Esophageal squamous cell carcinoma(ESCC)is a major histological subtype of esopha-geal cancer with a poor prognosis.Although several serum metabolomic investigations have been reported,ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined.Here,we enrolled 34 treatment-naive patients with ESCC and collected their pre-and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabo-lomic survey.Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites.Notably,postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome.Furthermore,we performed an examina-tion using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans.Notably,among these metabolites,the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization,and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice.Furthermore,this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest.Together,this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitor-ing therapeutic efficacy and disease relapse,presented evidence for refining parenteral nutrition composition,and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

The mechanisms underlying pregnancy complications caused by advanced maternal age(AMA)remain unclear.We analyzed the cellular signature and transcriptomes of human placentas in AMA women to elucidate these mechanisms.Placental tissues from two AMA women and two controls were used for single-cell RNA-sequencing(scRNA-seq).Controls consisted of AMA women who did not experience any pregnancy complications and pregnant women below the age of 35 years without pregnancy complications.Trophoblast cells were obtained from the placentas of another six pregnant women(three AMA women and three controls),and in-vitro transwell assays were conducted to observe the cell invasion ability.Thirty additional samples(from 15 AMA women and 15 controls)were analyzed to verify the specific expression of serine protease inhibitor clade E member 1(SERPINE1).Preliminary study of the role of SERPINE1 in cell invasion was carried out with HTR8-S/Vneo cells.High-quality transcriptomes of 27 607 cells were detected.Three types of trophoblast cells were detected,which were further classified into eight subtypes according to differences in gene expression and Gene Ontology(GO)function.We identified 110 differentially expressed genes(DEGs)in trophoblast cells between the AMA and control groups,and the DEGs were enriched in multiple pathways related to cell invasion.In-vitro transwell assays suggested that the invading trophoblast cells in AMA women were reduced.SERPINE1 was specifically expressed in the trophoblast,and its expression was higher in AMA women(P＜0.05).Transfection of human SERPINEl(hSERPINE1)into HTR8-S/Vneo trophoblast cells showed fewer invading cells in the hSERPINE1 group.Impaired cell invasion may underlie the increased risk of adverse pregnancy outcomes in AMA women.Abnormal expression of SERPINE1 in extravillous trophoblast(EVT)cells appears to play an important role.

Objective:To explore the influencing factors of all-cause death in patients with acute myocardial infarction (AMI) and renal insufficiency(RI), and establish a clinical prediction tool.Methods:Collected 727 patients who were hospitalized in Beijing Anzhen Hospital from January 1st 2014 to April 31th 2019, and diagnosed as AMI with RI. Recorded the patients' baseline characteristics, past medical history, current complications, laboratory and auxiliary examination results, treatment methods (included target vessel reconstruction methods, medications, etc.), and follow-up patients for all-cause deaths. Firstly, multivariate Cox regression analysis was used to construct the model in the training set(485 cases). Secondly, the receiver operating characteristic curve ( ROC), calibration curve and clinical decision curve analysis (DCA) were drawn in the validation set(242 cases) to further verify the effect of the prediction model. Finally, a nomogram was developed based on the verified risk factors. Results:Multivariate Cox regression analysis found that there were nine predictors for the prognosis of all-cause death in patients with AMI & RI, the dangerous factors included women, comorbidities, high direct bilirubin, cardiogenic shock, respiratory failure, co-infection and hemofiltration; the protective factors included PCI and taking aspirin. Model evaluation results showed that the AUC of the validation set was 0.82; the calibration line was close to the ideal calibration line, and the slope≈1, the intercept≈0, and the fitting effect was good. Clinical decision-making when the all-cause mortality rate was 35%, the net benefit of active intervention patients based on the Cox model was 38%. A visual nomogram model was developed based on the prognostic risk factors that have been evaluated and predicted to be good. Conclusion:Women, with a history of comorbidities, direct high bilirubin, combined with cardiogenic shock, combined with respiratory failure, combined infection, hemofiltration, PCI and taking aspirin, these nine factors will affect all causes of AMI & RI. For the probability of death, the model developed in this research has high accuracy.

Objective:To explore the correlation between preoperative serum hyaluronic acid (HA) level and prognosis of breast cancer patients.Methods:The 98 patients with breast cancer who underwent surgical treatment in the Oncology Department of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2004 to November 2014 in a historical cohort were included, aged (52.5±9.4) years.The preoperative serum HA contents of the patients were detected. According to the median of 53.7 μg/L, the patients were divided into high and low groups with 49 patients in each group.The χ 2 test was used to analyze the correlation between the serum HA content and the general clinical data of the patients, and the Kaplan-Meier method, Log-rank test and multivariate Cox regression model wereusedto analyze the correlation between HA content and patients′ survival. Results:The percentages of patients with high HA levels in menopause and non-menopause patientswere 55.7% and 40.5%, respectively; in progesterone receptor (PR) positive and negative patients were 54.1% and 43.2%, respectively; in estrogen receptor (ER) positive and negative patients were 45.7% and 60.7%, respectively; in Ki-67 positive and negative patients were 55.6% and 43.2%, respectively; in the tumor size stage TⅠ, TⅡ, TⅢ, and TⅣ patients were 50.0%, 41.7%, 72.7%, and 1/1, respectively; in lymph node metastasis and non-metastasispatients were 45.7% and 53.8%, respectively. There was no significant correlation between the level of HA and the menopausal status, the expressions of PR, ER and Ki-67, tumor size, and lymph node metastasis in breast cancer patients (χ2=2.128, 1.086, 1.800, 1.485, 4.273, 0.656, P>0.05). Patients with high HA levels accounted for 30.9% of patients aged 52 years or less and 74.4% of patients older than 52 years (χ2=18.274, P=0.000); 43.4% of patients with early TNM and 72.7% of patients with advanced TNM (χ2=5.861, P=0.015); 45.2% of patients without distant metastasis and 78.6% of patients with distant metastasis (χ2=5.333, P=0.023); 38.1% of Her-2 negative patients and 58.9% of Her-2 positive patients(χ2=4.167, P=0.041); and the median survival of patients with high HA levels was 70 months, which was shorter than 83 months for patients with low HA levels (χ2=6.799, P=0.007). Therefore, ahigh HA content predicts an older age, a later tumor stage, higher risk of distant metastasis, positive expression of Her-2 and shorter survival. Multivariate Cox regression model analysis suggested that high levels of serum HA may be a risk factor for patients′ survival, with HR (95% CI) value of 9.98 (1.16-85.88) and P value of 0.036. Conclusion:The high level of preoperative serum HA has a certain correlation with the poor prognosis of breast cancer patients.

Objective:To explore the correlation between preoperative serum hyaluronic acid (HA) level and prognosis of breast cancer patients.Methods:The 98 patients with breast cancer who underwent surgical treatment in the Oncology Department of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2004 to November 2014 in a historical cohort were included, aged (52.5±9.4) years.The preoperative serum HA contents of the patients were detected. According to the median of 53.7 μg/L, the patients were divided into high and low groups with 49 patients in each group.The χ 2 test was used to analyze the correlation between the serum HA content and the general clinical data of the patients, and the Kaplan-Meier method, Log-rank test and multivariate Cox regression model wereusedto analyze the correlation between HA content and patients′ survival. Results:The percentages of patients with high HA levels in menopause and non-menopause patientswere 55.7% and 40.5%, respectively; in progesterone receptor (PR) positive and negative patients were 54.1% and 43.2%, respectively; in estrogen receptor (ER) positive and negative patients were 45.7% and 60.7%, respectively; in Ki-67 positive and negative patients were 55.6% and 43.2%, respectively; in the tumor size stage TⅠ, TⅡ, TⅢ, and TⅣ patients were 50.0%, 41.7%, 72.7%, and 1/1, respectively; in lymph node metastasis and non-metastasispatients were 45.7% and 53.8%, respectively. There was no significant correlation between the level of HA and the menopausal status, the expressions of PR, ER and Ki-67, tumor size, and lymph node metastasis in breast cancer patients (χ2=2.128, 1.086, 1.800, 1.485, 4.273, 0.656, P>0.05). Patients with high HA levels accounted for 30.9% of patients aged 52 years or less and 74.4% of patients older than 52 years (χ2=18.274, P=0.000); 43.4% of patients with early TNM and 72.7% of patients with advanced TNM (χ2=5.861, P=0.015); 45.2% of patients without distant metastasis and 78.6% of patients with distant metastasis (χ2=5.333, P=0.023); 38.1% of Her-2 negative patients and 58.9% of Her-2 positive patients(χ2=4.167, P=0.041); and the median survival of patients with high HA levels was 70 months, which was shorter than 83 months for patients with low HA levels (χ2=6.799, P=0.007). Therefore, ahigh HA content predicts an older age, a later tumor stage, higher risk of distant metastasis, positive expression of Her-2 and shorter survival. Multivariate Cox regression model analysis suggested that high levels of serum HA may be a risk factor for patients′ survival, with HR (95% CI) value of 9.98 (1.16-85.88) and P value of 0.036. Conclusion:The high level of preoperative serum HA has a certain correlation with the poor prognosis of breast cancer patients.

Objective To investigate the relationship between sex hormone binding globulin (SHBG) in serum and diabetic retinopathy (DR) in patients with type 2 diabetic mellitus (T2DM).Methods A total of 160 hospitalized people with T2DM was enrolled into the study.The patients were divided into two groups with or without merged DR.Clinical and laboratorial data were collected, and the correlation was analyzed between sex hormone binding globulin and diabetic retinopathy.Results (1) Compared to the group without DR, patients in T2DM with DR had significant lower SHBG concentration, triglyceride (TG) and total cholesterol (TC) concentration were increased significantly (P ＜ 0.01).(2) The level of SHBG was associated with waist circumference, body weight, fasting blood glucose, and glycosylated hemoglobin (P ＜ 0.05).(3) While the level of SHBG was significantly increased from Quartile 1 to Quartile4, the prevalence of DR was also significantly decreased (A:70％, B:51.2％,C:40.5％, D:29.7％) (P ＜ 0.01).(4) Logistic regressing analysis shows that with the decrease of SHBG level, the increase of triglyceride levels, the risk of DR was significantly increased (SHBG:OR:0.616,95％ CI:0.447-0.850,P ＜ 0.01;TG:OR:1.323,95％ CI:1.025-1.707,P＜0.05).Conclusions With the decrease of SHBG, the prevalence of DR is significantly increased, lower SHBG may be one of the hazards of T2DM patients with DR.

Objective To investigate the relationship between with or without non?alcoholic fatty liver disease(NAFLD) and diabetic retinopathy(DR) in type 2 diabetes mellitus(T2DM)?Methods Clinical and laboratorial data of 517 cases T2DM hospitalized patients were collected,and the patients were divided into two groups according to if the NAFLD was complicated or not?Group A was T2DM with NAFLD and group B was T2DM without NAFLD?The general information and the laboratorial checking results were Compared, then various index were used as the independent variable, DR was used as the dependent variable for Logistic regression analysis?Results (1)In the 517 cases of T2DM patients,the incorporative rate of the NAFLD was 65?7%(349/517)?(2)Compared with group B,the levels of body mass index(BMI),insulin resistance index (HOMA?IR),glutamyltransferase(GGT),alanine aminotransferase(ALT),aspartate aminotransferase(AST), triglyceride(TG),total cholesterol(TC),low?density lipoprotein cholesterol(LDL?C) and uric acid(UA) for group A were significantly increased, while the high?density lipoprotein cholesterol ( HDL?C ) level was significantly decreased?All the differences were statistically significant( P<0?05)?( 3) Logistic analysis showed that the duration of the extension,hypertension,the increasing level of NAFLD,LDL?C were the risk factors of DR?Even though excluded the influence of duration,high blood pressure and LDL?C level,NAFLD was still the risk factor for T2DM complicated by the DR( OR=2?176,95% CI ( 1?354,3?199) )?Conclusion NAFLD and DR are closely related, so early diagnosis and intervention of NAFLD may prevent the occurrence and development of DR.

OBJECTIVE: The aim of this study was to find if systemic family therapy (SFT) does work in anxiety and depression with epilepsy in adolescents (ADAE). METHODS: 104 adolescents with epilepsy, aged 13-20 years old, were included from December 2009 to December 2010, the enrolled patients were with anxiety [Hamilton Anxiety Scale (HAMA) score ≥14 points] or depression [Hamilton Depression Scale (HAMD) score ≥20 points]. The patients were randomly divided into the control group (n=52) treated with antiepileptic drugs (AED) and the intervention group (n=52) undergone Systemic Family Therapy (SFT) as well as AED. The AED improvements, anxiety and depression scores, Social Support Rating Scale (SSRS), Family Assessment Device (FAD) and scale of systemic family dynamics (SSFD) were observed after 3-month treatment. RESULTS: The frequencies of epileptic seizures in intervention group was decreased much more significantly than the control group (4.22±3.54 times/month vs. 6.20±5.86 times/month, p=0.04); and the scores of anxiety (9.52±6.28 points vs. 13.48±8.47 points, p=0.01) and depression (13.86±9.17 points vs. 18.89±8.73 points, p=0.02) were significantly decreased than the control group; meanwhile, the family dynamics and family functions were significantly improved, and the social support was also increased (p<0.05). CONCLUSION: SFT combined with AEDs had better efficacies than AEDs alone, not only the frequency of epileptic seizures was decreased, but also the patients' anxiety and depression were improved, and the family dynamics, family functions and social support were improved.
Adolescent* ; Anticonvulsants ; Anxiety* ; Comorbidity* ; Depression* ; Epilepsy* ; Family Therapy* ; Humans

Objective To investigate the application of alpha-fetoprotein (AFP),α-L-fucosidase(AFU),5'-nucleotidase(5'-NT) and γ-glutamyltransferase (GGT) in diagnosis of hepatocellular carcinoma(HCC),and to provide the basis for its early and rapid diagnosis.Methods The clinical data of 120 cases with initial diagnosis as hepatocellular carcinoma,150 cases with liver cirrhosis,200 cases with hepatitis were analyzed retrospectively from June 2013 to August 2014,meanwhile,100 healthy people were selected as control group.The serum AFP,AFU,5'-NT and GGT levels were measured by electrochemiluminescence immunoassay,rate method,peroxidase method and enzymatic colorimetric assay,respectively.The results were analyzed by receiver operating characteristic (ROC) curve,while the sensitivity,specificity,AUC were calculated at the same time.Results The levels of serum AFP,AFU,5'-NT and GGT were significantly different among HCC group,liver cirrhosis group,hepatitis group and control group (all P＜0.05).When tested alone,the sensitivities of AFP,AFU,5'-NT and GGT were 58.33 ％(70/120),82.50 ％(99/120),85.00 ％(102/120),78.33 ％(94/120),the specificities were 88.33 ％(106/120),73.33 ％(88/120),88.33 ％(106/120),71.67 ％(86/120),and AUC were 0.655,0.702,0.814,0.754.When four indexes were performed with combined test,the sensitivity was 98.33 ％(118/120),specificity was 96.67 ％(116/120),AUC was 0.975,which were higher than the single detection (all P＜0.05).Conclusion The combined detection of serum AFP,AFU,5'-NT and GGT can greatly increase the sensitivity and specificity for diagnosing HCC and will gain mutual complement advantages,which is of great clinical value for early and rapid diagnosis.

Objective To explore the clinical application of single or combined detection of serum Cys-C,5'-NT and AFP in hepatocellular carcinoma (HCC) in order to provide the platform for early diagnosis and prognosis evaluation.Methods The serum levels of Cys-C,5'-NT and AFP from 148 cases of HCC patients (HCC group),135 cases of liver cirrhosis patients (LC group) and 155 cases of hepatitis (hepatitis group) and 100 healthy people (control group) were measured by latex-enhanced immunoturbidimetric assay (LEITD),peroxidase method and electrochemiluminescence immunoassay (ECLI),respectively.Then their differences had been compared.The sensitivity,specificity and Youden's index were calculated and the results were analyzed by receiver operating characteristic (ROC) curve.Results The levels of serum Cys-C,5'-NT and AFP were significantly different in 4 groups.The differences were statistically significant (F =12.35,42.25,58.12,P =0.000).The sensitivity of three indicators for diagnosing HCC was 100 ％,which was higher than that of single or two combined detection (P ＜ 0.05),and the specificity was 78.97 ％.The area under ROC curves of combined detection of three indicators was 0.977,which was also higher than single or two combined detection (P ＜ 0.05).Conclusions The combined detection of serum Cys-C,5'-NT and AFP can greatly increase the sensitivity and accuracy for diagnosing HCC,which has an important clinical value for early diagnosis.Therefore it is worth popularizing and applying on clinic.