Objective:To establish a method for the determination of eight N-nitrosamines (N-nitrosodimethylamine, N-nitrosodimethylamine, N-nitrosomethylmethylamine, N-nitrosodibutylamine, N-nitrosopropylamine, N-nitrosomorpholine, N-nitrosodianiline and N-nitrosopiperidine) in the air of workplace by gas chromatography-tandem mass spectrometry (GC-MS/MS) .Methods:From January to August 2023, eight N-nitrosamines in the air of workplace were collected by ThermoSorb/N column, eluted with 4 ml methanol-dichloromethane (1∶1 volume ratio), separated by VF-624 ms capillary column, detected by multiple reaction monitoring mode and quantified by external standard method. The detection limit and precision of the method were also analyzed.Results:The linear range of the method for the determination of eight N-nitrosamines was 1.0-20.0 μg/L, the correlation coefficient was 0.9993-0.9999, the detection limit was 0.051-0.132 μg/L, and the minimum quantitative concentration was 0.030-0.078 μg/m 3 (calculated by collecting 22.5 L of air sample and eluting with 4.0 ml stripping liquid). The within-run precisions were 2.05%-6.89% and the between-run precisions were 2.41%-8.26%. The desorption rates were 67.20%-102.60%. The sample can be kept at least 7 days at 4 ℃. Conclusion:GC-MS/MS method for the determination of eight N-nitrosamines in workplace air has high sensitivity and good precision, and can accurately determine the content of eight N-nitrosamines in workplace air.

This paper takes the teaching of pathogeny biology and clinical laboratory diagnostics for postgraduates in Shandong Second Medical University as examples. By constructing innovative thinking in scientific research, training research innovation skills, and establishing modular, multi-evaluation systems, a comprehensive training mode for scientific research and innovation ability of medical academic postgraduate students had been proposed, and the implementation and effects of this training mode were thoroughly explored. This mode is expected to bring a positive impact on the training of medical postgraduate students and improve their scientific research and innovation ability, thereby promoting the cultivation of more medical talents with a high degree of scientific research and innovation ability.

Objective:To establish a method for the determination of eight N-nitrosamines (N-nitrosodimethylamine, N-nitrosodimethylamine, N-nitrosomethylmethylamine, N-nitrosodibutylamine, N-nitrosopropylamine, N-nitrosomorpholine, N-nitrosodianiline and N-nitrosopiperidine) in the air of workplace by gas chromatography-tandem mass spectrometry (GC-MS/MS) .Methods:From January to August 2023, eight N-nitrosamines in the air of workplace were collected by ThermoSorb/N column, eluted with 4 ml methanol-dichloromethane (1∶1 volume ratio), separated by VF-624 ms capillary column, detected by multiple reaction monitoring mode and quantified by external standard method. The detection limit and precision of the method were also analyzed.Results:The linear range of the method for the determination of eight N-nitrosamines was 1.0-20.0 μg/L, the correlation coefficient was 0.9993-0.9999, the detection limit was 0.051-0.132 μg/L, and the minimum quantitative concentration was 0.030-0.078 μg/m 3 (calculated by collecting 22.5 L of air sample and eluting with 4.0 ml stripping liquid). The within-run precisions were 2.05%-6.89% and the between-run precisions were 2.41%-8.26%. The desorption rates were 67.20%-102.60%. The sample can be kept at least 7 days at 4 ℃. Conclusion:GC-MS/MS method for the determination of eight N-nitrosamines in workplace air has high sensitivity and good precision, and can accurately determine the content of eight N-nitrosamines in workplace air.

Objective:To investigate the relationship between Golgi membrane protein 1 (GOLM1) expression and the sensitivity of estrogen receptor (ER) positive breast cancer to endocrine therapy.Methods:Tamoxifen (TAM) -resistant ER-positive breast cancer cells were established, and the expression of GOLM1 in these cells was detected. The expression level of GOLM1 in the cells was regulated, and the effects of GOLM1 expression on cell proliferation and colony formation were detected by MTT and colony formation assay, respectively. Western blot was used to detect the effect of GOLM1 expression on the expression of drug resistance proteins P-gp and MRP1. Breast cancer patients recruited for endocrine therapy and patients without endocrine therapy were divided into high GOLM1 expression group and low GOLM1 expression group, and the effect of GOLM1 expression level on the survival rate of the two groups of patients was observed.Results:Colony formation assay showed that after TAM treatment, the colony formation ability of TAM-resistant MCF-7 cells was significantly higher than that of TAM-sensitive McF-7 cells (all P<0.05). The expression level of GOLM1 in MCF-7R cells (2.31±0.18) was higher than that in MCF-7 cells (1±0.10) ( t=11.02, P<0.001). Knockdown of GOLM1 in MCF-7R cells decreased the cell proliferation and colony formation ability, and the expression of drug resistance proteins P-gp and MRP1 also decreased (all P<0.05). The survival rate of patients with high GOLM1 expression was lower than that of patients with low GOLM1 expression after endocrine therapy ( χ2=5.45, P=0.020). In patients without endocrine therapy, there was no significant difference in survival between patients with high and low GOLM1 expression ( χ2=1.49, P=0.223) . Conclusion:High expression of GOLM1 is significantly associated with decreased sensitivity to endocrine therapy in ER-positive breast cancer patients.

Objective:To develop a method for the analysis of phenylglyoxylic acid (PGA) and mandelic acid (MA) in urine by ultra-high performance liquid chromatography tandem mass spectrometry.Methods:The study was conducted in April 2022. Urine samples were directly diluted with the initial mobile phase, separated by Waters HSS T3 column after passing through the membrane, and analyzed under negative ionization mode (ESI -) and multiple reaction monitoring (MRM) conditions, the contents of PGA and MA in human urine were quantitatively determined by external standard method. Results:The determination of PGA and MA showed a good linear relationship within the range of 10-1000 ng/ml, with a correlation coefficient of 0.9999. The linear regression equation of PGA was y=1141.4 x+2157.3, the detection limit and lower limit of quantification of the method were 0.081 ng/ml and 0.269 ng/ml, and the recovery rate was 90.47%-99.83%. The linear regression equation of MA was y=62.8 x+140.3, the detection limit and lower limit of quantification of the method were 0.551 ng/ml and 1.836 ng/ml, and the recovery rate was 92.75%-101.09%. The intra and inter batch precision of PGA and MA were both<5%. Conclusion:An ultra-high performance liquid chromatography tandem mass spectrometry method for the analysis of PGA and MA in urine was established.The sample pretreatment operation is simple, and the accuracy and precision of the method meet the standard requirements. It can be used for monitoring and evaluating PGA and MA in urine of the general population and occupational contact population.

Objective:To establish a method for determination of acetone in urine by headspace gas chromatography-mass spectrometry.Methods:From March to June 2021, the 3.0 ml urine sample was placed in a headspace bottle with 4.0 g of anhydrous sodium sulfate and sealed. Equilibration time was 30 min at 85 ℃. The separation was carried out on a DB-5MS column. The urine sample was detected by mass spectrometry and quantified by external standard method.Results:The method for the determination of acetone in urine by headspace gas chromatography-mass spectrometry had good linearity in the range of 51.2-1024.0 μg/L, and the correlation coefficient was 0.9995. The detection limit and the lower limit of quantification of acetone were 16.4 μg/L and 54.6 μg/L. The average recoveries of samples ranged from 94.9% to 96.8%. The intra-assay precision and inter-assay precision were both less than 10%. Samples can be stored at least 7 d at 4 ℃ or -20 ℃.Conclusion:This method has simple sample preparation and high sensitivity. It can be used for monitoring and evaluation of urinary acetone in the general population and occupationally exposed populations.

Objective:To develop a method for the analysis of phenylglyoxylic acid (PGA) and mandelic acid (MA) in urine by ultra-high performance liquid chromatography tandem mass spectrometry.Methods:The study was conducted in April 2022. Urine samples were directly diluted with the initial mobile phase, separated by Waters HSS T3 column after passing through the membrane, and analyzed under negative ionization mode (ESI -) and multiple reaction monitoring (MRM) conditions, the contents of PGA and MA in human urine were quantitatively determined by external standard method. Results:The determination of PGA and MA showed a good linear relationship within the range of 10-1000 ng/ml, with a correlation coefficient of 0.9999. The linear regression equation of PGA was y=1141.4 x+2157.3, the detection limit and lower limit of quantification of the method were 0.081 ng/ml and 0.269 ng/ml, and the recovery rate was 90.47%-99.83%. The linear regression equation of MA was y=62.8 x+140.3, the detection limit and lower limit of quantification of the method were 0.551 ng/ml and 1.836 ng/ml, and the recovery rate was 92.75%-101.09%. The intra and inter batch precision of PGA and MA were both<5%. Conclusion:An ultra-high performance liquid chromatography tandem mass spectrometry method for the analysis of PGA and MA in urine was established.The sample pretreatment operation is simple, and the accuracy and precision of the method meet the standard requirements. It can be used for monitoring and evaluating PGA and MA in urine of the general population and occupational contact population.

Objective:To establish a method for determination of acetone in urine by headspace gas chromatography-mass spectrometry.Methods:From March to June 2021, the 3.0 ml urine sample was placed in a headspace bottle with 4.0 g of anhydrous sodium sulfate and sealed. Equilibration time was 30 min at 85 ℃. The separation was carried out on a DB-5MS column. The urine sample was detected by mass spectrometry and quantified by external standard method.Results:The method for the determination of acetone in urine by headspace gas chromatography-mass spectrometry had good linearity in the range of 51.2-1024.0 μg/L, and the correlation coefficient was 0.9995. The detection limit and the lower limit of quantification of acetone were 16.4 μg/L and 54.6 μg/L. The average recoveries of samples ranged from 94.9% to 96.8%. The intra-assay precision and inter-assay precision were both less than 10%. Samples can be stored at least 7 d at 4 ℃ or -20 ℃.Conclusion:This method has simple sample preparation and high sensitivity. It can be used for monitoring and evaluation of urinary acetone in the general population and occupationally exposed populations.

Objective:To observe the characteristics of macular telangiectasia (MacTel) in multi-color and multi-mode fundus images.Methods:An abservational case series study was conducted.Sixteen eyes of 12 patients diagnosed with MacTel by fluorescein fundus angiography (FFA) from January to November 2019 in Shandong Eye Hospital were analyzed.There were 8 cases (8 eyes) with MacTel type Ⅰ, among which 4 cases were male and 4 cases were female, with an average age of (62.3±12.5) years.The other 4 cases (8 eyes) had MacTel type Ⅱ, all of which were female, with an average age of (58.7±10.5) years.Best corrected visual acuity, slit lamp microscopy, color fundus photography, multicolor scanning laser imaging, FFA, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) were carried out in all the patients.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shandong Eye Institute (No.2019S003).Results:In color fundus images of MacTel type Ⅰ eyes, annular macular exudation with macular edema occurred in 6 eyes, macular edema without hard exudates in 1 eye, and hard macular exudates without macular edema in 1 eye.However, the transparency of retina in temporal fovea in MacTel type Ⅱ eyes decreased, showing a gray color.In multi-color fundus images of MacTel type Ⅰ eyes, punctate granular yellow macular exudation and yellow-green macular edema were observed, which were clearer than those in color fundus images.Punctate exudation was seen in both the blue and green reflectance images, which was clearest in green reflectance image, followed by blue reflectance image and then the infrared reflectance image.In OCT images of MacTel type Ⅰ eyes, cystoid edema of inner retina or uneven reflection signal of outer plexiform retina were observed.Loss of inner and outer retinal structures and cavities were observable in MacTel type Ⅱ eyes, and outer retinal atrophy appeared in 2 eyes.In OCTA images, the destruction of superficial and deep capillary plexus in macular area were observed in both MacTel typeⅠand type Ⅱ eyes, and the destruction of deep capillary plexus was more obvious.In addition, more obviously increased vascular space, decreased vessel density, and increased foveal avascular zone were found in MacTel type Ⅱ eyes.In early stage of FFA, delayed capillary filling near fovea was seen in MacTel typeⅠeyes, and dilated temporal vessels in fovea, some of which showed tumor-like dilation, and the limited tumor-like dilation was enhanced in the later stage.Different degrees of dilated parafoveal blood vessels in the early stage, and the capillary in the temporal side of the macula showing diffuse strong fluorescence in the late stage of FFA was observed in MacTel type Ⅱ eyes.Conclusions:Multi-color scanning laser imaging can be used to observe the morphological characteristics of MacTel, and the imaging features of different types of MacTel are significantly different.

In this paper， the latest research progress on the mechanism of comorbid alcohol use disorder and depressive disorder at home and abroad is elucidated from genetic， neurochemical， neuroendocrine and neuroimmunologic perspectives. It aims to identify the gaps in current research and predict future research directions， providing a further basis for the clinical management of comorbid alcohol use disorder and depressive disorder.