OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs （irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate） in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture （1∶ 1， V/V） containing 0.1% formic acid， liquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to determine the plasma concentration， using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water （containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate） as mobile phase A and acetonitrile （containing 0.1% formic acid） as mobile phase B. The flow rate was 0.6 mL/min， and the column temperature was set at 40 ℃ . The sample size was 10 μL， and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode， and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 （irinotecan）， m/z 360.1→244.1 （capecitabine）， m/z 876.4→308.0 （paclitaxel）， m/z 830.3→304.2 （docetaxel）， m/z 372.1→129.1 （tamoxifen）， m/z 284.1→242.1 （letrozole）， and m/z 455.0→ 308.0 （methotrexate）. A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate were 2-1 000 ng/mL （r＝0.994 3）， 20-10 000 ng/mL （r＝0.997 5）， 2-1 000 ng/mL （r＝0.997 9）， 1-500 ng/mL （r＝0.995 8）， 1-500 ng/mL （r＝0.995 2）， 1-500 ng/mL （r＝0.996 4）， 10-5 000 （r＝0.997 7）， respectively. The quantitative lower limits were 2， 20， 2， 1， 1， 1 and 10 ng/mL； RSDs of intra-assay precision were 0.08%-14.86% （n＝6）. RSDs of inter-batch precision were 1.51%-11.55% （n＝3）， and the accuracies were 89.17%-114.93% （n＝6）. The matrix effects ranged from 89.89%-119.74% （n＝6）. RSDs of the stability tests were 1.98%-14.88% （n＝6）. The results of E-mail：hangpengzhou@163.com clinical application showed， the average plasma concentrations of irinotecan， capecitabine， paclitaxel and docetaxel were 704.09， 909.40， 36.45， 150.43 ng/mL， respectively. The values of the coefficient of variation were 25.24%， 62.65%， 122.69%， and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid， and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.

Objective To investigate the expression of Cyclin F in clear cell renal cell carcinoma (ccRCC), its clinicopathological characteristics, and its effect on the biological behavior of renal cancer cell lines Methods RT-qPCR and Western blot were used to detect the mRNA and protein expression of Cyclin F in fresh ccRCC specimens. Immunohistochemistry assay was performed to detect the expression of Cyclin F protein in 80 paraffin samples. CCK-8 assay, scratch assay, and flow cytometry were conducted to determine the effects of Cyclin F overexpression on the proliferation, migration, and apoptosis of renal cancer cell lines. Results The expression of Cyclin F in cancer tissues was higher than that in adjacent tissues at the mRNA level (P<0.0285). The expression of Cyclin Fprotein in cancer tissues was lower than that in adjacent tissues (P<0.001). The analysis of clinicopathological parameters showed that the low expression of Cyclin F was correlated with WHO/ISUP grade, Ki67 index, and age (P=0.041, 0.047, 0.008,). In vitro experiments confirmed that overexpression of Cyclin F promoted the proliferation (P<0.001) and migratory ability (24 h P=0.003, 48 h P=0.0058) of the RCC 786-O cell line, while inhibiting apoptosis (P=0.0019). Conclusion The low expression of Cyclin F protein in ccRCC tissuesis associated with high ISUP grade, high Ki67 index, oldage, and prognosis of patients.

AIM: To investigate the effect of inhibiting Ca2+/calmodulin-dependent protein kinase Ⅱ(CAMKⅡ)expression in adult retinal pigment epithelial cell line-19(ARPE-19)cells on the migration, invasion, and tube formation of human umbilical vein endothelial cells(HUVECs)in a non-contact co-culture system.METHODS: RNA sequencing was performed on ARPE-19 cells overexpressing CAMKⅡ-δ, and bioinformatics was used to analyze the biological functions of the differentially expressed genes. Transwell inserts was used to construct a non-contact co-culture system of ARPE-19 and HUVECs. The experimental groups included: blank group: only HUVECs were inoculated without ARPE-19 cells; control group: ARPE-19 and HUVECs cells were co-cultured with complete medium; AIP group(CAMKⅡ inhibition group): ARPE-19 cells in AIP(160 nmol/L)were co-cultured with HUVECs in complete medium. The migration, invasion and tube formation abilities of HUVECs were detected. The protein expression levels of CAMKⅡ/AMPK/mTOR/VEGFA were detected by Western blotting.RESULTS:Bioinformatics analysis found that the differentially expressed genes could affect biological processes such as cell growth and death and cell movement. The scratch test and transwell migration test showed that the relative mobility of HUVECs in the AIP group was significantly lower than that in the control group(all P<0.05). However, the invasion and tube formation assay showed that the relative invasion rate and tube formation rate of the AIP group were not significantly different from those of the control group(both P>0.05). Western blotting results showed that the expression levels of CAMKⅡ, P-mTOR, and VEGFA proteins in the AIP group were significantly lower than those in the control group, while the expression level of the P-AMPK protein was significantly higher than that in the control group(all P<0.05).CONCLUSION:In the non-contact co-culture system, inhibition of CAMKⅡ expression in ARPE-19 cells significantly reduced the migration ability of HUVECs, but it cannot change the invasion and tube formation ability, which may be achieved by AMPK/mTOR/VEGFA.

Twelve compounds were isolated from the ethyl acetate fraction of the 80% aqueous ethanol extract of the roots and stems of Dalbergia rimosa Roxb. by silica gel, MCI, Sephadex LH-20 column chromatography, and semi-preparative HPLC. Their structures were identified by spectral analysis such as UV, IR, MS, 1D/2D NMR and by comparison with literature information as dalbergiquinol A (1), dalbergiquinol B (2), R-(-)-3′-hydroxy-2,4,5-trimethoxydalbergiquinol (3), neokhriol A (4), mucronulatol (5), (3R)-7,2′,3′-trihydroxy-4′-methoxy-isoflavane (6), isomucronulatol (7), (3S)-violanone (8), 3′-O-methylviolanone (9), eryvarin M (10), (±)-α,3,4,2′,4′-pentahydroxydihydrochalcone (11) and (-)-butin (12). Compound 1 and 2 are new compounds, and compounds 3-12 were isolated from this plant for the first time. Compounds 1, 2, 4, 6, 8, 11, 12 showed good scavenging effect on DPPH free radical.

The analysis of ammonia nitrogen in real water samples is challenging due to matrix interferences and difficulties for rapid on-site analysis.On the basis of the standard method,i.e.water quality-determination of ammonia nitrogen-salicylic acid spectrophotometry(HJ 536-2009),a simple device for online detecting ammonia nitrogen was developed using a sequential injection analysis(SIA)system in this work.The ammonia nitrogen transformation system,color reaction system,and detection system were built in compatible with the SIA system,respectively.In particular,the detection system was assembled by employing light-emitting diode as the light source,photodiode as the detector,and polyvinylchloride tube as the cuvette,thus significantly reducing the volume,energy consumption and fabricating cost of the detection system.As a result,the accurate analysis of ammonia nitrogen in complex water samples was achieved.A quantitative detection of ammonia nitrogen in water sample was obtained in 12 min,along with linear range extending to 1000 μmol/L,precisions(Relative standard deviation,RSD)of 4.3%(C=10 μmol/L,n=7)and 4.2%(C=500 μmol/L,n=7),and limit of detection(LOD)of 0.65 μmol/L(S/N=3,n=7).The results of interfering experiments showed that the detection of ammonia nitrogen by the developed device was not interfered by the common coexisting ions and components,therefore the environmental water could be directly analyzed,such as reservoir water,domestic sewage,sea water and leachate of waste landfill.The analytical results were consistent with those obtained by the environmental protection standard method(Water quality determination of ammonia nitrogen-salicylic acid spectrophotometry,HJ 536-2009).In addition,the spiking recoveries were in the range of 92.3%-98.1%,further confirming the accuracy and practicality of the developed device.

Gold nanoparticles(AuNPs)present unique physicochemical characteristics,excellent biocom-patibility and ease of surface functionalization,which have become the research hotspots in the field of biosens-ing.This article reviews the synthesis methods,main properties and surface functionalization of AuNPs,as well as the research progress of application in various sensing platforms.

The essence of cirrhosis is the over-repairing reaction of liver tissue damage in the process of chronic liver disease.During repair,the liver parenchyma is gradually replaced by fibrosis tissue,resulting in changes in liver tissue morphology,followed by portal hypertension and other related manifestations.Liver failure are serious disorder of liver functions(synthesis,metabolism,transformation,regeneration,etc.)caused by various factors,often mainly manifested as jaundice,coagulation disfunction,hepatic encephalopathy,ascites,etc.The naming and typing of the two are different,and they can exist independently of each other or intersect with each other.In recent years,with the in-depth exploration of cirrhosis and liver failure,many new definitions and classification methods have been put forward in the research.However,due to the confusion of classification methods,there is still a lack of summary,so this article briefly reviews the current progress of clinical classification of liver cirrhosis and liver failure and their differences and intersections.

ObjectiveTo analyze the spectrum distribution characteristics of high-intensity productive noise in key industries in Guangdong Province. Methods A total of 2 806 enterprises in 21 prefecture-level cities in Guangdong Province were selected as the study subjects using the stratified sampling method. On-site investigations were conducted in workplaces. Noise in workplaces and work-sites, and the noise spectrum of the workplaces with sound pressure level ≥85.0 dB(A) were detected. Results The noise of a total of 23 076 workplaces and 20 969 work sites from 30 key industries were monitored. The median (M) and 25th and 75th percentiles (P₂₅, P₇₅) of workplace sound pressure level were 82.3 (78.6, 86.5) dB(A). The rate of the noise exceeded national standard was 30.4%. The sound pressure level M (P₂₅, P₇₅) of work-site was 78.6 (70.0, 83.5) dB(A). The rate of the noise exceeded national standard was 18.0%. Workplace noise and work site noise were positively correlated (Spearman correlation coefficient=0.86, P<0.01). The rate of the noise exceeded national standard was 46.5% in key work sites where the rate of noise exceeded the national standard was ≥25.0%, and corresponding rate of the workplace noise exceeded national standard was 58.1%. The noise spectrum result of 5 636 workplaces sound pressure level>85.0 dB(A) showed that most of the noise source was from grinding machines (441 cases), and the highest average sound pressure level of noise source was from screening machines [93.0 dB(A)]. Cluster analysis results showed that the main noise sources could be divided into three categories, including wideband noise with levels >80.0 dB in all frequency bands except 8 000.0 Hz, medium-high-frequency noise with the highest sound pressure level at 1 000.0, 2 000.0, and 4 000.0 Hz and low frequencies <75.0 dB, and medium-low-frequency noise below 500.0 Hz with sound pressure level >85.0 dB. Conclusion The rate of the noise exceeded national standard in workplace of key industries in Guangdong Province is high, involving a wide range of industries, with high sound pressure levels and obvious spectrum characteristics of corresponding noise sources. Corresponding noise control strategies can be formulated based on different spectrum characteristics and magnitudes.

Objective To investigate the expression levels of CXCL10 and CXCL12 in gallbladder carcinoma and their mechanism of action in tumor invasion.Methods Tumor tissue samples and adjacent tissue samples were collected from 56 patients with gallbladder carcinoma who underwent surgical resection in General Hospital of Central Theater Command from April 2020 to April 2023.RT-PCR was used to measure the mRNA expression levels of CXCL10 and CXCL12 in cancerous tissue and adjacent tissue,and the correlation of the mRNA expression levels of CXCL10 and CXCL12 in cancerous tissue with clinicopathological parameters was analyzed.The human gallbladder carcinoma cell line GBC-SD was used to construct gallbladder carcinoma cells with low expression of CXCL10 and CXCL12.CCK8 assay was used to observe the effect of low expression of CXCL10 and CXCL12 on the proliferation of gallbladder carcinoma cells,Transwell assay was used to observe the effect of low expression of CXCL10 and CXCL12 on the invasion ability of gallbladder carcinoma cells,and Western blot was used to measure the expression of the PI3K/Akt pathway in gallbladder carcinoma cells.The paired t-test or independent-samples t-test was used for comparison of measurement data between two groups;an analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results In the patients with gallbladder carcinoma,the relative mRNA expression levels of CXCL10 and CXCL12 in cancerous tissue were significantly higher than those in adjacent tissue(CXCL10:1.857±0.315 vs 1.024±0.203,t=16.342,P<0.05;CXCL12:2.038±0.374 vs 1.064±0.221,t=16.778,P<0.05).There were significant differences in the relative mRNA expression levels of CXCL10 and CXCL12 between the patients with different TNM stages,presence or absence of lymph node metastasis or distant metastasis,and tumor diameters(all P<0.05).Compared with the control group and the si-RNA group,the si-CXCL10 group had significantly lower relative mRNA and protein expression levels of CXCL10 and CXCL12,CCK-8 absorbance values,number of cell migration,and protein expression levels of p-PI3K and p-Akt(all P<0.05).Conclusion There are increases in the expression of CXCL10 and CXCL12 in gallbladder carcinoma tissue,and the proliferation and invasion of gallbladder carcinoma cells are significantly inhibited after inhibition of the expression of CXCL10 and CXCL12,which might be associated with the inhibition of the phosphorylation of the PI3K/Akt pathway.

Objective To investigate the correlation between tongue and pulse indicators and the out-come of live birth in patients undergoing frozen-thawed embryo transfer(FET),as well as the association between these indicators and patients'endocrine parameters. Methods This study was conducted at Reproductive Medicine Center,Shuguang Hospital Af-filiated to Shanghai University of Traditional Chinese Medicine,Shanghai,China,from March 8,2021 to January 5,2022.Patients undergoing FET were divided into live birth and non-live birth groups according to their live birth outcome.The differences between the endocrine pa-rameters[basic follicle stimulating hormone(b FSH),basic luteinizing hormone(b LH),basic estradiol(b E2),basic progesterone(b P),basal endometrial thickness,follicle stimulating hormone(FSH)on endometrial transition day,luteinizing hormone(LH)on endometrial transition day,estradiol(E2)on endometrial transition day,progesterone(P)on endometrial transition day,and endometrial thickness on endometrial transition day]and the tongue and pulse indicators[tongue body(TB)-L,TB-a,TB-b,tongue coating(TC)-L,TC-a,TC-b,perAll,perPart,h1,h4,h5,t1,h1/t1,and h4/h1]of patients in the two groups were analyzed,with the correlation between these variables analyzed as well using Spearman's correlation coefficient.Multivariate logistic regression was employed to identify the influential factors in the live birth prediction models across various datasets,including Model 1 consisting of endocrine indica-tors only,Model 2 solely consisting of tongue and pulse indicators,and Model 3 consisting of both tongue,pulse,and endocrine indicators,as well as to evaluate efficacy of the models de-rived from different datasets. Results This study included 78 patients in live birth group and 144 patients in non-live birth group.Compared with non-live birth group,live birth group exhibited higher levels of TB-L(P=0.01)and TB-a(P=0.04),while demonstrated lower levels of b FSH(P=0.01),perAll(P=0.04),and h4/h1(P=0.03).The Spearman's correlation coefficient analysis revealed statisti-cally significant correlation(P<0.05)between TB-L,TB-b,TC-L,TC-b,perAll,perPart,h4,h5,t1,h1/t1 and b FSH,b LH,basal endometrial thickness,LH on endometrial transition day,E2 on endometrial transition day,P on endometrial transition day,and endometrial thickness on endometrial transition day in live birth group.The multivariate logistic regression analysis showed that the prediction Model 3 for live birth outcome[area under the curve(AUC):0.917,95%confidence interval(CI):0.863-0.971,P<0.001]surpassed the Model 1(AUC:0.698,95%CI:0.593-0.803,P=0.001),or the Model 2(AUC:0.790,95%CI:0.699-0.880,P<0.001).The regression equations for the live birth outcomes,integrating tongue and pulse indicators with endocrine parameters,included the following measures:FSH on endometrial transition day[odds ratio(OR):0.523,P=0.025],LH on endometrial transition day(OR:1.277,P=0.029),TB-L(OR:2.401,P=0.001),perPart(OR:1.018,P=0.013),h1(OR:0.065,P=0.021),t1(OR:4.354,P=0.024),and h4/h1(OR:0.018,P=0.016). Conclusion In infertility patients undergoing FET,there exists a correlation between tongue and pulse indicators and endocrine parameters.The corporation of tongue and pulse indica-tors significantly improved the predictive capability of the model for live birth outcomes.Specifically,tongue and pulse indicators such as TB-L,perPart,h1,t1,and h4/h1 exhibited a discernible correlation with the ultimate live birth outcomes.