Objective To comapre and analyze the differences and commonalities of expression profiles of serum exosomal microRNA between patients with thyroid nodules and healthy persons at different iodine levels,and then provide evidence for screening early diag-nostic markers of thyroid nodules at different iodine levels.Methods The peripheral blood samples from 10 patients with thyroid nod-ules and healthy volunteers at different iodine levels were collected.Their serum iodine levels were measured by the arsenic cerium cat-alytic spectrophotometry.Serum exosomal microRNA were extracted and the expression levels of microRNA were determined by the high-throughput sequencing technology.The differential target genes were predicted and further performed Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Results Compared with healthy volunteers,there were 6 downreg-ulated miRNAs in the patients with thyroid nodules at different iodine levels,namely miR-324-5p,miR-6511b-3p,miR-9903,miR-550a-3p,miR-5001-3p,and miR-3688-3p.Differentially expressed exosomal microRNA could regulate the MAPK signaling path-way,PI3K-AKT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.Conclusion Six differentially expressed microRNAs is identified,which may serve as biological markers for the early diagnosis of thyroid nodules at different iodine levels.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective:To investigate the arsenic metabolism pattern and possible influencing factors in the population in drinking-water-borne endemic arsenic poisoning (drinking-water-borne arsenic poisoning for short) areas.Methods:In December 2004, a cluster sampling method was used to select arsenic poisoning population (arsenic poisoning group) and healthy population (control group) in drinking-water-borne arsenic poisoning area of Bayannur City, Inner Mongolia Autonomous Region as the survey subjects. A questionnaire survey was conducted. Arsenic content in drinking water at home of survey subjects, the levels of urinary arsenic and its metabolites, including [trivalent arsenic (As Ⅲ), inorganic arsenic (iAs), monomethylarsenic acid (pentavalent, MMA V), dimethylarsenic acid (pentavalent, DMA V), total arsenic (tAs), percentage of inorganic arsenic (iAs%), percentage of monomethylarsenic acid (MMA%), percentage of dimethylarsenic acid (DMA%), primary methylation index (PMI), secondary methylation index (SMI)] were tested using high performance liquid chromatography-inductively coupled plasma mass spectrometry; nail arsenic and nail selenium levels were tested using atomic fluorescence spectrometer. The influencing factors of arsenic metabolism pattern were analyzed by multiple linear regression. Results:A total of 536 survey subjects were included, including 155 individuals in the arsenic poisoning group and 381 in the control group. The water arsenic level ranged from 0.0 to 825.7 μg/L. Compared with the control group, there was no significant difference in the distribution of gender, education level and dental fluorosis in the arsenic poisoning group ( P > 0.05), but there were significant differences in the distribution of age, marital status, smoking, drinking and water arsenic ( P < 0.05). Compared with the control group, the levels of urinary As Ⅲ, iAs, MMA V, DMA V, tAs, MMA%, MMA/DMA and nail arsenic in the arsenic poisoning group were higher ( P < 0.05), while the levels of urinary DMA%, SMI and nail selenium were lower ( P < 0.05); but there was no statistically significant difference in the levels of urinary iAs% and PMI ( P > 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary As Ⅲ (β = - 19.82, - 23.83, 0.61, 0.21, 7.26, 2.98, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary tAs (β = 3.18, 3.25, 1.31, 15.59, P < 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary iAs (β = - 20.47, - 25.90, 0.64, 0.25, 7.87, 3.11, P < 0.05). Age, gender, education level, water arsenic and nail arsenic were the influencing factors of urinary MMA V (β = 0.52, - 17.07, - 21.84, 0.22, 2.77, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary DMA V (β = 2.35, 2.47, 0.85, 9.22, P < 0.05). Conclusions:Compared with healthy individuals, there are differences in arsenic metabolism pattern among individuals with drinking-water-borne arsenic poisoning. Age, gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic may be influencing factors of different arsenic metabolism patterns.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

The rare-earth-elements-doped upconversion nanoparticles NaYF4:Yb3+,Er3+were synthesized by solvothermal method,and NaYF4:Yb3+,Er3+@SiO2 were prepared by coating SiO2 on the surface of NaYF4:Yb3+,Er3+by inverse microemulsion method in this work.Based on the fluorescence quenching principle between NaYF4∶Yb3+,Er3+@SiO2 and SQA-Fe3+,a NaYF4∶Yb3+,Er3+@SiO2-SQA-Fe3+fluorescence nanosensor was constructed for detection of trace hydrogen peroxide(H2O2).Under optimal conditions,the linear range of this method for detecting H2O2 was 1.8?84.0 μmol/L,with detection limit(3σ)of 0.47 μmol/L.The recoveries of H2O2 spiked in milk were 98.4%?99.7%.This method could be used for detection of H2O2 residue in milk samples,with advantages such as low detection limit,good stability and strong anti-interference ability.

Infrared spectroscopy technology has many advantages such as high efficiency and non-destructiveness,and has an important research and application value in the field of petroleum pollutant classification and detection.In this study,a petroleum pollutant classification method by combing the discrete wavelet transform(DWT)algorithm and a one-dimensional convolutional neural network based on the Inception module(Inception-1D-CNN)was proposed.Firstly,the DWT algorithm was used to denoise the original infrared spectral data to eliminate the interference information caused by experimental environment,instrument error and manual operation.Then,the inception-1D-CNN model was used to obtain multi-scale infrared spectroscopy feature information,and then classify the petroleum pollutants.Experimental results showed that compared with preprocessing methods such as standard normal variable(SNV),adaptive iteratively reweighted penalized least squares(AirPLS),and Savitzky-Golay smoothing(S-G),the prediction accuracy of the DWT algorithm combined with the 1D-CNN model with a convolutional kernel size of 3×1 was 86.6%,which was 6.6%,6.6%and 3.3%higher,respectively.The prediction accuracy of DWT algorithm combined with 1D-CNN model with a convolutional kernel size of 5×1 was 93.3%,which was 10.0%,7.0%and 3.3%higher,respectively.The prediction accuracy of the DWT algorithm combined with the 1D-CNN model with a convolutional kernel size of 7×1 was 90.0%,which was 6.7%,10.0%and 3.4%higher,respectively.The prediction accuracy of the DWT algorithm combined with the inception-1D-CNN model was 100.0%,which was 10.0%,10.0%and 3.4%higher,respectively.Therefore,the DWT algorithm combined with the inception-1D-CNN model could accurately classify and predict petroleum pollutants,and provided a certain basis for the subsequent treatment of oil spills on the sea surface.

Objective:To observe the effects of Huatan Quyu Decoction on the protein expressions of β-catenin and GSK-3 β and the expression of anticardiolipin antibody and β-amyloid protein related to cognitive function in rats with vascular dementia based on Wnt/β-catenin signal pathway.Methods:A total of 96 male SD rats were divided into blank group, model group, Donepezil hydrochloride group and Huatan Quyu Decoction low-, midium-, high-dosage group according to random number table method, with 16 rats in each group. Except for the blank group, the rat model of vascular dementia was prepared by modified 2-VO method. Huatan Quyu Decoction low-, medium- and high-dosage groups were administrated with Huatan Quyu Decoction 6.1, 12.1 and 24.2 g/kg, respectively; the Western medicine group was administrated with Donepezil hydrochloride 0.5 mg/kg; the blank group and the model group were administrated with the same amount of normal saline for 28 consecutive days. On the 1st, 7th, 14th and 28th day after administration, the learning and memory ability of rats was evaluated by Morris water maze test, the levels of ACA and Aβ in serum were measured by enzyme linked immunosorbent assay (ELISA), and the expressions of β-catenin and GSK-3β proteins related to Wnt/β-catenin signal pathway in hippocampus were measured by Western blot.Results:Compared with model group, the escape latency was shortened in the Huatan Quyu Decoction high-dosage group and Donepezil group on 7 and 14 days of administration ( P<0.05), and the times of crossing the platform increased in Huatan Quyu Decoction high-dosage group on 1 and 28 days of administration ( P<0.05). Compared with model group, the serum ACA level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at day 1, 7, 14 and 28 after administration ( P<0.05). The serum Aβ level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at 7, 14 and 28 days after administration ( P<0.05); On the 14th and 28th days after administration, the levels of ACA and Aβ in TCM low-dosage group decreased ( P<0.05). Compared with model group, the expression of β-catenin protein in hippocampus of Donepezil group and Huatan Quyu Decoction medium- and high-dosage groups increased ( P<0.05), while the expression of GSK-3β in hippocampus of Donepezil group and Huatan Quyu Decoction low-, medium- and high-dosage groups decreased ( P<0.01). Conclusion:Huatan Quyu Decoction can activate the Wnt/β-catenin signaling pathway, up-regulate the expression of β-catenin protein in hippocampal tissue of rats, inhibit the expression of GSK-3β, reduce the levels of ACA and Aβ in serum of rats, and improve the cognitive function of rats with vascular dementia.

Objective:To investigate the relationship between the outcome of skin injury and urinary arsenic methylation metabolism levels in people exposed to arsenic through drinking water.Methods:Using cluster sampling method, permanent residents from drinking-water-borne endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region were selected as survey subjects in 2004 (before water improvement). In 2017 (after water improvement), 74 survey subjects from 2004 were tracked and followed up. Urine samples were collected from survey subjects and high-performance liquid chromatography inductively coupled plasma mass spectrometry was used to detect the levels of arsenic methylation metabolites in urine. According to the "Diagnosis of Endemic Arsenic Poisoning" (WS/T 211-2015), the clinical grading (normal, suspicious, mild, moderate and severe) of skin injury of the survey subjects and the outcome of 2017 (improved, unchanged, aggravated) were assessed. A database was established and SPSS 25.0 software was used for statistical analysis.Results:The clinical grading ratios of skin injuries among survey subjects in 2004 and 2017 were compared, the differences were statistically significant (normal, suspicious, mild, moderate and severe: 38, 18, 4, 14 cases in 2004 and 27, 31, 3, 13 cases in 2017, χ 2 = 53.02, P < 0.001). Compared with 2004, in 2017, the levels of total arsenic (tAs), inorganic arsenic (iAs), monomethylarsenic (MMA), dimethylarsenic (DMA), percentage of inorganic arsenic (iAs%), and ratio of monomethylarsenic to dimethylarsenic (MMA/DMA) in the urine of survey subjects were low, and the differences were statistically significant ( Z = - 8.24, - 9.07, - 7.81, - 8.04, - 8.24, - 3.56, P < 0.001). The levels of dimethylarsenic percentage (DMA%), monomethylation rate (PMI) and dimethylation rate (SMI) were higher, and the differences were statistically significant ( Z = - 6.39, - 8.24, - 3.52, P < 0.001). In 2004, patients with different clinical grading of skin injuries had different outcomes in 2017 (χ 2 = 30.80, P < 0.001). There were statistically significant differences in tAs, iAs, MMA and DMA variation in urine among skin injury patients with different outcomes ( H = 10.62, 9.35, 8.80, 9.13, P < 0.05). Conclusions:Improving water can significantly reduce the levels of tAs, iAs, MMA, and DMA in the urine of arsenic exposed individuals. The outcome of skin injury in individuals exposed to arsenic through drinking water is related to the variation of urinary arsenic methylation metabolites tAs, iAs, MMA, and DMA.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.