Positive response to trastuzumab deruxtecan in a patient with HER2-mutant NSCLC after multiple lines therapy, including T-DM1: a case report

Human epidermal growth factor 2 (HER2) mutations are uncommon in non-small cell lung cancer (NSCLC), and the lack of established, effective, targeted drugs has resulted in a persistently poor prognosis. Herein, we report the case of a non-smoking, 58-year-old man diagnosed with lung adenocarcinoma (cT3N0M1c, stage IVB) harboring a HER2 mutation (Y772_A775dupYVMA) and PD-L1 (-). The patient’s Eastern Cooperative Oncology Group performance status (PS) score was assessed as 1. He commenced first-line treatment with chemotherapy, followed by immuno-chemotherapy, and with disease progression, he received HER2-targeted therapy and chemotherapy with an anti-angiogenic agent. However, HER2-targeted therapy, including pan-HER tyrosine kinase inhibitors (afatinib, pyrotinib, and pozitinib) and antibody–drug conjugate (T-DM1), produced only stable disease (SD) as the best response. After the previously described treatment, primary tumor recurrence and multiple brain metastases were observed. Despite the patient’s compromised overall physical condition with a PS score of 3-4, he was administered T-DXd in addition to whole-brain radiotherapy (WBRT). Remarkably, both intracranial metastases and primary lesions were significantly reduced, he achieved a partial response (PR), and his PS score increased from 3-4 to 1. He was then treated with T-DXd for almost 9 months until the disease again progressed, and he did not discontinue the drug despite the occurrence of myelosuppression during this period. This is a critical case as it exerted an effective response to T-DXd despite multiple lines therapy, including T-DM1. Simultaneously, despite the occurrence of myelosuppression in the patient during T-DXd, it was controlled after aggressive treatment

A fatal case of febrile ulceronecrotic mucha-habermann disease which presenting as toxic epidermal necrolysis

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD), a severe form of pityriasis lichenoides et varioliformis acuta, is an inflammatory dermatosis of unknown etiology manifested by ulcerative and necrotic lesions accompanied by systemic manifestations. The mortality rate of FUMHD is about 15%. It is reported here a case of FUMHD presenting as toxic epidermal necrolysis that resulted in multiple organ failure and death

Effect of Climatic Conditions Caused by Seasons on Maize Yield, Kernel Filling and Weight in Central China

In order to evaluate the effects of climatic conditions on maize grain yield (GY), kernel weight (KW), and kernel filling and identify the optimal climatic factors for GY and KW, 2-year field experiments in three seasons, i.e., spring (SPM), summer (SUM), and autumn (AUM), on maize were conducted in Central China. The results showed that SUM had more growing degree days (GDDs) than SPM and AUM due to the higher mean temperature (MT), and also resulted in higher temperature stress (killing degree days (KDDs)) in maize growth duration. Meanwhile, after silking, SPM and SUM had more GDDs and KDDs than AUM because of the higher MT, and the accumulated solar radiation (Ra) for SUM was significantly higher than for SPM and AUM. The GY of SPM was significantly higher than that of SUM and AUM, while SUM’s GY was always the lowest, because the GDDGD, MTGD, and KDDGD played significantly negative roles on GY. The final KW for SUM was always the lowest, with GDD, MT, KDD, and Ra causing significantly negative effects, and M△T and precipitation having significant positive effects, resulting in a lower kernel filling rate during the linear kernel filling period (KFRlkf) and a lower GDD at the maximum kernel filling rate (GDDKFRmax). Maize KFRlkf has significant negative linear dependences on GDD, MT, and Ra. In summary, because of the higher MT, KDD, and GDD during maize growth and kernel filling duration negatively affecting the maize kernel filling rate, the GY and KW for SPM were the highest, and for SUM, they were the lowest; therefore, farmers should plant SPM first and then AUM in Central China

Curcumin Induces Ferroptosis in Follicular Thyroid Cancer by Upregulating HO-1 Expression

Follicular thyroid cancer (FTC) is a highly aggressive type of endocrine malignancy. It is necessary to investigate the mechanisms of tumorigenesis and therapeutic pathways in patients with FTC. Haem oxygenase-1 (HO-1) can regulate oxidative stress and the occurrence of tumors and diseases. In this study, we discovered that HO-1 was abnormally overexpressed in FTC compared with adjacent tissues. However, the HO-1 overexpression was demonstrated to decrease cell viability and to potentially activate the ferroptosis signalling pathway. Ferroptosis is a newly identified form of oxidative cell death and is currently being targeted as a new cancer treatment. Tumorigenesis is significantly inhibited by curcumin. The present study shows that curcumin inhibits the growth of FTC by increasing the HO-1 expression, further activating the ferroptosis pathway. This study demonstrates that the HO-1-ferroptosis signalling pathway might play an important role in FTC tumorigenesis, and that curcumin inhibits the growth of FTC cells by affecting this pathway

Global prevalence and burden of multidrug-resistant tuberculosis from 1990 to 2019

Abstract Background Tuberculosis(TB) remains a pressing public health challenge, with multidrug-resistant tuberculosis (MDR-TB) emerging as a major threat. And healthcare authorities require reliable epidemiological evidence as a crucial reference to address this issue effectively. The aim was to offer a comprehensive epidemiological assessment of the global prevalence and burden of MDR-TB from 1990 to 2019. Methods Estimates and 95% uncertainty intervals (UIs) for the age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), age-standardized disability-adjusted life years rate (ASR of DALYs), and age-standardized death rate (ASDR) of MDR-TB were obtained from the Global Burden of Disease (GBD) 2019 database. The prevalence and burden of MDR-TB in 2019 were illustrated in the population and regional distribution. Temporal trends were analyzed by using Joinpoint regression analysis to calculate the annual percentage change (APC), average annual percentage change (AAPC) and its 95% confidence interval(CI). Results The estimates of the number of cases were 687,839(95% UIs: 365,512 to 1223,262), the ASPR were 8.26 per 100,000 (95%UIs: 4.61 to 15.20), the ASR of DALYs were 52.38 per 100,000 (95%UIs: 22.64 to 97.60) and the ASDR were 1.36 per 100,000 (95%UIs: 0.54 to 2.59) of MDR-TB at global in 2019. Substantial burden was observed in Africa and Southeast Asia. Males exhibited higher ASPR, ASR of DALYs, and ASDR than females across most age groups, with the burden of MDR-TB increasing with age. Additionally, significant increases were observed globally in the ASIR (AAPC = 5.8; 95%CI: 5.4 to 6.1; P < 0.001), ASPR (AAPC = 5.9; 95%CI: 5.4 to 6.4; P < 0.001), ASR of DALYs (AAPC = 4.6; 95%CI: 4.2 to 5.0; P < 0.001) and ASDR (AAPC = 4.4; 95%CI: 4.0 to 4.8; P < 0.001) of MDR-TB from 1990 to 2019. Conclusions This study underscored the persistent threat of drug-resistant tuberculosis to public health. It is imperative that countries and organizations worldwide take immediate and concerted action to implement measures aimed at significantly reducing the burden of TB

Additional file 1 of Global prevalence and burden of multidrug-resistant tuberculosis from 1990 to 2019

Supplementary Material

Quantitative Proteomics Reveals Significant Changes in Cell Shape and an Energy Shift after IPTG Induction via an Optimized SILAC Approach for <i>Escherichia coli</i>

Stable isotope labeling by amino acids in cell culture (SILAC) has been widely used in yeast, mammalian cells, and even some multicellular organisms. However, the lack of optimized SILAC media limits its application in <i>Escherichia coli</i>, the most commonly used model organism. We optimized SILACE medium (SILAC medium created in this study for <i>E. coli</i>) for nonauxotrophic <i>E. coli</i> with high growth speed and complete labeling efficiency of the whole proteome in 12 generations. We applied a swapped SILAC workflow and pure null experiment with the SILACE medium using <i>E. coli</i> BL21 (DE3) cells hosting a recombinant plasmid coding for glutathione-<i>S</i>-transferase (GST) and ubiquitin binding domain before and after isopropyl thiogalactoside (IPTG) induction. Finally, we identified 1251 proteins with a significant change in abundance. Pathway analysis suggested that cell growth and fissiparism were inhibited accompanied by the down-regulation of proteins related to energy and metabolism, cell division, and the cell cycle, resulting in the size and shape change of the induced cells. Taken together, the results confirm the development of SILACE medium suitable for efficient and complete labeling of <i>E. coli</i> cells and a data filtering strategy for SILAC-based quantitative proteomics studies of <i>E. coli</i>

The Application of Ethnomedicine in Modulating Megakaryocyte Differentiation and Platelet Counts

Megakaryocytes (MKs), a kind of functional hematopoietic stem cell, form platelets to maintain platelet balance through cell differentiation and maturation. In recent years, the incidence of blood diseases such as thrombocytopenia has increased, but these diseases cannot be fundamentally solved. The platelets produced by MKs can treat thrombocytopenia-associated diseases in the body, and myeloid differentiation induced by MKs has the potential to improve myelosuppression and erythroleukemia. Currently, ethnomedicine is extensively used in the clinical treatment of blood diseases, and the recent literature has reported that many phytomedicines can improve the disease status through MK differentiation. This paper reviewed the effects of botanical drugs on megakaryocytic differentiation covering the period 1994–2022, and information was obtained from PubMed, Web of Science and Google Scholar. In conclusions, we summarized the role and molecular mechanism of many typical botanical drugs in promoting megakaryocyte differentiation in vivo, providing evidence as much as possible for botanical drugs treating thrombocytopenia and other related diseases in the future