BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.

Purpose: To investigate the therapeutic potential of eliminating insulin-like growth factor-binding protein 5 (IGFBP5) expression in improving erectile function in mice with cavernous nerve injury (CNI)-induced erectile dysfunction (ED). Materials and Methods: Eight-week-old male C57BL/6 mice were divided into four groups: a sham-operated group and three CNI-induced ED groups. The CNI-induced ED groups were treated with intracavernous injections 3 days before the CNI procedure.These injections included phosphate-buffered saline, scrambled control short hairpin RNA (shRNA), or shRNA targeting mouse IGFBP5 lentiviral particles. One week after CNI, erectile function was evaluated and the penile tissue was then harvested for histological examination and western blot analysis. Additionally, the major pelvic ganglia (MPG) and dorsal root ganglia (DRG) were cultured for ex vivo neurite outgrowth assays. Results: Following CNI, IGFBP5 expression in the cavernous tissues significantly increased, reaching its peak at day 7. First, ablation of IGFBP5 expression promotes neurite sprouting in MPG and DRG when exposed to lipopolysaccharide. Second, ablating IGFBP5 expression in CNI-induced ED mice improved erectile function, likely owing to increased neurovascular contents, including endothelial cells, pericytes, and neuronal processes. Third, ablating IGFBP5 expression in CNI-induced ED mice promoted neurovascular regeneration by increasing cell proliferation, reducing apoptosis, and decreasing Reactive oxygen species production. Finally, western blot analysis demonstrated that IGFBP5 ablation attenuated the JNK/c-Jun signaling pathway, activated the PI3K/AKT signaling pathway, and increased vascular endothelial growth factor and neurotrophic factor expression. Conclusions Ablating IGFBP5 expression enhanced neurovascular regeneration and ultimately improved erectile function in CNI-induced ED mice.

When prostate cancer （PCa） progresses to the metastatic castration-resistant stage， significant challenges arise in clinical treatment. Microtubulin inhibitors have become first-line drugs for the treatment of metastatic castration-resistant PCa due to their unique mechanism of action. Among them， taxanes （e.g. docetaxel and cabazitaxel） remain standard care with proven survival benefits， while other microtubule inhibitors （e.g. vincristine， colchicine） show limited clinical utility due to toxicity. Currently， the clinical approach primarily employs docetaxel-based triple therapy and combined with immune checkpoint inhibitors to improve the prognosis of PCa patients， reverse the immunosuppressive state of the tumor microenvironment， and enhance therapeutic efficacy. Despite the remarkable clinical efficacy of microtubule inhibitors in the treatment of PCa， the emergence of drug resistance has limited their long-term application. To address this issue， researchers have explored new solutions， including the development of novel microtubule inhibitors in combination with ATP-binding cassette subfamily B member 1 inhibitors， the concurrent use of fatty acid synthase inhibitors with microtubule inhibitors， and the development of degraders based on proteolysis-targeting chimeras technology. Future research should focus on target discovery， drug formulation optimization， and personalized approaches to overcome current therapeutic limitations.

Three 2,3-diketoquinoxaline alkaloids were isolated from Heterosmilax yunnanensis Gagnep. Their structures were determined through 1D and 2D NMR, HR-ESI-MS, UV, and IR as 1-[5′-(3″-hydroxy-3″-methyl) glutaryl] ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (1), 1-[2′-(3″-hydroxy-3″-methyl) glutaryl]ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (2), and 1-ribityl-2,3-diketo-1,2,3,4-tetrahydro-6,7-dimethylquinoxaline (3). Compounds 1 and 2 are novel compounds, and 3 was isolated from H. yunnanensis for the first time. The hepatoprotective activity of these three compounds was evaluated, with compound 3 showing promising hepatoprotective activity.

Objective:To evaluate whether index of microcirculatory resistance(IMR)is associated with left ventricular(LV)remodeling in acute anterior ST elevation myocardial infarction(STEMI)pa-tients undergoing primary percutaneous coronary intervention(PPCI).Methods:This was a single-center retrospective cohort study.The patients with first anterior STEMI who received PPCI from January 2014 to August 2017 in Peking University Third Hospital was enrolled.After PPCI,IMR was measured immediately by using pressure/temperature guidewire.The success rate of IMR measurement was 100％.Also we collected some related clinical data from the medical records and laboratory results.Infarct size[assessed as creatine kinase(CK)peak],echocardiography at baseline and 1 year follow-up were as-sessed.LV adverse remodeling(LVAR)was defined as ≥20％increase in LV end-diastolic volume(LVEDV).Results:A total of forty-three patients were enrolled,with an average age of(58.7±12.4)years.The patients were divided into two groups as IMR ≤25 and IMR＞25 by normal values recommen-ded by previous literature.Compared with IMR ≤25 group,IMR＞25 group had a higher percentage of initial thrombolysis in myocardial infraction(TIMI)grade 0(95.7％vs.65.0％,P=0.029),higher serum CK peak value[4 090(383,15 833)vs.1 580(396,5 583),P=0.004].The IMR＞25 group suffered higher rates of ventricular aneurysm(30.4％vs.5.0％,P=0.021).There was no difference in LVEDV[(111.0±18.8)mL vs.(115.0±23.6)mL,P=0.503]between the two groups 1 day after MI,but after 1 year,LVEDV in IMR＞25 group was significantly higher than in IMR≤25 group[(141.5± 33.7)mLvs.(115.9±27.9)mL,P=0.018].The incidence of LVAR was more significant in IMR＞25 group(47.4％vs.11.8％,P=0.024).Binary Logistics regression showed that IMR[B=0.079,exp(B)(95％CI)=1.082(1.018-1.149),P=0.011]and serum triglyceride level[B=1.610,exp(B)(95％CI)=5.005(1.380-18.152),P=0.014]were the predictors of LVAR 1 year after MI.IMR had a good predictive value for LVAR 1 year after MI[area under the curve(AUC)=0.749,P=0.019],IMR＞29 was a good cutoff value with sensitivity 81.8％and specificity 68.0％.Conclusion:Our study elaborates that immediate measurement of IMR after PPCI in patients with STEMI can reflect the microvas-cular function.And IMR could be used as a quantitative biomarker to predict LVAR after STEMI.

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.

A new method for simultaneous determination of 23 kinds of per-and polyfluoroalkyl substances(PFASs)(13 kinds of perfluoro carboxylic acids,4 kinds of perfluoro sulfonic acids,and 6 kinds of new substitutes)in plant leaf tissue by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)using automatic online solid phase extraction(SPE)to remove the matrix interference components in plant crude extracts was developed.The plant leaf samples were extracted twice with 1%formic acid-methanol solution,then evaporated to dry,redissolved with 70%methanol solution,and directly injected for analysis.After 23 kinds of target PFASs were purified automatically by online SPE with a WAX column,the six-way valve was switched to rinse PFASs onto an alkaline mobile phase system-compatible C18 analytical column.Then,the 23 kinds of target PFASs were separated within 16 min by gradient elution using a binary mobile phase system of methanol/water(Containing 0.4%ammonium hydroxide).Tandem mass spectrometry was performed in multiple reaction monitoring(MRM)mode for online detection of various PFASs,and quantification was carried out by internal standard method.The results of the method validation showed that satisfactory average recoveries of 23 kinds of PFASs in plant leaf samples(64.2%-125.5%),precision(relative standard deviations(RSDs)of 0.7%-12.8%),linearity(R2＞0.990),and sensitivity(the detection limits(S/N=3)were in the range of 0.02-0.50 μg/kg)were achieved.Finally,this method was used to detect PFASs in the marine green tide algae(Enteromorpha prolifera)and several tree leaves,and a total of 6 kinds of PFASs were detected,in which PFBA was the main contaminant.Compared with the reported offline SPE methods,the proposed online SPE technique significantly simplified the sample pretreatment process and provided an automatic,simple,and environment-friendly method for the routine monitoring of legacy and emerging PFASs in plant tissues.

The annexins(ANX)family is widely present in the cell membrane,cytoplasm or extracellular matrix.As key tumor regulatory molecules,annexins A(ANX A)family can promote or inhibit invasion and metastasis of breast cancer cells by influencing cell membrane and cytoskeleton formation and participating in signaling pathways.ANX A family also plays a role in the apoptosis of breast cancer cells by regulation of pro-apoptotic proteins and cell cycle independent kinases(CDKs)and related pathways.In addition,ANX A family can also promote therapeutic resistance to a large number of drugs.For instance,ANX A1 enhances triple-negative breast cancer resistance by in-ducing epithelial-mesenchymal transformation.ANX A4 induces resistance by forming ANX A4-Fhit complexes and secretion of exosomes containing ANX A6 promotes paclitaxel resistance in breast cancer cells in a YAP1-dependent manner.So ANX A family may be a new target for breast cancer treatment.

Objective:To investigate the incidence of thyroid dysfunction in patients with chronic kidney disease and analyze the influencing factors.Methods:One hundred and ninety-eight patients with chronic kidney disease who were treated in Chronic Disease Management Department of the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from Apr. 2021 to Apr. 2022 were selected, including 71 patients with abnormal thyroid function and 127 patients with normal thyroid function. The differences in TT3, FT3, TT4, FT4, and TSH between patients with abnormal thyroid function and those with normal thyroid function were analyzed. At the same time, the abnormal thyroid function of patients with different clinical characteristics and the influencing factors were analyzed. The intergroup differences were analyzed using t-test or χ2-test, and the influencing factors were analyzed using logistic regression analysis. Results:In one hundred and ninety-eight patients with chronic kidney disease, thyroid function abnormality occurred in 71 patients (35.86%), including two or more abnormal thyroid function indicators in 35 patients (49.30%). The total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4) and free thyroxine (FT4) in patients with abnormal thyroid function were (1.02 ± 0.29) nmol/mL, (3.03 ± 0.88) pmol/L, (77.93 ± 20.02) nmol/mL and (11.02 ± 1.95) pmol/L respectively, which was significantly lower in patients with normal thyroid function (1.32±0.25) nmol/mL, (4.20±0.92) pmol/L, (93.30±19.28) nmol/mL and (13.54±1.82) pmol/ ( P<0.05), while thyroid stimulating hormone (TSH) was (3.14 ± 0.96) mIU/L, which was significantly higher than that in patients with normal thyroid function (1.84±0.89) mIU/L ( P<0.05). The incidence of thyroid dysfunction in female patients was 50.59% (43/85), It was significantly higher than 24.78% (28/113) of male patients (P <0.05) ; The incidence of thyroid dysfunction in patients aged 60 years was 49.55% (55/111), It was significantly higher than 18.39% (16/87) of the patients aged <60 years ( P<0.05) ; The incidence of thyroid dysfunction in patients with 1-year duration of disease was 71.43% (30/42), It was significantly higher than 25.28% (41/156) of patients with a course of disease <1 year ( P<0.05) ; The incidence of thyroid dysfunction in patients with clinical stage G 4 to 5 was 50.62% (41/81), It was significantly higher than 25.64% (30/117) of patients in G1~3 stages ( P<0.05) ; The incidence of thyroid dysfunction in patients with diabetes was 74.36% (29/39), This was significantly higher than 26.42% (42/159) in patients without diabetes mellitus ( P<0.05). Logistic regression analysis showed that gender, age, course of disease and clinical stage were the influencing factors of thyroid dysfunction in patients with chronic kidney disease ( P<0.05) . Conclusion:A high proportion of patients with chronic kidney disease have abnormal thyroid function, which is affected by the patient's sex, age, course of disease and clinical stage,clinical attention should be paid to targeted intervention to prevent the incidence of thyroid dysfunction in chronic kidney disease population.

BACKGROUND:Dexmedetomidine has the effect of anti-ischemia-reperfusion injury,but the comprehensive and systematic review of its signaling pathway is less. OBJECTIVE:To focus on the review of dexmedetomidine's signaling pathway in the mechanisms of antioxidant stress,inhibition of inflammation,anti-apoptosis,autophagy,and so on. METHODS:The relevant articles on PubMed,CNKI,WanFang,and VIP databases were searched by computer with the key words"ischemia-reperfusion inquiry;dexmedetomidine;signal path;oxidative stress;inflammation;apoptosis"in Chinese and English.After excluding repetitive research and some basic articles with low correlation,57 articles were finally included for review. RESULTS AND CONCLUSION:(1)Dexmedetomidine plays an important role in organ protection through many mechanisms,such as anti-oxidative stress injury,anti-inflammation,anti-apoptosis and autophagy.This involves many pathways,including Nrf2 and its downstream protein antioxidant stress pathway,Toll-like receptor 4 family and nuclear factor-κB-related anti-inflammatory pathway,JAK2/STAT3-related anti-inflammatory pathway,and cholinergic anti-inflammatory pathway,and the cholinergic pathway is the upstream mechanism of many nuclear factor-κB signaling pathways.(2)PI3K/Akt pathway plays different roles according to its activated downstream signals,inhibiting the activation of NLRP3 inflammatory body,activating signal molecules endothelial nitric oxide synthase,mammalian target of rapamycin,and hypoxia-inducible factor 1α to play an anti-inflammatory role,and activate Bad or Bax residues to play an anti-apoptotic role,and PI3K/Akt activates glycogen synthetase kinase-3β.It can also play an anti-inflammatory and anti-apoptotic role.(3)Dexmedetomidine activates SIRT3 to mediate anti-apoptosis and inhibit endoplasmic reticulum stress to produce anti-apoptosis.(4)The detailed review of the anti-ischemia-reperfusion injury signaling pathway of dexmedetomidine can provide a basis for future mechanism research and diagnosis and treatment decisions.