The Regulatory Effects of Traditional Chinese Medicine on Ferroptosis.

Traditional Chinese medicine (TCM) has significantly contributed to protecting human health and promoting the progress of world civilization. A total of 2,711 TCMs are included in the 2020 version of the Chinese Pharmacopoeia, which is an integral part of the world's medical resources. Tu Youyou and her team discovered and purified artemisinin. And their contributions made the values and advantageous effects of TCM more and more recognized by the international community. There has been a lot of studies on TCM to treat diseases through antioxidant mechanisms, the reports on the new mechanisms beyond antioxidants of TCM has also increased year by year. Recently, many TCMs appear to have significant effects in regulating ferroptosis. Ferroptosis is an iron-dependent, non-apoptotic, regulated cell death characterized by intracellular lipid peroxide accumulation and oxidative membrane damage. Recently, accumulating studies have demonstrated that numerous organ injuries and pathophysiological process of many diseases are companied with ferroptosis, such as cancer, neurodegenerative disease, acute renal injury, arteriosclerosis, diabetes, and ischemia-reperfusion injury. This work mainly introduces dozens of TCMs that can regulate ferroptosis and their possible mechanisms and targets.

Stevens-Johnson Syndrome Following Non-steroidal Anti-inflammatory Drugs: A Real-World Analysis of Post-marketing Surveillance Data.

Background: The Stevens-Johnson syndrome (SJS) is a severe skin reaction to non-steroidal anti-inflammatory drugs (NSAIDs), and can even be life-threatening. However, there are still few real-world studies to compare the specific differences in the adverse effects of skin and mucosal invasion. Methods: Disproportionality analysis and Bayesian analysis were devoted to data-mining of the suspected SJS after using NSAIDs based on the FDA's Adverse Event Reporting System (FAERS) from January 2004 to March 2021. The times to onset, fatality, and hospitalization rates of antipyretic analgesic-associated SJS were also investigated. Results: A total of 1,868 reports of SJS adverse events were identified with NSAIDs. Among 5 NSAIDs monotherapies we studied (acetaminophen, ibuprofen, aspirin, diclofenac and celecoxib), ibuprofen had the highest association with SJS based on the highest reporting odds ratio (ROR = 7.06, 95% two-sided CI = 6.59-7.56), proportional reporting ratio (PRR = 6.98, χ2 = 4201.14) and empirical Bayes geometric mean (EBGM = 6.78, 95% one-sided CI = 6.40). However, ibuprofen-associated SJS had the lowest fatality rate (6.87%, p < 0.0001) and the highest hospitalization rate (79.27%, p < 0.0001). Celecoxib-associated SJS had the latest time to onset (317.56 days, p < 0.0001). Diclofenac-associated SJS cases appeared to be associated with the highest risk of death (25.00%, p < 0.0001). Conclusions: The analysis of FAERS data provides a more accurate profile of the incidence and prognosis of SJS after NSAIDs treatment, enabling continued surveillance and timely intervention in patients at risk of SJS following these NSAIDs.

Antifungal Drugs and Drug-Induced Liver Injury: A Real-World Study Leveraging the FDA Adverse Event Reporting System Database.

Aims: We aimed to estimate the risk of drug-induced liver injury (DILI) from various antifungal treatments with azoles and echinocandins causing in real-world practice. Methods: We performed disproportionality and Bayesian analyses based on data from the first quarter in 2004 to the third quarter in 2021 in the Food and Drug Administration Adverse Event Reporting System to characterize the signal differences of antifungal drugs-related DILI. We also compared the onset time and mortality differences of different antifungal agents. Results: A total of 2943 antifungal drugs-related DILI were identified. Affected patients tended to be aged >45 years (51.38%), with more males than females (49.03% vs. 38.09%). Antifungal drug-induced liver injury is most commonly reported with voriconazole (32.45%), fluconazole (19.37%), and itraconazole (14.51%). Almost all antifungal drugs were shown to be associated with DILI under disproportionality and Bayesian analyses. The intraclass analysis of correlation between different antifungal agents and DILI showed the following ranking: caspofungin (ROR = 6.12; 95%CI: 5.36-6.98) > anidulafungin (5.15; 3.69-7.18) > itraconazole (5.06; 4.58-5.60) > voriconazole (4.58; 4.29-4.90) > micafungin (4.53; 3.89-5.27) > posaconazole (3.99; 3.47-4.59) > fluconazole (3.19; 2.93-3.47) > ketoconazole (2.28; 1.96-2.64). The onset time of DILI was significantly different among different antifungal drugs (p < 0.0001), and anidulafungin result in the highest mortality rate (50.00%), while ketoconazole has the lowest mortality rate (9.60%). Conclusion: Based on the Food and Drug Administration Adverse Event Reporting System database, antifungal drugs are significantly associated with DILI, and itraconazole and voriconazole had the greatest risk of liver injury. Due to indication bias, more clinical studies are needed to confirm the safety of echinocandins.

Stevens-Johnson Syndrome Following Vancomycin and Linezolid: A Real-World Analysis of Post-Marketing Surveillance Data.

Background: Stevens-Johnson syndrome (SJS) has been reported as a serious adverse effect in patients treated with vancomycin or linezolid, and there is currently a lack of real-world studies comparing specific differences in adverse effects of SJS. Methods: According to the FDA's Adverse Event Reporting System (FAERS), from January 2004 to July 2021, the data of suspected SJS after the use of vancomycin and linezolid were analyzed by imbalance and Bayesian analysis. The onset time, fatality rate and hospitalization rate of vancomycin-associated SJS and linezolid-associated SJS were also investigated. Results: 276 cases of vancomycin-related SJS reports and 63 cases of linezolid-related SJS reports were identified. These two drugs are more common in middle-aged patients (45-64 years) than other age groups, and less common in underage children (<18). Among them, linezolid-related SJS is more common in middle-aged and elderly patients (45-74 years old) than other groups. Except for unspecified data, in vancomycin-associated SJS cases, there are more men than women (49.28% vs 43.84%), while in linezolid-associated SJS cases, the proportion of men and women is almost equal (44.44%). From the point of view of the areas where adverse reactions were reported, about 1/2 of the reports on Vancomycin-related SJS came from North America, and 1/3 of the reports came from Europe. The median onset time of Linezolid-related SJS was 5 days (interquartile range [IQR] 2-7.75), which was significantly earlier than that of Vancomycin-related SJS (12 days, IQR 4-20) (Mann-Whitney test, p < 0.0001). There were no significant differences in mortality and hospitalization rates after vancomycin and linezolid caused SJS. Conclusion: The analysis of faers data provides a comprehensive overview of the adverse reactions of SJS caused by the use of vancomycin and linezolid, and can warn clinical workers to timely intervene and continuously monitor the patients at risk of SJS when using such drugs.

Ibuprofen induced Stevens-Johnson syndrome and liver injury in children: a case report.

Stevens-Johnson syndrome (SJS) is a disorder that causes severe damage to the skin and mucous membranes with bullous and erosive properties. Drug-induced liver injury (DILI) is closely related to non-steroidal anti-inflammatory drugs (such as ibuprofen). Liver injury caused by ibuprofen is often related to overdose, and liver injury caused by normal dose is rare, and there are individual differences in different situations. In this case, a child developed SJS and acute liver injury after treatment with ibuprofen suspension. We described the characteristics of related adverse reactions induced by ibuprofen, and analyzed the relationship between SJS caused by the drug and related drug genes. Glucocorticoids and antihistamines were used to treat dermatitis, reduced glutathione (GSH) to protect the liver and plasma exchange detoxification. Finally, the patient's dermatitis healed and the liver injury was significantly improved. Many studies have suggested that DILI may be related to human leukocyte antigen (HLA) genotyping. The detection of drug-related genes revealed that the SJS and liver damage caused by ibuprofen might have been related to the positive HLA-B*5801. This article suggests that attention should be paid to checking liver function indicators after taking ibuprofen, and genetic screening can be used to reduce the risk of gene-related adverse reactions when necessary.

Kidney Injury Following Ibuprofen and Acetaminophen: A Real-World Analysis of Post-Marketing Surveillance Data.

Background: Although kidney injury has been reported as a serious adverse effect in patients treated with ibuprofen or acetaminophen (APAP), there are still few real-world studies to compare the specific differences in the adverse effects of nephrotoxicity. Methods: Disproportionality analysis and Bayesian analysis were devoted to data-mining of the suspected kidney injury after using ibuprofen and APAP based on the FDA's Adverse Event Reporting System (FAERS) from January 2004 to March 2021. The times to onset, fatality, and hospitalization rates of ibuprofen-associated kidney injury and APAP-associated kidney injury were also investigated. Results: 2,453 reports of ibuprofen-associated kidney injury and 1,288 reports of APAP-associated kidney injury were identified. Ibuprofen appeared to affected more middle-aged patients than elderly ones (27.76 vs 16.53%) while APAP appeared to affected more young patients than middle-aged patients (45.24 vs 29.10%) and elderly patients were fewer (13.99%). Compared to ibuprofen, APAP had the higher association with renal injury based on the higher reporting odds ratio (ROR = 2.45, 95% two-sided CI = 2.36-2.56), proportional reporting ratio (PRR = 2.39, χ 2 = 2002.94) and empirical Bayes geometric mean (EBGM = 2.38, 95% one-sided CI = 2.3). In addition, APAP-associated kidney injury had earlier onset (32.74 vs 115.82 days, p < 0.0001) and a higher fatality rate (44.43 vs 7.36%, p < 0.001) than those of ibuprofen-associated kidney injury. Conclusion: The analysis of FAERS data provides a more accurate profile on the incidence and prognosis of kidney injury after ibuprofen and acetaminophen treatment, enabling continued surveillance and timely intervention in patients at risk of kidney injury using these drugs.

Clinicopathologic and Prognostic Significance of Body Mass Index (BMI) among Breast Cancer Patients in Western China: A Retrospective Multicenter Cohort Based on Western China Clinical Cooperation Group (WCCCG).

INTRODUCTION: Clinicopathologic and prognostic significance of body mass index (BMI) in breast cancer (BC) patients remained conflicting. We aimed to investigate and modify the impact of BMI on clinicopathological significance and survival in western Chinese BC patients. MATERIALS AND METHODS: 8,394 female BC patients from Western China Clinical Cooperation Group (WCCCG) between 2005 and 2015 were identified. Multivariable logistic regression and Cox proportion hazard regressions were used to examine the difference of clinicopathologic and survival characteristics between BMI categories. RESULTS: For the premenopausal, overweight and obese (OW) patients tended to have large tumor size (>5cm) (odds ratio [OR], 1.30, P<0.01) and triple-negative BC (OR, 1.31; P=0.01) compared with normal weight (NW) patients. Premenopausal underweight (UW) patients had a significantly higher risk of HER2 positive (OR, 1.71; P=0.02) and distant metastasis (OR, 2.59; P=0.01). For postmenopausal patients, OW patients showed higher risks of large tumor size (>5cm) (OR, 1.46; P=0.01), nuclear grade III (OR, 1.24; P=0.04), and lymphovascular invasion (OR, 1.46; P=0.01) compared with NW patients. An "U" shaped relationship between BMI and DFS was found (UW versus NW, adjusted hazard ratio (HR), 2.80, P<0.001; OW versus NW, adjusted HR, 1.40, P=0.02), whereas no significant difference of disease-free survival (DFS) between OW and NW premenopausal patients (adjusted HR=1.34, P=0.18) was revealed. CONCLUSION: We concluded that UW and OW were associated with aggressively clinicopathological characteristics, regardless of menopausal status. An "U" shaped association of BMI and DFS was revealed, and no significant difference of DFS between OW and NW in postmenopausal subgroup was revealed.

Predictors of internal mammary lymph nodes (IMLN) metastasis and disease-free survival comparison between IMLN-positive and IMLN-negative breast cancer patients: Results from Western China Clinical Cooperation Group (WCCCG) database (CONSORT).

Limited studies performed a comprehensive assessment of risk factors for internal mammary lymph nodes (IMLN) metastasis, and disease-free survival (DFS) difference between IMLN-positive and IMLN-negative breast cancer (BC) patients undergoing IMLN dissection and systemic therapies was not clear.A retrospective study included 1977 BC patients from Western China Clinical Cooperation Group between January 2005 and December 2012. The impact of clinicopathological factors on the occurrence of IMLN metastasis was assessed in univariate and multivariate logistic regression analyses, and a nomogram (model) was constructed to predict the IMLN status. DFS difference was evaluated in univariate and multivariate Cox regression analyses between IMLN-negative and IMLN-positive patients, and univariate analysis was performed to compare DFS between individuals with high and low IMLN metastasis risk defined by proposed nomogram.Of 1977 enrolled patients, 514 cases underwent IMLN dissection and 1463 cases did not undergo IMLN irradiation or dissection. We found that initial disease symptoms and signs, mammographic calcification, tumor site, number of positive axillary lymph nodes (ALNs), American Joint Committee on Cancer pT stage, and human epidermal growth factor receptor 2 status were associated with IMLN metastasis (all P < .05). Those variables were included in nomogram, whose predictive ability was better than that of ALN classification (area under the curve: 0.82 vs 0.76, P < .001). Univariate cox proportional hazards model indicated that better DFS was observed in IMLN-negative patients than IMLN-positive group (hazard ratio [HR] = 1.87, 95% confidence interval [CI] = 1.05-3.34; P = .04), whereas no significant differences in DFS (HR = 0.99, 95% CI = 0.49-2.00; P = .97) were found after adjusting patient-, disease-, and treatment-related factors.Nipple inversion, mammographic calcification, larger tumor size, medial tumor site, negative HER-2 status, and more positive ALNs are independent risk factors for IMLN metastasis, and the individualized nomogram is a feasible tool to predict the status of IMLN. Equivalent DFS was found between positive and negative IMLN patients who all accepted IMLN dissection and systemic therapies.

Relationship between mammographic calcifications and the clinicopathologic characteristics of breast cancer in Western China: a retrospective multi-center study of 7317 female patients.

BACKGROUND AND PURPOSE: Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China. METHODS: This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared. RESULTS: A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (P < 0.0001), higher grade (P = 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)- (P = 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (P < 0.0001), and to have axillary lymph node metastasis (P = 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (P = 0.0108) and anti-HER2 therapy (P = 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (P < 0.0001). CONCLUSIONS: In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.