Objective: Caring for patients during the COVID-19 pandemic has placed considerable stress on health care professionals (HCPs), increasing their risk of moral injury (MI) and clinician burnout. The present study sought to examine the prevalence and correlates of MI among physicians and nurses in mainland China during the pandemic. Method: A cross-sectional study was performed via an online survey conducted from March 27, 2020 to April 26, 2020. The 10-item Moral Injury Symptoms Scale-Health Professional version (MISS-HP) was administered along with measures of clinician mental health and burnout. A total of 3,006 physicians and nurses who completed the questionnaire were included in the final analysis. Unconditional logistic regression modeling was performed to determine the associations, including that between COVID-19 patient exposure and the risk of moral injury. Results: MISS-HP scores strongly and positively correlated with depression, anxiety, low well-being, and burnout symptoms. The estimated prevalence of MI in the total sample was 41.3%, 95% confidence interval (CI) [39.3%, 43.0%]. HCPs providing medical care to COVID-19 patients experienced a 28% greater risk of MI than those providing medical care to patients without the coronavirus (odds ratio = 1.28, 95% CI [1.05, 1.56], p = .01). Conclusions: A significant proportion of HCPs in mainland China are at risk for significant MI symptoms as well as mental health problems and burnout during the COVID-19 pandemic. MI symptoms are strongly correlated with higher clinician burnout, greater psychological distress, and lower level of subjective well-being. Effective strategies are needed to address MI and other mental health problems in frontline health care workers treating those with and without COVID-19 disease. Clinical Impact StatementMoral injury (MI) symptoms are correlated with higher clinician burnout, greater psychological distress, and lower level of subjective well-being. Strategies shown to be effective for MI in former military personnel might be used to address burnout and mental health problems in frontline health care workers tasked with treating those with and without COVID-19 disease. Our findings provide a profile of HCPs who are at risk for MI symptoms and may help to identify those at risk of downstream effects in terms of psychological health and patient safety.

Background Moral injury among physicians and other health professionals has attracted attention in the mainstream literature, this study aim to assess the psychometric properties of the 10-item Moral Injury Symptoms Scale-Health Professional (MISS-HP) among healthcare professionals in China. Methods A total of 583 nurses and 2423 physicians were recruited from across mainland China. An online survey was conducted from March 27 to April 26, 2020 (during the middle of the COVID-19 pandemic) using the Chinese version of the MISS-HP. Reliability was assessed by internal consistency reliability and test-retest reliability. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to determine scale structure. Results Cronbach’s α of the scale for both samples was acceptable (0.71 for nurses and 0.70 for physicians), as was test-retest reliability (ICCs for the individual items ranged from 0.41 to 0.74, with 0.77 for the overall scale in physicians). EFA suggested three factors, and the CFA indicated good fit to the data. Convergent validity was demonstrated with the 4-item Expressions of Moral Injury Scale (r = 0.45 for physicians, r = 0.43 for nurses). Discriminant validity was demonstrated by correlations with burnout and well-being (r = 0.34–0.47), and concurrent validity was suggested by correlations with depression and anxiety symptoms (r = 0.37–0.45). Known groups validity was indicated by a higher score in those exposed to workplace violence (B = 4.16, 95%CI: 3.21–5.10, p < 0.001). Conclusions The MISS-HP demonstrated acceptable reliability and validity in a large sample of physicians and nurses in mainland China, supporting its use as a screening measure for moral injury symptoms among increasingly stressed health professionals in this country during the COVID-19 pandemic.

This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 rheostat to mediate DHA-induced apoptosis in HCC cells.

Aim: BAG-1 is a multifunctional anti-apoptotic gene with four isoforms, and different BAG-1 isoforms have different antiapoptotic functions. In this study, we transfected BAG-1 isoforms into the human breast cancer cell lines Hs578T (ER negative) and MCF-7 (ER positive) to study their effect on apoptosis with or without estrogens. Methods: The constructed recombinant expression vectors carrying individual BAG-1 isoforms was used to transfect human breast cancer cell lines Hs578T (ER negative) and MCF-7 (ER positive). After stable cell lines were made, a variety of apoptosis-inducing agents, including doxorubicin, docetaxel, and 5-FU, was used to treat these cell lines with or without estrogen to test the role of BAG-1. The mechanism by which BAG-1 affected the function of Bcl-2 was exploredby using the cycloheximide chase assay. Results: The BAG-1 p50 and p46 isoforms significantly enhanced the resistance to apoptosis in both cell lines according to flow cytometry analysis. BAG-1 p33 and p29 failed to protect the transfected cells from apoptosis. The cell viability assay showed that only BAG-1 p50, but not p46, p33, or p29, increased estrogen-dependent function in ER-positive cell line MCF-7. Only BAG-1 p50 dramatically increased its anti-apoptotic ability in the presence of estrogen, while estrogen has very little effect on the anti-apoptotic ability of other BAG-1 isoforms. In the detection of the expression of K-ras, Hsp70, cytochrome c, Raf-1, ER-α, and Bcl-2 in MCF-7 cells by Western blot, only Bcl-2 protein expression was significantly increased in MCF-7 cells transfected with BAG-1 p50 and p46, respectively. Furthermore, the cycloheximide chase assay indicated that the degradation of Bcl-2 protein was extended in the BAG-1 p50 and p46 transfected MCF-7 cells. Conclusion: Distinct isoforms of BAG-1 have different anti-apoptotic functions in breast cancer cells, and that the BAG-1 p50 isoform can potentiate the role of estrogen in ER-positive breast cancer.

This study aimed to compare the plasma levels of angiotensin-I converting enzyme (ACE), Angiotensin II (AngII), kallikrein (KLK1) and interleukin-6 (IL-6) in ST segment elevation myocardial infarction (STEMI) patients with different ACE Insertion/deletion (I/D) polymorphisms in a Chinese population. The ACE genotypes were determined in the 199 STEMI patients and 216 control subjects. STEMI patients were divided into three groups based on the ACE genotypes. Single polymerase chain reaction (PCR) was performed to characterize ACE I/D polymorphisms. Plasma levels of ACE, AngII, KLK1 and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). We found that the DD or ID genotype was significantly independently associated with high ACE (OR = 4.697; 95% CI = 1.927–11.339), KLK1 (3.339; 1.383–8.063) and IL-6 levels (OR = 2.10; 1.025–4.327) in STEMI patients. However, there was no statistical significance between the ACE I/D polymorphism and AngII plasma levels whether in univariate or multivariate logistic regression. Additionally, we detected a significantly positive correlation between plasma KLK1 levels and IL-6 levels in STEMI patients (r = 0.584, P < 0.001). The study showed high levels of ACE, KLK1 and IL-6 were detected when the D allele was present, but AngII plasma levels was not influenced by the ACE I/D polymorphism.

Tanshinone IIA (TSIIA), a natural diterpene quinone in the traditional Chinese medicinal herb Dan-Shen (Salvia miltiorrhiza), has extensively exerted antitumor activity in cellular and animal models. However, the molecular mechanisms underlying the antitumor effects of TSIIA remain largely unknown. The in vitro effects of TSIIA on apoptosis were investigated in A549 non-small cell lung cancer (NSCLC) cells. The data showed that TSIIA significantly suppressed the proliferation of A549 cells in a dose-dependent manner, with IC50 values of 16.0±3.7 and 14.5±3.3 µM at 48 h as determined by Cell Counting Kit-8 (CCK-8) assay and clone formation assay, respectively. The change of mitochondrial morphology and the loss of mitochondrial membrane potential (MMP) were observed during the induction. Furthermore, TSIIA induced A549 cell apoptosis as confirmed by typical morphological changes, with cytochrome c release from the mitochondria and Bax translocation to the mitochondria. Caspase activity data indicated that TSIIA activated caspase-9 and caspase-3 of mitochondria-mediated apoptosis, but not caspase-8 of receptor-mediated apoptosis, which could be largely rescued by SP600125 (JNK inhibitor). Taken together, these findings provide the first evidence that TSIIA inhibits growth of NSCLC A549 cells, induces activation of JNK signaling and triggers caspase cascade apoptosis mediated by the release of cytochrome c, which provides a better understanding of the molecular mechanisms of TSIIA on lung cancer.

Emerging evidence have discovered that circular RNAs (circRNAs) may serve as diagnostic or tumor promising biomarkers. This study aimed to investigate how circular RNA ADAMTS14 (circADAMTS14) regulates microRNA‐572/ regulator of calcineurin 1(miR‐572/ RCAN1) in hepatocellular carcinoma (HCC). The expression profiles of circRNA/microRNA (mRNA) between HCC tissues and paired adjacent tissues were analyzed via microarray analysis. The expressions of circADAMTS14, miR‐572, and RCAN1 were measured by real‐time polymerase chain reaction (PCR). The protein expression level of RCAN1 in HCC cells was detected by western blot. The viability and apoptosis levels of HCC cell lines were measured by the cell counting Kit‐8 (CCK‐8) assay and fluorescence‐activated cell sorter. The invasiveness and migration of cells were detected based on the transwell and wound‐healing assay, respectively. The dual‐luciferase reporter assays were used to reveal circADAMTS14 and RCAN1 as a potential target of miR‐572, which was predicted by TargetScan and miRBase. The effect of circADAMTS14 on HCC cells was demonstrated by tumor formation in nude mice in vivo. CircADAMTS14 and RCAN1 were lowly expressed in HCC clinical specimens and cell lines using microarrays and qRT‐PCR, but miR‐572 inversely. Our study further verified the direct interaction between circADAMTS14 and RCAN1 with miR‐572 via the dual‐luciferase reporter gene assay. Overexpressed circADAMTS14 and RCAN1 induced apoptosis of HCC cells and inhibited cell proliferation and invasion. But overexpressed miR‐572 could decrease apoptosis of HCC cells and promote proliferation and invasion. In vivo, circADAMTS14 inhibited the tumor growth, correlated positively with the protein expression levels of RCAN1. Our results demonstrated that circADAMTS14 might suppress HCC progression through regulating miR‐572/ RCAN1 as the competing endogenous RNA.

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