ObjectiveTo investigate the expression of serum Aldo-keto reductase family 1 member B10 （AKR1B10） in patients with hepatocellular carcinoma （HCC） in northern China， and to provide a new and valuable biomarker for the clinical diagnosis of HCC. MethodsThis study was conducted among 102 patients with HCC， 119 patients with benign liver disease， and 132 patients with other malignant tumors who attended The Affiliated Hospital of Chengde Medical University and 148 healthy individuals who underwent physical examination from May 2020 to May 2024. ELISA and chemiluminescence were used to measure the serum levels of AKR1B10 and alpha-fetoprotein （AFP）. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between three groups and further comparison between two groups； the chi-square test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to assess diagnostic efficiency. ResultsThe expression level of AKR1B10 was 3 053.79 （1 475.67‍ ‍—‍ ‍4 605.86） pg/mL in the HCC group， 1 324.42 （659.68‍ ‍—‍ ‍2 023.88） pg/mL in the benign liver disease group， 660.68 （377.56‍ ‍—‍ ‍2 087.77） pg/mL in the other malignant tumor group， and 318.30 （82.73‍ ‍—‍ ‍478.82） pg/mL in the healthy group， with a significant difference between the four groups （H=240.86， P<0.001）， and further comparison between two groups showed that the HCC group had a significantly higher level than the other three groups （all P<0.001）. The ROC curve analysis of the HCC group and the other three groups showed that serum AKR1B10 had an optimal cut-off value of 1 584.97 pg/mL in the diagnosis of HCC， with an AUC of 0.86 （95% confidence interval ［CI］： 0.82‍ ‍—‍ ‍0.90）， a sensitivity of 74.3%， and a specificity of 85.2%. Compared with each indicator alone， a combination of AKR1B10 and AFP could improve the sensitivity （81.8%） and specificity （91.4%） of HCC diagnosis. AKR1B10 had an AUC of 0.84 （95%CI： 0.78‍ ‍—‍ ‍0.90） in the diagnosis of patients with early- or middle-stage HCC， with a sensitivity of 76.2% and a specificity of 81.2%. AKR1B10 had an AUC of 0.85 （95%CI： 0.77‍ ‍—‍ ‍0.92） in the diagnosis of patients with AFP-negative HCC， with a sensitivity of 81.6% and a specificity of 79.9%. ConclusionAKR1B10 is a promising serological marker for the diagnosis of HCC， and a combination of AKR1B10 and AFP can improve the detection rate of HCC patients in northern China， especially those with early- or middle-stage HCC and AFP-negative HCC.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective To explore the correlation between thyroid antibody levels and early renal injury in patients with type 2 diabetes mellitus(T2DM)combined with Hashimoto's thyroiditis(HT).Methods A total of 375 T2DM patients hospitalized in The Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2022 were selectedas the study subjects,and 197 healthy people were selected as the control subjects.The patients with T2DM were divided into simple T2DM group(n=191)and T2DM combined with HT group(HT,n=184).According to the urinary albumin/creatinine ratio(UACR)level,T2DM patients with HT were divided into microalbuminuria subgroup(MUAlb,30≤UACR≤300 mg/g,n=70)and normal albuminuria subgroup(NUAlb,UACR<30 mg/g,n=114).According to whether the thyroid antibody was positive,they were divided into thyroid peroxides antibody[TPOAb(+)]subgroup(n=56),thyroglobulin antibody[TGAb(+)]subgroup(n=40)and TGAb and TPOAb double antibody positive subgroup(n=88).Results Compared with the NC group,the smoking,drinking,urinary creatinine,alpha 1-microglobulin,UACR,FPG,HbA1c,LDL-C,TC,and TG in the HT and T2DM groups increased(P<0.05),while HDL-C decreased(P<0.05).Compared with the NUAlb subgroup,the MUAlb subgroup showed age,DM duration,FPG,HbA1c,TGAb,TPOAb,thyroid stimulating hormone(TSH)increased(P<0.05),while FT3 and eGFR decreased(P<0.05).Spearman correlation analysis showed that UACR was positively correlated with age,HbA1c,TPOAb,TGAb,TSH(P<0.01),and negatively correlated with FT3(P<0.01).The UACR of the TGAb(+)+TPOAb(+)subgroup was higher than that of the TGAb(+)and TPOAb(+)subgroups(P<0.05).Logistic regression analysis showed that TSH,TGAb,TPOAb,and HbA1c were risk factors for MUAlb,while FT3 was a protective factor for MUAlb.Conclusions In T2DM with HT patients with normal thyroid function,TPOAb and TGAb are closely related to the occurrence of early renal injury.

OBJECTIVE To op timize the i ntegrated technology of producing area processing and decoction pieces processing of Curcuma longa （hereinafter refer to “integrated technology ”）. METHODS The content of ethanol-soluble extract in C. longa was determined by hot leaching method ；the contents of curcumin ，demethoxycurcumin and bisdemethoxycurcumin were determined by high performance liquid chromatography. On the basis of identification of producing area processing technology ， Using overall desirability （OD） value of the contents of ethanol-soluble extract ， curcumin， demethoxycurcumin and bisdemethoxycurcumin as evaluation indexes ，moisture content ，slice thickness and drying temperature as factors ，the integrated technology of C. longa was optimized by single factor tests combined with central composite design-response surface method ，and the validation tests were conducted. At the same time ，prepared product was compared with traditional decoction pieces prepared according to 2020 edition of Chinese Pharmacopoeia （part Ⅰ）. RESULTS The best integrated technology was that the fresh C. longa was boiled in boiling water for 5 min，dried at 50 ℃ to 40％ water content ，cut into 2 mm thin slices ，and dried at 50 ℃ until moisture content not exceeding 15.0％. After validation ，The deviation between the average OD value （0.811 3，RSD＝2.13％） and the predicted value （0.848 1）of the contents of ethanol-soluble extract ，curcumin，demethoxycurcumin and bisdemethoxycurcumin was 4.34％. OD value of the contents of ethanol-soluble extract ，curcumin，demethoxycurcumin and bisdemethoxycurcumin in decoction pieces prepared by integrated technology were all higher than those prepared by traditional technology. CONCLUSIONS The process optimized in this study is simple ，stable and feasible.

Objective:To identify the causative genes of sporadic thoracic aortic aneurysm or dissection (TAAD) and their correlation with clinical phenotype in the southern Chinese.Methods:We analyzed 11 core genes of TAAD probands without specific family history of 226 cases by next-generation sequencing technology, and performed sanger sequencing for their close relatives. Clinical data of each patient, including age of onset, syndromic phenotypes, involvement of aortic root, aortic maximum diameter and D-dimer were collected. And statistical software SPSS was used to evaluate the correlation between clinical phenotypes and gene mutations.Results:A total of 106 variants were detected in 226 probands with gene-positive frequency of 44.69%, consist of 16 pathogenic (P) variants, 18 likely pathogenic (LP) variants and 71 variants of uncertain significance (VUS). More than half of the mutations were from the non-syndromic TAAD, in which the FBN1 still was the most common causative gene. Earlier age of onset, an increase of women, larger diameter of aorta, Stanford B dissection and severe aortic regurgitation were likely to occur on carriers of P/LP, while thoracic aortic aneurysm occurs on carriers of VUS. Phenotype of both syndrome and dissection with aneurysm could increase the likelihood of carrying gene mutation, but D-dimer and involvement of aortic root couldn’t.Conclusion:Patients with sporadic aortic diseases in southern China have significant genetic heterogeneity and specific correlation between their clinical phenotype and gene mutation, especially in non-syndromic population. Earlier age of onset in carriers of FBN1 or ACTA2 genes, and larger maximum diameters of aorta in carrier of P/LP.

OBJECTIVE: To explore genetic mutation types and their correlation with clinical phenotypes in Uighur patients with aortic disease in Kashgar (Xinjiang Uighur Autonomous Region, China). METHODS: We examined 37 pathogenic genes in 19 Uighur families with aortic diseases including Marfan syndrome from Kashgar using next generation sequencing, and the results were confirmed by Sanger sequence in the first relatives. RESULTS: This study included 19 families with aortic diseases, in whom a total of 23 variants were identified, and 11 (57.89%) probands had one or more variants. Among them, definite pathogenic mutation was detected in one patient (5.26%), variants of uncertain significance (VUS) were found in 8 (42.11%), and benign/likely benign variants were detected in 7 (36.84%). The 23 variants identified included one (5.26%) pathogenic variant, 14 (60.87%) VUS, and 8 (34.78%) benign/likely benign variants. The 14 VUS were analyzed by prediction with SIFT and Polyphen2 HDIV, which identified 6 (42.86%) variants as deleterious/possibly damaging; all the 8 benign/likely benign variants were predicted to be deleterious/possibly damaging. CONCLUSIONS We detected 23 genetic variants in the 19 Uighur families with aortic diseases, and 22 of these variants remain to be verified by more patient data in future studies.
Aortic Diseases ; China ; Genetic Predisposition to Disease/genetics* ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Phenotype

Objective To study the clinical value of anti-oxidative stress biomarkers for diagnosing in-stent restenosis and in-reocclusion after coronary stent implantation in aged patients.Methods A total of 72 advanced-aged patients with in-stent restenosis and in-stent reocclusion after coronary stent implantation were successively recruited in this retrospective study from February 2010 to November 2017.Changes in serum superoxide dismutase 3(SOD3),nitric oxide(NO),endothelial cell nitric oxide synthase(eNOS)and malondialdehyde(MDA)levels were measured.Results Serum 1evels of SOD3,NO and eNOS decreased and serum MDA levels were elevated in advanced-aged patients with in-stent restenosis.There were significant differences in serum levels of SOD3,NO,eNOS and MDA between the advanced-aged patients without in-stent restenosis and the advanced-aged patients with multivessel in-stent restenosis or reocclusion[(20.0±3.2) × 103U/L vs.(10.9±3.9) ×103U/L,(61.2±14.2)μmol/L vs.(28.3±17.2)μmol/L,(75.9±24.7)ng/L vs.(33.0±119.6)ng/L,(2.2±1.4)nmol/L vs.(11.7±3.1)nmol/L,respectively,P＜0.01].Patients with 50-69％ restenosis had higher serum levels of SOD3,NO and eNOS and lower levels of MDA than patients with 100％ restenosis[(21.3 ± 2.9) × 103 U/L vs.(10.3 ± 4.0) × 103 U/L,(59.7 ± 16.7) μmol/L vs.(38.3 ±16.3)μmol/L,(74.5±21.1)ng/L vs.(41.9±26.8)ng/L,(2.6±3.9 nmol/L)vs.(10.1±3.1)nmol/L,respectively,P ＜ 0.01].Patients with left ventricular ejection fraction (LVEF) ≥ 55 ％ had higher serum levels of SOD3,NO and eNOS and lower levels of MDA than patients with LVEF＜30％ [(21.0±4.1) × 103 U/L vs.(5.3±1.9) × 103 U/L,(60.1 ± 14.2)μmol/L vs.(29.0± 13.2)μmol/L,(74.7±25.1)ng/L vs.(39.3 ± 20.3) ng/L,(2.3 ± 1.5) nmol/L vs.(10.0 ± 3.9) nmol/L,respectively,P ＜0.01].Serum levels of SOD3,NO and eNOS were higher and MDA levels were lower in patients with New York Heart Association(NYHA)Class Ⅰ than in patients with NYHA Class Ⅳ[(22.1±3.5)×103U/L vs.(9.7±2.9) × 103 U/L,(62.9± 13.9)μmol/L vs.(24.9± 13.3)μmol/L,(76.7±26.7) ng/L vs.(41.9±21.5)ng/L,(2.7± 1.9)nmol/L vs.(8.7±3.8)nmol/L,respectively,P＜0.01].Conclusions Serum level changes of anti-oxidative stress biomarkers such as SOD3,NO and eNOS may have clinical value in diagnosing in-stent restenosis and in-reocclusion after coronary stent implantation in aged patients.

Objective To reveal pathogenesis and etiology in adrenal incidentaloma. Methods The clinical data of 116 patients with adrenal incidentaloma from January 1, 2015 to January 1, 2017 were retrospectively analyzed. Results In 116 patients with adrenal incidentaloma, 49 cases (42.2％) were male and 67 cases (57.7％) were female; there were 14 cases (12.1％) aged from 20 to 40, 63 cases (54.3％) aged from 40 to 60, and 39 cases (33.6％) > 60 years. Forty-three patients (37.1％) were found by health examination, 26 patients (22.4％) were found because of hypertension, 27 patients (23.3％) were found by CT detection because of other diseases, and 20 cases (17.2％ ) were found because of other reasons. The result of endocrine function examination showed that nonfunctioning adrenal tumor was in 56 cases (48.3％); functional adrenal tumor was in 44 cases (37.9％), among whom primary aldosteronism was in 27 cases, Cushing syndrome was in 10 cases, and pheochromocytoma was in 7 cases;nonfunctioning non- adenoma was in 16 cases (13.8％ ). Conclusions It is frequent that the adrenal incidentaloma is found by health examination. The patients with adrenal incidentaloma should examine the endocrine function and identify the benign or malignant. And if necessary, surgical treatment should be performed.

Objective To investigate risk factors for in-stent restenosis and reocclusion after coronary stent implantation in aged patients.Methods 131 patients diagnosed with chronic total occlusion and old myocardial infarction due to coronary stenosis were recruited in this retrospective study from Mar 2004 to May 2015.Patients were divided into 50 to 59 years old group (n=51),60 to 69 years old group (n=43),and 70 to 80 years old group (n=37) to study coronary lesion characteristics.In-stent restenosis and reocclusion were detected at 6,12,18,and 24 months after coronary stent implantation.Results Before coronary stent implantation,the incidence rate of type 2 diabetes was significantly increased with three increasing age groups:9.8％ at ages 50-59 group (n=5),18.6％ at ages 60-69 group (n=8),and 27.0％ at ages 70-80 group (n=10) (all-P＜0.01).The incidence rates of multiple coronary artery disease,long coronary lesions (＞20 mm),eccentric coronary lesions,serious angle of coronary lesions,irregular coronary lesions,proximal coronary curvature,moderate to severe calcified coronary lesions,coronary restenosis (90％-99％ or 100％),and complex bifurcation lesions were significantly elevated with three increasing age groups (P ＜0.01 or P ＜0.05).The ratios of patients with in-stent restenosis at 24 months after coronary stent implantation were significantly elevated with three increasing age groups:at 9.8％ (n=5),18.6％ (n=8),and 27.0％(n=10) for 90％ 99％ restenosis sub-group,and at 5.9％ (n=3),14.0％ (n=6) and 24.3％ (n=9) for 100％ restenosis sub-group,respectively (all P＜0.05 or P＜0.01)Conclusions Type 2 diabetes is an independent risk factor for complex coronary lesions in aged patients Complex coronary lesions,three or more stents,and long coronary stents may lead to ir-stent restenosis and reocclusion after coronary stent implantation in aged patients.

Objective To explore the effect of infrared spectral analysis in analyzing of the chemical composition of renal staghorn calculi and its relationship with urinary tract infections. Methods From June 2014 to June 2016, the clinical data of 186 patients with renal staghorn calculi were collected. The stone composition were analyzed by infrared spectroscopy and traditional chemical titration, and the stones infection were detected by microbial analysis system. The relation between stones infection, urinary tract infection and stone composition were analyzed. Results The results of infrared spectroscopy and traditional chemical titration in detecting renal staghorn calculi ingredient had no significant differences (P>0.05). In 186 patients, 56 patients (30.11%) was in infected group, and 130 patients (69.89%)was in non-infected group. The abnormal urine rate, urinary tract infection rate, medistream urine positive infection rate and cotton swabs positive infection rate in infected group were was significantly higher than those in non-infected group: 73.21%(41/56) vs. 50.77%(66/130), 19.64%(11/56) vs. 3.85%(5/130), 50.00%(28/56) vs. 6.15%(8/130), 67.86%(38/56) vs. 8.46%(11/130), P<0.01. The carbonate apatite stones rate and six water magnesium ammonium phosphate rate in infected group were significantly higher than those in non-infected group: 21.43%(12/56) vs. 5.37%(7/130), 57.14%(32/56) vs. 2.31%(3/130), P<0.01. The calcium oxalate rate and uric acid rate in non-infected group were significantly higher than those in infected group:50.00%(65/130) vs. 5.36%(3/56), 24.62%(32/130) vs. 1.79%(1/56), P<0.01. Conclusions Analysis of staghorn calculi ingredient caused by urinary bacterial infection with infrared spectroscopy is simple, reliable and easy to operate. It is important for postoperative infection prevention.