ObjectiveTo review the methodological evolution, applicable scenarios, and HTA use of next-generation population-adjusted indirect comparison methods. MethodsBuilding on traditional indirect comparisons and first-generation population-adjusted methods, this review summarizes four major development paths—weight optimization, unified modelling, marginalization, and subgroup interpolation—and discusses the principles, assumptions, strengths, and limitations of two-stage matching-adjusted indirect comparison (2SMAIC), multilevel network meta-regression (ML-NMR), G-computation, multiple imputation marginalization (MIM), and network meta-interpolation (NMI). Publicly available HTA cases were also examined to identify major appraisal concerns. ResultsCompared with traditional matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC), these next-generation methods better address complex evidence networks, transportability to target populations, and incompatibility between conditional and marginal effects. ML-NMR is most useful for anchored evidence networks with multiple studies; 2SMAIC mainly improves precision within the MAIC framework; G-computation and MIM obtain decision-relevant marginal effects through model-based standardization; and NMI enables limited adjustment using subgroup results when individual patient data are unavailable. Published applications remain concentrated in pharmaceuticals. HTA agencies are cautiously open to these methods, but focus on target-population relevance, covariate overlap, key assumptions, and uncertainty analyses. ConclusionsNext-generation population-adjusted indirect comparison methods substantially expand the toolkit for evidence generation when head-to-head trials are unavailable, but they do not remove the dependence on data quality and methodological assumptions. Method choice should therefore be aligned with the evidence structure, data availability, and decision question, with transparent reporting and sensitivity analyses.
ObjectiveTo study the expressions of microRNA-221 (miR-221) and the protein of phosphatase and tension protein homologue (PTEN) in the proximal and distal stumps after sciatic nerve injury in rats and their correlation with the repair of peripheral nerve injury, so as to provide a new target for clinical diagnosis of peripheral nerve injury.MethodsNinety-six male Sprague-Dawley rats of SPF grade were selected to establish sciatic nerve injury models. Twenty-four rats were sacrificed at 0 (immediately after operation), 1, 4, and 7 days after operation. The proximal and distal sciatic nerve fragments were taken under aseptic conditions. The expression of miR-221 was detected by real-time fluorescent quantitative PCR, and the expression of PTEN protein was detected by Western blot and immunofluorescent staining. The relationship between miR-221 and PTEN was verified by dual-luciferase reporter gene. At the same time, the ultrastructure of nerve stump was observed by transmission electron microscopy.ResultsThe results of real-time fluorescent quantitative PCR, Western blot, and immunofluorescence staining showed that the relative expression of miR-221 in the proximal and distal stumps increased gradually with time, and the relative expression of PTEN protein decreased gradually, and the differences between different time points after operation were significant (P<0.05). At 1, 4, and 7 days after operation, the relative expression of miR-221 in proximal stump was significantly higher than that in distal stump, and the relative expression of PTEN protein in proximal stump was significantly lower than that in distal stump (P<0.05). Dual-luciferase reporter gene suggested that PTEN was the target for miR-221. Transmission electron microscopy observation showed that the normal morphological structure was observed at 0 day after operation, and the proliferation of Schwann cells and degeneration of axons and myelin sheaths gradually increased with time. There was no significant difference between proximal and distal stumps at 1 day after operation. At 4 and 7 days, Schwann cells proliferated more in proximal stump than in distal stump, and the degeneration of axons and myelin sheaths was less.ConclusionAfter sciatic nerve injury in rats, the up-regulation of the miR-221 expression targets the down-regulation of PTEN expression, which results in the difference of expression levels of miR-221 and PTEN in proximal and distal stumps. This phenomenon may play a role in promoting nerve repair after peripheral nerve injury.
