Non-small cell lung cancer (NSCLC) is often characterized by an underlying mutation in the epidermal growth factor receptor (EGFR),contributing to aggressive metastatic disease.Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me),a glycyrrhetinic acid derivative,reportedly improves the therapeutic response to erlotinib (ERL),an EGFR tyrosine kinase inhibitor.In the present study,we performed a series of studies to demonstrate the efficacy of CDODA-Me (2 μM) in sensitizing HCC827R(ERL-resistant) cells to ERL.Herein,we first established the selectivity of ERL-induced drug resistance in the HCC827R cells,which was sensitized when ERL was combined with CDODA-Me (2 μ.M),shifting the IC5o from 23.48 μM to 5.46 μM.Subsequently,whole transcriptomic microarray expression data demonstrated that the combination of ERL + CDODA-Me elicited 210 downregulated genes (0.44％ of the whole transcriptome (WT)) and 174 upregulated genes (0.36％ of the WT),of which approximately 80％were unique to the ERL + CDODA-Me group.Synergistic effects centered on losses to cell cycle pro-gression transcripts,a reduction of minichromosome maintenance complex components (MCM2-7),all key components of the Cdc45·MCM2-7GINS (CMG) complex,and replicative helicases;these effects were tantamount to the upregulation of processes associated with the nuclear factor erythroid 2 like 2 translational response to oxidative stress,including sulfiredoxin 1,heme oxygenase 1,and stress-induced growth inhibitor 1.Collectively,these findings indicate that the synergistic therapeutic effects of ERL +CDODA-Me on resistant NSCLC cells are mediated via the inhibition of mitosis and induction of oxidative stress.

Rickets, one of the leading causes of bony deformities and short stature, can be calciopenic (inciting event is defective intestinal calcium absorption) or phosphopenic (inciting event is phosphaturia). Early diagnosis and timely treatment of rickets are crucial for correction of the limb deformities. Guidelines exist for nutritional rickets, but the diagnosis and management of the relatively uncommon forms of rickets are complex. This consensus aims to formulate a simplified diagnostic approach for rickets, especially in resource-limited settings. The consensus statement has been formulated by a 29-member committee from the Endocrine Society of Bengal. The process included forming a working group, conducting a literature review, identifying controversies, drafting, and discussion at a consensus meeting. Participants rated their agreement with the clinical practice points, and a 70% consensus was required. Input integration and further review led to the final consensus statements. Children with suspected rickets should initially be examined for distinctive skeletal deformities. The diagnosis of rickets should be confirmed with characteristic radiographic abnormalities. It is advisable to order tests for serum calcium, inorganic phosphorus (Pi), liver function, 25-hydroxyvitamin D (25OHD), parathyroid hormone, creatinine, and potassium in all patients with rickets. In cases of refractory rickets, it is also recommended that assessments be conducted for spot urine calcium, Pi, creatinine, and, blood gas analysis. In children with rickets and metabolic acidosis, tests for glycosuria, uricosuria, aminoaciduria, low molecular weight proteinuria, and albuminuria should be conducted. In children with resistant calciopenic rickets and sufficient serum 25OHD levels, serum 1,25(OH)2D concentration should be tested. 1,25(OH)2 D and fibroblast growth factor 23 estimation is useful for certain forms of phosphopenic rickets.

Rickets, one of the leading causes of bony deformities and short stature, can be calciopenic (inciting event is defective intestinal calcium absorption) or phosphopenic (inciting event is phosphaturia). Early diagnosis and timely treatment of rickets are crucial for correction of the limb deformities. Guidelines exist for nutritional rickets, but the diagnosis and management of the relatively uncommon forms of rickets are complex. This consensus aims to formulate a simplified diagnostic approach for rickets, especially in resource-limited settings. The consensus statement has been formulated by a 29-member committee from the Endocrine Society of Bengal. The process included forming a working group, conducting a literature review, identifying controversies, drafting, and discussion at a consensus meeting. Participants rated their agreement with the clinical practice points, and a 70% consensus was required. Input integration and further review led to the final consensus statements. Children with suspected rickets should initially be examined for distinctive skeletal deformities. The diagnosis of rickets should be confirmed with characteristic radiographic abnormalities. It is advisable to order tests for serum calcium, inorganic phosphorus (Pi), liver function, 25-hydroxyvitamin D (25OHD), parathyroid hormone, creatinine, and potassium in all patients with rickets. In cases of refractory rickets, it is also recommended that assessments be conducted for spot urine calcium, Pi, creatinine, and, blood gas analysis. In children with rickets and metabolic acidosis, tests for glycosuria, uricosuria, aminoaciduria, low molecular weight proteinuria, and albuminuria should be conducted. In children with resistant calciopenic rickets and sufficient serum 25OHD levels, serum 1,25(OH)2D concentration should be tested. 1,25(OH)2 D and fibroblast growth factor 23 estimation is useful for certain forms of phosphopenic rickets.

Rickets, one of the leading causes of bony deformities and short stature, can be calciopenic (inciting event is defective intestinal calcium absorption) or phosphopenic (inciting event is phosphaturia). Early diagnosis and timely treatment of rickets are crucial for correction of the limb deformities. Guidelines exist for nutritional rickets, but the diagnosis and management of the relatively uncommon forms of rickets are complex. This consensus aims to formulate a simplified diagnostic approach for rickets, especially in resource-limited settings. The consensus statement has been formulated by a 29-member committee from the Endocrine Society of Bengal. The process included forming a working group, conducting a literature review, identifying controversies, drafting, and discussion at a consensus meeting. Participants rated their agreement with the clinical practice points, and a 70% consensus was required. Input integration and further review led to the final consensus statements. Children with suspected rickets should initially be examined for distinctive skeletal deformities. The diagnosis of rickets should be confirmed with characteristic radiographic abnormalities. It is advisable to order tests for serum calcium, inorganic phosphorus (Pi), liver function, 25-hydroxyvitamin D (25OHD), parathyroid hormone, creatinine, and potassium in all patients with rickets. In cases of refractory rickets, it is also recommended that assessments be conducted for spot urine calcium, Pi, creatinine, and, blood gas analysis. In children with rickets and metabolic acidosis, tests for glycosuria, uricosuria, aminoaciduria, low molecular weight proteinuria, and albuminuria should be conducted. In children with resistant calciopenic rickets and sufficient serum 25OHD levels, serum 1,25(OH)2D concentration should be tested. 1,25(OH)2 D and fibroblast growth factor 23 estimation is useful for certain forms of phosphopenic rickets.

Rickets, one of the leading causes of bony deformities and short stature, can be calciopenic (inciting event is defective intestinal calcium absorption) or phosphopenic (inciting event is phosphaturia). Early diagnosis and timely treatment of rickets are crucial for correction of the limb deformities. Guidelines exist for nutritional rickets, but the diagnosis and management of the relatively uncommon forms of rickets are complex. This consensus aims to formulate a simplified diagnostic approach for rickets, especially in resource-limited settings. The consensus statement has been formulated by a 29-member committee from the Endocrine Society of Bengal. The process included forming a working group, conducting a literature review, identifying controversies, drafting, and discussion at a consensus meeting. Participants rated their agreement with the clinical practice points, and a 70% consensus was required. Input integration and further review led to the final consensus statements. Children with suspected rickets should initially be examined for distinctive skeletal deformities. The diagnosis of rickets should be confirmed with characteristic radiographic abnormalities. It is advisable to order tests for serum calcium, inorganic phosphorus (Pi), liver function, 25-hydroxyvitamin D (25OHD), parathyroid hormone, creatinine, and potassium in all patients with rickets. In cases of refractory rickets, it is also recommended that assessments be conducted for spot urine calcium, Pi, creatinine, and, blood gas analysis. In children with rickets and metabolic acidosis, tests for glycosuria, uricosuria, aminoaciduria, low molecular weight proteinuria, and albuminuria should be conducted. In children with resistant calciopenic rickets and sufficient serum 25OHD levels, serum 1,25(OH)2D concentration should be tested. 1,25(OH)2 D and fibroblast growth factor 23 estimation is useful for certain forms of phosphopenic rickets.