Analyzing the Role of Septin9 Gene Methylation in the Diagnosis and Treatment of Primary Liver Cancer in the Elderly.

Context: Because the early symptoms of primary hepatocellular carcinoma (PHC) aren't significant, it's difficult to diagnose it by routine inspection clinically, and if the lesion's diameter is small, less than 2.0 cm, false negatives can occur in pathological examinations. Researchers need to actively search for more diagnostic methods. Objective: The study intended to detect and analyze the value of plasma Septin9 gene methylation for the diagnosis and therapeutic monitoring of PHC in older adults. Design: The research team performed a prospective controlled study. Setting: The study took place at the First Hospital of Qiqihar, an Affiliated Qiqihar Hospital at Southern Medical University in Qiqihar, China. Participants: Participants were 32 patients with PHC and 28 with cholangiocarcinoma (CCA) who had been admitted to the hospital between January 2021 and July 2022 and 40 healthy individuals. Groups: The research team divided participants into three groups: (1) patients with PHC, the PHC group; (2) patients with CCA, the CCA group; and (3) healthy individuals, the control group. Outcome Measures: The research team: (1) determined the positive expression rate of Septin9 gene methylation; (2) measured liver function indicators-alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), albumin (ALB); and (3) measured tumor markers-alpha-fetoprotein (AFP), carbohydrate antigen (CA) 199, CA125, and CA153. The team also: (1) established a binary logistic regression model based on levels of GGT and plasma Septin9 gene methylation to analyze risk factors and diagnosis accuracy, (2) created a receiver operating characteristic (ROC) curve to analyze diagnostic values; and (3) during followup, analyzed the negative conversion rate of Septin9 gene methylation in participants. Results: The positive expression rate of Septin9 methylation in the PHC group was significantly lower than that that of the CCA group and significantly higher than that of the control group (P < .05). The PHC group's ALT, AST, TBIL, DBIL, ALP, and GGT were significantly higher than those of the control group but significantly lower than those of the CCA group (all P < .05). PHC group's ALB was significantly lower than that of the control group (P < .05). The PHC group's AFP, CA199, and CA125 were significantly higher than those of the control group, and the PHC group's CA199 and CA125 were significantly lower than those in the CCA group (all P < .05). The positive expression of Septin9 gene methylation and the high expression of GGT were risk factors for PHC (OR>1, P < .05). The AUC of the Septin9 gene methylation, the GGT level, and the combined detection of both variables (all AUC > 0.70), suggests that the variables have a diagnostic value in the detection of PHC, with the combined detection having the highest value. The negative conversion rate after surgery of Septin9 gene methylation was 87.10%, for 27 out of 31 participants in the PHC and CCA groups (χ2 = 29.405, P < .001). Conclusion: Plasma Septin9 gene methylation is a sensitive molecular marker for the diagnosis and therapeutic monitoring of older adults with PHC, and combined with the serum GGT level, has a high diagnostic efficiency, which may reflect the treatment status of patients.

Low-kilovolt x-ray intraoperative radiotherapy for pT3 locally advanced colon cancer: a single-institution retrospective analysis.

BACKGROUND: Patients with locally advanced colon cancer (LACC) treated with surgery had a high risk of local recurrence. The outcomes can vary significantly among patients with pT3 disease. This study was undertaken to assess whether low-kilovolt (kV) x-ray intraoperative radiotherapy (IORT) can achieve promising results compared with electron beam IORT (IOERT) and whether specific subgroups of patients with pT3 colon cancer may benefit from low-kV x-ray IORT. METHODS: We retrospectively reviewed 44 patients with pT3 LACC treated with low-kV x-ray IORT. Clinicopathologic characteristics were analyzed to identify patients that could potentially benefit from low-kV x-ray IORT. The Kaplan-Meier survival analysis was used to assess overall survival (OS) and progression-free survival (PFS). Correlation analysis was used to discover the association of multiple factors to the results of treatment represented by the values of OS and PFS. RESULTS: The median follow-up of patients was 20.5 months (range, 6.1-38.8 months). At the time of analysis, 38 (86%) were alive and 6 (14%) had died of their disease. The 3-year Kaplan-Meier of PFS and OS for the entire cohort was 82.8% and 82.1%, respectively. At median follow-up, no in-field failure within the low-kV x-ray IORT field had occurred. Locoregional and distant failure had occurred in 2 (5%) patients each. The rate of perioperative 30-day mortality was 0%, and the morbidity rate was 11%. Five patients experienced 7 complications, including 4 early complications (30 days) and three late complications (> 30 days) leading early and late morbidity rates of 9% and 7%, respectively. CONCLUSION: Patients with LACC who had undergone an additional low-kV x-ray IORT can achieve encouraging locoregional control, PFS, OS, and distant control without an increase in short-term or long-term complications. Low-kV x-ray IORT can be considered as part of management in pT3 LACC.

Antigen-specific T cell response from dendritic cell vaccination using side population cell-associated antigens targets hepatocellular carcinoma.

Dendritic cell (DC) vaccination targeting cancer stem cells is an effective way to suppress tumor progression and reduce the metastasis and recurrence. In the present study, we explored the suitability of side population (SP) cells as source of antigens for DC vaccination against hepatocellular carcinoma (HCC) in a mouse model. In this study, we identified the "stem-like" characteristics of SP cells in the MHCC97 and Hepa 1-6 HCC cell lines. We found that SP cells express high levels of tumor-associated antigens and MHC class I molecules. Although loading with cell lysates did not change the characteristics of DCs, SP cell lysate-pulsed DCs induced antigen-specific T cell responses, including T cell proliferation and increased IFN-γ production by stimulated CD8(+) T cells. We investigated the cytotoxicity of T cells stimulated by SP cell lysate-pulsed DCs in nude mice co-injected with MHCC97 cells. To mimic the in vivo environment, we also confirmed the result in mouse HCC cell line Hepa 1-6 induced tumor-bearing C57/BL6 immune competent mice, and we demonstrated that vaccination with DCs loaded with Hepa 1-6 SP cell lysates could induce a T cell response in vivo and suppress the tumor growth. Our results may have applications for anti-HCC immunotherapy by targeting the cancer stem cells and may provide new insight for cancer vaccines.

Cu(II)-based complex loaded with drug paclitaxel hydrogels against thyroid cancer and optimizing novel derivatives.

This study introduces a novel approach for synthesizing a Cu(II)-based coordination polymer (CP), {[Cu(L)(4,4´-OBA)]·H2O}n (1), using a mixed ligand method. The CP was successfully prepared by reacting Cu(NO3)2·3H2O with the ligand 3,6-bis(benzimidazol-1-yl)pyridazine in the presence of 4,4´-H2OBA, demonstrating an innovative synthesis strategy. Furthermore, a novel hydrogel composed of hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) with a porous structure was developed for drug delivery purposes. This hydrogel facilitates the encapsulation of CP1, and enables the loading of paclitaxel onto the composite to form HA/CMCS-CP1@paclitaxel. In vitro cell experiments demonstrated the promising modulation of thyroid cancer biomarker genes S100A6 and ARID1A by HA/CMCS-CP1@paclitaxel. Finally, reinforcement learning simulations were employed to optimize novel metal-organic frameworks, underscoring the innovative contributions of this study.

Three trocars laparoscopic abdominal aortic aneurysm repair.

Total laparoscopic abdominal aortic aneurysm resection with tube graft interposition was performed in a 53-year-old woman diagnosed with an infrarenal abdominal aortic aneurysm. The operation was accomplished by a method using three trocars. The operation took 240 minutes. Blood loss was 600 mL. No complications occurred in 13 months of postoperative follow-up. These results show that total laparoscopic abdominal aortic aneurysm repair with three trocars is feasible and worthwhile.

A specific instrument to facilitate single-incision laparoscopic cholecystectomy: an initial experience.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is a promising technique with regard to reducing postoperative pain, decreasing complications, and improving cosmesis. Many instruments have been invented to overcome the limitation brought about by the chopstick effect, most of which are inflexible. This results in a limitation when the operator wants to move the tip of the instrument to a certain angle. Recently, the authors used a new instrument, which has 2 simultaneously movable wrists, in 30 cases of SILC. METHODS: From May 2010 to August 2010, 30 patients with symptomatic gallbladder disease underwent SILC through a 15- to 20-mm umbilical incision using a 3-trocar technique. A novel laparoscope instrument with adjustable and rotatable wrists (Liuyedao, Inc, Yuyao,China) was applied, combined with the use of harmonic scalpel. RESULTS: The mean operation time was 56.4 minutes (range = 26-170 minutes). The mean estimated blood loss was 16.6 mL (range = 5-60 mL). There were no conversions of the SILC technique. No drainage was placed, and no bleeding or bile leakage occurred. The mean hospital stay was 3 days (range = 1-5 days). CONCLUSIONS: The SILC technique with the novel instrument is safe, feasible, and effective. This new instrument facilitates the SILC procedure.

Association between population density and infection rate suggests the importance of social distancing and travel restriction in reducing the COVID-19 pandemic.

Currently, 2019-nCoV has spread to most countries of the world. Understanding the environmental factors that affect the spread of the disease COVID-19 infection is critical to stop the spread of the disease. The purpose of this study is to investigate whether population density is associated with the infection rate of the COVID-19. We collected data from official webpages of cities in China and in the USA. The data were organized on Excel spreadsheets for statistical analyses. We calculated the morbidity and population density of cities and regions in these two countries. We then examined the relationship between morbidity and other factors. Our analysis indicated that the population density in cities in Hubei province where the COVID-19 was severe was associated with a higher percentage of morbidity, with an r value of 0.62. Similarly, in the USA, the density of 51 states and territories is also associated with morbidity from COVID-19 with an r value of 0.55. In contrast, as a control group, there is no association between the morbidity and population density in 33 other regions of China, where the COVID-19 epidemic is well under control. Interestingly, our study also indicated that these associations were not influenced by the first case of COVID-19. The rate of morbidity and the number of days from the first case in the USA have no association, with an r value of - 0.1288. Population density is positively associated with the percentage of patients with COVID-19 infection in the population. Our data support the importance of such as social distancing and travel restriction in the prevention of COVID-19 spread.

Capacity of transportation and spread of COVID-19-an ironical fact for developed countries.

The widespread epidemic of the COVID-19 in developed countries such as Europe and the USA has sparked many speculations. What factors caused the rapid early pandemic of the COVID-19 in developed countries is the main goal of this study. We collected the main disease indicators and various environmental and economic factors in 61 countries around the world. Our results show that the number of cases is positively correlated with the country's GDP. We further analyzed the factors related to the spread of the disease. They indicate a strong positive correlation between the total patient numbers and the number of airline passengers, with an r value of 0.80. There is also a positive correlation between the number of car ownership and the total patient, with an r value of 0.35. Both the flight passengers and car ownership contribute 66% to the number of total patients. The total death numbers and the number of airline passengers are positively correlated, with an r value of 0.71. A positive correlation between the number of car ownership and the total deaths is with an r value of 0.42. The total contribution of both the flight passengers and car ownership to the number of total deaths is 57%. Our conclusion is that the main cause of the coronavirus pandemic in developed countries is related to the transportation. In other words, the number of travelers determined the early coronavirus pandemic. Therefore, it is necessary to strengthen restrictions and screening of passengers at airports, especially international airports.

CircDDX42 Accelerates the Development of Pancreatic Cancer via miR-613/ID4/PI3K/AKT Axis.

BACKGROUND: Pancreatic cancer (PC) is one of the fatal cancers globally. CircDEAD-box helicase 42 (circDDX42) has been reported to play an oncogenic role in many cancers. The purpose of our study was to explore the relationship between circDDX42 and PC development and the potential mechanism by which circDDX42 modulating the progression of PC. METHODS: The enrichment of circDDX42, miR-613 and inhibitor of DNA binding 4 (ID4) was determined by quantitative real-time polymerase chain reaction (qRT-PCR) in PC tissues and cells. The proliferation, apoptosis and metastasis of PC cells were examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Western blot, flow cytometry and transwell migration and invasion assays, respectively. The binding sites between miR-613 and circDDX42 or ID4 were predicted by Starbase bioinformatic software, and dual-luciferase reporter assay was conducted to verify the combination between miR-613 and circDDX42 or ID4. Western blot was carried out to detect the abundance of ID4, p-phosphatidylinositol 3-kinase (p-PI3K), PI3K, p-AKT serine/threonine kinase (p-AKT) and AKT in PC cells. The in vivo role of circDDX42 was verified through using murine xenograft model. RESULTS: The level of circDDX42 was enhanced in PC tissues and cells compared with that in matching normal tissues and HPDE cells. CircDDX42 promoted the proliferation and metastasis and suppressed the apoptosis of PC cells. CircDDX42 could sponge miR-613, and miR-613 was negatively regulated by circDDX42 in PC cells. MiR-613 suppressed the progression of PC. ID4 was a direct target of miR-613. ID4 was inversely modulated by miR-613 and positively regulated by circDDX42 in PC cells. ID4 played an oncogenic role in the tumorigenesis of PC. CircDDX42/miR-613/ID4 axis regulated the activation of PI3K/AKT pathway in PC cells. ID4 facilitated the progression of PC via activating PI3K/AKT signal pathway. CircDDX42 promoted the tumor growth of PC in vivo. CONCLUSION: CircDDX42 accelerated the proliferation and metastasis while impeded the apoptosis of PC cells via circDDX42/miR-613/ID4/PI3K/AKT axis. This axis might be a promising target for PC therapy.

Ferroptosis: past, present and future.

Ferroptosis is a new type of cell death that was discovered in recent years and is usually accompanied by a large amount of iron accumulation and lipid peroxidation during the cell death process; the occurrence of ferroptosis is iron-dependent. Ferroptosis-inducing factors can directly or indirectly affect glutathione peroxidase through different pathways, resulting in a decrease in antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells, ultimately leading to oxidative cell death. Recent studies have shown that ferroptosis is closely related to the pathophysiological processes of many diseases, such as tumors, nervous system diseases, ischemia-reperfusion injury, kidney injury, and blood diseases. How to intervene in the occurrence and development of related diseases by regulating cell ferroptosis has become a hotspot and focus of etiological research and treatment, but the functional changes and specific molecular mechanisms of ferroptosis still need to be further explored. This paper systematically summarizes the latest progress in ferroptosis research, with a focus on providing references for further understanding of its pathogenesis and for proposing new targets for the treatment of related diseases.

Modified technique of advanced core decompression for treatment of femoral head osteonecrosis.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a destructive condition most commonly affecting young and middle-aged patients. The leading consequence of ONFH is often a significant articular disability. Effective joint-preserving surgical treatments are urgently needed for patients with early stage ONFH when outcomes of treatment are in general better than the advanced stage disease. AIM: To introduce a new surgery procedure called percutaneous expanded core decompression and mixed bone graft technique, which is a new way of joint-preserving surgical treatments. METHODS: The clinical data of 6 patients with ONFH diagnosed and treated with the procedure called percutaneous expanded core decompression and mixed bone graft technique at The First Hospital of Qiqihar from March 2013 to August 2019 were retrospectively analyzed; the follow-up ended in December 2019. RESULTS: There were 6 male patients with an average age of 43 years in our study. Gratifying results have been obtained from the comparison of Harris hip score, visual analogue scale, and imaging examination before and after operation. CONCLUSION: This new modified technique is simple, safe, and reliable. No serious perioperative complications were observed in our cases. Advantages of the single blade expandable reamer are obvious. The adjuvant substance is inexpensive and easy to obtain. Thus, this technique is an effective joint-preserving surgical treatment for patients with early stage of ONFH.