[Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms].

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.

[HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems].

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

[Establishment of treatment center for peritoneal metastasis in colorectal cancer].

The prognosis of patients with peritoneal metastasis from colorectal cancer is poor. At present, the comprehensive treatment system based on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly improved the survival of these patients. However, CRS and HIPEC have strict indications, high procedural difficulty, and high morbidity and mortality. If CRS+HIPEC is performed in an inexperienced center, overall survival and quality of life of patients may bo compromised. The establishment of specialized diagnosis and treatment centers can provide a guarantee for standardized clinical diagnosis and treatment. In this review, we first introduced the necessity of establishing a colorectal cancer peritoneal metastasis treatment center and the construction situation of the diagnosis and treatment center for peritoneal surface malignancies at home and abroad. Then we focused on introducing our construction experience of the colorectal peritoneal metastasis treatment center, and emphasized that the construction of the center must be done well in two aspects: firstly, the clinical optimization should be realized and the specialization of the whole workflow should be strengthened; secondly, we should ensure the quality of patient care and the rights, well-being and health of every patient.

[Strategies and challenges in the diagnosis and treatment of colorectal cancer peritoneal metastasis].

Peritoneum is a common metastatic site of colorectal cancer and has worse prognosis compared with other metastatic sites. Peritoneal metastasis was previously considered as a terminal state of the disease, and palliative treatment with systemic chemotherapy was the main treatment method. With the gradual acceptance of the cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) treatment model by surgeons and the application of targeted and immunotherapeutic drugs, the prognosis of patients with colorectal cancer peritoneal metastasis has been greatly improved. However, the diagnosis and treatment of peritoneal metastasis still face many challenges and controversies. Based on the evolution of the understanding of colorectal cancer peritoneal metastasis, the possible mechanisms of peritoneal metastasis are discussed, including the theory of "oligometastases" and the theory of "seed and soil". Besides, we further investigate the diagnosis and treatment strategies of colorectal cancer peritoneal metastasis and the facing challenges, including the limitations of imaging examination, the controversy of laparoscopic exploration, the difficulty in assessing peritoneal metastatic load, the limited means of postoperative recurrence monitoring and efficacy evaluation, and the significant variation in the diagnosis and treatment level among different regions of China. Meanwhile, we emphasize the importance of multidisciplinary perioperative management of CRS+HIPEC, and propose that the basic and clinical transformation research of peritoneal metastasis should be strengthened, and the promotion of standardized diagnosis and treatment of peritoneal metastasis is the key to improve the prognosis of patients with colorectal cancer peritoneal metastasis.

Assessing adaptation measures on agricultural water productivity under climate change: A case study of Huai River Basin, China.

This study explored an integrated framework to assess the effectiveness of adaptation measures on the water productivity (WP) of the agricultural water management (AWM) system in the Huai river basin of China considering climate change impact. The adaptation measures include optimization of cropping pattern (OCP) and upgradation of irrigation techniques (UIT). The delta change method was used to downscale the climate variables from RCP4.5 and RCP8.5 of general circulation models (GCMs) during 2021-2050, the water footprint theory was used to estimate the spatial distribution of blue water to calculate the WP, and the nonlinear optimization model was used to seek optimal cropping pattern aiming at maximizing the system's WP. The changes in WP due to climate change and adaptation measures (e.g. combinations of OCP and UIT) were compared. Results indicated that WP under RCP4.5 and RCP8.5 would be 4.56% and 6.51% lower than those under the benchmark scenario, respectively. The mitigation rates to the negative impact of climate change on WP under RCP4.5 and RCP8.5 would be (1) 3.05% and 3.37% for the combination of spay irrigation technique and OCP, and (2) 4.34% and 4.59% for the combination of drip irrigation technique and OCP, respectively. It was revealed that the combination of drip irrigation and cropping pattern optimization could largely offset the adverse effect from climate change on WP under RCP4.5. Under such a scenario, the total plant areas of wheat and maize would reduce over the basin and so would the net export of crops in the basin; this would lead to a decrease in the crop trade benefit of 7.07 × 109 $ and a relief of 7.50 × 109 m3 of blue water loss. This study results could offer strategic decision support for long-term sustainable AWM of Huai river basin in a changing environment.

Evaluation of remedial options for a benzene-contaminated site through a simulation-based fuzzy-MCDA approach.

A simulation-based fuzzy multi-criteria decision analysis (SFMCDA) method is developed for supporting the selection of remediation strategies for petroleum contaminated sites. SFMCDA integrates process modeling (using BIOPLUME III) and fuzzy ranking (based on fuzzy TOPSIS) into a general management framework, and can compare various remediation alternatives, in light of both cost-risk tradeoffs and uncertainty impacts. The proposed method is applied to a hypothetical contaminated site suffering from a benzene leakage problem. Six remediation alternatives are taken into consideration, including natural attenuation (NA), pump-and-treat (PAT), enhanced natural attenuation (ENA), and a number of their combinations. Six fuzzy criteria, including both cost and risk information, are used to compare different alternatives through fuzzy TOPSIS. The results demonstrates that the proposed method can help systematically analyze fuzzy inputs from contaminant transport modeling, cost implications and stakeholders' preferences, and provide useful ranking information covering a variety of decision-relevant remediation options for decision makers.

An interval-parameter stochastic robust optimization model for supporting municipal solid waste management under uncertainty.

A stochastic robust interval linear programming model (IPRO) was developed for supporting municipal solid waste management under uncertainty. The model improves upon the existing stochastic robust optimization (SRO) and interval linear programming (ILP) methods by allowing evaluations of trade-offs among expected costs, cost variability, and risk of violating relax constraints simultaneously, as well as reflections of complex uncertainties through both interval and stochastic theories. A long-term waste management problem was used to demonstrate the applicability of IPRO model. The results indicated that IPRO normally led to interval solutions, where waste-management alternatives could be generated by adjusting the decision-variable values within their intervals. The model could also help waste managers to identify desired policies that under various environmental, economic, system-feasibility and system-reliability constraints.

Simulation and optimization technologies for petroleum waste management and remediation process control.

Leakage and spill of petroleum hydrocarbons from underground storage tanks and pipelines have posed significant threats to groundwater resources across many petroleum-contaminated sites. Remediation of these sites is essential for protecting the soil and groundwater resources and reducing risks to local communities. Although many efforts have been made, effective design and management of various remediation systems are still challenging to practitioners. In recent years, the subsurface simulation model has been combined with techniques of optimization to address important problems of contaminated site management. The combined simulation-optimization system accounts for the complex behavior of the subsurface system and identifies the best management strategy under consideration of the management objectives and constraints. During the past decades, a large number of studies were conducted to simulate contaminant flow and transport in the subsurface and seek cost-effective remediation designs. This paper gives a comprehensive review on recent developments, advancements, challenges, and barriers associated with simulation and optimization techniques in supporting process control of petroleum waste management and site remediation. A number of related methodologies and applications were examined. Perspectives of effective site management were investigated, demonstrating many demanding areas for enhanced research efforts, which include issues of data availability and reliability, concerns in uncertainty, necessity of post-modeling analysis, and usefulness of development of process control techniques.

Risk management of BTEX contamination in ground water--an integrated fuzzy approach.

Abstract An integrated fuzzy simulation-assessment method (FSAM) was developed for assessing environmental risks from petroleum hydrocarbon contamination in ground water. In the FSAM, techniques of fuzzy simulation and fuzzy risk assessment were coupled into a general framework to reflect a variety of system uncertainties. A petroleum-contaminated site located in western Canada was selected as a study case for demonstrating applicability of the proposed method. The risk assessment results demonstrated that system uncertainties would significantly impact expressions of risk-level outputs. A relatively deterministic expression of the risks would have clearer representations of the study problem but may miss valuable uncertain information; conversely, an assessment under vaguer system conditions would help reveal potential consequences of adverse effects but would suffer from a higher degree of fuzziness in presenting the modeling outputs. Based on the risk assessment results, a decision analysis procedure was used to calculate a general risk index (GRI) to help identify proper responsive actions. The proposed method was useful for evaluating risks within a system containing multiple factors with complicated uncertainties and interactions and providing support for identifying proper site management strategies.

Characterizing effects of uncertainties in MSW composting process through a coupled fuzzy vertex and factorial-analysis approach.

A coupled fuzzy vertex and factorial-analysis approach was developed in this study for systematically characterizing effects of uncertainties in a municipal solid waste composting process. A comprehensive composting process model was also embedded into the system framework and used to address substrate decomposition and biomass growth, as well as the interactions between moisture contents, temperatures, and oxygen concentrations. The applicability of the proposed method was verified through a custom-made pilot-scale composting system. Results from fuzzy simulation indicated that the fuzzy vertex method could effectively communicate implicit knowledge into dynamic simulations and thus provide valuable information for enhancing composting process control under uncertainty. The factorial analysis was effective in quantifying the proportion to which the uncertainty of each single or interactive effect of model parameters contributes to the overall uncertainty of the system outcomes. Thus, sensitive parameters that may lead to errors or unreasonable predictions can be determined. The proposed study system could not only be used in characterizing combined effects of uncertainties for composting processes, but was also applicable to many other environmental modelling systems.

Simulation-based process optimization for surfactant-enhanced aquifer remediation at heterogeneous DNAPL-contaminated sites.

Widespread use of dense non-aqueous phase liquids (DNAPLs) such as TCE and PCE has resulted in contamination of enormous valuable groundwater resources and become high-priority environmental problems. However, experiences from the past decades have demonstrated that DNAPL-contaminated sites were difficult to investigate and challenging to remediate. In this study, a simulation-based process optimization system was developed through integrating a multidimensional simulator, a multivariate statistical tool and an optimization model within a general framework for supporting decisions of surfactant-enhanced aquifer remediation (SEAR). A 3D multiphase and multi-component subsurface model was first provided to simulate SEAR process; dual-response surface models were then established to build a bridge between remediation actions and system performance; a nonlinear optimization model was then formulated for identifying optimal operating conditions for SEAR operations. The results in simulating a typical PCE spill event and the associated SEAR remediation operations in a heterogeneous subsurface indicated that SEAR would be capable of cleaning up the contaminated aquifer with improved efficiencies and cost-effectiveness compared with direct pump-and-treat actions. The regression-analysis results demonstrated that the proposed dual-response surface models were able to predict system responses under given operating conditions. The optimization results demonstrated that the developed simulation-optimization approach was effective in seeking cost-effective SEAR strategies for DNAPL-contaminated sites. With the developed method, optimum operation conditions under various environmental and economic considerations could be compiled into a database that would supports further studies of on-site process-control with injection and extraction rates being the main control variables.

Immunological detection of in vivo aflatoxin B1-DNA adduct formation in rats, rainbow trout and coho salmon.

Immunological detection of carcinogen-DNA adducts in organs or tissues should prove a particularly useful approach for monitoring carcinogen exposure, for characterization of carcinogen binding to DNA and for investigating DNA repair processes in vivo. In one of a series of experiments aimed at raising antibodies against several carcinogen-modified DNAs, rabbits were immunized in our laboratory with aflatoxin B1 (AFB1)-modified DNA. After the titer and specificity of the antibodies produced were checked against standards by the enzyme-linked immunosorbent assay (ELISA) method, they were used to investigate DNA extracted from livers of rats and rainbow trout (Salmo mykiss) injected with tritium-labeled AFB1 at doses of 1-2 mg/kg (rats) or 0.1-0.5 mg/kg (rainbow trout). Adduct levels were compared using both radioactivity and ELISA methods. Positive DNA binding could be detected in both rats and rainbow trout by the immunological method at similar levels to those estimated with the radioactive analysis. To throw light on possible mechanisms underlying the wide variation in response to aflatoxins among salmonid fish, DNA extracted from the livers of rainbow trout (susceptible species) and coho salmon (Oncorhynchus kisutch) (less susceptible species) were compared following AFB1 treatment. A high rate of DNA binding was observed in rainbow trout, whereas significantly lower values were evident in coho salmon, suggesting a direct relationship between binding levels and susceptibility to mycotoxin carcinogenicity.

Species and organ differences in DNA adduct formation and repair after treatment with 4-hydroxyaminoquinoline 1-oxide.

4-Hydroxyaminoquinoline 1-oxide (4HAQO) demonstrates obvious organotropic and species specificity in its carcinogenesis and the present investigation concerns 4HAQO DNA adduct formation and repair as studied in various organs of four animal species (rats, mice, guinea pigs and hamsters). Three hours after an iv injection of 10 mg per kg body weight of tritium-labeled 4HAQO, the major organs were removed and used for assessment of label incorporation in the DNA. The results showed that the DNA binding levels generally correlated well with the reported species and organ specificity of 4HAQO tumorigenesis. For example, rats showed highest DNA binding in the pancreas and kidney, major target organs. The levels of DNA binding in the liver were invariably low in all 4 animal species, in agreement with the lack of hepatocarcinogenicity associated with 4HAQO exposure. A clear relationship between DNA adduct formation and carcinogen dose was also found after treatment of mice with 4HAQO at doses of 1, 5, 10 and 20 mg per kg body weight in all tissues (pancreas, kidney and lung) except for the liver. Comparison of DNA repair processes in rats, a highly susceptible species, and hamsters, a resistant species in terms of 4HAQO carcinogenicity, revealed highest formation and slowest removal of adducts in the target organs of the rat. In the hamster organs and the rat lung and liver, DNA adduct formation was generally low and in the case of elevation in the initial phase, quickly removed.

DNA adduct formation and unscheduled DNA synthesis in rat esophagus in vivo after treatment with N-methyl-N-nitrosourea.

An in vivo method for assessment of DNA adduct formation and unscheduled DNA synthesis (UDS) in the esophagus of rats was devised. Small ventral incisions were made in the neck and upper abdomen regions of 6 week old F344 rats and ligation of the esophagus with thread at the two extreme ends performed to make an esophageal pouch. For the DNA adduct formation study, a solution (0.5 ml) containing various concentrations of N-[3H]methyl-N-nitrosourea ([3H]MNU) was injected into the pouch. DNA binding levels were calculated from radioactivity of the isolated DNA and dose-dependent DNA adduct formation could be detected 2 h after the treatment with MNU. By HPLC analysis, both 7-methylguanine (7-mGua) and O6-methylguanine (O6-mGua) adducts were identified in the esophageal DNA, the ratio of 7-mGua/O6-mGua being 5.7-12:1. For UDS measurement, a solution containing MNU plus [3H]thymidine (200 microCi/ml) was similarly injected into the pouch. UDS was dose-dependently demonstrated as silver grains over the nuclei of the epithelial cells by autoradiography. The results thus showed that MNU, when injected into the esophageal lumen, can penetrate the surface mucosa, react with the epithelial cell DNA and induce DNA adduct formation and DNA repair synthesis dose-dependently.