OBJECTIVE To investigate the relationship between metformin and sarcopenia-related traits. METHODS Based on the data from publicly genome-wide association study-related databases， using single nucleotide polymorphisms strongly associated with metformin as instrumental variables， the two-sample Mendelian randomization （MR） analysis methods [inverse variance weighting （IVW） method， MR-Egger regression method and weighted median estimator method] were employed to investigate the relationship between metformin and three sarcopenia-related traits （low grip strength， muscle mass and walking speed）. Cochran’s Q test was used to assess heterogeneity， MR-Egger intercept test was used to detect horizontal pleiotropy， and leave-one-out analysis was performed for sensitivity analysis. RESULTS The results of IVW method showed that metformin use was significantly associated with an increased risk of low grip strength （β＝1.550， 95%CI was 0.389-2.711， P＝0.009） and reduced limb muscle mass （right leg lean body mass： β＝－0.665， 95%CI was －1.018-－0.312， P＜0.001； left leg lean body mass： β＝－0.710， 95%CI was －1.049-－0.371，P＜0.001； right arm lean body mass： β＝－0.471， 95%CI was －0.890-－0.053， P＝0.027； left arm lean body mass： β＝－0.463， 95%CI was －0.865-－0.061， P＝0.024），but was not associated with walking speed. The results or causal effects of the other two methods are consistent with it. The Cochran’s Q test indicated some degree of heterogeneity in the result of this study. No horizontal pleiotropy was detected by the MR-Egger intercept test. The sensitivity analysis suggested that the results of this study were stable. CONCLUSIONS Metformin may increase the risk of sarcopenia.

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

Trace amines(TAs)are metabolically related to catecholamine and associated with cancer and neuro-logical disorders.Comprehensive measurement of TAs is essential for understanding pathological pro-cesses and providing proper drug intervention.However,the trace amounts and chemical instability of TAs challenge quantification.Here,diisopropyl phosphite coupled with chip two-dimensional(2D)liquid chromatography tandem triple-quadrupole mass spectrometry(LC-QQQ/MS)was developed to simul-taneously determine TAs and associated metabolites.The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS.This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib.The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells.This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.

Objective:To develop a deep learning model which can automatically and accurately detect osteoporotic vertebral compression fractures (OVCF) based on artificial intelligence.Methods:MRI images of 500 patients diagnosed with OVCF at The First People＇s Hospital of Guangzhou from January 2019 to October 2021 were collected retrospectively. There were 396 males and 204 females, with an age of (74.5±6.0) years. The T value of bone mineral density was -2.9±0.8. The fracture segments were L1 in 128 cases, L2 in 113 cases, L3 in 109 cases, L4 in 115 cases, and L5 in 108 cases. The multimodal layered converged network was used to train, test, and verify the robustness and generalization ability of a deep learning model based on MRI images of OVCF. The grad-cam was applied to visualize the results. The diagnostic value of the model for OVCF was assessed by comparing the diagnoses between the artificial intelligence model and 2 senior spinal surgeons on the MRI images of 30 OVCF patients randomized from the 500 ones.Results:Of the precise auxiliary diagnosis model for OVCF based on MRI images, the diagnostic accuracy was 96.7%, the sensitivity 93.5%, the specificity 88.9%, the positive predictive value 100.0%, and the negative predictive value 86.6%, all significantly higher than those of the 2 senior spinal surgeons (70.0%, 72.7%, 28.6%, 82.1%, and 28.6%) ( P<0.05). Conclusion:The present study has successfully established a deep learning model which can automatically and accurately diagnose OVCF based on MRI images, showing a high diagnostic efficiency than human spinal surgeons.

The development of multifunctional nanocontrast agents with high sensitivity, high specificity, and low toxicity so that they can precisely localize tumors and reflect tumor biological information in real time is the core of promoting the development of tumor molecular imaging technology and realizing early and precise tumor diagnosis. Polydopamine (PDA) nanomaterials are bionanomaterials with a structure extremely similar to that of natural melanin. They can be easily fabricated and functionalized, and can achieve controlled assembly of functional molecules such as contrast components and targeting ligands via metal coordination, π-π stacking, electrostatic adsorption, and other methods. They have good biocompatibility and biodegradability, show great potential for clinical translation, and have been widely used in molecular imaging of tumors. In this review paper, the preclinical studies of PDA nanoparticles are reviewed as well as the synthesis methods, functionalized modification, and assembly strategies of PDA nanoparticles and their applications in tumor molecular imaging. The development trends of PDA are also presented to promote their application in the field of tumor molecular imaging.

Objective:To fabricate tAu@glutathione(GSH)@Gd nanoprobe for tumor angiogenesis bimodal (MR/CT) imaging, and evaluate its characteristics and potential for MR/CT imaging in vivo. Methods:The tAu@GSH@Gd nanoprobes were constructed by encapsulating Au and Gd atoms into the GSH shell with cyclic asparagine-glycine-arginine (cNGR) peptide conjugation. EMT-6 BALB/c mice subcutaneous transplantation tumor models were established ( n=30) and divided into blank control group (saline), control group (Au@GSH@Gd nanoparticles) and experimental group (tAu@GSH@Gd nanoprobes) ( n=10 in each group). In vivo MR/CT imaging and distribution study were performed at different time points after tail intravenously injection. Relative MR signal value and relative CT value of tumor site and main organs in mice were used to evaluate MR/CT imaging property and biological distribution. After that, tumor tissues were collected for silver staining to study the accumulation of Au@GSH@Gd nanoparticles and tAu@GSH@Gd nanoprobes. Independent-sample t test was used for data analysis. Results:The tAu@GSH@Gd nanoprobes were (6.40±0.22) nm with high T 1 relaxation efficiency ((36.91±0.07) mmol·L -1·s -1). MR/CT imaging of tAu@GSH@Gd nanoprobes showed good performance in vitro. In vivo MR/CT imaging demonstrated MR/CT imaging of tumor was significantly enhanced by tAu@GSH@Gd nanoprobes after 2 h post injection. The strongest enhancement was observed at 24 h, with an increased relative MR signal value from 1.04±0.12 (before injection) to 1.84±0.26 ( t=12.61, P=0.006), and increased relative CT value from 1.01±0.04 (before injection) to 1.95±0.05 ( t=15.34, P=0.004). The highest MR/CT effect in control group appeared at 16 h, with the relative MR signal value of 1.50±0.06 and the relative CT value of 1.53±0.10, which were significantly lower than those in experimental group (1.84±0.26 and 1.95±0.05; t values: 5.35 and 16.46, both P<0.05). Distribution in normal tissues showed that most of tAu@GSH@Gd nanoprobes were metabolized through the kidneys. Tissue silver staining experiment verified the tumor angiogenesis targeting effect. Conclusion:The tAu@GSH@Gd nanoprobes exhibit favorable tumor angiogenesis target MR/CT imaging ability, providing a new design concept and basis for assessing tumor angiogenesis.

OBJECTIVES: Psoriasis is a chronic inflammatory skin disease that affects adults and children. The most common subtype is psoriasis vulgaris. This article analyzes the characteristics and clinical features of children with psoriasis vulgaris to strengthen the understanding, treatment, and management for children with psoriasis. METHODS: A total of 208 children with psoriasis vulgaris, who were first admitted to the Department of Dermatology, Xiangya Hospital, Central South University from October 2012 to December 2018, were retrospectively analyzed. Their clinical characteristics, results of laboratory examination, treatment options and efficacy were summarized. RESULTS: The age of the 208 children with psoriasis vulgaris was (11.19±3.97) years old, the peak incidence was 12 years old, the disease duration was (27.46±31.30) months, and the male-female ratio was 1∶0.96. The most common site of the first attack was the scalp (37.98%), followed by the trunk (26.44%) and the limbs (22.12%). The causes leading to exacerbation were more common in infections and diets. There were 33 patients (15.87%) with a family history of psoriasis, showing the higher score of Psoriasis Area and Severity Index (PASI) and the higher Dermatological Quality of Life Index (DLQI) (both <0.05). In all patients, 29 cases (13.94%) were overweight, 19 cases (9.14%) were obese, and the rate of overweight and obesity in children with psoriasis vulgaris was higher than that of normal children in China. In the laboratory test, the serum levels of 25-hydroxyvitamin D (25-OH-VD) were decreased in most patients (47.5%), and the serum 25-OH-VD levels were found to be moderately negatively correlated with PASI score (<0.05). The score of DLQI in the patient was 5.56±3.57, the score of PASI was 7.25±6.83, and they were positively correlated (=0.409, <0.001). In most patients (72.11%), the severity of the disease was mild to moderate. Their treatment was often dominated by topical drugs and Chinese patent medicine (65.67%). Retinoids showed a good effect on children. Cyclosporine and methotrexate were effective in more severe cases. CONCLUSIONS Children with psoriasis vulgaris are mainly caused by infection and diet. Patients with family history have more serious illness, lower quality of life, and are more likely to have metabolic abnormalities such as overweight and obesity. The serum 25-OH-VD levels in children with psoriasis vulgaris are negatively correlated with the score of PASI.
Adolescent ; Adult ; Child ; China ; epidemiology ; Female ; Humans ; Male ; Pediatric Obesity ; Psoriasis ; epidemiology ; Quality of Life ; Retrospective Studies ; Severity of Illness Index

Objective To study the expression level of cathepsin S in elderly patients with different degree of coronary heart disease(CHD),and to evaluate the correlation between cathepsin S level and the severity of CHD.Methods A total of 126 elderly patients with CHD were enrolled,including 36 cases with acute myocardial infarction(group AMI),48 cases with unstable angina(group UAP),and 42 cases with stable angina(group SAP).During the same period,40 healthy subjects were selected as controls.Venous blood was collected immediately after admission.Arterial blood was taken through radial/femoral artery sheath in AMI patients who underwent primary percutaneous coronary intervention,and coronary arterial blood was taken in AMI patients undergoing intracoronary thrombus aspiration.SYNTAX score was assessed in patients undergoing coronary angiography.Serum levels of high sensitivity C reactive protein(hs-CRP),matrix metalloproteinase-9 (MMP-9) and cathepsin S were determined in all specimens and compared between groups.Results Serum levels of cathepsin S,MMP-9 and hs-CRP were higher in CHD patients than in the control group(P＜0.05).Among CHD patients,group AMI had the highest serum levels of cathepsin S,MMP-9 and hs-CRP,followed by group UAP and group SAP(F =106.830,197.035 and 310.442,all P =0.000).Spearman's rank correlation test suggested that cathepsin S level was positively correlated with serum levels of MMP-9 (r=0.816,P =0.000)and hs-CRP(r =0.827,P =0.000).SYNTAX score was positively correlated with serum levels of cathepsin S(r=0.581,P=0.000),MMP-9(r=0.511,P=0.000),and hs-CRP (r=0.557,P =0.000).Among the 24 patients with AMI who underwent intracoronary thrombus aspiration,the levels of cathepsin S,MMP-9 and hs-CRP were higher in coronary artery blood than in peripheral artery blood (t =217.288,3.177 and 681.479,all P =0.000).Cathepsin S and hs-CRP levels in peripheral arterial blood had positive correlations with those in coronary arterial blood respectively(r =0.962 and 0.494,P =0.000 and 0.014),but such correlation between in peripheral arterial blood versus in coronary artery blood was not found in MMP-9 levels (r =-0.188,P =0.380).Conclusions Serum cathepsin S level is higher in elderly CHD patients than in healthy people,increases along with the increased severity of CHD,and positively correlates with the degree of coronary stenosis.

Objective: To explore the dynamic variation trend of bronchial wall thickness (BWT) in severely burned patients combined with inhalation injury, and to determine the value of BWT to prognosis of patients. Methods: Forty-three severely burned patients with inhalation injury hospitalized in Intensive Burn Department of the Affiliated Hospital of Nankai University (Tianjin No.4 Hospital) from July to November 2016, conforming to the study criteria, were divided into survival group (n=27) and death group (n=16) according to the prognosis of patients within 14 days after admission. All patients underwent fiberoptic bronchoscopy and inhalation injury rating based on abbreviated injury scale at admission. High resolution CT examination was performed in patients of two groups at admission and 24 h post admission, 3, 7, and 14 d post admission to measure the BWT of right superior lobar bronchus trunk opening. Receiver operating characteristic curves of rating of inhalation damage at admission and BWT at admission were drawn to evaluate the predictive value for death of 43 patients. Data were processed with chi-square test, independent sample t test, Wilcoxon rank sum test, analysis of variance for repeated measurement and least-significant difference-t test. Results: (1) The numbers of patients rated as 0, 1, 2, 3, and 4 grade for inhalation injury in survival group and death group were 0, 19, 6, 2, and 0, and 0, 2, 7, 7, and 0, respectively. There were statistically significant differences between the two groups (Z=-3.79, P<0.01). (2) BWT of patients in death group at admission and 24 h post admission, 3, 7, and 14 d post admission was respectively (2.72±0.26), (3.18±0.22), (2.98±0.18), (2.29±0.17), and (1.45±0.21) mm, which was significantly larger than (2.24±0.15), (2.49±0.15), (1.51±0.17), (1.04±0.16), and (1.01±0.13) mm in survival group (t=7.55, 12.14, 27.11, 19.99, 7.11, P<0.01). BWT of patients in survival group and death group at 24 h post admission, 3, 7, and 14 d post admission showed statistically significant difference when compared with that at admission within the corresponding group (t=5.97, 16.63, 28.21, 38.57, 5.34, 3.31, 4.39, 6.48, P<0.01). BWT of patients in survival group and death group on 3, 7, and 14 d post admission was significantly smaller than that at 24 h post admission within the corresponding group (t=22.27, 34.02, 45.03, 2.77, 10.53, 10.59, P<0.01). BWT of patients in survival group and death group on 7 and 14 d post admission was significantly smaller than that on 3 d post admission within the corresponding group (t=10.49, 18.26, 9.57, 11.44, P<0.01). BWT of patients in survival group and death group on 14 d post admission was significantly smaller than that on 7 d post admission within the corresponding group (t=6.97, 6.15, P<0.01). (3) The total areas under ROC curves of inhalation injury rating at admission and BWT at admission for predicting death of 43 patients were 0.880 and 0.956, respectively (with 95% confidence intervals 0.768-0.991, 0.882-1.000, P<0.05). Grade 1.5 and 2.75 mm were respectively chosen as the optimal threshold values of inhalation injury rating at admission and BWT at admission, with sensitivity of 87.50%, 83.33% and specificity of 77.78%, 96.00%, respectively. Conclusions The BWT of survived and dead patients with severe burn and inhalation injury increases significantly post burn, while the BWT of survived patients restores to normal level faster. BWT can be used to assess the severity of inhalation injury and to predict death in severely burned patients combined with inhalation injury.

Objective To develop an method for detecting the characteristic chromatograms of Qihong decoction by high-performance liquid chromatography coupled with diode arry and evaporative light-scattering detectors (HPLC-DAD-ELSD). Methods The determination was carried out with Venusil MP-C18 (250 mm × 4.6 mm, 5 μm) column,using acetonitrile-0.2％ formic acid as mobile phase with gradient elution at a flow rate of 1.0 ml/min and detected at the wave length 254 nm, 290 nm, 365 nm. The drift tube temperature for ELSD was set at 70 ℃, and the nebulizing gas flow rate was 2.8 L/min. Results There were 34 chemical compositions in characteristic chromatograms of Qihong decoction. Among them, 16 peaks came from Polygoni Orientalis Fructus, 17 from Astagali Radix, respectively. A total of 18 chemical constituents were identified. Conclusions The method was simple, steady and reliable which could be applied to the quality control of Qihong decoction.