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BackgroundMethamphetamine (METH), a confirmed neurotoxic drug, has also reportedly caused several intestinal inflammatory injury cases. The NLRP3 (Nod-like receptor 3 protein) inflammasome can induce several inflammatory injuries by activating IL-1β and IL-18 when overexpressed. We designed experiments to determine whether METH can cause intestinal inflammatory injury via NLRP3 inflammasome overexpression.Material/MethodsIEC-6 cells were classified as control, METH (0.5 mM), and METH (0.5 mM)+MCC950 (100 μM) groups. C57BL/6 mice were separated into control, NS, METH (5 mg/kg), and METH (5 mg/kg)+MCC950 (10 mg/kg) groups (n=10). We detected apoptosis, transepithelial electrical resistance (TEER), and proinflammatory factors (IL-6, INF-γ, TNF-α, and NF-κB) in the METH cell model. We also assessed proinflammatory factors (IL-6, INF-γ, TNF-α, and NF-κB) and observed intestinal tissues stained with hematoxylin and eosin (HE) in the METH animal model to explore intestinal inflammatory injury due to METH. After adding MCC950 (an NLRP3 inflammasome inhibitor), we additionally detected NLRP3 inflammasome components (NLRP3, Caspase-1, and ASC), IL-1β, and IL-18 to estimate the relationship of the NLRP3 inflammasome with intestinal inflammatory injury due to METH.ResultsMETH can lead apoptosis, increase proinflammatory factors (e.g., IL-6, INF-γ, TNF-α, and NF-κB), and decrease TEER in the METH cell model. In the METH animal model, METH can cause obvious injury and increase proinflammatory factors (e.g., IL-6, INF-γ, TNF-α, and NF-κB). All the intestinal inflammatory changes due to METH depended on overexpression of the NLRP3 inflammasome and could be ameliorated by MCC950, except for ASC and NF-κB.ConclusionsMETH, in addition to being a confirmed neurotoxic drug, can also cause severe intestinal inflammatory injury via NLRP3 inflammasome overexpression. NF-κB may be an activator of the NLRP3 inflammasome in METH intestinal inflammatory injury.

BackgroundDevelopmental dysplasia of the hip (DDH) is a common orthopedic disease in children. In clinical surgery, it is essential to quickly and accurately locate the exact position of the lesion, and there are still some controversies relating to DDH status. We adopt artificial intelligence (AI) to solve the above problems.MethodsIn this paper, automatic DDH measurements and classifications were achieved using a three-stage pipeline. In the first stage, we used Mask-RCNN to detect the local features of the image and segment the bony pelvis, including the ilium, pubis, ischium, and femoral heads. For the second stage, local image patches focused on semantically related areas for DDH landmarks were extracted by high-resolution network (HRNet). In the third stage, some radiographic results are obtained. In the above process, we used 1,265 patient x-ray samples as the training set and 133 samples from two other medical institutions as the verification set. The results of AI were compared with three orthopedic surgeons for reliability and time consumption.ResultsAI-aided diagnostic system's Tönnis and International Hip Dysplasia Institute (IHDI) classification accuracies for both hips ranged from 0.86 to 0.95. The measurements of numerical indices showed that there was no statistically significant difference between surgeons and AI. Tönnis and IHDI indicators were similar across the AI system, intermediate surgeon, and junior surgeon. Among some objective interpretation indicators, such as acetabular index and CE angle, there were good stability and consistency among the four observers. Intraclass consistency of acetabular index and CE angle among surgeons was 0.79–0.98, while AI was 1.00. The measurement time required by AI was significantly less than that of the doctors.ConclusionThe AI-aided diagnosis system can quickly and automatically measure important parameters and improve the quality of clinical diagnosis and screening referral process with a convenient and efficient way.

Epithelial ovarian cancer (EOC) contributes the majority of death cases among various ovarian malignancies. Although a standard method of treatment is the surgical removal of malignant tissue followed by platinum‐based chemotherapy, a group of patients does not respond appropriately to cisplatin. An appropriate response to cisplatin has been linked with the nucleotide excision repair mechanism. The present study aims to investigate the role of polymorphisms in DNA repair genes, excision repair cross‐complementation group 1 (ERCC1) with susceptibility to EOC development and tumour response to platinum‐based chemotherapy in Chinese EOC patients. Patients (n = 559) reporting to the Department of Oncology and general surgery, the First Affiliated Hospital of Kunming Medical University, were enrolled in the study. Three hundred twenty‐three healthy controls hailing from similar geographical areas without a history of cancer enrolled as healthy controls. Excision repair cross‐complementation group 1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were genotyped by appropriate methods. Distribution of genotypes and allele for ERCC1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were comparable among healthy controls and EOC patients. Interestingly, homozygous mutant and the minor allele for rs11615 and rs3212986 polymorphisms were significantly higher in nonresponder EOC patients when compared to those with a proper response to cisplatin treatment. The prevalence of other SNPs was comparable among the two treated clinical categories. Furthermore, combined genotype revealed significant association of rs11615: TT/ rs3212986: AA genotype combination with cisplatin nonresponder. Variants of rs11615, rs3212986 polymorphisms are associated with cisplatin resistance in Chinese EOC patients. Combined rs11615 and rs3212986 genotypes can be used as a predictive biomarker for platinum‐based chemotherapy outcomes.

Aim: To investigate whether systemic inflammation-based predictors can predict tumor response to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC). Materials and Methods: Totally, 205 LARC patients undergoing neoadjuvant CRT and curative surgery between 2008 and 2017 were analyzed. After propensity score matching, 132 patients were included in the study. Hematological parameters were collected, and their relationship with tumor response was investigated. Results: After propensity score matching, patients in good response group before CRT displayed significantly lower neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) than those in poor response group, while there were no significant differences in all hematological characteristics between the two groups after CRT. The cutoff values of pre-CRT NLR and pre-CRT PLR after receiver operating characteristic analysis were 3.10 and 198.7, respectively. Multivariate analysis revealed that while there was no association between pre-CRT PLR and tumor response, pre-CRT NLR ≥3.1 was identified as the predictor of poor tumor response (P = 0.007). Conclusion: An increased NLR before CRT can serve as a hematological factor for predicting a poor tumor response in LARC.