Medical Journal: Volume-11, Issue-7, July 2025

Abstract—
Background: Epidemiology of obesity and hypertension are in high prevalence on low- and middle-neighborhood socioeconomic status (nSES) area. Later, the subjects become Diabetes and Chronic Kidney Diseases (CKDs) 1-5, and cancer due to p53, p21 and p16 mutation in AFB1 exposure population. Neglected p16/INK4a upregulated in early years which induce stunting, later induce proliferation of BAT (Uncoupling Protein UCPs132) or central Obesity, and vascular smooth muscle cells (VSMCs)/Hypertension.
Aims: p16 first upregulated in p21 and p53 mutation due to AFB1 exposure cause stunting, then when p16 downregulated in the older age induce cancer cells proliferation. This study recorded more the proliferation, reveal proliferation of BAT and VSMCs in healthy young age, in the downregulated p16 stage.
Method: Review article of Systematic Review and Meta-Analysis references of p16/INK-4a decreasing induced proliferation, also p16 Knock Out (KO) in p21/ p53 mutation population (AFB1 exposure).
Result: Mutation of p21/p53 in AFB1 exposure, induce p16/INK-4a downregulated in central Obese & VSMCs patients. Silencing/ downregulated p16/INK-4a induced proliferation, but still controversial with the upregulated in p53/p21 mutation (before).
Discussion: Proliferation of UCPs132 BAT cells, proliferation of SMCs, SGLT-2/GLP-1 therapy.
Conclusion: proliferation of BAT UCPs132 (central obesity) or VSMCs (hypertension) is due to downregulated p16 under p21/p53 mutation due to AFB1 exposure in low- and middle-nSES area population.
Keywords— AFB1 exposure population, Hypertension, INK-4a, Obesity, p21/p53.

Abstract—
Introduction: Nowadays, incidence of Lymphoma Malignant with mortality is high. Peoples and former health ministry of Indonesia, FS, suspect Wolbachia-Aedes aegypti (DHF), but pediatrician thought to DENV-3/-4 secondary heterogeneity infection in endemic DENV -1/-2 in tropical rainforest area.
Method: Review the pathogenesis of the two Lymphoma Malignant dead cases report, in association with DENV-3 or -4 as secondary heterogeneity infection in tropical rainforest area, Indonesia.
Result: Severity Grade of DHF associated with secondary heterogenous DENV-3 or -4 infections. Conclusion: DENV 1-4 is ss RNA in association with emergency pandemic booster of SARS-CoV-2 which is also ss-RNA virus coated, secondary heterogeneity infection, is in one group with virus which could associated as the caused to Leukemia revealed Immune Thrombocytopenia and other tumor incl. Lymphoma Malignant-non-Hodgkin.
Conclusions: Ss RNA incl. DENV-4 infection as secondary heterogenous DENV-1/-2 or vice versa, which induce anemia and thrombocytopenia ITP with splenomegaly/Lymphoma Malignant, should be classified to DLMF (grade-4) of DHF classification.
Keywords— ITP-MDS, Large Granular Chronic Leukemia, Neutrophil Lymphocyte Ratio (NLR), Secondary heterogeneity infection DENV-4, Sepsis, Splenectomy.