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.

Malignant tumors have become the main cause of human death.With the prolonged use of chemotherapeutic drugs during the treatment process,tumor cell resistance is also constantly increasing.long non-coding RNA(lncRNA)is an important mem-ber of the non-coding RNA family.Cancer susceptibility candidate 2(CASC2)is a type of long non-coding RNA,high expression of CASC2 can inhibit tumor cell development and reduce drug resistance of tumor cells by promoting apoptosis,regulating signaling path-ways,participating in cellular transmission pathways,competitively binding of miRNA,and changing the protein structure or functional status.This article will provide a comprehensive review of the regulatory effects and mechanism of lncRNA CASC2 on chemotherapy resistance in malignant tumors.

Objective To explore the computed tomography(CT)-specific imaging findings of extra-adrenal pheochromocytoma and their diagnostic value.Methods We retrospectively analyzed the clinical records of 83 patients with extra-adrenal pheochromocytoma.All patients underwent preoperative abdominal CT.We then assessed the relationship between tumor size and tumor cystic changes and between tumor CT features and clinical manifestations.Results The typical CT image of extra-adrenal pheochromocytoma is a round or oval mass with photoplastic margins and uneven density,enhanced marginal high-density areas with mostly central low-density necrotic areas,and a location beside large abdominal vessels.The occurrence of cystic changes in the tumor was significantly correlated with a large tumor size(P=0.001).Clinical manifestations such as abdominal discomfort and a history of hypertension were not significantly associated with tumor location or cystic changes(P>0.05).Severe intraoperative blood pressure fluctuations were associated with tumor location(P=0.020).Patients with larger tumors were more likely to have abdominal discomfort(P=0.032)and a history of hyper-tension(P=0.043).Conclusion CT is an important imaging modality for the localization and qualitative diagnosis of extra-adrenal phe-ochromocytomas and can improve the clinical diagnosis rate.

Objective To compare the contents of alkaloid in Aconiti Kusnezoffii Radix with different degrees of processing and their effects on electrocardiogram and vagus nerve action potential in SD rats;To establish a toxicity evaluation method for Aconiti Kusnezoffii Radix and its processed products.Methods HPLC was used to determine the contents of six alkaloid components,including benzoyl neoaconitine,benzoyl aconitine,benzoyl subeaconitine,neoaconitine,subeaconitine and aconitine in Aconiti Kusnezoffii Radix and Aconiti Kusnezoffii Radix Cocta of soaking and boiled for 30 minutes,boiled for 4 h without soaking,soaking and boiled for 4 h,and soaking and boiled for 8 h.SD rats were subjected to sublingual drainage with Aconiti Kusnezoffii Radix and four types of processed products.The vagus nerve action potential and electrocardiogram of rats before and after administration were recorded,and the correlation analysis between alkaloid content and vagus nerve action potential and heart rate was conducted.Results The contents of alkaloid of the four processed products showed that the content of diester alkaloids was soaking and boiled for 30 min>boiled for 4 h without soaking>soaking and boiled for 4 h>soaking and boiled for 8 h;monoester alkaloid content:boiled for 4 h without soaking>soaking and boiled for 30 min>soaking and boiled for 4 h>soaking and boiled for 8 h.After the administration of each sample,compared with the basal discharge,the vagus nerve discharge of rats with different processed products was changed by sublingual administration,heart rate increased,the degree of arrhythmia increased,and it varied with the degree of processing;the results of correlation analysis showed that there was a significant correlation between the nerve discharge area and the contents of diester alkaloids and total alkaloids.Conclusion The action potential of the vagus nerve and electrocardiogram of rats after sublingual drainage administration can reflect the degree of numbness in the tongue,which can provide reference for the study of tongue sensation of Aconiti Kusnezoffii Radix.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

Objective:To construct and validate a nomogram model based on clinical factors and PET/CT metabolic parameters of 18F-FDG for predicting epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma. Methods:From January 2014 to January 2019, 114 patients (59 males, 55 females, age (60.0±10.8) years) with lung adenocarcinoma in the First Affiliated Hospital of Harbin Medical University were retrospectively enrolled. Clinical data (smoking status, tumor location, clinical stage and carcinoembryonic antigen (CEA) level), 18F-FDG PET/CT metabolic parameters (SUV max, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) and EGFR mutation status were analyzed. Patients were divided into training group (80 cases) and validation group (34 cases). In the training group, univariate analyses (independent-sample t test, Wilcoxon rank sum test, χ2 test or Fisher′s exact probability method) were used for categorical variables. Variables that showed significant differences between EGFR mutation group and wild type group were selected. Variance inflation factors (VIF) were calculated and the collinearity variables were deleted, and a nomogram model of optimal logistic model was constructed based on Akaike information criterion (AIC). The effect of the model was evaluated by the concordance index (C-index), sensitivity, specificity, accuracy, calibration and decision curve analysis (DCA) in the training group and the validation group. Results:Among 114 patients, 56 were with EGFR mutations and 58 were with EGFR wild type. In the training group, there were significant differences in gender (male/female: 14/26 vs 25/15; χ2=6.05, P=0.014), smoking status (with/without smoking history: 4/36 vs 22/18; χ2=18.46, P<0.001) and SUV max (5.72(3.90, 8.32) vs 8.09(4.56, 12.55); W=1 045.50, P=0.018) between EGFR mutation group and wild type group. However, there were no significant differences in other factors ( t=-0.54, χ2 values: 0.20 and 0.20, W values: 921.50 and 983.00, all P>0.05). The VIF of gender, smoking status and SUV max were all less than 10, and the nomogram model with three factors showed the minimum AIC (90.06). In the training group, C-index value of the model was 0.798 (95% CI: 0.699-0.897), with the sensitivity of 85.0%(34/40), the specificity of 70.0%(28/40) and the accuracy of 77.5%(62/80). In the validation group, C-index value was 0.854(95% CI: 0.725-0.984), with the sensitivity of 13/16, the specificity of 14/18, and the accuracy of 79.4%(27/34). The calibration curve and the goodness of fit test showed good calibration, and DCA showed that the model could benefit patients clinically within a large risk threshold range (training group: 0-0.59, validation group: 0-0.65). Conclusion:The nomogram model based on gender, smoking status and SUV max can be used to easily predict EGFR mutation status in lung adenocarcinoma.

Objective:To analyze the case characteristics and outcomes of 12 idiopathic giant cell myocarditis(IGCM)cases after heart transplantation(HT).Methods:From June 2004 to May 2022, clinical data were retrospectively reviewed for 12 cases with pathologically confirm IGCM after HT at Fuwai Hospital.General characteristics, clinical manifestations, pathological examinations and postoperative follow-ups are recorded.Results:From June 2004 to May 2022, a total of 1 143 HT operations are performed at Fuwai Hospital and 12 cases of IGCM(1.05%)are confirmed by postoperative pathology.The age is(47.6±7.3)years.There are 5 boys and 7 girls.Initial presenting manifestations are congestive heart failure(7 cases, 58.3%)and arrhythmia(4 cases, 33.3%). Median time from symptom onset to HT is 6 months.All of them are undiagnosed pre-operation.And dilated cardiomyopathy(5 cases, 41.7%)and arrhythmogenic right ventricular cardiomyopathy(3 cases, 25%)are confirmed.The follow-up period is(4~142)months post-HT.One death occurred during perioperative period and another is due to heart failure at 68 months post-HT.Only 1 case of grade 1R transplant heart rejection occurrs at 9 years post-HT and there is no case of recurrence.According to Kaplan-Meier survival analysis, cumulative survival rates of 1/5/10 years post-HT in IGCM patients are 91.7%, 91.7% and 73.3% respectively.No significant difference exist in survival rate for other etiologies post-HT(Log-rank P=0.265). Conclusions:HT is efficacious for end-stage IGCM.Regular and sufficient postoperative immunosuppression is vital for preventing heart transplant rejection and recurrent IGCM.Most IGCM patients have a decent prognosis post-HT.

Objective:To observe the effect of positive psychological intervention based on PERMA model on core emergency competence and empathy of ICU nurses in infectious disease emergencies.Methods:From February to April 2020, a total of 136 ICU nurses from 3 ClassⅢ Grade A hospitals in Beijing were selected as the research objects. The patients were divided into the control group and the experimental group by the random number table method, with 68 cases in each group. The control group was given professional knowledge training, while the experimental group was given professional knowledge training combined with PERMA positive psychological intervention. The core emergency competence and compassion load of ICU nurses in the two groups before and after intervention were compared by using the Core Emergency Competence Questionnaire for Infectious Disease Emergencies and Nurses' Compassion Load Scale.Results:After intervention, scores of emergency competence of nurses in both groups were higher than before intervention, and the score of emergency competence in the experimental group was higher than that in control group, and the differences were statistically significant ( P<0.05) . After the intervention, the scores of the satisfaction subscale of helping and caring for others in Nurses' Compassion Load Scale in the experimental group were higher than those before the intervention, and the subscale scores of burnout and compassion fatigue were lower than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Positive psychological intervention based on the PERMA model can effectively increase the core emergency competence of ICU nurses in infectious disease emergencies and reduce their psychological load.

Background: The dietary agent sulforaphane (SFN) has been reported to reduce diabetes-induced renal fibrosis, as well as inhibit histone deacetylase (HDAC) activity. Bone morphologic protein 7 (BMP-7) has been shown to reduce renal fibrosis induced by transforming growth factor-beta1. The aim of this study was to investigate the epigenetic effect of SFN on BMP-7 expression in diabetes-induced renal fibrosis. Methods: Streptozotocin (STZ)-induced diabetic mice and age-matched controls were subcutaneously injected with SFN or vehicle for 4 months to measure the in vivo effects of SFN on the kidneys. The human renal proximal tubular (HK11) cell line was used to mimic diabetic conditions in vitro. HK11 cells were transfected to over-express HDAC2 and treated with high glucose/palmitate (HG/Pal) to explore the epigenetic modulation of BMP-7 in SFN-mediated protection against HG/Pal-induced renal fibrosis. Results: SFN significantly attenuated diabetes-induced renal fibrosis in vivo. Among all of the HDACs we detected, HDAC2 activity was markedly elevated in the STZ-induced diabetic kidneys and HG/Pal-treated HK11 cells. SFN inhibited the diabetes-induced increase in HDAC2 activity which was associated with histone acetylation and transcriptional activation of the BMP-7 promoter. HDAC2 over-expression reduced BMP-7 expression and abolished the SFN-mediated protection against HG/Pal-induced fibrosis in vitro. Conclusion Our study demonstrates that the HDAC inhibitor SFN protects against diabetes-induced renal fibrosis through epigenetic up-regulation of BMP-7.