Background and Aims:Papillary thyroid carcinoma(PTC)is the most common endocrine malignancy in China,with cervical lymph node metastasis being a frequent and critical clinical feature that directly affects patient prognosis and recurrence risk.In recent years,with the rapid increase in the prevalence of overweight and obesity in China,the role of body mass index(BMI)in various tumors has attracted growing attention.This study aimed to investigate the association between overweight and cervical LNM in PTC,analyze sex-specific differences and influencing factors,and provide evidence for precise clinical management.Methods:A retrospective analysis was conducted on the clinicopathologic data of 1 445 patients with classical PTC treated at Xiangya Hospital of Central South University between August 2021 and June 2022.Patients were divided into groups based on the presence or absence of lymph node metastasis.Restricted cubic spline analysis explored the nonlinear relationship between BMI and lymph node metastasis risk.Univariate and multivariate Logistic regression analyses were applied to identify independent risk factors.Furthermore,sex-stratified analysis was performed among overweight patients(BMI≥24 kg/m2)to determine sex-specific risk factors for lymph node metastasis.Results:Among all patients,716(49.6%)had lymph node metastasis.Univariate analysis showed that BMI,sex,age,tumor diameter,multifocality,and extrathyroidal extension were significantly associated with cervical lymph node metastasis in PTC patients(all P<0.05).A nonlinear positive correlation was observed between BMI and lymph node metastasis risk,which was more pronounced in male patients.Additionally,BMI was positively correlated with triglyceride levels and negatively correlated with high-density lipoprotein cholesterol.Sex-stratified analysis revealed that in overweight male patients,younger age(OR=0.954),larger tumor diameter(OR=1.085),and multifocality(OR=2.776)were independent risk factors for LNM;in overweight female patients,younger age(OR=0.943)and larger tumor diameter(OR=1.074)were the main influencing factors.Conclusion:Overweight is closely associated with cervical lymph node metastasis in PTC,and the high-risk factors for LNM differ between male and female overweight patients.Young age,larger tumor size,and multifocality in overweight males,and young age and larger tumors in overweight females indicate a higher risk of metastasis.It is recommended that high-risk populations receive enhanced preoperative evaluation and individualized lymph node dissection strategies to achieve precise treatment and improved risk control.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Background and Aims:Papillary thyroid carcinoma(PTC)is the most common endocrine malignancy in China,with cervical lymph node metastasis being a frequent and critical clinical feature that directly affects patient prognosis and recurrence risk.In recent years,with the rapid increase in the prevalence of overweight and obesity in China,the role of body mass index(BMI)in various tumors has attracted growing attention.This study aimed to investigate the association between overweight and cervical LNM in PTC,analyze sex-specific differences and influencing factors,and provide evidence for precise clinical management.Methods:A retrospective analysis was conducted on the clinicopathologic data of 1 445 patients with classical PTC treated at Xiangya Hospital of Central South University between August 2021 and June 2022.Patients were divided into groups based on the presence or absence of lymph node metastasis.Restricted cubic spline analysis explored the nonlinear relationship between BMI and lymph node metastasis risk.Univariate and multivariate Logistic regression analyses were applied to identify independent risk factors.Furthermore,sex-stratified analysis was performed among overweight patients(BMI≥24 kg/m2)to determine sex-specific risk factors for lymph node metastasis.Results:Among all patients,716(49.6%)had lymph node metastasis.Univariate analysis showed that BMI,sex,age,tumor diameter,multifocality,and extrathyroidal extension were significantly associated with cervical lymph node metastasis in PTC patients(all P<0.05).A nonlinear positive correlation was observed between BMI and lymph node metastasis risk,which was more pronounced in male patients.Additionally,BMI was positively correlated with triglyceride levels and negatively correlated with high-density lipoprotein cholesterol.Sex-stratified analysis revealed that in overweight male patients,younger age(OR=0.954),larger tumor diameter(OR=1.085),and multifocality(OR=2.776)were independent risk factors for LNM;in overweight female patients,younger age(OR=0.943)and larger tumor diameter(OR=1.074)were the main influencing factors.Conclusion:Overweight is closely associated with cervical lymph node metastasis in PTC,and the high-risk factors for LNM differ between male and female overweight patients.Young age,larger tumor size,and multifocality in overweight males,and young age and larger tumors in overweight females indicate a higher risk of metastasis.It is recommended that high-risk populations receive enhanced preoperative evaluation and individualized lymph node dissection strategies to achieve precise treatment and improved risk control.

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Liver size is regulated by circadian clock and exhibits a diurnal rhythm. Pregnane X receptor (PXR) and peroxisome proliferator-activated receptor α (PPARα), members of nuclear receptor superfamily, are important regulators of liver size. We previously demonstrated that mPXR agonist pregnenolone 16α-carbonitrile (PCN) and mPPARα agonist pirinixic acid (WY-14643) promoted liver enlargement and liver regeneration after partial hepatectomy. However, whether PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations remains unclear. The aim of this study was to investigate the diurnal rhythm of PXR or PPARα activation-induced liver enlargement. Male C57BL/6 mice were intraperitoneally injected with corn oil, PCN or WY-14643 for three days, and liver samples were weighed and collected at various time points for analysis. The animal experiment protocol was reviewed and approved by Institutional Animal Care and Use Committee of Sun Yat-sen University (approval No. SYSU-IACUC-2023-001613, SYSU-IACUC-2023-001783). The results showed that PXR or PPARα activation at various time points significantly induced liver enlargement, and liver size maintained normal diurnal oscillations during PXR or PPARα activation-induced hepatomegaly, without significant effects on the expression of core clock genes. This study reveals PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations, and provides novel data for nuclear receptor-induced liver enlargement and liver diurnal rhythm.

Oxidative Phosphorylation ; Acetylglucosamine ; Uridine Diphosphate N-Acetylglucosamine/metabolism*

Objective: To analyze the status of statins use and low-density lipoprotein cholesterol (LDL-C) management in patients with atrial fibrillation (AF) and very high/high risk of atherosclerotic cardiovascular disease (ASCVD) from Chinese Atrial Fibrillation Registry (CAFR). Methods: A total of 9 119 patients with AF were recruited in CAFR between January 1, 2015 to December 31, 2018, patients at very high and high risk of ASCVD were included in this study. Demographics, medical history, cardiovascular risk factors, and laboratory test results were collected. In patients with very high-risk, a threshold of 1.8 mmol/L was used as LDL-C management target and in patients with high risk, a threshold of 2.6 mmol/L was used as LDL-C management target. Statins use and LDL-C compliance rate were analyzed, multiple regression analysis was performed to explore the influencing factors of statins use. Results: 3 833 patients were selected (1 912 (21.0%) in very high risk of ASCVD group and 1 921 (21.1%) in high risk of ASCVD group). The proportion of patients with very high and high risk of ASCVD taking statins was 60.2% (1 151/1 912) and 38.6% (741/1 921), respectively. Attainment rate of LDL-C management target in patients with very high and high risk were 26.7% (511/1 912) and 36.4% (700/1 921), respectively. Conclusion: The proportion of statins use and attainment rate of LDL-C management target are low in AF patients with very high and high risk of ASCVD in this cohort. The comprehensive management in AF patients should be further strengthened, especially the primary prevention of cardiovascular disease in AF patients with very high and high risk of ASCVD.
Humans ; Atrial Fibrillation/drug therapy* ; Cardiovascular Diseases ; Cholesterol, LDL ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Atherosclerosis ; Dyslipidemias/drug therapy*

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.

Rhein is an anthraquinone compound extracted from rhubarb, aloe vera, Polygonum multiflorum. In this study, we screened the potential targets of rhein through protein chip technology and investigated the underlying mechanism of its inhibition of colorectal cancer. Colony formation assay and scratch assay were used to examine the effect of rhein on the proliferation and migration abilities of HCT116 cell; KEGG and protein interaction analyses of rhein specific binding proteins by screening rhein binding proteins using protein chip; qRT-PCR and Western blot assays were used to determine the effect of rhein on the expression levels of BCL-2-associated X protein (BAX), B-cell lymphoma-2 (BCL-2) and argininosuccinate synthetase 1 (ASS1) in HCT116 cell. The antitumor effect of rhein was verified by azoxymethane combined with dextran sodium sulfate (AOM/DSS) induced colorectal cancer model. Experimental animal procedures were performed in accordance with animal welfare and the standards of the Laboratory Animal Ethics Committee of South China Agricultural University, with approval from the ethics committee. In vivo and in vitro results indicate that rhein specific binding proteins are mainly involved in amino acid anabolism, especially the arginine anabolic signaling pathway. Rhein inhibited the proliferation and migration of HCT116 cell in a concentration-dependent manner. Treated with rhein for 24 h significantly enhanced the expression of BAX and ASS1 in HCT116 cells, as well as the level of nitric oxide (NO) metabolism. In a mouse model of colorectal cancer, rhein significantly alleviated AOM/DSS induced weight loss and reduced fecal occult blood score. Meanwhile, rhein enhanced BAX and ASS1 expression in colon tumor tissue, as well as increased arginine and NO in serum. IHC and HE stain indicated that rhein alleviated Ki67 expression and macrophage infiltration in the colonic tissue of mice with AOM/DSS and delayed tumor formation. In conclusion, rhein can exert antitumor activity by regulating arginine and NO metabolism through ASS1.

Objective: We investigated changes in the intestinal flora of children with Mycoplasma pneumoniae pneumonia (MPP). Methods: Between September 2019 and November 2019, stool samples from 14 children with MPP from The Fourth Hospital of Baotou city, Inner Mongolia Autonomous Region, were collected and divided into general treatment (AF) and probiotic (AFY) groups, according to the treatment of "combined Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus cereus tablets live". High-throughput 16S rDNA sequencing was used to identify intestinal flora. Results: Intestinal flora abundance and diversity in children with MPP were decreased. Both Shannon and Simpson indices were lower in the AF group when compared with healthy controls ( P < 0.05). When compared with healthy controls, the proportion of Enterorhabdus was lower in the AF group, while the proportion of Lachnoclostridium was higher ( P < 0.05). The proportion of Bifidobacteria and Akkermansia was lower in the AFY group but Enterococcus, Lachnoclostridium, Roseburia, and Erysipelatoclostridium proportions were higher. The proportion of Escherichia coli- Shigella in the AFY group after treatment was decreased ( P < 0.05). Conclusions The intestinal flora of children with MPP is disturbed, manifested as decreased abundance and diversity, and decreased Bifidobacteria. Our probiotic mixture partly improved intestinal flora disorders.
Child ; DNA, Ribosomal ; Escherichia coli ; Gastrointestinal Microbiome ; Humans ; Mycoplasma pneumoniae ; Pneumonia, Mycoplasma ; Technology