OBJECTIVE To conduct a clinical rapid evaluation of the marketed proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors in China， including evolocumab， tafolecimab， recaticimab， ebronucimab， ongericimab and inclisiran. METHODS Based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions （second edition）， drug instructions， clinical diagnosis and treatment guidelines， and literature for six drugs were retrieved from CNKI， Wanfang Data， VIP， PubMed， Embase， Cochrane Library and related official websites. The clinical rapid evaluation was conducted from five aspects： pharmaceutical characteristics， effectiveness， safety， economy， and other attributes. RESULTS The pharmaceutical characteristics， effectiveness， safety， economy， other attributes， and total score of evolocumab scored 24， 27， 15.7， 10， 5.3， and 82 points， respectively. Tafolecimab scored 23.5， 23， 11.5， 9.97， 4.6， and 72.57 points， respectively. Recaticimab scored 20.5， 22， 15.5， 6.37， 3.5， and 67.87 points. Ebronucimab scored 20， 23， 11， 6.48， 3.5， and 63.98 points. Ongericimab scored 20.5， 23， 8.5， 4.83， 3.5， and 60.33 points. Inclisiran scored 25.5， 24， 13， 6.48， 5， and 73.98 points. CONCLUSIONS Evolocumab is the optimal choice for treating hypercholesterolemia and is recommended as the first-line option. Tafolecimab is the second-line option， and recaticimab is suitable for patients who are sensitive to drug adverse reactions. Inclisiran is suitable for patients with poor compliance. Ebronucimab and ongericimab are weakly recommended due to their later market introduction. Clinicians should make individualized drug selections based on factors such as patient risk level and compliance requirements.

Background: The management of distal radius fractures (DRFs) has evolved with the introduction of volar locking plate (VLP) fixation.Nevertheless, despite the low occurrence rates, reduction loss following VLP fixation has been reported in several studies. Our objective was to determine the incidence and features of reduction loss in patients despite the appropriate application of VLP fixation for DRF. Methods: This retrospective study was conducted between March 2017 and August 2023, during which a single hand surgeon performed VLP procedures for DRFs. This study included 379 patients (382 wrists) including 3 patients who underwent bilateral surgery. We identified patients who experienced reduction loss after VLP fixation (group 1) and patients without stability problems (group 2) and compared the 2 groups. Results: The mean age of the patients was 63.5 years, with a standard deviation of 13.8. There were 90 male patients (23.6%) and 289 female patients (75.7%). We identified 14 cases of DRFs, in which reduction loss occurred even after VLP fixation during the follow-up period (group 1, 3.7%). The remaining DRFs were assigned to group 2 (n=368, 96.3%). Among the 14 patients, 7 cases of screw breakage were identified as causing the loss of fracture reduction. As the joint surface collapsed and sank down to the distal row locking screw, 4 cases presented with distal locking screws penetrating into the radiocarpal joint. There were no significant differences between the 2 groups in terms of sex, weight, fracture arm direction, and Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association (AO/OTA) fracture classification. However, patients in group 1 were statistically significantly older than those in group 2 (average age, 77.5 years vs. 62 years). Among 4 patients experiencing distal screw violation of the radiocarpal joints, 3 underwent partial or complete screw removal immediately after fracture consolidation or union. Conclusions While rare, reduction loss remains a potential complication following VLP fixation, especially in elderly patients with intra-articular DRFs. However, with diligent monitoring and timely intervention, such as implant removal if necessary, acceptable outcomes can still be attained.

Background: Patients with diabetes are known to be at high risk for end-stage kidney disease (ESKD), but the accurate annual risk data for new-onset ESKD is still limited. In South Korea, the prevalence and incidence of ESKD are increasing more rapidly compared to the global average. This study aimed to determine the incidence rate (IR) of ESKD by diabetes status from 2012 to 2022. Methods: Using data from the Korean National Health Insurance Service, we calculated the IR and hazard ratio (HR) for newonset ESKD in the general population. Individuals were categorized based on diabetes status into nondiabetes, impaired fasting glucose (IFG), diabetes duration <5 and ≥5 years. Results: Among the participants, 67.6% were nondiabetic, 22.3% had IFG, and 10% had diabetes. In Korea, the IRs of ESKD were 139 per million population (pmp) for nondiabetes, 188 pmp for IFG, 632 pmp for diabetes <5 years, and 3,403 pmp for diabetes ≥5 years. An advanced estimated glomerular filtration rate (eGFR) category was the strongest risk factor for ESKD development. However, even in patients with normal renal function, those with long-standing diabetes had a 14-fold higher risk of ESKD compared to nondiabetic individuals. The risk of ESKD associated with diabetes increased exponentially with declining renal function. Notably, IFG showed an increasing tendency for ESKD in younger patients (<65 years) with early-stage chronic kidney disease (CKD; eGFR ≥60 mL/min/1.73 m²). Conclusion Longer diabetes duration amplifies ESKD risk, particularly as renal function declines. Even in patients with normal renal function, long-standing diabetes significantly increases ESKD risk, while IFG is associated with elevated risk only in younger individuals with early-stage CKD.

Background: Recombinant human follicle-stimulating hormone (rhFSH) is commonly used to treat female infertility, but its short half-life necessitates multiple doses. Even corifollitropin alfa, with an extended half-life, requires supplementary injections of rhFSH after 7 days. This study aimed to develop and evaluate a long-acting follicle-stimulating hormone (FSH) formulation using anti-serum albumin Fab-associated (SAFA) technology to avoid additional injections and enhance ovarian function. Methods: SAFA-FSH was synthesized using a Chinese hamster ovary expression system. Its biological efficacy was confirmed through assays measuring its ability to stimulate cyclic adenosine monophosphate (cAMP) production, estradiol synthesis, and the expression of human cytochrome P450 family 19 subfamily A member 1 (hCYP19α1) and human steroidogenic acute regulatory protein (hSTAR) in human ovarian granulosa (KGN) cells. To evaluate the effects of SAFA-FSH, we compared its impact on serum estradiol levels and ovarian weight increase with that of rhFSH in Sprague-Dawley (SD) rats using the modified Steelman-Pohley test. Results: The results indicated that SAFA-FSH induces cAMP synthesis in KGN cells and upregulates the expression of hCYP19α1 and hSTAR in a dose-dependent manner. Female SD rats, aged 21 days, receiving daily subcutaneous human chorionic gonadotropin injections for 5 days exhibited a significant increase in serum estradiol levels and ovarian weight when administered SAFA-FSH on the first day or when given nine injections of rhFSH over 5 days. Notably, the group receiving SAFA-FSH on the first and third days demonstrated an even greater rise in serum estradiol levels and ovarian weight. Conclusion These findings suggest that SAFA-FSH presents a promising alternative to current rhFSH treatments for female infertility. However, further research is essential to thoroughly assess its safety and efficacy in clinical contexts.

Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

Background/Aims: The aim of this study was to investigate the effect of a surgical treatment algorithm recently proposed by the American Association for the Study of Liver Diseases (AASLD) on survival outcomes in patients with early-stage hepatocellular carcinoma (HCC) and identify effective alternative treatment modalities when liver transplantation (LT) is not available. Methods: We studied the clinical data of 1,442 patients who were diagnosed with early-stage HCC (a single lesion measuring 2–5 cm in size or 2 to 3 lesions measuring ≤3 cm in size) be-tween 2013 and 2018 and classified as Child-Turcotte-Pugh (CTP) A or B. Analyses were separately performed for individuals recommended for resection (single lesion, CTP A and no clinically significant portal hypertension) and those recommended for LT (single lesion with impaired liver function such as CTP B or clinically significant portal hypertension or multiple lesions). Results: Of 791 patients recommended for surgical resection, 85.8% underwent resection. The 5-year survival rate was higher for patients who underwent surgical resection than for those who received other treatments (89.4% vs 72.3%). Among 651 patients recommended for LT, only 3.4% underwent the procedure. The most common alternative treatment modalities were transarterial therapy (39.3%) followed by resection (28.9%) and ablation (27.8%). The overall survival rate associated with transarterial therapy was lower than that for resection and ablation, whereas that of the latter two treatments were comparable. Conclusions The survival outcomes of treatment strategies that most closely aligned with the algorithm proposed by the AASLD were superior to those of alternative treatment approaches.However, LT in patients with early-stage HCC can be challenging. When LT is not feasible, resection and ablation can be considered first-line alternative options.

Background/Aims: Elevated gamma-glutamyl transferase (GGT) levels indicate hepatic dysfunction and have been linked to an increased risk of pancreatobiliary cancers. However, this association, particularly in individuals with diabetes mellitus (DM), requires elucidation. We aimed to examine the association between elevated serum GGT levels and pancreatobiliary cancer risk in patients with diabetes. Methods: Our study included data from the National Health Insurance Service (NHIS) database for 2,459,966 adults aged >20 years diagnosed with DM between 2009 and 2012. We examined the association between serum GGT levels and pancreatobiliary cancer risk, considering DMrelated factors. Serum GGT levels were categorized into quartiles, and Cox proportional hazards analysis was performed to evaluate the association between serum GGT levels and pancreatobiliary cancer risk. Results: Over a median follow-up period of 7.2 years, 21,795 patients (0.89%) were newly diagnosed with pancreatobiliary cancer. The adjusted hazard ratio for pancreatobiliary cancer in quartiles 2–4 compared with that in quartile 1 was 1.091, 1.223, and 1.554, respectively, demonstrating a significant upward trend (p<0.001). This association remained consistent across all cancer types and was independent of the DM duration or treatment regimen. Conclusions Elevated serum GGT levels were independently associated with an increased risk of pancreatobiliary cancer, regardless of the duration of DM or the use of oral hypoglycemic agents and insulin. While these findings suggest the potential utility of serum GGT as a biomarker for identifying individuals at higher risk of pancreatobiliary cancer within the diabetic population, further research is needed to validate its clinical applicability.

Pertussis is endemic worldwide, with epidemics occurring every 2 to 5 years despite a high vaccination coverage.After limited circulation during the coronavirus disease 2019 (COVID-19) pandemic, pertussis cases have increased rapidly worldwide since mid-late 2023, returning to pre-pandemic patterns. In Korea, 90 cases of pertussis were reported from April 2020 to May 2023, with elderly individuals aged ≥65 years accounting for 48.9%. Pertussis cases have increased sharply since June 2024, showing a nationwide epidemic, with a large increase among adolescents aged 13–15 years. As of August 2024, the national incidence rate of pertussis was estimated to be 37.75 per 100,000 population, with the highest incidence of 526.2 per 100,000 population in 13-year-olds. In Europe, during 2023–2024, an increase in pertussis incidence among infants was observed, along with large increases in 10–19-yearolds. In China, the number of reported cases of pertussis has increased rapidly since late 2023, with an age shift to older children, increase of vaccine escape, and a marked increase in the prevalence of macrolide-resistant Bordetella pertussis. The recent global resurgence of pertussis is due to decreased opportunities for boosting immunity by natural infection during the COVID-19 pandemic in combination with waning of immunity-induced pertussis vaccines.

Probiotics exert various effects on the body and provide different health benefits. Previous reports have demonstrated that the P8 protein (P8), isolated from Lactobacillus rhamnosus, has anticancer properties. However, its efficacy in stem cells and normal cells has not been reported. In this study, the effect of P8 on cell proliferation and wound healing was evaluated, investigating its underlying mechanism. Based on scratch assay results, we demonstrated that P8 treatment significantly increases wound healing by activating the cell cycle and promoting stem cell stemness.Cellular mechanisms were further investigated by culturing stem cells in a medium containing Lactobacillus-derived P8 protein, revealing its promotion of cell proliferation and migration. Also, it is found that P8 enhances the expression of stemness markers, such as OCT4 and SOX2, along with activation of the mitogen-activated protein kinase (MAPK) signaling and Hippo pathways. These results indicate that P8 can promote cell growth by increasing stem cell proliferation, migration, and stemness in a manner associated with MAPK and Hippo signaling, which could contribute to the increased wound healing after P8 treatment. Furthermore, P8 could promote wound healing in keratinocytes by activating the MAPK signaling pathways. These results suggest that P8 might be a promising candidate to enhance stem cell culture efficiency by activating cell proliferation, and enhance therapeutic effects in skin diseases.