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.

ObjectiveTo investigate the mechanism of salvianolic acid F （Sal F） in repairing the high glucose-induced injury in human kidney-2 （HK-2） cells via the B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）/cysteinyl aspartate-specific proteinase 3 （Caspase-3）/gasdermin-E （GSDME） pathway. MethodThe cell counting kit-8 （CCK-8） was used to measure the relative viability of HK-2 cells exposed to high glucose and different concentrations （2.5， 5， 10， 20 μmol·L^-1） of Sal F and the relative viability of HK-2 cells treated with Sal F for different time periods. The levels of lactate dehydrogenase （LDH） and interleukin-1β （IL-1β） in the supernatant of the cell culture were measured by the LDH assay kit and enzyme-linked immunosorbent assay （ELISA） kit， respectively. Flow cytometry combined with Annexin V-FITC/propidium iodide （PI） and Hoechst 33342/PI staining was employed to reveal the proportion of PI-positive HK-2 cells exposed to high glucose. Western blotting was employed to determine the protein levels of Bax， Bcl-2， cytochrome C， cysteinyl aspartate-specific proteinase （Caspase）-9， Caspase-3， and GSDME in the HK-2 cells exposed to high glucose and treated with Sal F. The 2，7-dichlorodihydrofluorescein diacetate fluorescence probe （DCFH-DA） and mitochondrial membrane potential assay kit （JC-1） were used to determine the production of reactive oxygen species （ROS） and the mitochondrial membrane potential in the HK-2 cells exposed to high glucose and treated with Sal F. ResultCompared with the blank group， the model group showed decreased cell viability （P<0.01）， elevated levels LDH and IL-1β， increased proportion of PI-positive cells （P<0.01）， up-regulated protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME （P<0.01）， down-regulated protein level of Bcl-2 （P<0.01）， decreased mitochondrial membrane potential， and excessive ROS accumulation. Compared with the model group， Sal F repaired the high glucose-induced injury in HK-2 cells （P<0.05）， lowered the levels of LDH and IL-1β （P<0.05， P<0.01）， and decreased the proportion of PI-positive cells （P<0.01）. In addition， Sal F down-regulated the protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME and up-regulated the protein level of Bcl-2 （P<0.05， P<0.01）， increased the mitochondrial membrane potential， and decreased the accumulation of ROS in HK-2 cells. ConclusionSal F can reduce the production of ROS， restore the balance of mitochondrial membrane potential， and inhibit pyroptosis via the Bax/Caspase-3/GSDME signaling pathway to repair the high glucose-induced injury in HK-2 cells.

Fibrosis refers to the final outcome of damage in multiple-type tissue and the imbalance of tissue repair especially in the process of chronic inflammatory response diseases.Fibrosis can occur in various organ tissues.Its continuous progression may lead to organ dysfunction and failure,which is a huge threat to human health.Traditional Chinese medicine has significant therapeutic effects in preventing and treating fibrosis.Due to its characteristics of multiple components,pathways,and targets,it has become a hot research topic in the field of fibrosis.Astragali Radix,a Chinese medicinal for supplementing qi,is the root of Astragalus membranaceus(Fisch.)Bge.var.mongholicus Hisao or Astragalus membranaceus(Fisch.)Bge.It has the effects of replenishing qi and elevating yang,generating fluid and nourishing blood,expelling toxin and draining pus,astringing sore and promoting granulation.It has found that Astragali Radix contains many chemical components such as polysaccharides,saponins,and flavonoids,which have good anti-inflammatory and antioxidant effects.Astragali Radix can effectively intervene in the fibrosis process of multiple organ tissues such as the heart,kidney,liver,and lung.Therefore,this article reviews the anti-fibrotic effects and mechanisms of Astragali Radix and its chemical components,hoping to provide ideas and references for the development and utilization of Astragali Radix.

Objective:To explore the effect of scenario simulation combined with "finding fault" teaching method on prevention and control of nosocomial infection training in standardized residency training of cardiovascular surgery.Methods:A total of 31 residents trained in the Department of Cardiovascular Surgery, The First Affiliated Hospital of Naval Medical University from April 2018 to March 2019 were selected as the control group, and another 31 residents trained from April 2019 to March 2020 were selected as the study group. All subjects were required to receive nosocomial infection prevention and control training. The control group was given conventional teaching method, while the study group was given scenario simulation combined with "finding fault" teaching method, all of which were taught for 1 month. The theoretical and operational assessment results of nosocomial infection prevention and control after teaching, the clinical core competence related to nosocomial infection prevention and control after teaching, and the recognition rate of teaching mode were compared between the two groups. SPSS 25.0 was used for t test and chi-square test. Results:The scores of theoretical assessment [(91.29±6.64) vs. (86.73±6.02)] and operational assessment [(90.32±6.80) vs. (83.51±7.43)] of nosocomial infection prevention and control after teaching in the study group were higher than those in the control group, with statistical differences ( P<0.05). The scores of clinical core competence in learning initiative, doctor-patient communication, problem thinking and problem solving of nosocomial infection prevention and control knowledge after teaching in the study group were higher than those in the control group, with statistical differences ( P<0.05). The recognition rates of innovation, interest, effectiveness and practicability of the teaching mode in the study group were 83.87%, 96.77%, 90.32% and 93.55% respectively, while those in the control group were 61.29%, 58.06%, 67.74% and 74.19% respectively, which were higher in the study group than in the control group, with statistically significant differences ( P<0.05). Conclusion:In the training of prevention and control of nosocomial infection for standardized residency training in the department of cardiovascular surgery, scenario simulation combined with "fault finding" teaching method can improve the theoretical and practical examination results of the residents, enhance their clinical core competence related to nosocomial infection prevention and control, and reach a higher recognition rate of the teaching mode.

Teratoma is a rare tumor, mainly occurring in the ovary, sacrococcygeal region, testis, central nervous system and mediastinum, rarely occurring in the kidney, and adult immature teratoma originating in the kidney is extremely rare. A case of adult left renal immature teratoma was reported in this paper. After radical nephrectomy, pathological examination found that the tumor tissue contains malignant epithelial tissue and a small number of brain tissue. BEP regimen chemotherapy was performed after operation.The patient was followed up for 26 months, and died of organ failure caused by systemic metastasis.

Objective: Based on the KAP and Prospect theory, to explore, construct and verify the theoretical model and formation mechanism of driving factors of primary care doctors′ willingness to carry out the primary diagnosis. Methods: Using the random cluster sampling method, from April to May 2019, a questionnaire survey was conducted among doctors at 20 primary medical and health service institutions in Hangzhou. The survey covered the primary care doctors′ cognition level of primary diagnosis, their self-evaluation of primary medical care capabilities, evaluation of policies and systems, expectation of primary medical care, and their job satisfaction. Descriptive statistic, multiple linear regression and structural equation model were used to analyze and explore the driving factors and formation mechanism of their willingness to carry out the primary diagnosis. Results: Primary care doctors′ willingness rate for primary diagnosis was 76.4%(308/403). Positive expectation(beta=0.309), cognition level(beta=0.216), evaluation of policies and systems(beta=0.184), and self-evaluation of primary diagnosis capability(beta=0.170), all of which directly affect the said willingness. The total effect of the five types of driving factors on the willingness of the primary diagnosis was as follows: cognitive level of the primary diagnosis(0.536), evaluation of the policy system(0.494), self-evaluation of the primary diagnosis capability(0.436), positive expectations of the primary diagnosis work(0.186), job satisfaction(0.146). Conclusions The cognition of the primary diagnosis, the capability of the primary diagnosis, the policy system and the positive expectation are the important premises, key driving forces, and a strong guarantee and motivation to drive primary care doctors to carry out the primary diagnosis. It is suggested that the government and medical institutions should further improve the cognition level of primary care doctors, focusing on systematically improving the service capability of primary care doctors′ primary consultation, coordinating to improve policy guidance measures such as financial input, medical insurance reimbursement and referral system, establishing and improving incentive measures such as career development, performance appraisal, salary and welfare of primary care doctors.

Objective: To establish a mouse model of osteoarthritis (OA) and study the bone microarchitecture and bone metabolism of tibial subchondral bone in early stage of OA. Methods: The mouse model of post-traumatic osteoarthritis (PTOA) with anterior cruciate ligament (ACLT) was established by using c57 mice. The Sham operation group served as the control group. All mice were fed with conventional diet. All mice were sacrificed after 4 weeks. The degeneration of knee joint was observed by HE staining and Safranin O-Fast Green staining. The number of osteoclasts was counted by TRAP staining. Micro CT was used to analyze the quantitative parameters of the microstructure of tibia subchondral bone in mice. Serum levels of bone resorption biomarker CTX I and cartilage degeneration marker CTX II were determined. Results: After ACLT 4 weeks, the average score of OARSI in ACLT group was 3.2, which was higher than that in Sham group, and the joint degeneration occurred in mice, presenting the pathological characteristics of early OA. Compared with the sham operation phase, the total subchondral bone volume (TV) of ACLT group was 4.72 mm³, increased by 13.6%; the bone trabecular resolution (Tb.Sp) was 0.130 and 0.154 mm, respectively, and the ACLT group also increased by 18.8%; the bone volume/tissue volume (BV/TV) was 0.470 and 0.294, respectively, and the ACLT group decreased by 48.9%; the bone trabecular thickness (Tb.Th) was 0.162 and 0.083 mm groups, ACLT decreased by 37.5%. Trap staining showed that the number of osteoclasts per unit volume in ACLT group was 72, which was significantly higher than that in sham operation group. The CTX I of mice in the sham operated ACLT group and sham operated group were 20.9 ng/ml and 18.29 ng/ml, with an increase of 48.9% in the ACLT group; the CTX II of mice in the ACLT group and sham operated group were 35.5 ng/ml and 28.6 ng/ml, with an increase of 24.1% in the ACLT group. Conclusion ACLT Mouse model can successfully construct early OA, which confirms the early loss of osteochondral bone and the pathological changes of osteoclast activation in OA, and provides a new specific target for the treatment of OA.

Objective To investigate the clinical effects of radical intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy in the treatment of metastatic nasopharyngeal carcinoma. Methods Ninety patients with metastatic nasopharyngeal carcinoma in the First Affiliated Hospital of Hainan Medical University from August 2010 to April 2015 were selected as the research objects. All the patients were randomly divided into the observation group (45 cases) and the control group (45 cases) according to the random lottery envelope. The control group was treated with conventional chemotherapy treatment, and the observation group was treated with radical IMRT based on the treatment of the control group. The efficacy of the patients in both groups was evaluated after the treatment for 4 periods. Results The effective rate in the observation group was higher than that in the control group [66.7 % (30/45) vs. 33.3 % (15/45); χ2= 4.552, P＜ 0.05]. In the observation group, there were 3 cases of radiation esophageal injury and 3 cases of lung injury, and the incidence rate was 13.3 % (6/45), bringing the better treatment outcome. The incidence of side effects such as hair loss, nausea and vomiting, liver and kidney damage, bone marrow suppression in the observation group was 71.1 % (32/45), which was higher than that in the control group [66.7 % (30/45)] and there was no significant difference (χ 2= 0.331, P＞ 0.05). All the patients were followed up. 1 yeas and 2 year survival rates in the observation group were 95.6 % (43/45) and 86.7 % (39/45) respectively, while the control group were respectively 75.6 % (34/45) and 64.4 % (29/45) (χ2values were 6.393 and 5.309, both P＜0.05). Conclusion Radical IMRT combined with concurrent chemotherapy for metastatic nasopharyngeal carcinoma can improve the therapeutic effect and show good safety, and the radiation damage would not affect the treatment process.

Objective To synthesize 18F-AlF-1,4,7-triazacyclononane-l,4,7-triacetic acid (NOTA)-c (CGRRAGGSC),which could specifically bind to the α chain of interleukin (IL)-11 receptor (IL-11 R),and evaluate its targeting potential to IL-11 R-positive tumors.Methods Polypeptide c (CGRRAGGSC) was first coupled with NOTA and then labeled with 18F by AlF labeling method.The radiochemical purity and radiochemical yield of 18F-AlF-NOTA-c(CGRRAGGSC) were analyzed by high performance liquid chromatography,and the stability in vitro was evaluated.The tracer biodistribution in tumor-bearing mice (cell line SKOV3) was evaluated by the dynamic imaging with microPET 30 min,1 h,2 h after injection of 18F-AlF-NOTA-c (CGRRAGGSC).The tracer kinetics was performed in normal mice.Pharmacokinetics parameters were calculated using DAS2.0 software.Results The radiochemical purity of 18F-AlF-NOTA-c(CGRRAGGSC) was higher than 95％ and the radiochemical yield was (30.0±7.4)％.It could be stably maintained in phosphatebuffered solution and plasma for at least 2 h.MicroPET imaging showed that 18F-AlF-NOTA-c(CGRRAGGSC)had a good affinity to SKOV3 tumor.The tumor/muscle ratios at 30 min,1 h,2 h after the injection of 18F-AlF-NOTA-c(CGRRAGGSC) were 6.26±2.98,7.19±3.63 and 9.05±4.30,respectively.The tracer was cleared rapidly in blood and mainly excreted by the liver and kidneys.The T1/2α and T1/2β were (0.38±0.14) h and (2.64±0.28) h,respectively.Conclusions 18F-AlF-NOTA-c(CGRRAGGSC) is easy to be synthesized and has a good affinity to IL-11R-positive tumors.It will be a potential IL-11R-targeting imaging agent.

Objective To study the application of implantable telemetry and whole-body plethysmography to observe the changes of circadian rhythm in conscious rats and evaluate the pharmacological safety of doxofylline, and to provide a basis for the future application of this technological system for drug safety evaluation.Methods Eight healthy SPF Sprague-Dawley rats were used in this study, 4 males and 4 females.The rats were implanted with telemetry transmitters by surgery to establish a telemetry system combined with plethysmography to observe the changes of 24 h physiological parameters and circadian rhythm in conscious rats at 14 d after operation, including heart rate (HR), blood pressure, the time interval from the Q wave to point A in the ECG of the aortic pressure wave (QA interval), respiration, activity, body temperature and pulmonary function parameters.The rats were divided into 3 groups: normal control group, doxofylline 40 mg/kg and 80 mg/kg groups, and the performance was validated by aerosolizing saline, doxofylline 40 mg/kg and 80 mg/kg inhalation, respectively, to observe the changes in physiological parameters after the drug administration.Results The physiological parameters of rats showed obvious changes in circadian rhythms at 14 d after operation.Compared with the normal control group, the doxofylline 40 mg/kg-treated group showed significantly increased changes of HR, tidal volume (TV), minute ventilation (MV), 50% expiratory flow (EF50), peak inspiratory flow (PIF) and peak expiratory flow (PEF) (P<0.01), significantly decreased respiratory frequency, QA interval and enhance pause (Penh) (P<0.05, P<0.01), but no significant differences in the blood pressure, activity and body temperature (P>0.05).Compared with the normal control group, the group treated with doxofylline 80 mg/kg had significantly increased HR, blood pressure, TV, MV, EF50, PIF and PEF (P<0.01), significantly decreased respiratory frequency, QA interval and Penh not (P<0.01), but not significantly changed activity and body temperature (P>0.05).Conclusions The application of implantable telemetry and whole-body plethysmography in this study does not obviously affect the circadian rhythm, and can sensitively monitor the relevant cardiovascular and respiratory parameters in conscious rats.It can be used in drug safety pharmacological research of cardiovascular and respiratory systems in conscious rats.