Corrigendum to "Potential pre-COPD indicators in association with COPD development and COPD prediction models in Chinese: a prospective cohort study" [The Lancet Regional Health - Western Pacific 44 (2024) 100984].

[This corrects the article DOI: 10.1016/j.lanwpc.2023.100984.].

Potential pre-COPD indicators in association with COPD development and COPD prediction models in Chinese: a prospective cohort study.

Background: Lung injury might take place before chronic obstructive pulmonary disease (COPD) occurs. A clearer definition of "pre-COPD" based on the effects of potential indicators on increasing risk of COPD development and a prediction model involving them are lacking. Methods: A total of 3526 Chinese residents without COPD aged 40 years or older derived from the national cross-sectional survey of COPD surveillance in 2014-2015 were followed up for a mean of 3.59 years. We examined the associations of chronic bronchitis, preserved ratio impaired spirometry (PRISm), low peak expiratory flow (PEF), spirometric small airway dysfunction (sSAD), low maximal mid-expiratory flow (MMEF), low forced expiratory flow 50% of pulmonary volume (FEF50), and low FEF75 with subsequent COPD and constructed a prediction model with LASSO-Cox regression. Findings: 235 subjects in the cohort developed COPD during the follow-up. Subjects with PRISm, low PEF, sSAD, low MMEF, low FEF50, and low FEF75 had an increased risk of developing COPD (adjusted hazard ratio [HR] ranging from 1.57 to 3.01). Only chronic bronchitis (HR 2.84 [95% CI 1.38-5.84] and 2.94 [1.43-6.04]) and sSAD/low MMEF (HR 2.74 [2.07-3.61] and 2.38 [1.65-3.43]) showed effects independent of the other indicators and their concurrence had the strongest effect (HR 5.89 and 4.80). The prediction model including age, sex, low MMEF, low FEF50, and indoor exposure to biomass had good performance both internally and temporally. The corrected C-index was 0.77 (0.72-0.81) for discrimination in internal validation. For temporal validation, the area under the receiver operating characteristic curve was 0.73 (0.63-0.83). Good calibration was indicated in plot for internal validation and by Hosmer-Lemeshow test for temporal validation. Interpretation: Individuals with concurrent chronic bronchitis and sSAD/low MMEF indicating pre-COPD optimally require more high attention from physicians. Our prediction model could serve as a multi-dimension tool to predict COPD comprehensively. Funding: The Ministry of Finance and the Ministry of Science and Technology of the People's Republic of China and the National Natural Science Foundation of China.

Assessing interventions to encourage primary care health workers to recommend influenza vaccination and the impact on vaccination uptake for persons with Non-Communicable diseases in China.

BACKGROUND: Influenza vaccination coverage is low among persons with non-communicable diseases (NCDs) in China. Chinese health workers (HWs) do not routinely recommend influenza vaccination despite evidence that recommendations increase vaccine uptake. This study aims to assess whether interventions increased primary care HWs' recommendation for influenza vaccination and measure their impact on influenza vaccine uptake in persons with NCDs. METHODS: We conducted a cluster randomized controlled study in public primary healthcare clinics in Hubei from November 2018 through April 2019. In the intervention clinics, primary care HWs received training on the benefits of influenza vaccination and were asked to recommend influenza vaccine in routine primary healthcare for persons with NCDs. In the control clinics, primary care HWs did not receive training and provided standard services. We conducted questionnaire surveys before and after the intervention to collect information about recommendations made and receipt of influenza vaccines. RESULTS: A total of 896 primary care HWs and 4552 persons with NCDs were included. After intervention, a higher percentage of HWs recommended influenza vaccines in intervention clinics compared to control clinics. Vaccinated primary care HWs were more likely to recommend vaccination. Persons with NCDs reported higher influenza vaccination coverage in intervention than control clinics, and primary care HWs' recommendation increased vaccination uptake among persons with NCDs. CONCLUSIONS: Vaccinated primary care HWs were more likely to recommend influenza vaccination than unvaccinated HWs. Promoting primary care HWs' vaccination and encouraging them to recommend influenza vaccination during routine primary healthcare could increase influenza vaccine receipt among persons with NCDs. Registration number ChiCTR2200067140.

A Scd1-mediated metabolic alteration participates in liver responses to low-dose bavachin.

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs, such as bavachin (BV) in Fructus Psoraleae, has a prolonged latency to overt drug-induced liver injury in the clinic. Several studies have described BV-induced liver damage and underlying toxicity mechanisms, but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level, and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase, making it much harder for early recognition of hepatotoxicity. Here, we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests, but found subtle steatosis in BV-treated hepatocytes. We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver. Among these, the hepa3 subtype suffered from a vast alteration in lipid metabolism, which was characterized by enhanced expression of apolipoproteins, carboxylesterases, and stearoyl-CoA desaturase 1 (Scd1). In particular, increased Scd1 promoted monounsaturated fatty acids (MUFAs) synthesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids (PUFAs) generation, which participates in the initiation of ferroptosis. Additionally, we demonstrated that multiple intrinsic transcription factors, including Srebf1 and Hnf4a, and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes. Collectively, our study deciphered the features of hepatocytes in response to BV insult, decoded the underlying molecular mechanisms, and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.

Undesirable ER stress induced by bavachin contributed to follicular atresia in zebrafish ovary.

Fructus psoraleae (FP) is a commonly used herb with potential reproductive toxicity. Bavachin (BV), one of essential active ingredients of FP, was found to exhibit estrogenic activity, but its effect on female reproductive system remains unknown. In this study, the impact of BV on the female zebrafish reproductive system and underlying molecular mechanism were determined in vivo and ex vivo. The results showed that BV could accumulate in zebrafish ovary, leading to obvious follicular atresia and increase in gonadal index and vitellogenin content. Endoplasmic reticulum (ER) swelling and hypertrophy were observed in the BV-treated zebrafish ovary, accompanied by an increase in the expressions of ER stress and unfolded protein response (UPR) related genes, namely atf6, ire-1α and xbp1s. In the ex vivo study, BV was found to decrease the survival rate and maturation rate of oocytes, while increasing the expression of Ca2+. Additionally, BV led to an elevation in the level of estrogen receptor ESR1 and the expressions of genes involved in ER stress and UPR, including atf6, ire-1α, xbp1s, chop and perk. Moreover, molecular docking revealed that BV could directly bind to immunoglobulin heavy chain binding protein (BiP) and estrogen receptor 1 (ESR1). Besides, the alterations induced by BV could be partially reversed by fulvestrant (FULV) and 4-phenylbutyric acid (4-PBA), respectively. Thus, long-termed BV-containing medicine treatment could generate reproductive toxicity in female zebrafish by causing follicular atresia through BiP- and ESR-mediated ER stress and UPR, providing a potential target for the prevention of reproductive toxicity caused by BV.

Depressive Symptoms and Sleep Duration as Risk Factors for Breast Cancer - China, 2020.

What is already known about this topic?: Psychological and lifestyle factors are known to potentially play a significant role in the development of breast cancer. However, current evidence-based studies present controversial findings on the associations between depression, sleep duration, and breast cancer risk. What is added by this report?: This study investigated the potential risk factors of depressive symptoms and short sleep duration for breast cancer within the Breast Cancer Cohort Study in Chinese Women. The findings revealed that women experiencing depressive symptoms and short sleep duration exhibited a heightened risk of developing breast cancer, particularly among the older population. What are the implications for public health practice?: Public policy ought to prioritize early health education interventions targeting psychological factors in order to facilitate the prevention of breast cancer.

Breast Cancer Awareness and Association with Frequency of Screening Among Women - China, 2020.

What is already known about this topic?: Breast cancer awareness plays a crucial role in promoting screening attendance, enabling early detection, and improving survival rates associated with breast cancer. Nevertheless, a persistent issue is the low public awareness of breast cancer warning signs and risk factors. What is added by this report?: Breast cancer awareness rate was 10.2%, with particularly low rates among never-screened and inadequately screened women. Factors associated with low awareness levels included low income, agricultural occupation, limited educational attainment, smoking, and the absence of professional recommendations. What are the implications for public health practice?: Consideration should be given to effective health education and delivery strategies aimed at women who have never been screened or have received inadequate screening.

HPV-negative high-grade cervical precancerous lesions or invasive cancer in China: A post hoc analysis of a multicentric clinical study.

OBJECTIVE: To evaluate HPV-negative cervical high-grade precancerous lesions or cancer in China. METHODS: Histologically confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) were searched in a multicentric clinical study. All patients underwent cobas HPV testing, liquid-based cytology, DNA ploidy analysis, and colposcopy-guided biopsy. According to clinical practice, patients underwent p16ink4a staining and cone biopsy. Comparisons were made between HPV-negative and -positive patients for clinical characteristics. RESULTS: The study found 61 cases of cobas HPV-negative CIN2+ among 797 cases of histologically confirmed CIN2+, including 38 CIN2, 20 CIN3, and 3 invasive cancers. The prevalence of HPV-negative CIN2+ and CIN3+ was 7.7% (95% confidence interval [CI] 5.8-9.5) and 5.7% (95% CI 3.5-8.0), respectively. Among 24 cases with p16 staining, 20 showed p16 positivity. The proportions of normal or minor abnormalities in terms of colposcopy, cytology, and DNA ploidy were higher in HPV-negative cases than in HPV-positive cases. When adding cytology to the screening of symptomatic or previously HPV-positive women, the prevalence of HPV-negative CIN2+ or CIN3 would decrease by approximately 50%. CONCLUSION: Less than one-tenth of CIN2+ are missed by HPV-only screening, and they have smaller lesions than HPV-positive cases. Colposcopy should be considered for symptomatic or previously HPV-positive women with HPV-negative results.

Pinelliae rhizoma alleviated acute lung injury induced by lipopolysaccharide via suppressing endoplasmic reticulum stress-mediated NLRP3 inflammasome.

Pinelliae rhizoma (PR), one kind of commonly-used Chinese herbs, is generally prescribed to treat various respiratory diseases, including acute lung injury (ALI). However, the accurate bioactive ingredients of PR and the underlying pharmacological mechanism have both not been fully elucidated. Therefore, this study aimed to identify the bioactive ingredients that could alleviate lipopolysaccharide (LPS)-induced ALI and explore the possible mechanism involved. Our results confirmed that LPS infection indeed caused acute inflammatory damage in mice lung, accompanying with the enhancement of IL-1ß contents and the activation of the NLRP3 inflammasome in lung tissue and macrophagocyte, all of which were remarkably ameliorated by PR treatment. Next, mechanistically, LPS was found to trigger endoplasmic reticulum (ER) stress and downstream cellular calcium ions (Ca2+) release via activating Bip/ATF4/CHOP signaling pathway. Like PR, 4-PBA (a specific inhibitor of ER stress) not only obviously reversed Bip/ATF4/CHOP-mediated ER stress, but also significantly attenuated LPS-induced activation of the NLRP3 inflammasome. Furthermore, the bioactive ingredients of PR, which generated the anti-inflammatory effects, were screened by metabolomics and network pharmacology. In vitro experiments showed that chrysin, dihydrocapsaicin, and 7,8-dihydroxyflavone (7,8-DHF) notably suppressed LPS-induced ER stress and following NLRP3 inflammasome activation. In conclusion, our findings suggested that PR alleviated LPS-induced ALI by inhibiting ER stress-mediated NLRP3 inflammasome activation, which is mainly relevant with these three bioactive ingredients. This study provided a theoretical basis for the clinical application of PR to treat ALI, and these bioactive ingredients of PR would be promising therapeutic drugs for the treatment of ALI.

School assets and bullying in Chinese youth: A multiple mediation model of intentional self-regulation and internet gaming disorder.

Bullying is a severe social problem affecting young people all over the world. Previous studies suggested that engagement in bullying had massive effects on teenagers' physical and psychological development. It is critical and necessary to investigate the antecedents and underlying mechanisms of this phenomenon among young generations. The present study, based on the positive youth development perspective and the developmental assets theory, attempts to explore the positive factors in the school subsystem that could effectively prevent adolescents from bullying, as well as the multiple mediation effects of intentional self-regulation (ISR) and internet gaming disorder (IGD). In this study, we adopted a two-wave design and recruited a sample of 768 Chinese adolescents using a randomized cluster sampling method in the post-pandemic era. The results revealed that T1 school assets significantly and negatively predicted T2 adolescent bullying. Furthermore, T2 ISR and T2 IGD mediated the association between T1 school assets and T2 bullying separately and sequentially. Overall, school resources play a protective role in adolescent development and could effectively prevent them from negative outcomes. These current findings contribute to the literature by providing a further understanding of the direct and indirect protective effects of school assets on adolescent bullying. Moreover, practitioners could also benefit from these findings in preventing and intervening in bullying in the school subsystem.

Ginsenoside Rb1 Ameliorated Bavachin-Induced Renal Fibrosis via Suppressing Bip/eIF2α/CHOP Signaling-Mediated EMT.

The nephrotoxicity of Fructus Psoraleae, an effective traditional Chinese medicine for vitiligo treatment, has been reported. As one of the main toxic components in Fructus Psoraleae, bavachin (BV) was considered to be related to Fructus Psoraleae-caused adverse outcomes, but the direct evidence and molecular mechanism underlying BV-induced nephrotoxicity are not well elucidated. Therefore, this study was designed to confirm whether BV would cause toxic effects on the kidney and explore the possible mode of action. Our results demonstrated that days' treatment with 0.5 µM BV indeed caused obvious renal fibrosis in the zebrafish kidney. The obvious E- to N-cadherin switch and the expressions of proteins promoting epithelial-mesenchymal transition (EMT) were observed in BV-treated human renal tubular epithelial and zebrafish kidneys. In addition, elevated reactive oxygen species (ROS) levels and Bip/eIF2α/CHOP-mediated endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) were caused by BV, both of which could be reversed by ROS scavenger N-acetyl-L-cysteine (NAC). Also, blocking ER stress-caused cytoplasmic Ca2+ overload with 4-PBA notably alleviated BV-induced alterations in key molecular events related to EMT and renal fibrosis. Furthermore, of the natural compounds subjected to screening, ginsenoside Rb1 significantly downregulated BV-induced ER stress by inhibiting ROS generation and following the activation of Bip/eIF2α/CHOP signaling in HK2 cells. Subsequently, BV-triggered EMT and renal fibrosis were both ameliorated by ginsenoside Rb1. In summary, our findings suggested that BV-induced ROS promoted the appearance of EMT and renal fibrosis mainly via Bip/eIF2α/CHOP-mediated ER stress. This ER stress-related toxic pathway might be a potential intervention target for BV-caused renal fibrosis, and ginsenoside Rb1 would be a promising drug against BV- or Fructus Psoraleae-induced nephrotoxicity.

Cumulative Family Risk and Cyberbullying Among Chinese Adolescents: The Chain Mediating Role of School Connectedness and Cyber Victimization.

Abundant evidence has demonstrated that cumulative family risk is associated with cyberbullying. However, few studies to date have investigated how cumulative family risk links to cyberbullying. To fill in these gaps, the present study examined the mediating role of school connectedness and cyber victimization in the relation between cumulative family risk and cyberbullying. A sample of 1,804 Chinese adolescents was recruited to complete measures of cumulative family risk, cyberbullying, school connectedness, cyber victimization, and demographic variables through convenience sampling. There were 813 boys and 991 girls, aged from 13 to 18, with an average age of 16 years (SD = 1.71). Correlational analyses and SPSS macro PROCESS (Model 6) were used for major data analysis. Results indicated that cumulative family risk was positively associated with cyberbullying, and this link could be mediated by school connectedness and cyber victimization. The present study identifies the potential underlying mechanism by which cumulative family risk is associated with adolescent cyberbullying, which has important implications for theory and prevention.

Cumulative Family Risk and Internet Gaming Disorder Among Adolescents: A Serial Mediating Model of Personal Growth Initiative and Gratitude.

In the digital era, playing internet games enriches the entertainment forms for young generations. At the same time, it also raises some social issues, and internet gaming disorder (IGD) is one of them. Abundant studies demonstrate that IGD is harmful to individual physiological and psychological health. Therefore, it is necessary to figure out the reasons and mechanisms behind this phenomenon. Based on the ecological systems theory, the present study investigated the cumulative effect of family risks on adolescent IGD and the serial mediating effects of personal growth initiative (PGI) and gratitude in a chain mediation model. Using random cluster sampling, a sample of 600 Chinese adolescents was recruited to complete the questionnaire. Results of regression analysis suggested that cumulative family risks could positively predict IGD among adolescents. Moreover, PGI and gratitude mediated the relationship between cumulative family risk and IGD, separately, and sequentially. These findings may provide some guidance for the prevention and intervention to prevent or reduce IGD in adolescents.

Developmental Assets, Self-Control and Internet Gaming Disorder in Adolescence: Testing a Moderated Mediation Model in a Longitudinal Study.

From the perspective of positive youth development, developmental assets and self-control play critical roles in promoting adolescent development. However, their effects have not been evaluated in the current issue, internet gaming disorder (IGD). IGD is gradually becoming an important social problem among worldwide youth and has been included in the eleventh International Classification of Diseases (ICD-11). Therefore, the present study was determined to investigate the relationship between developmental assets, self-control, and IGD. A two-wave longitudinal study, with each wave spanning half a year apart, was conducted in a sample of 1023 adolescents (aging from 11 to 15, 49.36% boys) during the COVID-19 pandemic. Results of the moderated mediation model revealed that T1 developmental assets could predict less IGD at T2 directly or through T1 self-control indirectly. Furthermore, the moderating effect of gender was not significant in the mediation model. Overall, adolescents who experience more developmental assets are less likely to suffer IGD. Moreover, developmental assets are conducive to developing a higher level of self-control, which in turn contributes to preventing or intervening in IGD as well. Therefore, measures should be taken to construct developmental assets to prevent or reduce IGD during adolescence.

Low-dose radiation-induced demethylation of 3ß-HSD participated in the regulation of testosterone content.

The effects of low-dose radiation (LDR, ≤0.1 Gy) on living organisms have been the hot areas of radiation biology but do not reach a definitive conclusion yet. So far, few studies have adequately accounted for the male reproductive system responses to LDR, particularly the regulation of testosterone content. Hence, this study was designed to evaluate the effects of LDR on Leydig cells and testicular tissue, especially the ability to synthesize testosterone. We found that less than 0.2-Gy 60 Co gamma rays did not cause significant changes in the hemogram index and the body weight; also, pathological examination did not find obvious structural alterations in testis, epididymis, and other radiation-sensitive organs. Consistently, the results from in vitro showed that only more than 0.5-Gy gamma rays could induce remarkable DNA damage, cycle arrest, and apoptosis. Notably, LDR disturbed the contents of testosterone in mice serums and culture supernatants of TM3 cells and dose dependently increased the expression of 3ß-HSD. After cotreatment with trilostane (Tril), the inhibitor of 3ß-HSD, increased testosterone could be partially reversed. Besides, DNA damage repair-related enzymes, including DNMT1, DNMT3B, and Sirt1, were increased in irradiated TM3 cells, accompanying by evident demethylation in the gene body of 3ß-HSD. In conclusion, our results strongly suggest that LDR could induce obvious perturbation in the synthesis of testosterone without causing organic damage, during which DNA demethylation modification of 3ß-HSD might play a crucial role and would be a potential target to prevent LDR-induced male reproductive damage.

Prevalence of High-Risk Human Papillomavirus in Cervical Intraepithelial Neoplasia in the Pre-Vaccine Era - China, 2017-2018.

What is already known about this topic?: Human papillomavirus (HPV) type-specific strategies play a key role in the prevention of cervical intraepithelial neoplasia (CIN), but evidence on the HPV type-specific prevalence in CIN is limited. What is added by this report?: This multicentric study estimates the prevalence of high-risk HPV types in CIN cases and the associations of HPV infection patterns with high-grade CIN in China in 2017-2018. What are the implications for public health practice?: Population-based prevention strategies should give preference to HPV-16 and 18, and strategies for non-16/18 high-risk HPV are essential for the elimination of cervical cancer.

The influence of molecular alignment and orientation in the ground state and excited state on the resonance-enhanced multi-photon ionization dynamics.

We explore the influence of molecular alignment and orientation in the ground and excited states on the ionization probability, photoelectron angular distribution (PAD), energy-resolved photoelectron energy spectrum (PES) and two-dimensional momentum spectrum in the resonance-enhanced multiphoton ionization (REMPI) process. The calculated results for the LiH molecule show that molecular pre-alignment and -orientation have different effects on molecular photoionization. The ionization probability and energy-resolved photoelectron spectrum are associated with molecular pre-alignment. The angular distribution of photoelectrons and angular distribution of the momentum spectra are closely dependent on molecular pre-orientation. The ionization probability is also related to the center time and overlap area of the pump and probe pulses.

Phenotype and management of chronic obstructive pulmonary disease patients in general population in China: a nationally cross-sectional study.

This study aims to investigate the characteristics of the phenotype and management of chronic obstructive pulmonary disease (COPD) patients in the general population in China. We analyzed spirometry-confirmed COPD patients who were identified from a population-based, nationally representative sample in China. All participants were measured with airflow limitation severity based on post-bronchodilator FEV1 percent predicted, bronchodilator responsiveness, exacerbation history, and respiratory symptoms. Among a total of 9134 COPD patients, 90.3% were non-exacerbators, 2.9% were frequent exacerbators without chronic bronchitis, 2.0% were frequent exacerbators with chronic bronchitis, and 4.8% were asthma-COPD overlap. Less than 5% of non-exacerbators ever had pulmonary function testing performed. The utilization rate of inhaled medication in non-exacerbators, exacerbators without chronic bronchitis, exacerbators with chronic bronchitis, and asthma-COPD overlap was 1.4, 23.5, 29.5, and 19.4%, respectively. A comprehensive strategy for the management of COPD patients based on phenotype in primary care is urgently needed.

Emodin-Induced Oxidative Inhibition of Mitochondrial Function Assists BiP/IRE1α/CHOP Signaling-Mediated ER-Related Apoptosis.

Cassiae Semen is a widely used herbal medicine and a popular edible variety in many dietary or health beverage. Emerging evidence disclosed that improper administration of Cassiae Semen could induce obvious liver injury, which is possibly attributed to emodin, one of the bioactive anthraquinone compounds in Cassiae Semen, which caused hepatotoxicity, but the underlying mechanisms are not completely understood. Hence, the present study firstly explored the possible role of oxidative stress-mediated mitochondrial dysfunction and ER stress in emodin-cause apoptosis of L02 cells, aiming to elaborate possible toxic mechanisms involved in emodin-induced hepatotoxicity. Our results showed that emodin-induced ROS activated ER stress and the UPR via the BiP/IRE1α/CHOP signaling pathway, followed by ER Ca2+ release and cytoplasmic Ca2+ overloading. At the same time, emodin-caused redox imbalance increased mtROS while decreased MMP and mitochondrial function, resulting in the leaks of mitochondrial-related proapoptotic factors. Interestingly, blocking Ca2+ release from ER by 2-APB could inhibit emodin-induced apoptosis of L02, but the restored mitochondrial function did not reduce the apoptosis rates of emodin-treated cells. Besides, tunicamycin (TM) and doxorubicin (DOX) were used to activate ER stress and mitochondrial injury at a dosage where obvious apoptosis was not observed, respectively. We found that cotreatment with TM and DOX significantly induced apoptosis of L02 cells. Thus, all the results indicated that emodin-induced excessive ROS generation and redox imbalance promoted apoptosis, which was mainly associated with BiP/IRE1α/CHOP signaling-mediated ER stress and would be enhanced by oxidative stress-mediated mitochondrial dysfunction. Altogether, this finding has implicated that redox imbalance-mediated ER stress could be an alternative target for the treatment of Cassiae Semen or other medicine-food homologous varieties containing emodin-induced liver injury.

Global metabolomic and lipidomic analysis reveals the potential mechanisms of hemolysis effect of Ophiopogonin D and Ophiopogonin D' in vivo.

BACKGROUND: OPD and OPD' are the two main active components of Ophiopogon japonicas in Shenmai injection (SMI). Being isomers of each other, they are supposed to have similar pharmacological activities, but the actual situation is complicated. The difference of hemolytic behavior between OPD and OPD' in vivo and in vitro was discovered and reported by our group for the first time. In vitro, only OPD' showed hemolysis reaction, while in vivo, both OPD and OPD' caused hemolysis. In vitro, the primary cause of hemolysis has been confirmed to be related to the difference between physical and chemical properties of OPD and OPD'. In vivo, although there is a possible explanation for this phenomenon, the one is that OPD is bio-transformed into OPD' or its analogues in vivo, the other one is that both OPD and OPD' were metabolized into more activated forms for hemolysis. However, the mechanism of hemolysis in vivo is still unclear, especially the existing literature are still difficult to explain why OPD shows the inconsistent hemolysis behavior in vivo and in vitro. Therefore, the study of hemolysis of OPD and OPD' in vivo is of great practical significance in response to the increase of adverse events of SMI. METHODS: Aiming at the hemolysis in vivo, this manuscript adopted untargeted metabolomics and lipidomics technology to preliminarily explore the changes of plasma metabolites and lipids of OPD- and OPD'-treated rats. Metabolomics and lipidomics analyses were performed on ultra-high performance liquid chromatography (UPLC) system tandem with different mass spectrometers (MS) and different columns respectively. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to screen the differential metabolites and lipids. RESULTS: Both OPD and OPD' groups experienced hemolysis, Changes in endogenous differential metabolites and differential lipids, enrichment of differential metabolic pathways, and correlation analysis of differential metabolites and lipids all indicated that the causes of hemolysis by OPD and OPD' were closely related to the interference of phospholipid metabolism. CONCLUSIONS: This study provided a comprehensive description of metabolomics and lipidomics changes between OPD- and OPD'-treated rats, it would add to the knowledge base of the field, which also provided scientific guidance for the subsequent mechanism research. However, the underlying mechanism require further research.