Novel molecular insights into pyroptosis in triple-negative breast cancer prognosis and immunotherapy.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) often have a poor prognostic outcome. Current treatment strategies cannot benefit all TNBC patients. Previous findings suggested pyroptosis as a novel target for suppressing cancer development, although the relationship between TNBC and pyroptosis-related genes (PRGs) was still unclear. METHODS: Gene expression data and clinical follow-up of TNBC patients were collected from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO). PRGs were screened using weighted gene co-expression network analysis. Cox regression analysis and the least absolute shrinkage and selection operator (i.e. LASSO) technique were applied to construct a pyroptosis-related prognostic risk score (PPRS) model, which was further combined with the clinicopathological characteristics of TNBC patients to develop a survival decision tree and a nomogram. The model was used to calculate the PPRS, and then the overall survival, immune infiltration, immunotherapy response and drug sensitivity of TNBC patients were analyzed based on the PPRS. RESULTS: The PPRS model was closely related to clinicopathological features and can independently and accurately predict the prognosis of TNBC. According to normalized PPRS, patients in different cohorts were divided into two groups. Compared with the high-PPRS group, the low-PPRS group had significantly higher ESTIMATE (i.e. Estimation of STromal and Immune cells in MAlignantTumours using Expression data) score, immune score and stromal score, and it also had overexpressed immune checkpoints and significantly reduced Tumor Immune Dysfunction and Exclusion (TIDE) score, as well as higher sensitivity to paclitaxel, veliparib, olaparib and talazoparib. A decision tree and nomogram based on PPRS and clinical characteristics can improve the prognosis stratification and survival prediction for TNBC patients. CONCLUSIONS: A PPRS model was developed to predict TNBC patients' immune characteristics and response to immunotherapy, chemotherapy and targeted therapy, as well as their survival outcomes.

Clinical Evaluation of Primary Suturing of Normal-Diameter Common Bile Ducts After Microincision of Cystic Duct Confluence for Stone Removal.

PURPOSE: In patients with gallstones complicated by common bile duct (CBD) stones, both normal and dilated common bile ducts have been reported. The goal of this study was to investigate the efficacy and safety of primary suturing after microincision of the cystic duct confluence in treating these patients. METHOD: Between July 2018 and December 2021, 104 patients were admitted to the Department of General Surgery at Guannan County People's Hospital with gallstone complications, and their records were reviewed retrospectively. The patients were divided into 2 groups: normal CBD group (n=70, CBD diameter: 6.0 to 8.0 mm) and dilated CBD group (n=34, CBD diameter: >8.0 mm). In these 104 patients, there were 75 cases of CBD stones with acute cholangitis, 12 cases of CBD stones without cholangitis, and 17 cases of mild biliary pancreatitis with CBD stones (including 2 cases of biliary pancreatitis with cholangitis). Among all patients, there were 37 cases with jaundice, 67 cases without jaundice, and 5 cases of emergency surgery. All patients underwent microincision of the cystic duct confluence followed by primary suturing. Both groups were compared on a variety of general and perioperative indicators. RESULT: All patients underwent laparoscopy combined with choledochoscopy; there were no cases of biliary tract injury or conversion to laparotomy. There was no statistically significant difference in operation duration (P=0.286), blood loss (P=0.06), length of stay (P=0.821), and time to drainage tube removal (P=0.096) between the 2 groups. CONCLUSION: Microincision of the cystic duct confluence, followed by a primary suture, is a safe and effective treatment for CBD stones in patients with a normal CBD diameter, as determined by preoperative imaging.

Hsa_circ_0001925 promotes malignant progression in triple-negative breast cancer via miR-1299/YY1 axis.

BACKGROUND: Circular RNAs (circRNAs) are related to the pathogenesis and progression of triple-negative breast cancer (TNBC). The aim of this study was to investigate the role and mechanism of hsa_circ_0001925 in TNBC progression. METHODS: Hsa_circ_0001925, microRNA (miR)-1299 and Yin Yang 1 (YY1) levels were examined in TNBC via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell counting kit-8 (CCK-8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry, wound healing assay and tube formation assay were conducted to estimate the effects of hsa_circ_0001925 on malignant phenotypes of TNBC tumors. Several protein levels were measured with western blot. The regulatory relationship between miR-1299 and hsa_circ_0001925 or YY1 was validated using a dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft assay was used to estimate the effect of hsa_circ_0001925 in TNBC in vivo. RESULTS: Hsa_circ_0001925 and YY1 levels were upregulated, while miR-1299 abundance was downregulated in TNBC tissues and cells. Hsa_circ_0001925 silencing constrained cell proliferation, migration and angiogenesis whereas it promoted apoptosis in vitro, and hsa_circ_0001925 silencing significantly curbed xenograft tumor growth in vivo. Hsa_circ_0001925 acted as a miRNA sponge for miR-1299. Hsa_circ_0001925 decreased YY1 expression by sponging miR-1299. MiR-1299 downregulation alleviated the effects of hsa_circ_0001925 knockdown on BC progression. MiR-1299 interacted with the 3' untranslated region (3' UTR) of YY1, and YY1 overexpression partly reversed the effects of miR-1299 overexpression on BC progression. CONCLUSION: Our findings showed that hsa_circ_0001925 mediated TNBC progression via regulating miR-1299/YY1 axis, providing a potential target for BC treatment.

[The application study of community-based tele-screening system for diabetic retinopathy in Beixinjing Blocks, Shanghai].

OBJECTIVE: To design the community-based tele-screening system for diabetic retinopathy and evaluate the feasibility of it. METHODS: Cross-sectional study. The tele-screening system was based on non-mydriatic digital eye fundus camara photography and computer network technology. 109 type 2 diabetes mellitus residents were randomly selected for system evaluation, which included: (1) The consistency of the far visual acuity examined by an ophthalmologist and a trained inspector, evaluated by paired t-sample test; the consistency of diagnosis of diabetic retinopathy by tele-screening system and traditional screening method by ophthalmoscope, slit-lamp bimicroscope combined with non-contact lens after pupil dilation, evaluated by kappa value and intraclass coefficient correlation. (2) The proper compression ratio of the fundus photographs transferring through the internet, evaluated by intraclass coefficient correlation. (3) The working time for the tele-screening on the residents, comparing with the traditional screening method. RESULTS: The visual acuities of the 218 eyes in 109 residents examined by an ophthalmologist were < 0.05 in 13 eyes, between 0.05 and 0.3 in 61 eyes, > or = 0.3 in 144 eyes. No significant difference was found between the vision acuity given by different examiner (t = -0.572, P = 0.568). 52 eyes were diagnosed as DR by traditional screening method, while 51 eyes were diagnosed as DR by the tele-screening method, so in DR diagnosis, high consistency were found with kappa value as 0.885, 95%CI 0.807 to 0.963, and in DR degree diagnosis with ICC value as 0.91, 95%CI 0.85 to 0.94. The most compression ratio of fundus photographs was as low as 15% (526 x 350). It took 5 to 7 minutes for the tele-screening system to examining and giving diagnosis of a diabetes mellitus resident, a little bit sooner than traditional screening method. CONCLUSIONS: This community-based tele-screening system can meet the requirements of mass screening for diabetic retinopathy.

[A prevalence survey of blindness and visual impairment in adults aged equal or more than 60 years in Beixinjing blocks of Shanghai, China].

OBJECTIVE: To investigate the prevalence rate of blindness and low vision and the leading cause of blindness in residents aged > or = 60 years in Beixinjing blocks, Shanghai. METHODS: A cross-sectional study was carried out by Shanghai First People's Hospital, affiliated Shanghai Jiaotong University and Shanghai Beixinjing Community hospital from November 2007 to April 2008. Randomly cluster sampling method was used, and all the individuals aged > or = 60 years in 8 communities from Beixinjing blocks, Shanghai was enrolled in this study. The pinhole visual acuity and presenting visual acuity were measured separately in each eye. External eye, anterior segment and ocular fundus were examined by the ophthalmologist using slit lamp-microscopes, direct ophthalmoscopy and non-mydriatic digital camara. Assigned ophthalmologic doctors assured the leading blind causes of every blind person. The survey was preceded by a pilot study where operational methods were refined and quality assurance evaluation was carried out. RESULTS: 3851 individuals were examined, and the response rate was 92.73%. According to WHO diagnostic criteria: 29 persons were diagnosed as blindness, 11 male (37.93%) and 18 female (62.07%). 104 persons were diagnosed as low vision, 37 male (35.58%) and 67 female (64.42%). The prevalence rates of blindness and low vision were 0.75% and 2.70%. The leading causes of blindness were macular degeneration, cataract, corneal diseases, and retinal detachment. According to presenting vision diagnostic criteria: 61 persons were diagnosed as severe binocular blindness, 20 male (32.79%) and 41 female (67.21%). 66 persons were diagnosed as slight binocular blindness, 27 male (40.91%) and 39 female (59.09%). 276 persons were diagnosed as monocular blindness, 120 male (43.48%) and 156 female (56.52%). The prevalence of severe binocular blindness, slight binocular blindness and monocular blindness was 1.58%, 1.71% and 7.17%, respectively. The leading causes of blindness were macular degeneration, cataract, ametropia and corneal diseases. CONCLUSION: The leading cause of blindness was macular degeneration. The prevalence of degenerative retinopathy in this area is on the rise.

A five-year prospective study of diabetic retinopathy progression in chinese type 2 diabetes patients with "well-controlled" blood glucose.

PURPOSE: To determine the progression rate and risk factors for diabetic retinopathy (DR) in Chinese type 2 diabetic patients who have reached the target hemoglobin A1c (HbA1c) level recommended by the American Diabetes Association. METHODS: This was a 5-year community-based prospective study. The study population consisted of patients with type 2 diabetes with HbA1c less than 7.0%. Demographic information, systemic examination results and ophthalmological test results for each participant were collected. The outcome of this study was the progression of DR, which was defined as an increase in DR grade in one or both eyes at the final visit in comparison to the baseline status. The association between each potential risk factor and DR progression was studied. RESULTS: A total of 453 patients with HbA1c less than 7.0% were included in the study group. In 146 patients (32.22%), DR developed or progressed during the five-year follow-up. Baseline HbA1c level was the only independent risk factor for DR progression (p<0.01, OR = 2.84, 95%CI: 2.11~3.82). The logistic regression function suggested that the possibility of DR progression increased fastest when baseline HbA1c increased from 5.2% to 6.4%. The 5-year DR progression rate in patients with baseline HbA1c less than 5.2%, between 5.2% and 6.4%, and over 6.4% were 19.62%, 24.41%, and 76.83%, respectively. CONCLUSIONS: To slow the progression of DR in Chinese patients with type 2 diabetes, more intensive glucose control is recommended.

The 5-year onset and regression of diabetic retinopathy in Chinese type 2 diabetes patients.

PURPOSE: To determine the rate and risk factors of diabetic retinopathy (DR) onset and regression in Chinese type 2 diabetes mellitus patients. METHODS: This is a 5-year community-based prospective study. The demographic information, systemic examination results and ophthalmological test results of each participant were collected. The study outcomes were DR incidence, defined as the onset of DR in at least one eye, and DR regression, defined as full regression from existing DR to no retinopathy without invasive treatments. The associations between each potential risk factor and the outcomes were studied. RESULTS: In total, 778 participants were enrolled. There were 322 patients without DR at baseline, of which 151 participants developed DR during follow-up (DR incidence rate = 46.89%). Baseline hyperglycemia and high blood pressure were two independent risk factors associated with DR incidence. Among the 456 participants with existing DR at entry, 110 fully recovered after 5 years (DR regression rate = 24.12%). Low baseline glucose and low serum triglyceride were two independent factors associated with DR regression. CONCLUSIONS: DR incidence occurred more frequently in patients with hyperglycemia and high blood pressure. DR regression occurred mostly in patients with lower glucose and lower serum triglyceride levels among Chinese type 2 diabetes patients.