Questions

1 MCQ

A 28-year-old woman with known SLE presents with new nephrotic-range proteinuria (4.2 g/24h), haematuria, and elevated creatinine (142 µmol/L). Serology reveals strongly positive anti-dsDNA (240 IU/mL), low C3 (0.42 g/L), and low C4 (0.06 g/L). Renal biopsy shows diffuse proliferative glomerulonephritis (ISN/RPS Class IV) with granular subendothelial and mesangial immune complex deposits.

Which sequence of events best explains the complement consumption and glomerular injury in this patient?

เลือกคำตอบ 1 (1 ตัวเลือกที่ถูกต้อง).

A. Anti-dsDNA IgG immune complexes activate C1q, triggering the classical pathway with sequential C4, C2, and C3 cleavage; C3a/C5a recruit neutrophils and C5b-9 causes direct podocyte and endothelial injury, consuming both C3 and C4

B. Mannose-binding lectin recognises glycan patterns on chromatin released from apoptotic cells, activating the lectin complement pathway via MASP-1/2 to generate C3b deposits in the mesangium

C. Properdin stabilises the alternative pathway C3 convertase (C3bBb) on glomerular surfaces, causing C3 consumption with normal C4 levels and progressive mesangial deposition

D. Anti-dsDNA IgG binds mesangial FcγRIIb receptors, triggering ITIM-mediated suppression of complement regulation proteins and secondarily consuming C3 and C4

E. CD4+ T helper cells activated by nucleosome antigens recruit complement-independent neutrophil-mediated glomerular injury via CXCL8 and NET formation

เลือก 0 จาก 1

2 MCQ

A 32-year-old man is newly diagnosed with HIV-1 infection (CD4 count 380 cells/µL, viral load 45,000 copies/mL). He is commenced on first-line antiretroviral therapy with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).

At which specific step in the HIV replication cycle does bictegravir exert its antiviral effect?

เลือกคำตอบ 1 (1 ตัวเลือกที่ถูกต้อง).

A. Inhibition of reverse transcriptase, preventing synthesis of double-stranded DNA from the viral RNA genome

B. Binding to gp41 in the HIV envelope, preventing fusion of the viral and cell membranes during viral entry

C. Chelation of Mg2+ ions in the HIV integrase catalytic site, blocking strand transfer of viral DNA into host chromosomal DNA

D. Competitive inhibition of HIV protease, preventing cleavage of Gag and Gag-Pol polyprotein precursors into functional structural and enzymatic proteins

E. Inhibition of nuclear import of the pre-integration complex by blocking interaction with the nuclear pore complex importin pathway

เลือก 0 จาก 1

3 MCQ

A 61-year-old man of East Asian descent undergoes percutaneous coronary intervention with drug-eluting stent placement for NSTEMI. He is commenced on dual antiplatelet therapy with aspirin and clopidogrel. Pharmacogenomic testing reveals he is homozygous for the CYP2C19*2 loss-of-function allele (poor metaboliser phenotype).

Which of the following best explains the pharmacological consequence of this genotype and its clinical implication?

เลือกคำตอบ 1 (1 ตัวเลือกที่ถูกต้อง).

A. Clopidogrel is an active drug that is directly detoxified by CYP2C19; the *2 allele reduces detoxification, causing toxic accumulation and excessive platelet inhibition, increasing bleeding risk

B. Clopidogrel is bioactivated by CYP2C19, and poor metaboliser status causes excessive active metabolite accumulation, leading to supratherapeutic P2Y12 inhibition and increased bleeding

C. CYP2C19 catalyses the first-pass intestinal absorption of clopidogrel; the *2 allele reduces intestinal uptake, requiring dose escalation to achieve therapeutic plasma levels

D. Clopidogrel is a prodrug requiring two-step hepatic bioactivation; CYP2C19 catalyses the critical second oxidation to the active thiol metabolite; the *2 splice defect produces negligible active metabolite, impairing P2Y12 inhibition and increasing stent thrombosis risk

E. CYP2C19 *2 allele reduces vitamin K epoxide reductase complex subunit 1 (VKORC1) sensitivity to antiplatelet drugs, necessitating increased monitoring of INR when clopidogrel is co-administered with anticoagulants

เลือก 0 จาก 1

4 MCQ

A 56-year-old man presents with an acutely swollen, erythematous right first metatarsophalangeal joint. Joint aspiration demonstrates needle-shaped, negatively birefringent crystals under polarised light microscopy. His serum urate is 0.58 mmol/L.

Which of the following correctly describes the intracellular molecular mechanism by which monosodium urate (MSU) crystals trigger the acute inflammatory response in synovial macrophages?

เลือกคำตอบ 1 (1 ตัวเลือกที่ถูกต้อง).

A. MSU crystals adsorb IgG antibodies, forming immune complexes that activate Fc-gamma receptors on macrophages and trigger NF-kappaB-mediated IL-1beta transcription and direct secretion

B. Phagocytosis of MSU crystals causes lysosomal membrane permeabilisation and cathepsin B release, activating the NLRP3 inflammasome to cleave procaspase-1, which processes pro-IL-1beta into its active secreted form

C. MSU crystals are recognised as DAMPs by HMGB1 receptor RAGE on macrophage surfaces, directly activating MyD88-dependent signalling to produce and secrete IL-1beta without intracellular processing

D. MSU crystals activate neutrophil extracellular trap (NET) formation, which releases citrullinated histones that cross-activate synovial macrophage TLR9, triggering the NLRP3 pathway

E. MSU crystals activate caspase-8 via the extrinsic apoptosis pathway, which processes pro-IL-1beta as a secondary function distinct from its role in apoptosis

เลือก 0 จาก 1

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