Yufeng Chen

The occurrence of treatment resistance in women with postpartum depression (PPD) and risk factors for treatment resistance remain less studied. This study aimed to determine the rate of treatment resistance and the associated risk factors among women with PPD in a nationwide setting. Here we conducted a nationwide register-based cohort study of 58,618 patients with a first-ever PPD during 2006–2021 in Sweden. Information on demographics, pregnancy characteristics, pre-existing physical and psychiatric conditions and treatment was retrieved from Swedish national registers. The outcome was treatment-resistant PPD (TRPPD) within 1 year following PPD diagnosis. Associations between potential risk factors and TRPPD were assessed using multivariable Poisson regression. Among the 58,618 patients with PPD, 3,522 (6.0%) met the criteria for TRPPD during 1 year after PPD diagnosis. Lower educational level, lower household income, being non-cohabiting, smoking in early pregnancy, delivery by cesarean section, pre-existing physical conditions and pre-existing psychiatric disorders were significantly associated with a higher risk of TRPPD. In addition, patients with two births (versus primiparity) or with a prior premenstrual disorder had a lower risk of TRPPD. Treatment resistance in patients with PPD is common and is notably associated with specific demographic and clinical profiles. These findings may provide grounds for practical risk assessment at PPD diagnosis and highlight the need for personalized management strategies.

Importance: Childhood bereavement increases the risk of common psychiatric disorders later in life. However, the role of stress resilience in this association remains underexplored.Objective: To assess whether stress resilience mediates the association between childhood bereavement and psychiatric disorder risk in adulthood.Design, Setting, and Participants: Three matched cohort studies were performed using data recorded in the Swedish Military Conscription Register. Individuals with childhood loss of either a parent or a sibling (19 162 participants), a parent (16 247 participants), or a sibling (3023 participants) due to death from 1987 to 2020, together with 10 unexposed individuals per exposed individual, were matched on sex, birth year, and county of birth. All participants had available stress resilience measure at conscription. Data were analyzed from February to December 2024.Exposures: Childhood bereavement was ascertained from the Swedish Multi-Generation and Causes of Death Registers.Main outcomes and Measures: Incident diagnosis of depression, anxiety, substance use disorder, and stress-related disorder was ascertained from the Swedish Patient Register. Cox models were used to estimate the association between childhood bereavement and risk of postconscription psychiatric disorders after multivariable adjustment. Causal mediation analysis was conducted to examine if stress resilience measured at conscription mediated this association.Results: Among 1 733 085 conscripted individuals (median [IQR] age at conscription 18.2 [18.0-18.5] years; 1 707 960 [98.5%] male), the median (IQR) age of individuals exposed to loss of either a parent or a sibling, parent, or sibling was 13.4 (9.6-15.8), 13.7 (10.4-15.9), and 10.7 (5.5-14.9) years, respectively. The crude incidence rate of any psychiatric disorder was 7.9, 8.1, and 6.6 per 1000 person-years among the 3 groups (5.3, 5.8, and 5.5 per 1000 person-years among the respective unexposed groups). A positive association was noted for loss of either a parent or a sibling (HRs ranged from 1.13; 95% CI, 1.06-1.20 for anxiety to 1.31; 95% CI, 1.23-1.40 for substance abuse disorder) and loss of a parent (HRs ranged from 1.10; 95% CI, 1.01-1.20 for stress-related disorders to 1.19; 95% CI, 1.12-1.27 for depression). For loss of a sibling, the statistically significant associations were for any common psychiatric disorder (HR, 1.12; 95% CI, 1.00-1.25) and stress-related disorders (1.27; 95% CI, 1.04-1.55). Stress resilience partially mediated the associations (proportions for loss of either a parent or a sibling ranged from 10.6%-19.4%, for a parent ranged from 15.6%-21.7%, and for a sibling ranged from 6.2% for stress-related disorders to 18.4% for any common psychiatric disorder).Conclusions and Relevance: In this cohort study of a nationwide Swedish sample, altered stress resilience was found to be one mechanism through which childhood bereavement is associated with risk of psychiatric disorders later in life.

Although major depression, characterized by a pro-inflammatory profile, genetically overlap with autoimmune disease (AD) and the perinatal period involve immune system adaptations and AD symptom alterations, the bidirectional link between perinatal depression (PND) and AD is largely unexplored. Hence, the objective of this study was to investigate the bidirectional association between PND and AD. Using nationwide Swedish population and health registers, we conducted a nested case-control study and a matched cohort study. From 1,347,901 pregnancies during 2001–2013, we included 55,299 incident PND, their unaffected full sisters, and 10 unaffected matched women per PND case. We identified 41 subtypes of AD diagnoses recorded in the registers and compared PND with unaffected population-matched women and full sisters, using multivariable regressions. Women with an AD had a 30% higher risk of subsequent PND (95% CI 1.2–1.5) and women exposed to PND had a 30% higher risk of a subsequent AD (95% CI 1.3–1.4). Comparable associations were found when comparing exposed women with their unaffected sisters (nested case-control OR: 1.3, 95% CI 1.2–1.5, matched cohort HR: 1.3, 95% CI 1.1–1.6), and when studying antepartum and postpartum depression. The bidirectional association was more pronounced among women without psychiatric comorbidities (nested case-control OR: 1.5, 95% CI 1.4–1.6, matched cohort HR: 1.4, 95% CI 1.4–1.5) and strongest for multiple sclerosis (nested case-control OR: 2.0, 95% CI 1.6–2.3, matched cohort HR: 1.8, 95% CI 1.0–3.1). These findings demonstrate a bidirectional association between AD and PND independent of psychiatric comorbidities, suggesting possibly shared biological mechanisms. If future translational science confirms the underlying mechanisms, healthcare providers need to be aware of the increased risk of PND among women with ADs and vice versa.

Purpose: This study aimed to assess the efficacy and safety of adjuvant transarterial chemoembolization (TACE) plus tyrosine kinase inhibitor (TKI) treatment in patients with hepatocellular carcinoma (HCC) with a high risk of early recurrence after curative resection. Patients and Methods: Patients from multiple centres were divided into postoperative adjuvant TACE with (n=57) or without (n=142) TKI administration groups. The disease-free survival (DFS) curve was depicted by the Kaplan–Meier method, and the difference between the two groups was tested using the log rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for DFS. Additionally, three propensity score analyses were performed to minimise the potential confounding factors to facilitate a more reliable conclusion. Adverse events (AEs) were assessed according to the Common Terminology Criteria for Adverse Events, version 4.0. Results: The 1-and 2-year DFS rates of the TACE plus TKI treatment group were 45.5% and 34.9%, respectively, which were significantly better than those of the TACE alone group (26.8% and 18.3%, respectively). Multivariate analysis identified adjuvant TACE plus TKI treatment as an independent prognostic factor for DFS (hazard ratio: 0.611, 95% confidence interval: 0.408– 0.915, P=0.017). Further analysis based on the various propensity score methods yielded similar results. Subgroup analysis showed that patients with tumour diameter ≥ 5 cm, tumour number < 3, absence of hepatic vein tumour thrombus and bile duct tumour thrombus, ruptured tumours, and stage IIIB could benefit more from TACE plus TKI treatment (all P< 0.05). Some patients (33.33%) experienced grade ≥ 3 AEs in the TACE plus TKI group. Conclusion: TACE plus TKI treatment can reduce the incidence of early recurrence with tolerable adverse events in HCC patients at high risk of recurrence after hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment.

A mild, radical cascade cyclization of N-arylacrylamides with diselenides for the preparation of oxindoles via iodine oxidation is disclosed that provides an environmentally friendly process for the construction of C–Se bonds. Twenty-five examples of N-arylacrylamide substrates were investigated, and excellent yields were achieved. The tandem cyclization of acrylamide with diphenyl disulfide was also applicable under the same conditions.

Hexokinase 1 (HK1) has been implicated in tumorigenesis. However, its role in tumor metastasis and progression has not been evaluated. The aim of this study is to evaluate the role of HK1 in the metastasis in CRC. Methods: The expression level of HK1 was detected using quantitative RT-PCR and western blot in 9 CRC cell lines and 1 human colon epithelial cell line NCM460 (Figure 1A). HK1 was overexpressed via lentiviral vector system and silenced using specific small interference RNA (si-HK1) in DLD1 and HCT8. Then wound-healing, migration assay and invasion assay were carried out to investigate the function of HK1 in CRC cells. RT-PCR and Western blot was performed to detect the change of Snail2 following the up-regulated expression of HK1. Results: HK1 expression was overexpressed by HK1-cDNA and was inhibited by si-HK1 in DLD1 and HCT8 (Figure 1B and 1C). Ectopic expression of HK1 promoted cell migration and invasion in CRC cells and promoted lung metastasis in mouse models (Figure 1D). Furthermore, HK1 induced migration and invasion in CRC cells was found to activate expression of Snail2 and in turn, induce epithelial-mesenchymal transition (EMT) and cancer progression (Figure 1E). Conclusions: High expression of HK1 could activate expression of Snail2 and in turn, induce EMT. Our findings suggest that HK1 may be a potential prognostic biomarker and therapeutic target for CRC invasion and metastasis. Keywords: Colorectal Cancer, HK1, Migration, Invasion Figure 1. A. The expression level of HK1 in 10 cell lines. B, C. HK1 expression was overexpressed by HK1-cDNA and was inhibited by si-HK1 in DLD1 and HCT8. *P< 0.05. D. Overexpression of HK1 in HCT8 increased the capacity of cell migration and invasion in vitro and in vivo. E. Expression levels of Snail2 and EMT were induced after HK1 overexpression. Citation Format: Xiaobin Zheng, Huashan Liu, Xiaoli Zhong, Xuanhui Liu, Zerong Cai, Yufeng Chen, Xiaosheng He, Ping Lan, Xiaojian Wu. HK1 induces epithelial-mesenchymal transition and promotes metastasis of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2840.