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Dihydroorotate dehydrogenase (DHODH) is a flavin-dependent metabolic enzyme that oxidizes dihydroorotate acid to orotic acid in the de novo synthesis pathway of pyrimidine metabolism. DHODH is located in mitochondria, closely related to cellular oxidative phosphorylation, and an important suppressor of the ferroptosis pathway. This study investigates the influence of DHODH on the progression of malignant tumors, including its important role in the de novo synthesis of pyrimidine, oxidative phosphorylation, and ferroptosis. The objective is to present evidence that DHODH is a potential target for the clinical treatment of tumors.

Objective To investigate the correlation between drinking habits and pathological characteristics of patients with upper tract urothelial carcinoma (UTUC). Methods A preoperative questionnaire survey was conducted to understand the drinking habits of UTUC patients who were admitted to the Department of Urology, Peking University First Hospital for radical nephroureterectomy within one year from August 2020 to July 2021, and statistical analysis was performed in combination with their postoperative pathological characteristics. The statistical procedure was performed using SPSS 22.0 software, and firstly, the preliminary analysis was performed one by one using the columnar χ2 test on the pathological characteristics of UTUC tumors as the dependent variable and the factors related to patients' general information, past history and drinking habits as the independent variables, and the independent variables that met P < 0.2 between the case and control groups for each dependent variable were specified for screening. The screened variables were included in the binary Logistic regression analysis. A difference of P < 0.05 was used to indicate a statistically significant difference. Results A total of 239 patients, 134 males and 105 females, with a mean age of (68.1±9.98)years and a median disease duration of 4.8 months, were included in this study. Multifactorial Logistic regression results suggested that after adjusting for the effects of other variables, UTUC patients who had the habit of drinking at least once every hour during the daytime had a significantly increased risk of high grade (G3) tumors(OR=1.941, 95%CI: 0.352-1.029, P < 0.01); these patients also had a significantly decreased risk of multifocal UTUC tumors (OR=0.344, 95% CI: 1.18-5.582, P=0.004). The patients who had the habit of drinking over 100 mL water each time had a significantly decreased risk of mutifocal UTUC incidence (OR=0.477, 95%CI: 0.225-1.012, P=0.046). Patients who pay attention to daily water intakes had a significantly increased risk of renipelvic carcinoma (OR=2.530, 95%CI: 1.434-4.463, P=0.001) and a significantly decreased risk of ureteral carcinoma (OR=0.314, 95%CI: 0.172-0.573, P < 0.01). Other variables included in the regression model did not differ significantly in their effects on the occurrence of tumor pathological characteristics. Conclusion Having the awareness of drinking water every 1 h during the day, drinking over 100 mL water each time, having the awareness of daily drinking habits correlated significantly with pathological characteristics of UTUC such as the presence of G3 tumor, multifocal tumors and location of the tumor. This conclusion still needs to be verified by subsequent trials with higher levels of evidence.

This article reported the clinical features of a rare patient with anti-metabotropic glutamate receptor 5 （mGluR5） encephalitis with mental disorders as the initial symptom， so as to provide references for clinical diagnosis and treatment. The patient was a 38-year-old male， developed pharyngeal pain as prodromal symptoms， and the main clinical manifestations included rapidly progressive memory loss， anxiety and depression， and psychomotor excitement symptoms including irritability and impulsive behaviors. The disease had a progressive deterioration. In the most severe state， the patient became unconscious in a shallow coma， with further cognitive decline， hallucinations and delusions， and lack of self-awareness. Both cerebrospinal fluid and serum anti-mGluR5 antibody were strongly positive （1∶100）. After two sessions of hormone shock therapy， the patient showed significantly improvement in consciousness， cognitive， emotional and psychiatric dimensions.

Objectives: To quantitatively assess the differences in parameters of dynamic contrast-enhanced MRI (DCE–MRI) in HER2-zero, HER2-low, or HER2-positive tumors, and to build optimal model for early prediction of HER2-low breast cancer (BC). Materials and methods: Clinical and DCE–MRI data from 220 BC patients receiving neoadjuvant chemotherapy (NACT) were retrospectively analyzed. Quantitative and semi-quantitative DCE–MRI parameters were compared in the HER2-zero, HER2-low, or HER2-positive groups before and after early NACT. Empirical models were developed to predict HER2-low BC using logistic regression analysis and receiver operating characteristic (ROC) analysis. Results: Patients of HER2-low BC have a lower pCR rate compared with HER2-zero and HER2-positive (17.9% vs. 10.4% vs. 29.5%, p < 0.001), predominantly in the HR (hormone receptor) negative group (22.2% vs. 7.7% vs. 40.5%, p < 0.001). Before NACT, HER2-low BC exhibited higher Kep, Ktrans, Washin, and lower TME intratumoral perfusion characteristics, and higher Kep and lower TME in peritumoral region compared to HER2-zero and HER2-positive BC patients. Notably, after early NACT, changes in intratumoral perfusion (Kep) and in peritumoral perfusion (Ktrans, Washin) were more pronounced in the HER2-low group compared to HER2-zero and HER2-positive group. The ROC curves (AUC) for the pre-NACT intratumoral, peritumoral, and combined perfusion models were 0.675(95% CI 0.600–0.750), 0.661(95% CI 0.585–0.738), 0.731(95% CI 0.660–0.802). The combined pre-and-post-NACT perfusion model further improved predictive performance accordingly, with AUCs of 0.764 (95% 0.637–0.865), 0.795 (95% CI 0.711–0.878), 0.850 (95% CI 0.774–0.926). Conclusions: The study revealed perfusion heterogeneity between different HER2 statuses and identified the best imaging model as a non-invasive tool to predict HER2-low BC, which can help pre-treatment clinical decision-making. Highlights: In the NACT cohort, the pathological complete response (pCR) rates were notably lower in patients with HER2-low breast cancer compared to patients with other HER2 statuses, particularly within the HR(-) subtype. HER2-low breast cancers exhibit distinct perfusion characteristics on quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE–MRI). The combined baseline and early NACT perfusion model is expected to early predict HER2-low breast cancer. [ABSTRACT FROM AUTHOR]

This paper examines the earnings management behavior of target insurers before mergers and acquisitions by investigating their reserving conservatism compared to control insurers. Contrary to the expectation that acquisition targets would manipulate their earnings to increase acquisition premiums, we find that target insurers are generally more conservative in their loss reserving practices before acquisitions than control firms. This finding provides support for the effectiveness of due diligence and the contractual risk shifting arguments, and the result holds regardless of whether acquirers are insurers or non‐insurers. Furthermore, we discover that target loss reserve conservatism is negatively associated with target CEO turnover post‐acquisition. In line with existing literature, we also find evidence suggesting that targets involved in stock acquisitions tend to adopt a less conservative reserving strategy than in deals that do not include stock payments. [ABSTRACT FROM AUTHOR]