Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Lung Neoplasms/diagnosis* ; Retrospective Studies ; Autoantibodies ; Bayes Theorem ; Tumor Suppressor Protein p53 ; Carcinoembryonic Antigen ; Antigens, Neoplasm ; Biomarkers, Tumor ; Algorithms ; Pneumonia

Male ; Humans ; Germ-Line Mutation ; Prostatic Neoplasms/genetics* ; BRCA2 Protein/genetics* ; Genetic Predisposition to Disease

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Background/Aims: The gastrointestinal symptom of diabetes mellitus, chronic constipation, seriously affects patients’ life. Whereas, the mechanism of chronic constipation is still ambiguous, resulting in a lack of effective therapies for this symptom. As a part of the smooth muscle cells, interstitial cells of Cajal, and platelet-derived growth factor receptor alpha-positive (PDGFRα+ ) cells syncytium (SIP syncytium), PDGFRα+ cells play an important role in regulating colonic motility. According to our previous study, in PDGFRα+cells in colons of diabetic mice, the function of the P2Y1 purinergic receptor/type 3 small-conductance calcium-activated potassium (SK3) channel signaling pathway is strengthened, which may lead to colonic dysmotility. The purpose of this study is to investigate the changes in SK3 channel properties of PDGFRα+ cells in diabetic mice. Methods: Whole-cell patch clamp, Western blotting, superoxide dismutase activity measurement, and malondialdehyde measurement were main methods in the present study. Results: The present study revealed that when dialysed with low calcium ion (Ca 2+ ) solution, the SK3 current density was significantly decreased in PDGFRα+ cells from diabetic mice. However, the SK3 current density in PDGFRα+ cells was enhanced from diabetic mice when dialysed with high Ca 2+ solution. Moreover, hydrogen peroxide-treatment mimicked this phenomenon in SK3 transgenic HEK293 cells. The subunit of SK3 channels, protein kinase CK2, was up-regulated in colonic muscle layers and hydrogen peroxidetreated HEK293 cells. Additionally, protein phosphatase 2A, the subunit of SK3 channels, was not changed in streptozotocin-treated mouse colons or hydrogen peroxide-treated HEK293 cells. Conclusion The diabetic oxidative stress-induced upregulation of CK2 contributed to modulating SK3 channel sensitivity to Ca 2+ in colonic PDGFRα+ cells, which may result in colonic dysmotility in diabetic mice.

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.
Humans ; Carcinoma, Non-Small-Cell Lung/surgery* ; Lung Neoplasms/diagnosis* ; Retrospective Studies ; Autoantibodies ; Bayes Theorem ; Tumor Suppressor Protein p53 ; Carcinoembryonic Antigen ; Antigens, Neoplasm ; Biomarkers, Tumor ; Algorithms ; Pneumonia

Diabetic cardiomyopathy， one of the cardiovascular complications of diabetes， is characterized by cardiac systolic and diastolic dysfunction at the early stage， which can later develop into heart failure. Due to the high incidence and mortality， it has been a hot topic in recent years. The pathogenesis of diabetic cardiomyopathy is complicated. It has been proved related to abnormal glucose and lipid metabolism， cardiac insulin resistance， mitochondrial dysfunction， abnormal calcium homeostasis， activation of renin-angiotensin-aldosterone system， increased oxidative stress， endoplasmic reticulum stress， inflammation， autophagy， and so on. The specific pathogenesis remains unclear. Currently， the diabetic cardiomyopathy is mainly tackled with both western medicine and traditional Chinese medicine （TCM）. Traditional western medicine has no specific remedy for diabetic cardiomyopathy， and the resulting side effect cannot be neglected. In order to improve the efficacy and reduce the side effects， researchers have tried some potential medical treatments， such as vaspin， melatonin， Coenzyme Q10， and non-coding RNA， which still need further clinical trials. Diabetic cardiomyopathy is not recorded in ancient TCM books. According to the symptoms and signs， modern physicians often consider it as a "consumptive disease"， whose main therapeutic principles lie in benefiting Qi， tonifying Yin， activating blood， and removing stasis. The individual Chinese herbs such as Astragali Radix and Salviae Miltiorrhizae Radix et Rhizoma and Chinese herbal compounds like Huotan Jiedu Tongluoyin are effective in protecting the heart. But there are few studies exploring the pharmacodynamic mechanisms of TCM. With the continuous emergence of new drugs， the integration of TCM with western medicine may be a more promising treatment in the future. In conclusion， the pathogenesis of diabetic cardiomyopathy is unclear， and there is a lack of effective prevention and treatment. This paper reviewed the latest findings in pathogenesis and treatment of diabetic cardiomyopathy， in order to provide reference for further research.

This study aims to compare the prevalence of sexually transmitted infections (STIs) with semen quality in men from couples with primary and secondary infertility. Semen samples were collected from 133 men who requested fertility evaluation. Seminal tract infection with Ureaplasma spp. (UU), Mycoplasma hominis (MH), Mycoplasma genitalium (MG), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and herpes simplex virus-2 (HSV-2) was assessed by PCR-based diagnostic assays. Among all patients, the prevalence of STIs was higher in men from couples with primary infertility than that in men from couples with secondary infertility (39.7% vs 21.7%, P = 0.03). The prevalence of UU was 28.8% and 13.3% in men from couples with primary and secondary infertility, respectively. Men from couples with primary infertility were more likely to be positive for UU than men from couples with secondary infertility (P = 0.04). Regarding the UU subtype, the prevalence of Ureaplasma urealyticum (Uuu) and Ureaplasma parvum (Uup; including Uup1, Uup3, Uup6, and Uup14) did not differ between the two groups. No associations between the prevalence rates of MH, MG, and CT were found in men from either infertility group. A lower sperm concentration was associated with STI pathogen positivity in men with primary infertility according to the crude model (P = 0.04). The crude and adjusted models showed that semen volume (both P = 0.03) and semen leukocyte count (both P = 0.02) were independently associated with secondary infertility. These findings suggest the importance of classifying the type of infertility during routine diagnosis of seminal tract infections.
Female ; Humans ; Infertility, Male/epidemiology* ; Male ; Mycoplasma genitalium ; Mycoplasma hominis ; Prevalence ; Semen ; Semen Analysis ; Sexually Transmitted Diseases/epidemiology* ; Ureaplasma urealyticum

Objective:To analyze the clinical characteristics and prognosis of infants with rhabdomyosarcoma (RMS), thus enhancing the understanding of this disease.Methods:Clinical data of all RMS patients younger than 12 months treated in the Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University from May 2006 to June 2019 were retrospectively analyzed, including the age, gender, histological type, tumor primary site, tumor size, and the prognosis.Patients were followed up until December 31, 2019.The 3-year event free survival (EFS) rate of children was performed by plotting the Kaplan-Meier survival curves.Results:A total of 15 RMS children younger than 12 months were enrolled, accounting for 4.9% of all RMS cases in the same period, including 6 males and 9 females.The median age at diagnosis was 7.0 months (3.0-11.5 months). Classified by the primary site, 40.0% (6 cases) located in the head and neck, followed by 26.7% (4 cases) located in the limbs, 26.7% (4 cases) located in other parts, and 6.7% (1 case) located in the urogenital system.Embryonal RMS, alveolar RMS and spindle cell RMS accounted for 46.6% (7 cases), 26.7% (4 cases), and 26.7% (4 cases), respectively.Ten cases (66.7%) were stage Intergroup Rhabdomyosarcoma Study (IRS)-Ⅲ and 1 case (6.7%) was in stage Ⅳ.There were 10 cases (66.6%) in the middle-risk group, 4 cases (26.7%) in the low-risk group, and 1 case (6.7%) in the high-risk group.Two cases had a larger than 5 cm primary tumor; lymph node involvement was confirmed in 3 cases, and pulmonary metastasis occurred in 1 case at the time of diagnosis.All children were treated with chemotherapy, and 13 cases received postoperative chemotherapy and 1 case received preoperative chemotherapy.One case were not operated.Only 3 children underwent radiotherapy, including 1 case underwent particle implantation and 2 cases received external radiotherapy.Among the 15 children with RMS, 5 cases had relapse and disease progression with the 3-year EFS rate of (59.1±14.5)%, and 2 died with the 3-year overall survival rate of (80.8±12.6)%.Conclusions:The median age of diagnosis of RMS in single-center infants is 7 months.Head and neck are the most common primary sites of RMS.Nearly 50% of the children have the primary site of RMS with poor prognosis.More than a quarter of the pathological subtypes are the spindle cell type.Local treatment significantly influences the local progression or recurrence of RMS.