Lipid metabolites abnormally expressed in pelvic fluid as potential biomarkers for ovarian cancer: A case-control study.

BACKGROUND: Ovarian cancer is insidious and usually detected in advanced stages of the disease. As the ovaries are pelvic organs, changes in their pelvic fluid metabolites may be associated with ovarian cancer. METHODS: Metabolomic changes in the pelvic fluid were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patients with ovarian cancer, ovarian cysts and uterine fibroids. Area under the curve (AUC) analysis was used to assess the diagnostic performance of lipid metabolites and blood tumor indices. The Pearson correlation algorithm was used to analyze the correlation between clinical characteristics and lipid metabolites in ovarian cancer patients. RESULTS: There were 24 lipid metabolites significantly changed in the pelvic fluid of ovarian cancer patients (p < 0.05). Palmitoylcarnitine, lipoamide, lipid metabolites, and blood tumor indices (CA15-3 and CA125) showed AUC > 0.8, with palmitoylcarnitine reaching a high of 0.942. In addition, we found that some lipid metabolites were significantly associated with the clinical stage, abdominal water volume, lymphatic metastasis, and recurrence (p < 0.05, r > 0.5). CONCLUSION: Levels of specific lipid metabolites are potential biomarkers of ovarian cancer and may play a key role in the early diagnosis and prognostic assessment of ovarian cancer. SIGNIFICANCE: Our results showed that pelvic metabolites, especially some lipid metabolites, play an important role in the diagnosis of ovarian cancer. Meanwhile, partial lipid metabolites were closely associated with the clinical presentation and prognosis of patients with ovarian cancer. We believe that our study makes a significant contribution to the literature because it provides a potential approach that is more effective for ovarian cancer detection.

Comparative Analysis of Postoperative Sagittal Balance in Expansive Open-Door Laminoplasty versus Laminectomy with Fusion for Multilevel Ossification of Posterior Longitudinal Ligament: A Retrospective Study.

BACKGROUND This single-center study included 80 patients with multilevel cervical ossification of the posterior longitudinal ligament (OPLL) and aimed to compare postoperative sagittal balance following treatment with expansive open-door laminoplasty (LP) vs total laminectomy with fusion (LF). MATERIAL AND METHODS Data of 80 patients with multilevel OPLL treated with LP vs LF between January 2017 and January 2022 were retrospectively analyzed. The basic data, cervical sagittal parameters, and clinical outcomes of the patients were counted in the preoperative and postoperative periods, and complications were recorded. Forty patients underwent LP and 40 underwent LF. Cervical sagittal parameters were compared between and within the 2 groups. Clinical outcomes and complications were compared between the 2 groups. RESULTS At last follow-up, the postoperative C2-C7 Cobb angel, T1 slope (T1S), and C7 slope (C7S) were significantly higher in the LF group than in the LP group (P<0.001). C2-C7 SVA (cSVA) was slightly higher in the LF group (P>0.05) and significantly higher in the LP group (P<0.05). The incidence of postoperative complications in the LP group was significantly lower than in the LF group (P=0.02). The postoperative scores on the Visual Analog Scale (VAS), Neck Disability Index (NDI), and Japanese Orthopedic Association (JOA) were significantly improved in both groups (P<0.001). CONCLUSIONS Both procedures had good outcomes in neurological improvement. After posterior surgery, the cervical vertebrae all showed a tilting forward. Compared to LP, LF may change cervical balance in Cobb angel, T1S. LF has better efficacy in improving cervical lordosis compared with LP. Patients with high T1 slope after surgery may has more axial pain.

Development and status quo of digestive endoscopy in China: An analysis based on the national census in 2013 and 2020.

Background and Objectives: Technique and practice of digestive endoscopy are undergoing speedy development all over the world. This study aimed to evaluate its status quo and development in China. Methods: All hospitals performing digestive endoscopy in mainland China participated in the national census in 2013 and 2020. Retrospective data of hospitals, endoscopists, volumes, and qualities were collected via an online structured questionnaire, and its accuracy and rationality were verified by logical tests and manual reviews. Data from other countries were used to compare with that of China. Results: From 2012 to 2019, the number of hospitals performing digestive endoscopy increased from 6,128 to 7,470 (1.22-fold), in which primary healthcare played a minor role. The median hospitals per 100,000 inhabitants per provincial region increased from 0.49 (IQR, 0.39-0.57) to 0.55 (IQR, 0.49-0.63). The endoscopists increased from 26,203 to 39,638 (1.51-fold), but their average workload even expanded. Overall volume increased from 28.8 million to 44.5 million (1.55-fold), and most types of endoscopic procedures recorded a high growth rate. Contrastingly, the specific utilization rates were low and paled in comparison with some developed countries. Nationwide, regional utilization rates showed a significant correlation with GDP per capita (P <0.001). Overall qualities of digestive endoscopy were excellent, but certain results of quality indicators posed a huge challenge, such as the detection rates of adenoma and early cancers. Conclusions: Impressive progress has been made in digestive endoscopy with rapidly expanding economy in China. However, primary healthcare, utilization rates, and income-related inequality of regional services were needed to be improved to promote public health better.

Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value.

BACKGROUND: Ovarian cancer (OC) is a severe gynecological malignancy with significant diagnostic and therapeutic challenges. The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identify novel biomarkers for OC and their pathogenic causes. METHODS: The present study used the differentially expressed genes (DEGs) obtained from the "Limma" package and WGCNA modules for intersection analysis to obtain DEGs in OC. Three hub genes were identified-claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)-by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases. The correlation between IRF6 and the prognosis of OC patients was further confirmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels of IRF6 in the OC samples. The effect of IRF6 on OC was explored using transwell invasion and scratch wound assays. Finally, we constructed a ceRNA network of hub genes and used bioinformatics tools to predict drug sensitivity. RESULTS: The joint analysis results of TCGA, GTEx, and GEO databases indicated that IRF6 RNA and protein levels were significantly upregulated in serous OC and were associated with OS and PFS. Cell function experiments revealed that IRF6 knockdown inhibited SKOV3 cell proliferation, migration and invasion. CONCLUSION: IRF6 is closely correlated with OC development and progression and could be considered a novel biomarker and therapeutic target for OC patients.

Solanine induces ferroptosis in colorectal cancer cells through ALOX12B/ADCY4 molecular axis.

OBJECTIVES: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer worldwide. Solanine is a phytochemical extracted from traditional Chinese medicine with widely reported anticancer effects. Here, we investigated the potential role of solanine in regulating ferroptosis in CRC cells and scrutinized the molecular mechanism. METHODS: Cell growth and cytotoxicity were examined using CCK-8 proliferation assay and lactate dehydrogenase assay. Oxidative stress was determined by measuring glutathione (GSH), malondialdehyde, and reactive oxygen species (ROS) levels. Subcellular changes in mitochondria were examined by transmission electron microscopy. Gene and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein-protein interaction was determined by co-immunoprecipitation. KEY FINDINGS: Solanine arrested cell proliferation in CRC cells and induced typical ferroptotic changes. Solanine treatment promoted ROS production, lipid peroxidation, and cell membrane disruption, while the cellular level of antioxidant GSH was reduced upon solanine treatment. ALOX12B was identified as a molecular mediator of solanine to promote ferroptosis. Solanine treatment upregulated ALOX12B levels and silencing ALOX12B could suppress solanine-induced ferroptosis. Further, ADCY4 was found to physically associate with ALOX12B and maintain ALOX12B protein stability. Silencing ADCY4 destabilized ALOX12B and attenuated solanine-induced ferroptosis. CONCLUSIONS: Our data demonstrated the ferroptosis-inducing effect of solanine in CRC cells, and revealed ALOX12B/ADCY4 molecular axis as the ferroptosis mediator of solanine. Solanine may synergize with existing ferroptosis inducer as an anticancer strategy in CRC, which warrants further validation in animal experiments.

Factors influencing DVT formation in sepsis.

INTRODUCTION: Sepsis is a global public health burden. Deep vein thrombosis (DVT) is the third most common cause of death from cardiovascular disease after heart attacks and strokes. We designed this experiment to investigate the factors influencing DVT formation in patients with sepsis. METHODS: In this survey, 918 septic patients admitted to Peking Union Medical College Hospital, who underwent DVT screening were enrolled. The data were collected from June 8, 2013 to October 12, 2022. The differences between septic patients with and without DVT were studied from following aspects: basic information, comorbidities, inflammatory cytokines, albumin, source of infection, sequential organ failure assessment (SOFA) score, coagulation and prognosis. MAIN RESULTS: In this study, the prevalence of DVT in patients with sepsis was 0.23. Elderly patients with sepsis were prone to DVT (p value < 0.001). In terms of comorbidities, septic patients with hypertension and atrial fibrillation were prone to DVT (p value 0.045 and 0.048). Inflammatory cytokines, such as procalcitonin (PCT), C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, had no significant correlation with DVT in patients with sepsis (p value 0.364, 0.882, 0.912, 0.789, 0.245, and 0.780). Levels of serum albumin correlated with DVT in patients with sepsis (p value 0.003). The SOFA total score had no relationship with DVT formation (p value 0.254). Coagulation and respiration function were negatively correlated with DVT (p value 0.018). Liver function was positively correlated with DVT (p value 0.020). Patients in the DVT group had longer duration of mechanical ventilation and longer intensive care unit (ICU) stays (p value < 0.001 and 0.006). There was no significant difference in survival in septic patients with and without DVT (p value 0.868). CONCLUSIONS: The SOFA total score had no relationship with DVT formation. The function of each organ had different effects on DVT formation. Better coagulation and respiration function, easier DVT formation. Poorer liver function, easier DVT formation. DVT was associated with longer duration of mechanical ventilation and longer ICU stays.

Cadmium accumulation in paddy soils affected by geological weathering and mining: Spatial distribution patterns, bioaccumulation prediction, and safe land usage.

The abnormal enrichment of cadmium (Cd) in soil caused by rock weathering and mining activities is an issue in southern China. Although the soil Cd content in these regions is extremely high, the bioavailability of Cd in the soils differs significantly. The carbonate area (CBA) and tin-mining area (TIA) in Hezhou City were investigated to determine the primary features of soil Cd mobility in these regions and improve environmental management. Lateral and vertical spatial distributions revealed different accumulation and migration mechanisms of soil Cd in the CBA and TIA. Further analyses revealed that mining activities and geological weathering resulted in different soil geochemical parameters, thus yielding significantly lower levels of Cd in rice grains in the CBA than in the TIA. The random forest (RF) model predicted the bioaccumulation factor (BAF) (R2 = 0.69) better than the support vector machine (SVM) model (R2 = 0.68). Subsequently, a novel land management scheme was proposed based on soil Cd and the prediction of Cd in rice to optimize the spatial resources of agricultural land and ensure the safety of rice for consumption. This study provides a novel approach for land management in Cd-contaminated areas.

A novel Natural killer cell-related gene signature for improving the prediction of prognosis and immunotherapy response in bladder cancer.

BACKGROUND: Bladder cancer (BLCA) is a commonly diagnosed cancer worldwide that exhibits high rates of recurrence and metastasis. Immunotherapy is increasingly being recognised in the clinical management of bladder cancer. In addition, the prospect of developing Natural Killer (NK) cell-related immunotherapy is promising in BLCA. METHODS: We established and verified a prognostic signature based on NK cell-related gene expression. We then calculated the NKscore of BLCA samples and correlated it with the clinical outcomes, molecular subtypes of BLCA, tumour microenvironment (TME), and predicted efficacy of immune checkpoint inhibitors (ICI) and chemotherapy drugs to thoroughly explore the implications of the NKscore. Finally, the role of the NK signature gene HECTD1 in BLCA was verified by Quantitative Real-time PCR, Cell Counting Kit-8 Assay (CCK-8), Transwell Assay and Colony Formation Experiment. RESULTS: We analysed NK cell-associated genes and identified six genes with significant prognostic relevance. A high NK score significantly represents a worse prognosis. NKscore was significantly correlated with seven types of classical molecular subtype classifications of BLCA. In addition, NKscore positively correlates with NK-related immune checkpoints, suggesting that emerging NK cell immune checkpoint inhibitors, such as monalizumab, may have potential therapeutic promise for patients with high NKscore. The results of the T cell inflamed score (TIS) and tumour immune dysfunction exclusion (TIDE) score confirmed the suitability of immunotherapy for patients with a high NK score. Likewise, patients with a high NK score may be more suitable for several significant chemotherapeutic drugs. Functional experiments showed that the knockdown of HECTD1 significantly attenuated the proliferation, migration, and invasion ability of tumour cells. CONCLUSION: to sum up, the capability of our signature to predict prognosis and immunotherapy response was robust. Hopefully, these results will provide new insights for BLCA research and patient immunotherapy.

Development and validation of a nomogram for predicting osteoporosis in prostate cancer patients: A cross-sectional study from China.

BACKGROUND: The specific risk factors contributing to the development of osteoporosis and the appropriate timing of treatment in Chinese prostate cancer (PCa) patients remain unclear. Our objective was to develop and validate a nomogram capable of predicting the occurrence of osteoporosis in PCa patients. METHODS: We conducted a cross-sectional study with PCa patients attending the Second Hospital of Tianjin Medical University, collecting data from June 2021 to February 2023. The patients were divided into training and validation sets in a 7:3 ratio. The LASSO regression was used to identify the most relevant predictive variables, and the multivariable logistic regression was used to construct the nomogram. The nomogram's performance was validated through receiver operating characteristic (ROC) curves, C-index, calibration curves, and decision curve analysis (DCA) in both the training and validation sets. RESULTS: We collected data from a total of 596 patients and then constructed the nomogram using age, body mass index, hemoglobin, vitamin D3, testosterone, and androgen deprivation therapy duration. The C-index of the nomogram was 0.923 in the training set and 0.859 in the validation set. The nomogram showed good consistency in both sets. DCA demonstrated the clinical benefit of the nomogram across various prediction thresholds. Furthermore, a separate nomogram was constructed to predict bone loss in patients undergoing ADT, exhibiting equally favorable diagnostic performance and clinical benefit. CONCLUSION: This study constructed two reliable nomograms to predict osteoporosis and bone loss, integrating personal health information and PCa-specific treatment data. These nomograms offer an easy and individualized approach to predict the occurrence of osteoporosis and bone loss in PCa patients.

Prediction of cadmium contents in rice grains from Quaternary sediment-distributed farmland using field investigations and machine learning.

The Quaternary sediment-distributed regions of South China are suitable for rice cultivation, which is crucial for ensuring food security. Spatial correlations between soil cadmium (Cd) and rice Cd contents are generally poor, making the evaluation of rice quality and associated health risks challenging. In this study, we developed machine learning algorithms for predicting rice Cd contents using 654 data pairs of soil-rice samples collected in Guangxi province, China. After a comprehensive comparison, our results showed that the random forest (RF) had the better performance than artificial neural network (ANN) based on all the data (RMSEtesting 0.066 vs. 0.099 and R2testing 0.860 vs. 0.688). The feature importance analysis showed that soil CaO, Cd, elevation, and rainfall were the four most important features affecting the rice Cd contents in the study area. Using the established RF-predicated model, the rice Cd contents were predicted at the provincial level with an additional dataset of 1176 paddy soil samples. The prediction result revealed about 23 % of farmland cultivated rice with Cd content over 0.2 mg kg-1 in the study area. Therefore, it is recommended to implement strict measures by local agricultural departments to reduce rice Cd contents and ensure food safety in these areas. Our study provides valuable insights into the prediction of rice Cd contents, thus contributing to ensuring food safety and preventing Cd exposure-associated health risks.

Mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension.

BACKGROUND: This study aimed to investigate the potential mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension (ICMT). METHODS: According to the Pfirrmann grade evaluation classification, 30 human endplate cartilage tissues were divided into the lumbar vertebra fracture (LVF) group and lumbar disc herniation (LDH) group. Then, quantitative reverse transcription polymerase chain reaction, western blot, flow cytometry, hematoxylin-eosin staining, and senescence-associated ß-galactosidase staining were performed. The difference in extracellular matrix expression between LVF and LDH endplate cartilage was detected. Second, the effect of ICMT on endplate chondrocytes degeneration was observed. Finally, the key regulatory role of YAP1 in ICMT-induced endplate cartilage degeneration was further verified. RESULTS: In degraded human endplate cartilage and tension-induced degraded endplate chondrocytes, the expression of YAP1, COL-2A, and Sox9 was decreased. Conversely, the expression of p53 and p21 was increased. By regulating YAP1 in vivo and in vitro, we can achieve alleviation of ICMT-induced senescence of endplate chondrocytes and effective treatment of disc degeneration. CONCLUSIONS: ICMT could induce senescence and degeneration of endplate chondrocytes, and ICMT-induced senescence and degeneration of endplate chondrocytes could be alleviated by regulating YAP1 expression.

Regulation of Hippo/YAP signaling pathway ameliorates cochlear hair cell injury by regulating ferroptosis.

Cisplatin, which is effective for the treatment of solid tumors, also can induce cochlear hair cell damage. Therefore, this study was intended to explore how Hippo/YAP signaling pathway affects the cochlear hair cell injury by regulating ferroptosis. After cisplatin induction, or LAT1-IN-1 (YAP activator) and verteporfin (YAP inhibitor) treatment or transfection, the viability of HEI-OC1 cells was detected by cell counting kit-8 (CCK-8) assay. The iron level and the levels of oxidative stress markers (ROS, MDA and 4-HNE) were analyzed by iron assay kit, reactive oxygen species (ROS), malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) assay kits, respectively. The expression of ferritin light chain (FTL) in HEI-OC1 cells was detected by immunofluorescence and protein expressions of yes associated protein (YAP,) phosphorylated YAP (p-YAP), transferrin receptor (TFRC), glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) in HEI-OC1 cells were detected by western blot. The transcription of FTL and TFRC by YAP1 was verified by dual-luciferase reporter assay. The transfection efficiency of small interfering RNA (si-RNA) specific to FTL (siRNA-FTL) and TFRC (siRNA-TFRC) was confirmed by reverse transcription­quantitative polymerase chain reaction (RT­qPCR). As a result, cisplatin inhibited the viability of HEI-OC1 cells by increasing free Fe2+ level and decreasing FTL level. LAT1-IN-1 promoted the viability of cisplatin-induced HEI-OC1 cells by suppressing oxidative stress level, free Fe2+ level, ferroptosis and increasing FTL level, while the effect of verteporfin was the opposite. YAP1 transcriptionally regulated the expression of FTL and TFRC. Inhibition of FTL suppressed the viability of cisplatin-induced HEI-OC1 cells by increasing oxidative stress level, free Fe2+ level, ferroptosis and decreasing FTL level, while the effect of TFRC inhibition was the opposite. In conclusion, YAP1 ameliorated cochlear hair cell injury by upregulating FTL and TFRC to suppress ferroptosis.

Identification of the spatial patterns and controlling factors of Se in soil and rice in Guangxi through hot spot analysis.

Selenium (Se) is essential to human health, anti-cancer, possessing antioxidant, and antiviral properties. In this study, the spatial patterns of rice Se and their varying relationship with soil Se on a regional scale were studied using hot spot analysis for the agricultural soils in Guangxi. According to the hot and cold spot maps, rice Se correlates positively with soil Se in Guangxi agricultural soils. High rice Se accompanies high soil Se in the central part of Guangxi (e.g., Liuzhou, Laibin), and low rice Se is in line with low soil Se in the western part (e.g., Baise). However, the hot spot analysis maps indicate that southwestern Guangxi exhibits a special characteristic of low rice Se with high soil Se (e.g., Chongzuo). This special pattern is strongly associated with the high concentrations of Fe2O3 (ferromanganese nodules) in the carbonate rock area. The hot spot analysis proves useful in revealing the spatial patterns of rice Se in Guangxi and identifying the hidden patterns.

Systematic evaluation of guidelines for laparoscopic surgery and endoscopic management for colon cancer.

PURPOSE: To understand the methodological quality of recent guidelines for laparoscopic surgery and endoscopic management for colon cancer and to analyze the heterogeneity and possible reasons for the main recommendations. METHODS: A systematic and comprehensive search of databases and relevant websites was conducted to collect guidelines for laparoscopic surgery for colon cancer in the last 10 years that met the inclusion criteria. The AGREE II manual was used to evaluate the included guidelines and to assess and analyze the heterogeneity and reasons for key recommendations about the surgery. RESULTS: A total of fifteen guidelines were included in this study. Only two guidelines had an overall score greater than 60% and were recommended for clinical use. Eleven guidelines had an overall score of 30-60%, and two guidelines had an overall score of less than 30%. Further analysis of the reasons for heterogeneity in the guideline recommendations and evidence was performed for nine guidelines. This study found that only 36.1% of the evidence levels recommended in the guidelines were high. Significant heterogeneity exists in the main recommendations, mainly because the relevant content is not mentioned or described in detail. CONCLUSION: The quality of guidelines for laparoscopic colon cancer surgery is variable, and there is significant heterogeneity among key recommendations. And the level of evidence underlying the recommendations was generally not high. Further guideline updates should address the causes of the above heterogeneity.

Apatinib Inhibits Bladder Cancer through Suppression of the VEGFR2- PI3K-AKT Signaling Pathway as Revealed by Network Pharmacology and in vitro Experimental Verification.

AIMS: This study aimed to evaluate the underlying pharmacological mechanisms of Apatinib anti-bladder cancer via network pharmacology and experimental verification. METHODS: Network pharmacology was used to screen the possible signaling pathways of Apatinib in bladder cancer, and the most likely pathway was selected for in vitro validation. CCK-8 and colony formation assay were used to detect the effect of Apatinib on the proliferation of bladder cancer cells. Hoechst staining and flow cytometry detected apoptosis of bladder cancer cells induced by Apatinib. Western blot was performed to distinguish the effect of Apatinib on the expression levels of key targets. RESULTS: Apatinib can affect many signaling pathways and the correlation of the PI3K-AKT signaling pathway was the greatest. In vitro experiments showed that Apatinib could inhibit bladder cancer cell proliferation, induce apoptosis, and up-regulate the expression of apoptosisrelated proteins Cleaved-PARP and down-regulate the expression of Bcl-2. Furthermore, Apatinib could decrease the protein expression of VEGFR2, P-VEGFR2, P-PI3K and P-AKT. CONCLUSIONS: Apatinib could promote apoptosis of bladder cancer cells by inhibiting the VEGFR2- PI3K-AKT signaling pathway.

Combination with vorinostat enhances the antitumor activity of cisplatin in castration-resistant prostate cancer by inhibiting DNA damage repair pathway and detoxification of GSH.

BACKGROUND: Like DNA methylation, histone modifications are considered important processes for epigenetic alterations in gene function, and abnormally high expression of histone deacetylases (HDACs) plays a key role in many human diseases. In addition to regulating the acetylation levels of histone and non-histone proteins and gene transcription, HDAC inhibitors as antitumor drugs can also affect the DNA damage repair (DDR) pathway in tumor cells. Prostate cancer (PCa) is one of the most heritable malignancies in which DDR pathway defects can be detected in a considerable proportion of cases. Such defects are more prevalent in castration-resistant prostate cancer (CRPC) and are highly enriched in metastatic lesions. There is currently evidence that DDR pathway-deficient PCa is associated with high-risk biological behaviors and response sensitivity to platinum-based chemotherapy. Platinum-based drugs have been used in multiple clinical trials as monotherapy or in combination with other chemotherapeutic agents for the treatment of CRPC. METHODS: This study evaluated the combined anticancer effect of (cisplatin) CDDP and the HDAC inhibitors vorinostat (SAHA) on three androgen-dependent cell lines PC-3, DU-145, and C4-2B in vitro. The efficacy and safety of SAHA combined with CDDP in the treatment of CRPC were further verified through animal experiments. RESULTS: The combination of the two drugs increases cytotoxic effects by increasing DNA damage. Our results showed that the SAHA could not only reduce the expression of homologous recombinant repair proteins BRCA2, BRCA1, PARP1, and RAD51, but also decrease enzymes that Reduce the key enzymes of GSH biosynthesis, GSS and GCLC, and GSTP1 which can catalyze the binding of GSH to cisplatin. The intracellular GSH level also decreased with the increase of SAHA concentration, at the same time, the content of intracellular Pt element. CONCLUSION: The combination of CDDP and SAHA can produce synergistic anticancer effects in androgen-independent PCa cells in vitro and in vivo. Our results open up a new avenue for the effective treatment of CRPC. To optimize the chemotherapy regimen for patients with advanced PCa, it is necessary to further study the molecular mechanism of platinum drugs, HDAC inhibitors, and their combined action.

Utilization and quality assessment of digestive endoscopy in China: results from 5-year consecutive nationwide surveys.

BACKGROUND: Worldwide, the volume and availability of digestive endoscopy have undergone dramatic development in recent years, with increasing attention on quality assurance. We investigated the utilization and quality of digestive endoscopy in China from 2015 to 2019 and developed a quantitative quality evaluation tool for medical institutions. METHODS: We invited all tertiary/secondary hospitals in Chinese mainland to participate in the survey annually. The questionnaires included the personnel, annual volume, and quality indicators of endoscopy. An endoscopy quality index (EQI) was developed based on recorded quality indicators using principal component analysis to determine the relative weight. RESULTS: From 2015 to 2019, 806, 1412, 2644, 2468, and 2541 hospitals were respectively enrolled in this study. The average annual volume of endoscopy increased from 12,445 to 16,206 (1.30-fold) and from 2938 to 4255 (1.45-fold) in tertiary and secondary hospitals, respectively. The most obvious growth was observed in diagnostic colonoscopy (1.44-fold for all hospitals after standardization). The proportion of early cancer among all esophageal and gastric cancers during diagnostic esophagogastroduodenoscopy increased from 12.3% (55,210/448,861) to 17.7% (85,429/482,647) and from 11.4% (69,411/608,866) to 16.9% (107,192/634,235), respectively. The adenoma detection rate of diagnostic colonoscopy increased from 14.9% (2,118,123/14,215,592) to 19.3% (3,943,203/20,431,104). The EQI model included 12 quality indicators, incorporating 64.9% (7.792/12) of the total variance into one comprehensive index. According to the EQI measurements, the quality of endoscopy was higher in tertiary hospitals and hospitals in developed areas with higher volume or more endoscopists than that in other hospitals. CONCLUSIONS: Digestive endoscopy in China has developed considerably in recent years in terms of both volume and quality. The EQI is a promising tool to quantify the quality of endoscopy at different hospitals.

SNHG3 Affects Gastric Cancer Development by Regulating SEPT9 Methylation.

Background: Gastric cancer (GC) is a common malignancy that can be formed by methylation-induced deactivation of tumor silencer genes, which is one of the key mechanisms of tumorigenesis. SEPT9 methylation, a symptomatic marker for tumors, can downregulate gene expression. Long noncoding RNA small nucleolar host gene 3 (lncRNA SNHG3) is a new type of lncRNA related to cancer. Our study investigated the mechanism of SNHG3 regulation of SEPT9 methylation and its effects on the growth, metastasis, and spread of gastric cancer cells. Methods: Quantitative real-time PCR (qRT-PCR) was used to detect SNHG3 and miR-448 in gastric cancer, and a dual-luciferase experiment verified the effects of SNHG3, miR-448, and DNMT1. After abnormally expressing SNHG3, miR-448, and DNMT1 alone or together, methylation-specific PCR was performed to determine the methylation of SEPT9, Western blotting was performed to detect the expression of DNA methyltransferase 1 (DNMT1) and SEPT9, and Transwell, scratch, and CCK-8 assays were performed to reveal the invasion, migration, and cell growth of gastric cancer cells. Results: We found that SNHG3 was upregulated in gastric cancer and that SNHG3 knockdown or miR-448 overexpression inhibited SEP9 methylation and therefore increased its expression, thereby inhibiting the growth, metastasis, and spread of gastric cancer cells. Conclusion: Our study indicates that SNHG3 regulates SEPT9 methylation by targeting miR-448/DNMT1 and subsequently affecting the occurrence and development of gastric cancer.

Use of artificial neural network to evaluate cadmium contamination in farmland soils in a karst area with naturally high background values.

In recent years, the naturally high background value region of Cd derived from the weathering of carbonate has received wide attention. Due to the significant difference in soil Cd content and bioavailability among different parent materials, the previous land classification scheme based on total soil Cd content as the classification standard, has certain shortcomings. This study aims to explore the factors influencing soil Cd bioavailability in typical karst areas of Guilin and to suggest a scientific and effective farmland use management plan based on the prediction model. A total of 9393 and 8883 topsoil samples were collected from karst and non-karst areas, respectively. Meanwhile, 149 and 145 rice samples were collected together with rhizosphere soil in karst and non-karst areas, respectively. The results showed that the higher CaO level in the karst area was a key factor leading to elevated soil pH value. Although Cd was highly enriched in karst soils, the higher pH value and adsorption of Mn oxidation inhibited Cd mobility in soils. Conversely, the Cd content in non-karst soils was lower, whereas the Cd level in rice grains was higher. To select the optimal prediction model based on the correlation between Cd bioaccumulation factors and geochemical parameters of soil, artificial neural network (ANN) and linear regression prediction models were established in this study. The ANN prediction model was more accurate than the traditional linear regression model according to the evaluation parameters of the test set. Furthermore, a new land classification scheme based on an ANN prediction model and soil Cd concentration is proposed in this study, making full use of the spatial resources of farmland to ensure safe rice consumption.