Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear. Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship. Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv). Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv_2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnv_OHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P₅₀), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P₇₅) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group. Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

BACKGROUND: Durvalumab after chemoradiotherapy (CRT) failed to bring survival benefits to patients with epidermal growth factor receptor ( EGFR ) mutations in PACIFIC study (evaluating durvalumab in patients with stage III, unresectable NSCLC who did not have disease progression after concurrent chemoradiotherapy). We aimed to explore whether locally advanced inoperable patients with EGFR mutations benefit from tyrosine kinase inhibitors (TKIs) and the optimal treatment regimen. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from inception to December 31, 2022 and performed a meta-analysis based on a Bayesian framework, with progression-free survival (PFS) and overall survival (OS) as the primary endpoints. RESULTS: A total of 1156 patients were identified in 16 studies that included 6 treatment measures, including CRT, CRT followed by durvalumab (CRT-Durva), TKI monotherapy, radiotherapy combined with TKI (RT-TKI), CRT combined with TKI (CRT-TKI), and TKI combined with durvalumab (TKI-Durva). The PFS of patients treated with TKI-containing regimens was significantly longer than that of patients treated with TKI-free regimens (hazard ratio [HR] = 0.37, 95% confidence interval [CI], 0.20-0.66). The PFS of TKI monotherapy was significantly longer than that of CRT (HR = 0.66, 95% CI, 0.50-0.87) but shorter than RT-TKI (HR = 1.78, 95% CI, 1.17-2.67). Furthermore, the PFS of RT-TKI or CRT-TKI were both significantly longer than that of CRT or CRT-Durva. RT-TKI ranked first in the Bayesian ranking, with the longest OS (60.8 months, 95% CI = 37.2-84.3 months) and the longest PFS (21.5 months, 95% CI, 15.4-27.5 months) in integrated analysis. CONCLUSIONS: For unresectable stage III EGFR mutant NSCLC, RT and TKI are both essential. Based on the current evidence, RT-TKI brings a superior survival advantage, while CRT-TKI needs further estimation. Large randomized clinical trials are urgently needed to explore the appropriate application sequences of TKI, radiotherapy, and chemotherapy. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022298490.
Humans ; Carcinoma, Non-Small-Cell Lung/therapy* ; ErbB Receptors/genetics* ; Lung Neoplasms/drug therapy* ; Mutation/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Chemoradiotherapy ; Antibodies, Monoclonal/therapeutic use*

BACKGROUND: It is inaccurate to reflect the level of dust exposure through working years. Furthermore, identifying a predictive indicator for lung function decline is significant for coal miners. The study aimed to explored whether club cell secretory protein (CC16) levels can reflect early lung function changes. METHODS: The cumulative respiratory dust exposure (CDE) levels of 1,461 coal miners were retrospectively assessed by constructed a job-exposure matrix to replace working years. Important factors affecting lung function and CC16 were selected by establishing random forest models. Subsequently, the potential of CC16 to reflect lung injury was explored from multiple perspectives. First, restricted cubic spline (RCS) models were used to compare the trends of changes in lung function indicators and plasma CC16 levels after dust exposure. Then mediating analysis was performed to investigate the role of CC16 in the association between dust exposure and lung function decline. Finally, the association between baseline CC16 levels and follow-up lung function was explored. RESULTS: The median CDE were 35.13 mg/m³-years. RCS models revealed a rapid decline in forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), and their percentages of predicted values when CDE exceeded 25 mg/m³-years. The dust exposure level (<5 mg/m³-years) causing significant changes in CC16 was much lower than the level (25 mg/m³-years) that caused changes in lung function indicators. CC16 mediated 11.1% to 26.0% of dust-related lung function decline. Additionally, workers with low baseline CC16 levels experienced greater reductions in lung function in the future. CONCLUSIONS CC16 levels are more sensitive than lung indicators in reflecting early lung function injury and plays mediating role in lung function decline induced by dust exposure. Low baseline CC16 levels predict poor future lung function.
Uteroglobin/blood* ; Humans ; Dust/analysis* ; Occupational Exposure/analysis* ; Male ; Middle Aged ; Adult ; Retrospective Studies ; Lung Injury/chemically induced* ; Coal Mining ; Biomarkers/blood* ; China/epidemiology* ; Air Pollutants, Occupational ; Female

Thyroid carcinoma is closely related to environmental factors. Gene mutations and molecular biological changes of gland tissue caused by environmental changes are important factors inducing thyroid carcinoma. Although the molecular mechanism of thyroid carcinoma has not been fully elucidated,increasingly specific genetic changes and molecular markers for thyroid carcinoma have been discovered with the development of molecular biology techniques. This article reviews the recent progresses on the etiology,specific molecular markers,diagnosis and targeted therapies of thyroid carcinoma,so as to provide theoretical support for the clinical diagnosis and treatment of thyroid carcinoma.

Talents are the main force for the development of traditional Chinese medicine（TCM）， and the construction of TCM talents and the reformation of talent evaluation system are essential to promote the inheritance and innovation of TCM. At present， we are still exploring and developing in the fields of the formulation， implementation and evaluation indicators of TCM talent evaluation system. However， there are shortcomings and difficulties. For instance， insufficient stratification in the evaluation， excessive emphasis on the quantity of achievements， neglecting the quality of the achievements and the actual contribution， imperfect assessment indicators， and the weak characteristics of TCM. Therefore， national ministries and commissions have jointly issued a document requesting to break the four only and set a new standard， in order to promote the construction of a scientific and technological talent evaluation system oriented by innovation value， ability and contribution. For the evaluation of TCM clinical talents， China Association for Science and Technology commissioned China Association of Chinese Medicine to build the China Clinical Cases Library of TCM（CCCL-TCM）， which aims at collecting the most authoritative and representative TCM clinical cases and exploring the advantages of applying clinical cases as masterpiece of achievement in TCM clinical talents evaluation. CCCL-TCM can promote the construction of a talent evaluation system that is more in line with the development characteristics of TCM industry， and to carry out relevant pilot in TCM colleges and institutions across the country in order to promote the reformation of TCM talent evaluation system.

【Objective】 To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). 【Methods】 A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). 【Results】 Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P<0.05) and history of infection within 30 days before transplantation (OR 3.37, 95% CI 1.59-7.17, P<0.05) may be independent risk factors for CRE intestinal colonization. Of the 95 CRE strains, the top five species were carbapenem-resistant Klebsiella pneumoniae (38/95, 40.0%), carbapenem-resistant Escherichia coli (29/95, 30.5%), carbapenem-resistant Enterobacter cloacae (13/95, 13.6%), carbapenem-resistant Klebsiella acidophilus (6/95, 6.3%) and carbapenem-resistant Proteus mirabilis (3/95, 3.1%). The incidence of post-transplant BSI was 12.0% (29/241) in the CRE-colonized group and 3.3% (8/241) in the non-colonized group. In the colonization group, 100% of the pathogens of BSI were identical with those of CRE colonization. 【Conclusion】 Bacterial culture of anal swab during haplo-HSCT is helpful for detection of CRE colonization in intestinal tract, which provides some clinical basis for active monitoring of key flora, prevention and control of infection.

{L-End}Objective To study and develop a suitable scale to identify and assess risks of occupational stress in workplaces of enterprises, and to explore the establishment of a workplace occupational stress risk assessment method aimed at guiding enterprises to improve working conditions based on the electronics industry in Beijing City. {L-End}Methods The initial version of the Workplace Occupational Stress Risk Assessment Scale (WOSRAS) was constructed based on literature review and expert evaluation. A total of 1 284 employees from four electronics enterprises in Beijing City were selected as the research subjects using a convenient sampling method. Item analysis and exploratory factor analysis were used to determine the final items of the scale and test its reliability and validity. The method of percentile norms was used to establish risk assessment method for the electronics industry workplace and its stress sources, and the cut-off values of low, medium, high risk was graded by the 50th and 80th percentiles of the total score and the score of each dimension of the risk assessment scale. {L-End}Results i) Based on item analysis and exploratory factor analysis, a WOSRAS consisting of six dimensions and 23 items was constructed, which could explain 63.2% of the total variation of occupational stress. The results of confirmatory factor analysis showed that the root mean square error of approximation and standardized root mean square residual were both <0.080, and the comparative fit index and Tucker-Lewis index were both >0.900. The total criterion validity of the scale was 0.816. The total Cronbach's α coefficient of the scale was 0.835, and the Spearman-Brown coefficient was 0.802. ii) The cut-off values of WOSRAS scores for high, medium and low risk in electronics industry were <53.0, 53.0-60.0 and >60.0,respectively. According to the result, the workplace stress risk levels of the production, research and development, and logistics departments of the electronics industry in Beijing were medium risk, while the management department was low risk. {L-End}Conclusion The WOSRAS constructed in this study has good reliability and validity. The proposed risk assessment method can reflect the actual risk status of enterprises in the electronic industry and is convenient for widespread application.

Objective:To explore the clinical correlation between peripheral blood basophil levels and chronic sinusitis （CRS） subtypes. Methods:One hundred and twenty-six patients with CRS and 103 healthy cases from physical examination admitted to the First Affiliated Hospital of Soochow University from January 2021 to October 2022 were retrospectively analyzed. According to the histopathological classification, CRS patients were divided into eosinophilic chronic sinusitis （eCRS） group （47 cases） and non eosinophilic chronic sinusitis （non-eCRS） group （79 cases）. The differences among the three groups in peripheral blood inflammation cell counts, eosinophils-to-basophils ratio（bEBR）, basophils-to-neutrophils ratio（BNR）, basophils-to-lymphocytes ratio（BLR）, basophils-to-monocytes ratio（BMR） were compared, and study the correlation between each index and Lund-Mackay score, and the correlation between basophils in peripheral blood and other inflammatory cells. Results:The counts of basophils in the peripheral blood of the healthy control group, eCRS group and non-eCRS group were 0.03±0.01, 0.04±0.02, 0.03±0.02, respectively, the eosinophils-to-basophils ratio（bEBR） were 5.64±4.22, 8.38±5.95, 4.55±3.90, the basophils-to-neutrophils ratio（BNR） were 0.01±0, 0.01±0.01, 0.01±0.01, and the basophils-to-lymphocytes ratio（BLR） were 0.01±0.01, 0.02±0.01, and 0.02±0.01, respectively, the basophils-to-monocytes ratio（BMR） were 0.08±0.04, 0.11±0.06, and 0.08 ±0.04 respectively. There was a statistically significant difference between eCRS group and healthy control group, non-eCRS group（P<0.01）, while there was no statistically significant difference between non-eCRS group and healthy control group（P>0.05）. Basophil counts （r=0.185 5, P<0.05）, BLR（r=0.226 9, P<0.05）, BMR（r=0.228 1, P<0.01） in patients with CRS were positively correlated with Lund Makey score. In addition, basophils were also positively correlated with eosinophils（r=0.479 2, P<0.01）, lymphocytes（r=0.259 4, P<0.01）, and monocytes（r=0.256 4, P<0.01） in patients with CRS. Conclusion:The peripheral blood basophil count, BLR and BMR were significantly increased in eCRS, and were significantly positively correlated with Lund -Makey score. It has the potential to develop into disease biomarkers and new therapeutic targets of eCRS.
Humans ; Basophils ; Retrospective Studies ; Rhinitis/surgery* ; Eosinophils ; Sinusitis/surgery* ; Chronic Disease ; Nasal Polyps/pathology*

OBJECTIVE To analyze the difference between the payment limitations of anti-cancer drugs and application scope of drug instructions， so as to better implement the payment policy of medical insurance drugs. METHODS The differences between the payment limitations of anti-cancer drugs and application scope of drug instructions in the National Catalogue of Drugs for Basic Medical Insurance， Industrial Injury Insurance and Maternity Insurance （2022） were compared and analyzed； the evidence-based basis of the difference was discussed， and the scope of limited payment was interpreted. RESULTS Totally 118 drugs had payment limitations； limitations scope mainly included limited evidence of gene detection results， limited indications， limited second-line and above treatment， limited payment duration， limited specialist prescription， limited medical institution grade， etc. Among them， 43 drugs had differences between the payment limitations and drug instructions， and the indications of 31 drugs were greater than payment limitations； for seven drugs， the drug indications beyond the payment limitations were recommended by the guidelines. The payment limitations of 75 drugs were consistent with drug instructions. The second-line and multi-line treatment was ineffective or intolerable with first-line drugs. There was a certain relationship between locally advanced， advanced or metastatic tumor and tumor stage， but different tumors had different criteria. Systemic treatment mainly referred to systemic treatment with drug. The results of limited genetic test required that the result was positive or negative. In addition， six kinds of TCM injections were limited to the level of medical institutions； the payment of two drugs did not exceed 12 months； when lenalidomide was combined with isazomide citrate， the medical insurance only paid for one of the drugs. CONCLUSIONS The payment limitations of some anti- cancer drugs are inconsistent with the drug indications. The drug payment limitations should be expanded according to the actual situation of clinical medication and the recommendations of guidelines. At the same time， the payment limitations should be formulated accurately and in detail， thus clinical and medical insurance staff can understand it and fully protect the interests of patients.

Objective:To investigate whether silencing signal transducer and activator of transcription 6 (STAT6) with siRNA can inhibit eosinophilic inflammation of sinonasal mucosa in a mouse model of eosinophilic chronic rhinosinusitis (ECRS).Methods:The study was conducted from March to September in 2022. Forty-eight female BALB/c mice were randomly divided into four groups: the control group, the Vehicle (transfection reagent)-treated group, the Scramble siRNA (Control siRNA)-treated group, and the STAT6 siRNA-treated group, with twelve mice in each group. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was established. SiRNA prepared in Lipofectamine was locally administered to the nasal cavity. After administration, samples of the peripheral blood and sinonasal mucosa were collected. Eosinophils in peripheral blood were detected by hematology analyzer. Total and OVA-specific IgE (OVA-sIgE) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Mucosal levels of cytokines and chemokines, including interleukin (IL)-5, IL-17A, interferon-γ (IFN-γ) and eotaxin-1, were also measured using ELISA. Mucosal histological changes of eosinophil infiltration were examined using hematoxylin, and eosin staining, and tissue eosinophil count was performed using a microscope under a high-power field (HPF). Tissue expression of STAT6 and phosphorylated STAT6 (p-STAT6) was detected with the western blot method. Immunofluorescence staining was used to localize the expression of p-STAT6 in sinonasal mucosa. Statistical analysis was conducted using SPSS 18.0 software.Results:Peripheral blood eosinophil count, percentage of peripheral blood eosinophil, total serum IgE level, and serum OVA-sIgE level in the STAT6 siRNA-treated group [(0.318±0.045)×10 3/μl, (3.667±0.479)%, (102.070±13.205) ng/ml, and (38.870±7.352) ng/ml] were significantly different from those of the Vehicle-treated group [(0.532±0.049)×10 3/μl, (6.710±1.061)%, (203.102±29.653) ng/ml, and (74.575±6.432) ng/ml, Z value was -2.56, -2.24, -2.40, and -2.56, respectively, all P<0.05] and Scramble siRNA-treated group [(0.493±0.036)×10 3/μl, (5.858±0.872)%, (189.964±30.042) ng/ml, and (80.935±8.358) ng/ml, Z value was -2.17, -2.08, -2.24, and -2.72, respectively, all P<0.05]. Besides, IL-5 and eotaxin-1 levels in the STAT6 siRNA-treated group [(312.279±34.281) pg/ml and (25.297±4.323) pg/ml] were significantly lower than those in the Vehicle-treated group [(689.667±31.905) pg/ml and (68.278±6.485) pg/ml, Z value was -2.73 and -2.88, respectively, both P<0.01] and Scramble siRNA-treated group [(661.783±42.094) pg/ml and (63.015±7.416) pg/ml, Z value was -2.72 and -2.81, respectively, both P<0.01]. Tissue eosinophil count in sinonasal mucosa was (29.132±4.163)/HPF in the STAT6 siRNA-treated group, and were significantly less than those in the Vehicle-treated group [(78.050±7.912)/HPF, Z=-2.88, P<0.01] and Scramble siRNA-treated group [(73.864±8.671)/HPF, Z=-2.72, P<0.01]. The expression level of STAT6 protein (0.105±0.021) was significantly decreased in the mice treated with STAT6 siRNA compared with PBS, Vehicle, and Scramble siRNA (0.232±0.037, 0.243±0.039, and 0.228±0.032, Z value was -2.25, -2.49, and -2.56, respectively, all P<0.05). Corresponding, p-STAT6 protein level (0.292±0.038) was markedly decreased by the introduction of STAT6 siRNA, the difference was statistically significant as compared with the Vehicle-and Scramble siRNA-treated groups (0.613±0.046 and 0.641±0.050, Z value was -2.81 and -2.88, respectively, both P<0.01). Immunofluorescence staining showed that p-STAT6 was mainly located in the nucleus of nasal epithelial cells and inflammatory cells. The green fluorescence of p-STAT6 expression in sinonasal mucosa in the STAT6 siRNA-treated group was weaker than that in the Vehicle-and Scramble siRNA-treated groups. Conclusion:Intranasal administration of STAT6 siRNA can significantly downregulate STAT6 expression, decrease p-STAT6 level, and prohibit the development of Th2-skewed ECRS.