This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Diabetic osteoporosis （DOP） is a kind of bone complication caused by diabetes， which is characterized by the decrease of bone mineral density， the change of bone microstructure and the increase of bone fragility. The process of DOP is closely related to high glucose， insulin resistance， oxidative stress and other mechanisms. The Wnt/β-catenin signaling pathway plays an important role in mediating insulin resistance and bone metabolic balance in diabetes. Regulation of Wnt signal transduction promotes the expression of glycogen synthase kinase-3β（GSK-3β）phosphorylation and improves glucose and lipid metabolism. The Wnt/β-catenin signaling pathway is also an important way regulating osteocyte-driven bone remodeling， which not only plays an important regulatory role in the balance between osteoblasts and osteoclasts and improve bone metabolic homeostasis， but also promotes the expression of osteopontin， osteocalcin and type Ⅰ collagen， and improves bone proliferation and osteogenic differentiation by regulating the Wnt pathway. In recent years， the research of traditional Chinese medicine （TCM） in the prevention and treatment of DOP has gradually increased， and the exploration of TCM to interfere with the Wnt pathway to improve DOP has made some progress. This paper collects and summarizes the studies on the Wnt signaling pathway in glucose metabolism， bone metabolism and DOP worldwide in the past decade， as well as the related literature on the intervention of DOP by TCM compounds （classical and other compounds）， single Chinese medicine and TCM monomers based on the Wnt pathway， in order to provide a reference and direction for the development of new drugs for clinical prevention and treatment of DOP.

Objective:To construct and evaluate a parotid mass malignancy risk model based on ultrasound image characteristics and clinical features of parotid masses.Methods:Ultrasound images and clinical features of 214 patients with parotid masses in the First People′s Hospital of Foshan were retrospectively collected from June 2018 to August 2020. The pathology results were taken as the golden standard. All the clinical features and ultrasound image features were first screened using regression analysis, and then the screened features were used to build a prediction model.Results:Malignant tumors of the parotid gland appeared on ultrasound as hypoechoic solid masses with or without abnormal cervicofacial lymph nodes with poorly defined borders and irregular morphology. Multifactorial analysis showed that facial nerve function, cervicofacial lymph node abnormalities, maximum diameter, morphology and borders of the mass were independent predictors of the risk of malignant parotid masses. A Nomogram prediction model was established using the above 5 indicators, and the results showed a concordance index(C-index) of 0.896 (95% CI=0.834-0.958) for Nomogram. The standard curve showed good agreement between the predictive effect of Nomogram and the actual situation of benign and malignant parotid swellings, with an internally validated C-index of 0.878. Conclusions:Ultrasound is of great value in identifying benign and malignant parotid tumors. The Nomogram model using ultrasound image features and clinical characteristics can assess the biocharacteristics of parotid masses, and the model shows high accuracy in predicting the risk of malignancy of parotid masses.

Objectives:To investigate the clinicopathological and prognostic significance of International Endocervical Adenocarcinoma Criteria and Classification (IECC) in classifying endocervical adenocarcinomas among Chinese women.Methods:A total of 286 endocervical adenocarcinomas diagnosed from January 2013 to December 2019 at the Women′s Hospital, Zhejiang University School of Medicine were identified and included. The cases were reviewed and reclassified based on IECC. The histological types were correlated with p16 immunostaining, human papilloma virus (HPV) mRNA status, the clinicopathological parameters including the International Federation of Gynecologic Oncology (FIGO) stage, and clinical follow-up data.Results:The patients aged from 19 to 77 (median 47) years. There were 223 patients at FIGO stage Ⅰ, 22 at stage Ⅱ, 38 at stage Ⅲ and 3 at stage Ⅳ. The IECC types included 213 (74.5%) HPV-related adenocarcinomas (HPVA), 60 (21%) non-HPV-related adenocarcinomas (NHPVA), and 13 (4.5%) adenocarcinomas, no other specified (NOS). The major histological subtypes in HPVA and NHPVA were common type ( n=156, 54.5%) and gastric type (GAC, n=46, 15.9%), respectively. The p16 positive rates in HPVA, NHPVA and adenocarcinoma, NOS were 92% (173/188), 26.6% (17/64) and 61.5% (8/13), respectively, and those of HPV mRNA hybridization in situ were 89.4% (144/161), 0/18 and 7/13, respectively. Compared to HPVA, NHPVA was more frequently associated with older age, FIGO stage Ⅱ-Ⅳ, neural involvement, lymphovascular invasion and aberrant p53 expression ( P<0.05). Univariate survival analysis showed that age (>47 years), NHPVA, GAC, FIGO stage Ⅱ-Ⅳ, neural involvement, lymphovascular invasion and aberrant p53 expression were indicators for a poorer overall survival and tumor recurrence ( P<0.05). Mucinous HPVA showed worse clinical outcomes compared to usual-type HPVA ( P<0.01). Multivariate survival analysis demonstrated that FIGO stage Ⅱ-Ⅳ, NHPVA and aberrant p53 expression were independent indicators for poor overall survival while FIGO stage Ⅱ-Ⅳ and GAC were independently associated with tumor recurrence ( P<0.05). Conclusions:The two broad IECC categories, HPVA and NHPVA, not only provide morphological links to the etiology (HPV infection), but also have significant clinicopathological and prognostic relevance.

Objective    To analyze the risk factors of anastomotic leakage after esophagectomy. Methods    The clinical data of 1 328 patients with esophageal cancer, who underwent esophagectomy in the First Affiliated Hospital of Henan University of Science and Technology from January 2010 to December 2016, were retrospectively analyzed. There were 726 males and 602 females, at an average age of 67.2±14.1 years. According to whether there was anastomotic leakage after operation, patients were divided into two groups: an anastomotic leakage group (167 patients) and a non-anastomotic leakage group (1 161 patients). Univariate and multivariate logistic regression analysis was used to identify related risk factors of anastomotic leakage after operation. Results     The incidence of postoperative anastomotic leakage was 12.6% (167/1 328). Univariate analysis showed that body mass index, arrhythmia, chronic obstructive pulmonary disease (COPD), diabetes, preoperative albumin level, preoperative chemotherapy and chemoradiotherapy, lesion location, anastomosis types and postoperative pulmonary infection were associated with statistically significant increase in risk of cervical anastomotic leakage (P<0.05). Logistic regression analysis showed that preoperative COPD, lesion location and postoperative pulmonary infection were independent risk factors of cervical anastomotic leakage after esophagectomy (P<0.05). Conclusion    The occurrence of cervical anastomotic leakage after esophageal cancer is related to many factors. The preoperative COPD, the lesion location and the postoperative pulmonary infection are independent high risk factors. Paying attention to these factors and doing perioperative management can effectively reduce the occurrence of anastomotic leakage.

Objective: To assess the outcomes and toxic effects of 5-day actinomycin D (Act-D) salvage therapy and to explore the predictors of Act-D resistance in patients with low-risk gestational trophoblastic neoplasia (GTN)who failed 5-day methotrexate (MTX) chemotherapy. Methods: This retrospective study analyzed patients with low-risk GTN administered Act-D salvage therapy after failing MTX chemotherapy at Women's Hospital, School of Medicine Zhejiang University between January 2000 and December 2015. The clinical parameters of these patients were collected and analyzed. Results: The final analysis included 89 cases. Of these, 73 cases (82.02%) responded to salvage Act-D. The remaining 16 resistant cases were switched to etoposide, MTX, Act-D/ cyclophosphamide, and vincristine chemotherapy and achieved complete remission. Serum human chorionic gonadotrophin levels before Act-D salvage therapy (hCG Act-D )in the Act-Dresistant cases were significantly higher than those in the Act-D responders (median 605 vs.103 IU/L, p=0.009). However, the range of hCGAct-D values in Act-D responders was wider than that in Act-D-resistant cases (5.76–16,664 IU/L vs. 11.43–6,732 IU/L). Thus, assigning a general cut-off value was difficult considering the individual setting. Except for 2 cases requiring other salvage regimens due to Act-D toxicity, 97.80% of cases (89/91) tolerated the toxicity. During at least 1-year follow-up, the survival rate was 100.00% and no case developed recurrence. Conclusion Based on the good therapeutic effect and tolerable toxicity, we recommend Act-D salvage therapy for all patients with low-risk GTN who fail primary MTX chemotherapy.The higher serum hCG levels before Act-D salvage therapy may be associated with resistance to this treatment.

Objective: To assess the diagnostic performance of contrast-enhanced spectral mammography (CESM) in suspected breast lesions. Methods: A total of 97 patients with suspected breast cancer identified by clinical examination or screening underwent two-views CESM examination on the basis of digital breast tomosynthesis (DBT) combined with full-field digital mammography (FFDM), and they were finally confirmed by biopsy or pathology. Three senior radiologists analyzed images, including lesion visibility, lesion characteristics, enhancement type, degree of enhancement, BIRDS classification, etc. Finally, based on the pathology, we compared the CESM+DBT+FFDM and DBT+FFDM two models according to sensitivity, specificity and ROC for diagnostic performance. Results: There were a total of 120 lesions. Eighty-nine lesions were malignant, 31 benign; CESM was not enhanced in 2 cases, mild enhancement was performed in 22 cases, moderately intensive in 15 cases, highly intensive in 81 cases, and 2 cases were not enhanced; mass-enhanced in 96 cases, including ring-enhanced in 12 cases, 22 cases of non-mass type. The sensitivities of the combination of CESM and not combination of CESM were 91.0% and 80.9%, respectively, and the specificities were 93.5% and 87.1%, respectively. The area under the ROC curve of combination of CESM was higher than the without combination of CESM (0.923 and 0.900, P<0.05), The difference was statistically significant. Conclusion For suspicious lesions, CESM examination can improve the diagnosis accuracy of breast cancer.

Objective To evaluate etoposide,methotrexate and dactinomycin (EMA)/ cyclophosphamide and vincristine (CO) regimen for treatment of ultra high-risk gestational trophoblastic neoplasia (GTN).Methods A total of twenty-four ultra high-risk patients who had International Federation of Gynecology and Obstetrics (FIGO) prognostic scores greater or equal to 12 with liver,brain,or extensive metastases did poorly when treated with primary chemotherapy admitted in Women's Hospital,School of Medicine,Zhejiang University from January 2001 to December 2015.All of the patients were treated by EMA/CO regimen and followed up to death or December 2017.The clinical data of patients were analyzed retrospectively and the efficacy and toxicity of EMA/CO were evaluated.Results All of the cases with ultra high-risk GTN had FIGO prognostic scores ≥12 (ranged 12-18,median 13.0).Twenty patients (83％,20/24) received EMA/CO regimen as primary treatment and 4 patients (17％,4/24) had a history of failed chemotherapy.Seven patients (29％,7/24) had metastasis of liver or brain and 17 patients (71％,20/24)had no metastasis of liver and brain.Twenty-four patients received totally 167 courses of EMA/CO regimen (average 7.0 courses).Sixteen patients achieved complete remission and 8 patients showed drug-resistant.The complete remission rate was 67％ (16/24) and the resistance rate was 33％ (8/24).Of the 16 patients who got complete remission,6 cases were treated with EMA/CO regimen alone,and 10 cases were treated by chemotherapy combined with surgery.For the 8 patients who showed drug-resistant to EMA/CO,5 cases of them received EMA/etoposide and cisplatin (EP) regimen and 3 cases got remission,1 case received methotrexate,dactinomycin and cyclophosphamide (MAC) regimen and got remission,2 cases gave up treatment because of economic factors.The side effects of EMA/CO mainly included Ⅲ-Ⅳ degree neutropenia,anemia and alopecia.The incidence of Ⅲ-Ⅳ degree neutropenia during the treatment of EMA/CO was 21.6％ (36/167),the incidence of anemia was 96.4％ (161/167),and the incidence of alopecia was 60.5％ (101/167).In these 24 ultra high-risk GTN patients,4 patients died during follow-up.In the 20 patients who got complete remission,no recurrence or secondary tumor by chemotherapy were occurred.Conclusion EMA/CO is an effective regimen with manageable toxicity for patients with ultra high-risk GTN.

Objective To evaluate the diagnostic performance of digital breast tomosynthesis (DBT) breast X-ray photography image texture characteristics based deep learning classification model on differentiating malignant masses. Methods Retrospectively collected 132 cases with simplex breast lesions (89 benign lesions and 43 malignant lesions) which were confirmed by pathology and DBT during January 2016 to December 2016 in Nanfang Hospital. DBT was performed before biopsy and surgery. Image of cranio-caudal view (CC) and medio-lateral oblique (MLO) were captured. The lesion area was segmented to acquire ROI by ITK-SNAP software. Then the processed images were input into MATLAB R2015b to establish a feature model for extracting texture features. The characteristics with high correlation was analyzed from Fisher score and one sample t test. We built up support vector machine (SVM) classification model based on extracted texture and added neural network model (CNN) for deep learning classification model. We randomly assigned collected cases into training group and validation group. The diagnosis of benign and malignant lesions were served as the reference. The efficiency was evaluated by ROC classification model. Result We extracted 82 texture characteristics from 132 images of leisure (132 images of CC and 132 images of MLO) by establishing deep learning classification model of breast lesions. We randomly chose and combined characteristics from 15 texture characteristics with statistical significance, then differentiated benign and malignant by SVM classification model. After 50 iterations on each combination of characteristics, the average diagnostic efficacy was compared to obtained the one with higher efficacy. Nine of CC and 8 of MLO was selected. The result showed that the sensitivity, specificity, accuracy and area under curve (AUC) of the model to differentiate simplex breast lesions for CC were 0.68, 0.77, 0.74 and 0.74, for MLO were 0.71, 0.71, 0.71 and 0.76. Conclusions MLO has better diagnostic performance for the diagnosis than CC. The deep learning classification model on breast lesions which was built upon DBT image texture characteristics on MLO could differentiate malignant masses effectively.

Objective To explore the significance of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) for the death risk evaluation in elderly patients with chronic disease in five years.Methods A total of 765 elderly patients with chronic disease[136 patients with coronary heart disease (CHD),76 patients with hypertension disease (HD),86 patients with chronic obstructive pulmonary disease (COPD),75 patients with Type 2 diabetic mellitus (T2DM),76 patients with cerebral infarction (CI),73 patients with coronary heart disease combined with hypertension,71 patients with coronary heart disease combined with chronic obstructive pulmonary disease,61 patients with coronary heart disease combined with diabetic,51 patients with coronary heart disease combined with cerebral infarction,and 60 patients with three comorbidity] were classified into the survival group (312 cases) and the death group (453 cases) according to disease prognosis.The serum NT-proBNP levels of 88 healthy controls and 765 elderly patients with chronic disease were determined by bi-directional lateral flow immunoassay.The death events were followed up and observed for an average of 5 years.The results were analyzed statistically.Results The serum NT-proBNP levels in the death group with various diseases were significantly higher than the survival group (P ＜0.01),the patient's age and the proportion of male in the death group and the survival group had no significant difference (P ＞ 0.05).The serum NT-proBNP levels,the patient's age and the Proportion of male in the death group with various elderly chronic diseases had no statistical significance (P ＞ 0.05).The serum NT-proBNP levels in the death group with various elderly chronic diseases had no statistical significance (P ＞ 0.05),and were significantly higher than the survival group (P ＜ 0.01).The patient's age and the proportion of male in the death group and the survival group had no significant difference (P ＞ 0.05).The serum NT-proBNP levels in the death group in the different periods had statistical significance (P ＜ 0.01),and were significantly higher than the survival group and healthy control group (P ＜ 0.01).The more shorter of the survival time was,the higher the serum NT-proBNP 1eve was.The serum NT-proBNP levels were negatively correlated with the survival time of the patients (r =-0.378,P =0.000).The receiver operator characteristic (ROC) curve indicated that the optimal cut-off values of serum NT-proBNP levels for the death risk evaluation in elder patients with chronic disease were 1 499.50 ng/L.Kaplan-Meier survival curve showed that the survival rates of serum NT-proBNP levels had significant difference (P ＜0.01).The higher the serum NT-proBNP level was,the more shorter of the Survival rates were.Conclusions The levels of serum NT-proBNP have an important prognostic value in the death risk evaluation in elderly patients with various chronic disease.It is an independent risk factor for the death occurred in eiderly patients with chronic disease.The levels of serum NT-proBNP are closely correlated with the survival rates and survival time of elderly patients,It can be used as a monitoring indicator of the elderly patients with chronic disease in risk stratification.