatment conditions of solid phase extraction(SPE)were op-timized by orthogonal experimental design and the surface water samples were concentrated and ex-tracted by Oasis? HLB and Oasis? MCX SPE columns in series.The extracts were separated by Kine-tex? EVO C18 column,with gradient elution of 0.1%formic acid aqueous solution and 0.1%formic acid methanol solution.Q-TOF-MS'fullscan'and'targeted MS/MS'modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion,prod-uct ion and retention times.Results The 34 emerging contaminants exhibited good linearity in the con-centration range respectively and the correlation coefficients(r)were higher than 0.97.The limit of de-tection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%.The intra-day precision was 0.78%-18.70%.The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected,with a concentration range of 1.93-157.71 ng/L.Conclusion The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Outer membrane vesicles (OMVs) are nanoscale vesicles secreted by Gram-negative bacteria. As a unique bacterial secretion, OMV secretion can help bacteria maintain the outer membrane stability or remove harmful substances. Studies have shown that local separation of outer membrane and peptidoglycan layers led by abnormalities in outer membrane protein function, abnormal structure or excessive accumulation of LPS, and erroneous accumulation of phospholipids in the outer leaflet, which can all lead to bacterial outer membrane protrusion and eventually bud formation of OMVs. Since OMVs are mainly composed of bacterial outer membrane and periplasmic components, the pathogen associated molecular patterns (PAMPs) on their surface can trigger strong immune responses. For example, OMVs can recruit and activate neutrophils, polarize macrophages to secrete large amounts of inflammatory factors. More importantly, OMVs can act as adjuvants to induce dendritic cell (DC) maturation to enhance adaptive immune response in the body. At the same time, OMVs are derived from bacteria, which make it easy to modify. The methods by genetic engineering and others can improve their tumor targeting, give them new functions, or reduce their immunotoxicity, which is conducive to their application in tumor therapy. OMVs not only induce apoptosis or pyroptosis of tumor cells, but also regulate the host immune system, which makes OMVs themselves have a certain killing effect on tumors. In addition, the tendency of neutrophils to inflammatory tumor sites and the formation of neutrophil extracellular traps enable OMVs to target tumor sites, and the suitable size and the characteristic that they are easily taken up by DCs give OMVs a certain lymphatic targeting ability. Therefore, OMVs are often employed as excellent drug or vaccine carriers in tumor therapy. This review mainly discusses the biological mechanism of OMVs, the regulatory effects of OMVs on immune cells, the functional modification strategies of OMVs, and their research progress in tumor therapy.

AIM To study the extraction process,enzymatic properties and practical application of glucuronic hydrolase in Scutellaria baicalensis stems and leaves(sbsl GUS).METHODS With granularity,water consumption,extraction time and extraction frequency as influencing factors,enzymatic activity as an evaluation index,the extraction process was optimized by orthogonal test on the basis of single factor test.The relationship between substrate(baicalin)concentration and enzymolysis rate,after which Vmax and Km were calculated,the effects of pH value,temperature and metal ion on enzymatic activity were investigated,pH stability and heat stability were evaluated.sbsl GUS was adotped in the enzymolysis of baicalin to prepare baicalein,then the effects of pH value,temperature,reaction time,initial substrate concentration and enzyme addition on transfer rate were investigated.RESULTS The optimal extraction process was determined to be 40 mesh for granularity,10 times for water consumption,15 min for extraction time,and 3 times for extraction frequency.The enzymolysis accorded with the kinetics of enzymatic reaction,Km was 0.006 3 mol/L,Vmax was 70.42 μmol/h,the strongest enzymatic activity was found at the pH value of 6.0,temperature of 45℃and metal ion of 100 mmol/L Cu2+,sbsl GUS demonstrated good stability at the ranges of 4.0-7.0 for pH value and 4-30℃for temperature.The optimal preparation process was determined to be 6.0 for pH value,45℃for temperature,more than 12 h for reaction time,67.2 mmol/L for initial substrate concentration,and 1 mL/0.269 mmol baicalin for enzyme addition,the transfer rate was 97.83%.CONCLUSION sbsl GUS enzymolysis exhibits high efficiency and mild condition,which can provide a simple preparation method for obtaining baicalein,and expand the application path of Scutellaria baicalensis stems and leaves.

Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98％in 2014 to 85.01％in 2022(P＜0.001),and HA case infection incidence decreased from 1.21％to 0.83％(P＜0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P＜0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P＜0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.

Objective To explore the impact of contrast agent concentration on the excimer laser's effect on plaque ablation.Methods Using a laser catheter with a diameter of 0.9 mm,we conducted plaque model ablation experiments employing a 308-nanometer xenon chloride excimer laser.During the excimer laser ablation process,five groups were formed based on the injected contrast agent concentrations:a saline group,25%concentration group,50%concentration group,75%concentration group,and 100%concentration group.Optical coherence tomography was utilized to assess the changes in plaque lumen area after excimer laser ablation,evaluating the impact of contrast agent concentration on the excimer laser's ablation efficacy.Simultaneously,a water manometer was used to measure the shockwave pressure generated by the excimer laser in liquids with different contrast agent concentrations,aiming to explore the correlation between the shockwave pressure of the excimer laser and its ablative effect.Results The ablation areas in the 75%concentration group and the 100%concentration group were similar(P＞0.05),both exceeding those in the 50%concentration contrast agent group,25%concentration group,and saline group(all P＜0.001).Specifically,the ablation area in the 50%concentration group was significantly larger than that in the 25%concentration group and saline group(both P＜0.001),while the 25%concentration group was larger than the saline group(P＜0.001).The influence of contrast agent concentration on the shockwave pressure of the excimer laser exhibited a similar trend.Additionally,there was a significant positive correlation between the shockwave pressure generated by the excimer laser and its ablation area(r=0.9987,P＜0.001).Conclusions The intensity of excimer laser ablation on plaque tissue can be modulated by altering the contrast agent concentration.These findings offer guidance for the application of excimer laser in conjunction with contrast agent injection techniques in the treatment of coronary artery disease.

Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.