Current Research in Medical Sciences

Activation of Prodrugs Depend on the Metabolism of These Prodrugs

2026-03-25T10:10:41+00:00

Prodrugs depend on enzymatic processes, essentially in the liver, but can also occur in other tissues to release the active metabolite. These metabolic biotransformations are often enzymatically controlled, ensuring the drug becomes pharmacologically active at its site of action. Metabolism may occur at the target site (e.g., in viruses, where drugs are phosphorylated) or in the liver or other tissues. For example, codeine is activated by demethylation to morphine, which is a more active analgesic than codeine. Clopidogrel oxidized to 2-oxoclopidogrel which is active and 2-oxoclopidogrel which is metabolized in two active thiol metabolite. Enalapril is a prodrug that is metabolized to enalaprilat, the active form. L-Dopa is a prodrug that is converted into dopamine in the brain by decarboxylation. Azathioprine is metabolized to mercaptopurine, which is immunosuppressive. Sulfasalazine is a prodrug metabolized by azoreductase and converted to 5-aminosalicylic acid and sulfapyridine, which are more active than sulfasalazine. Prontosil is a prodrug converted into sulfanilamide, which is more active than prontosil. Salicin is a glycoside that is metabolized into salicylic acid, which is active as an analgesic. Valacyclovir is metabolized into acyclovir, which is an active antiviral.

Structural and Functional Neuroimaging in Major Depressive Disorder with Suicidal Ideation: A Review

2026-03-25T10:25:34+00:00

Major depressive disorder with suicidal ideation (MDD-SI) represents a clinically high-risk subtype of depressive disorders characterized by marked neurobiological heterogeneity and has become a major focus of suicide prevention and precision intervention research. In recent years, neuroimaging studies have increasingly demonstrated that patients with MDD-SI exhibit distinct structural and functional brain alterations compared with depressed patients without suicidal ideation. These abnormalities primarily involve the prefrontal–cingulate–limbic system, the default mode network (DMN), and reward-related circuits. With the growing number of longitudinal neuroimaging studies, accumulating evidence suggests that biological treatments—particularly electroconvulsive therapy (ECT)—not only lead to significant reductions in depressive symptoms and suicidal ideation but also induce measurable structural and functional plasticity in these key brain regions and networks.

Structural MRI studies indicate that, at baseline, patients with MDD-SI commonly show gray matter abnormalities in regions such as the anterior cingulate cortex, prefrontal cortex, and hippocampus. Following ECT treatment, regionally selective structural changes have been observed, most notably hippocampal volume increases and structural recovery in the anterior cingulate cortex and ventromedial prefrontal cortex. Functional neuroimaging studies further demonstrate that treatment-related reductions in suicidal ideation are accompanied by enhanced prefrontal–limbic regulatory control, normalization of anterior cingulate cortex function, and suppression of excessive self-referential processing within the DMN. Collectively, these findings suggest that treatment-related neuroimaging changes may constitute an important neural substrate underlying the improvement of suicidal ideation.

This review summarizes current structural and functional neuroimaging findings in patients with MDD-SI before and after treatment, with particular emphasis on treatment-related plasticity in key brain regions and networks. Furthermore, an integrative conceptual framework—linking baseline structural abnormalities, treatment-induced neuroplasticity, and the alleviation of suicidal ideation—is proposed to provide insights for future research on imaging-based predictive biomarkers and the neurobiological mechanisms underlying treatment response.

Research Progress on the Safety of Oliceridine in Perioperative Application

2026-03-25T10:27:46+00:00

Oliceridine is the first approved biased μ-opioid receptor agonist. It produces analgesia by selectively activating the G protein pathway while minimizing β-arrestin recruitment, a mechanism that theoretically uncouples analgesia from adverse effects. This article systematically reviews the pharmacological basis for the perioperative use of oliceridine, the clinical evidence for its safety, and its value in special patient populations. Studies indicate that at equianalgesic doses, oliceridine is associated with a significantly lower incidence of respiratory depression and better gastrointestinal tolerability compared to conventional opioids. In elderly patients and those with renal or hepatic impairment, no or only mild dose adjustment is required. Cardiovascular and central nervous system adverse effects are manageable, with no risk signals identified beyond those of conventional opioids. Within the framework of multimodal analgesia, oliceridine demonstrates good synergy with other analgesic agents. However, critical questions remain insufficiently addressed, including the risks of long‑term tolerance and dependence, as well as its impact on hard endpoints such as postoperative ileus. Future research should focus on long‑term follow‑up studies and clinical trials centered on bowel function recovery to refine its positioning within Enhanced Recovery After Surgery (ERAS) pathways.

Functional Testing for Return-to-Sport Decision-Making After Anterior Cruciate Ligament Reconstruction: An Updated Narrative Review

2026-04-20T03:24:58+00:00

Return-to-sport (RTS) decision-making after anterior cruciate ligament reconstruction (ACLR) has moved away from time alone toward criterion-based models, yet the optimal composition of a functional testing battery remains debated. Functional tests are still essential because they quantify residual deficits in strength, power, neuromuscular control, balance, and confidence; however, contemporary evidence shows that no single test has adequate validity to clear an athlete independently. This updated narrative review synthesizes landmark cohort studies together with recent reviews, guidelines, and meta-analyses on functional RTS assessment after primary ACLR. The current literature indicates that hop tests remain clinically valuable, especially the single-leg hop for distance, crossover hop, 6-m timed hop, and single-leg vertical hop, but isolated pass/fail thresholds show inconsistent ability to predict second injury or successful RTS. Quadriceps strength remains indispensable, although limb symmetry index (LSI) should not be interpreted without consideration of absolute strength, time since surgery, graft type, sex, and possible deconditioning of the contralateral limb. Movement-quality assessments during landing, single-leg squat, or change-of-direction tasks may reveal high-risk patterns that distance-based tests miss. Psychological readiness, most commonly assessed with the ACL-Return to Sport after Injury scale, is another core domain because fear of reinjury and low confidence often persist despite acceptable physical scores. Importantly, recent evidence shows that RTS testing is commonly administered around 7 months post-operatively, which is earlier than timelines associated with lower reinjury risk in pivoting sports. A contemporary RTS strategy should therefore rely on a domain-based battery combining clinical status, strength testing, at least two hop or jump tasks, movement-quality assessment, patient-reported outcomes, and psychological readiness. For unrestricted return to level I pivoting sports, final clearance is best delayed until at least 9 months after surgery and only after satisfactory performance is demonstrated across domains.

The Policy-Driven Evolution of Non-Public Hemodialysis Centers in China: A Retrospective Analysis from 2009 to 2025

2026-04-20T03:48:42+00:00

Background: The number of patients with end-stage renal disease (ESRD) in China continues to rise, while hemodialysis services have long been concentrated in large public hospitals, creating a significant service gap in rural and grassroots areas. Non-public hemodialysis centers, as a crucial supplement to the national healthcare system, have seen their developmental trajectory profoundly shaped by phased adjustments in health policy. Methods: This study employs a qualitative policy analysis combined with a historical case study approach to examine the evolution of non-public hemodialysis centers in China from 2009 to 2025. We conducted a systematic review of publicly available primary sources, including official policy documents issued by the National Health Commission (NHC), the National Healthcare Security Administration (NHSA), and provincial-level health and medical insurance authorities. Complementary data were drawn from authoritative industry reports, peer-reviewed academic literature, and publicly disclosed corporate information from leading non-public dialysis providers. The analytical framework is structured around a three-phase historical periodization: (1) the Pilot Exploration Phase (2009–2015), (2) the Regulated Expansion Phase (2016–2020), and (3) the Quality-Driven Deepening Phase (2021–2025). Within each phase, we analyzed the interplay between key policy interventions and the strategic responses of the non-public dialysis sector, focusing on how these dynamics shaped operational models and market structures. The authors confirm that large language models (LLMs) or other artificial intelligence (AI)-based tools were used during the preparation of this manuscript solely for language polishing, grammatical refinement, and translation assistance. Specifically, AI tools (including Deepseek) were employed to improve the clarity and fluency of certain English-language passages in the Introduction, Methods, and Discussion sections. All intellectual content, conceptualization, data interpretation, analytical framework, and final editorial decisions were made exclusively by the human authors. No AI tool was used to generate original scientific content, analyze data, or draft core arguments. In accordance with journal policy, no AI system is listed as an author, nor did it fulfill any authorship role. Results: The industry’s evolution exhibits three distinct phases: Pilot Exploration Phase (2009–2015): Policy shifted from strict control to cautious deregulation, primarily through local pilots, fostering the initial forms of industry-driven and service-driven models. Regulated Expansion Phase (2016–2020): The policy system, centered on the “Basic Standards and Management Regulations for Hemodialysis Centers (for Trial Implementation)” (National Health Commission Document No. [2016] 67), was established, leading to explosive industry growth. The three dominant operational models—industry-driven, service-driven, and capital-driven—were formally established and rapidly expanded. Quality Deepening Phase (2021–2025): Policy focus shifted towards resource decentralization, quality homogenization, and value-based payment, driving the industry from scale-based competition to quality-based competition. The three operational models are now exhibiting trends of deep convergence and upgrading. Conclusion: The development of non-public hemodialysis centers in China exemplifies a typical path of “state-guided market creation.” Through staged interventions characterized by “pilot breakthroughs—regulatory guidance—quality and efficiency enhancement,” policy has effectively mobilized social capital to fill public service gaps. This “policy-driven evolution” framework offers a systematic reference for other emerging economies facing similar shortages in specialized medical services. In the future, the industry will continue to evolve towards greater quality, digitalization, and value orientation, becoming deeply integrated into the national chronic kidney disease prevention and treatment system.

Current Status and Future Perspectives of Endocrine Therapy for Breast Cancer: From Classical Approaches to the Evolution of Precision Systemic Medicine

2026-04-28T07:56:27+00:00

Hormone receptor-positive breast cancer is the most prevalent molecular subtype of breast cancer. Its therapeutic strategy has progressively evolved from simple endocrine deprivation toward a systematic management model centered on endocrine therapy and integrated with molecularly targeted treatment and dynamic monitoring. This review summarizes the developmental trajectory of endocrine therapy for breast cancer, outlines the classical therapeutic agents and combination strategies used after endocrine resistance, and discusses future directions driven by liquid biopsy, artificial intelligence, and emerging estrogen receptor degradation technologies.

Local Treatment Strategies in Renal Cell Carcinoma: Current Evidence and Future Directions

2026-04-28T07:59:14+00:00

The role of local treatment in renal cell carcinoma has been substantially refined in recent years. In localized disease, partial nephrectomy remains the standard treatment because it offers durable oncologic control, complete pathological assessment, and nephron preservation. With the development of cryoablation, radiofrequency ablation, microwave ablation, and stereotactic body radiotherapy, non-surgical local therapies have become important options for selected patients. Percutaneous ablation is best supported in small and technically accessible tumors, whereas stereotactic body radiotherapy provides a noninvasive alternative for patients unsuitable for surgery or invasive procedures. In metastatic renal cell carcinoma, cytoreductive nephrectomy has shifted from a routine upfront strategy to a selective intervention determined by patient selection and treatment sequencing. In oligometastatic and oligoprogressive disease, metastasis-directed local therapy may delay systemic treatment initiation, maintain the benefit of ongoing systemic therapy, and prolong disease control. Overall, local treatment for renal cell carcinoma has moved from isolated technical application toward stage-specific and precision-based integration. Future studies should further clarify indication boundaries, patient selection, treatment timing, long-term renal outcomes, and prospective comparative evidence.