The new era of lung cancer therapy: Combining immunotherapy with ferroptosis.

Ferroptosis is an unconventional programmed cell death mode caused by phospholipid peroxidation dependent on iron. Emerging immunotherapies (especially immune checkpoint inhibitors) have the potential to enhance lung cancer patients' long-term survival. Although immunotherapy has yielded significant positive applications in some patients, there are still many mechanisms that can cause lung cancer cells to evade immunity, thus leading to the failure of targeted therapies. Immune-tolerant cancer cells are insensitive to conventional death pathways such as apoptosis and necrosis, whereas mesenchymal and metastasis-prone cancer cells are particularly vulnerable to ferroptosis, which plays a vital role in mediating immune tolerance resistance by tumors and immune cells. As a result, triggering lung cancer cell ferroptosis holds significant therapeutic potential for drug-resistant malignancies. Here, we summarize the mechanisms underlying the suppression of ferroptosis in lung cancer, highlight its function in the lung cancer immune microenvironment, and propose possible therapeutic strategies.

Chinese Herbal Medicines Have Potentially Beneficial Effects on the Perinatal Outcomes of Pregnant Women.

Introduction: Tocolytic treatment is beneficial to pregnant women with a risk of premature labor or miscarriage. However, previous reports have shown that progestogen might not be effective and ritodrine may increase the risk of maternal vascular-related diseases. Chinese herbal products (CHP) are used as alternative therapies for pregnant women. The goal was to evaluate the efficacy of combined tocolytic therapy and CHP therapy in pregnancy outcomes for pregnant women in Taiwan. Materials and Methods: We conducted a retrospective cohort study based on the National Health Insurance Research Database. A total of 47,153 pregnant women treated with tocolytics aged 18-50 years from 2001 to 2015 were selected from two million random samples. According to the medical use of tocolytics and CHP, we divided the users into two groups: western medicine (WM) only (n = 40,961) and WM/CHP (n = 6,192) groups. A propensity score (PS)-matched cohort (6,192 pairs) was established based on baseline confounders. All participants were followed up to perinatal outcomes. Conditional logistic regression analysis was used to examine the effects of CHP use on the odds of miscarriage and preterm birth. Results: The adjusted odds ratio (OR) for premature birth in the WM/CHP group (n = 411, 6.64%) was significantly lower than in the WM group (n = 471, 7,61%) (0,86, 95% confidence interval [CI], 0.74-0.99). Further subgroup analysis based on the usage of formulae that activate blood and remove stasis or purgative formulae, the adjusted OR of preterm birth of those using these formulae was significantly lower in the WM/CHP group (n = 215, 6.32%) than that in the WM group (n = 265, 7.77%) (OR: 0.79, 95% CI: 0.65-0.96). Conclusion: We found that the combination of CHP and tocolytics can be beneficial to pregnant women in the prevention of premature birth. Further research is required to investigate causal relationships.

Prescription patterns and factors influencing the use of Chinese herbal medicine among pregnant women in Taiwan: a population-based retrospective study.

BACKGROUND: The use of Chinese herbal medicine (CHM) has been widely promoted as a natural and safe way to treat illness during pregnancy. However, prescription patterns and factors influencing its use are largely unknown. Therefore, we conducted a population-based study to address these questions. METHODS: Pregnant women aged 18-50 years were selected from Taiwan's National Health Insurance Research Database between 2001 to 2011. CHM prescriptions and diagnostic records were collected. Demographic data and pre-existing diseases were compared between CHM users and non-users. A multivariate logistic regression analysis was performed to identify possible factors influencing the use of CHM during pregnancy. RESULTS: A total of 81,873 eligible prescription records were identified, and 16,553 pregnant women were prescribed CHM during pregnancy, yielding a CHM prescription rate of 20.2%. The three most frequently used herbs were Scutellariae Radix (Huang Qin) (4.4%), Eucommiae cortex (Du Zhong) (2.5%), and Atractylodes Rhizome (Bai Zhu) (2.4%). The most frequently used herbal formulae were Dang-Guei-Shao-Yao-San (4.1%), Jia-Wei-Xiao-Yao-San (3.5%), and Xiang-Sha-Liu-Jun-Zi-Tang (2.6%). Multivariate logistic regression revealed that subjects with an older age, a university education, a pre-pregnancy history of CHM use, asthma, chronic renal disease, and cardiac valvular disease and living in a residential area other than northern Taiwan had an increase in adjusted odds ratio for CHM use during pregnancy. CONCLUSIONS: In this population-based study, we found that demographic factors and pre-existing diseases were associated with the use of CHM among pregnant women. It is worth noting that Leonuri Herba (Yi Mu Cao) and Shao-Fu-Zhu-Yu-Tang should be used with caution in the first trimester. Further research is needed to explore the safety and effectiveness of the use of CHM in pregnant women.

Concurrent use of Chinese herbal medicine among hormone users and its association with ischemic stroke risk: A population-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies had indicated that hormone therapy (HT) may increase the risk of ischemic stroke (IS) in menopausal women. However, little is known about the benefits and risks of use of Chinese herbal medicine (CHM) in conditions related to hormone use. The aim of this study is to explore the risk of IS in menopausal women treated with HT and CHM. MATERIALS AND METHODS: A total of 32,441 menopausal women without surgical menopause aged 40-65 years were selected from 2003 to 2010 using the 2-million random samples of the National Health Insurance Research Database in Taiwan. According to the medication usage of HT and CHM, we divided the current and recent users into two groups: an HT use-only group (n = 4989) and an HT/CHM group (n = 9265). Propensity-score matching samples (4079 pairs) were further created to deal with confounding by indication. The adjusted hazard ratios (HR) of IS were estimated by the robust Cox proportional hazards model. RESULTS: The incidence rate of IS in the HT/CHM group was significantly lower than in the HT group (4.5 vs. 12.8 per 1000 person-year, p < 0.001). Multivariate analysis results indicated that additional CHM use had a lower risk of IS compared to the HT group (HR = 0.3; 95% confidence interval [CI], 0.21-0.43). Further subgroup analyses and sensitivity analyses had similar findings. CONCLUSION: We found that combined use of HT and CHM was associated with a lower risk of IS. Further study is needed to examine possible mechanism underlying this association.

Effect of early use of Chinese herbal products on mortality rate in patients with lung cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Patients with lung cancer are frequently treated with Western medical treatments. Recently, patients have begun to use Chinese medicine to strengthen the immune system and alleviate side effects. AIM OF THE STUDY: We aimed to evaluate the association between mortality rate and early use of Chinese herbal products (CHPs) among patients with lung cancer. MATERIALS AND METHODS: We conducted a retrospective cohort study based on the National Health Insurance Research Database, Taiwan Cancer Registry, and Cause of Death Data. Patients with newly diagnosed lung cancer between 2002 and 2010 were classified as either the CHP (n = 422) or the non-CHP group (n = 2828) based on whether they used CHP within 3 months after first diagnosis of lung cancer. A robust Cox regression model was used to examine the hazard ratio (HR) of death for propensity score (PS) matching samples. RESULTS: After PS matching, average survival time of the CHP group was significantly longer than that of the non-CHP group. The adjusted HR (0.82; 95% CI: 0.73-0.92) in the CHP group was lower than the non-CHP group. Stratified by clinical cancer stages, CHP group had longer survival time in stage 3 subgroup. When the exposure period of CHP use was changed from 3 to 6 months, results remained similar (HR = 0.85; 95% CI: 0.76-0.95). CONCLUSION: Results indicated that patients with lung cancer who used CHP within 3 months after first diagnosis had a lower hazard of death than non-CHP users, especially for stage 3 lung cancer. Further experimental studies are needed to examine the causal relationship.

Predictive factors of silent reflux in subjects with erosive esophagitis.

BACKGROUND: Asymptomatic erosive esophagitis by definition is a condition lacking any reflux symptom. AIMS: We aimed to investigate the prevalence of asymptomatic erosive esophagitis in a general population undergoing periodic health checkup. METHODS: Consecutive subjects undergoing a medical checkup were enrolled for evaluation of reflux disease with upper endoscopy and a validated reflux questionnaire. The presence and severity of erosive esophagitis were evaluated. In all subjects, demographic characteristics and biochemical data were recorded, and sleep and psychological characteristics were assessed by means of self-administered Pittsburgh Sleep Quality Index score, Taiwanese Depression Questionnaire score, and State-Trait Anxiety Inventory score. RESULTS: Of 2568 subjects eligible for this study, erosive esophagitis was found in 676 subjects (26.3%), in whom the proportions of asymptomatic and symptomatic erosive esophagitis were 59.2% (400 subjects) and 40.8% (276 subjects) respectively. At a univariate analysis, it was found that asymptomatic erosive esophagitis subjects were more frequently of female gender, of older age, with a lower level of education. They also showed less alcohol and tea consumption, less depression, less anxiety, lower serum level of triglyceride, and lower prevalence of metabolic syndrome. Multivariate analysis revealed that female sex (OR = 1.645, p = 0.0146) was a positive predictive factor for asymptomatic erosive esophagitis, whereas higher level of education (OR = 0.564, p = 0.044), higher Taiwanese Depression Questionnaire score (OR = 0.922, p < 0.001), and the presence of metabolic syndrome (OR = 0.625, p = 0.0379) were negative predictive factors. CONCLUSIONS: Asymptomatic erosive esophagitis is a common feature in otherwise healthy subjects and is independently associated with female gender, lower education level, less depression, and lower prevalence of metabolic syndrome.