This study was based on the multicenter, double-blind, randomized phase III HOPE CLTI-2 trial. An exploratory post hoc analysis was performed to investigate the association between intramuscular injection site and ulcer healing outcomes in patients with chronic limb-threatening ischemia (CLTI) treated with recombinant human hepatocyte growth factor (rh-HGF), and to explore factors associated with ulcer healing. The analysis included 108 patients with CLTI treated with rh-HGF, comprising 184 ischemic lower-limb ulcers. Patients were classified according to injection site into a single-segment group, with injections limited to the calf muscles, and a multi-segment group, with injections administered to both the thigh and calf muscles. Outcomes included ulcer healing rate, time to ulcer healing, ankle-brachial index (ABI), Rutherford category, Wound, Ischemia, and foot Infection (WIfI) classification, and adverse clinical events. At the study endpoint, the unadjusted ulcer healing rate was significantly higher in the single-segment group than in the multi-segment group (75.0% vs. 57.1%, p = 0.014), and the observed time to ulcer healing was shorter (153.00 [91.00–184.00] days vs. 181.00 [94.00–191.00] days, p = 0.022). No significant between-group differences were observed in changes in ABI ( p = 0.290) or in WIfI classification ( p = 0.407). However, the distribution of Rutherford categories at study endpoint favored the single-segment group ( p = 0.016). In the multivariable logistic regression analysis, baseline ulcer area (odds ratio [OR]: 0.684, 95% confidence interval [CI]: 0.519–0.901, p = 0.007) and male sex (OR: 3.924, 95% CI: 1.164–13.232, p = 0.028) were independently associated with ulcer healing. Although the unadjusted comparisons favored the single-segment group, injection site was not independently associated with ulcer healing after multivariable adjustment (OR: 1.560, 95% CI: 0.703–3.460, p = 0.269). Therefore, these findings should be considered hypothesis-generating. Whether a more anatomically targeted rh-HGF injection strategy under a fixed-dose regimen can improve ulcer healing requires evaluation in prospectively designed studies.
Background/Objectives: Pigmented lesions arising at sites of remote trauma can create diagnostic uncertainty when their clinical appearance overlaps with melanocytic neoplasms. This report describes a graphite foreign-body granuloma presenting decades after a childhood pencil injury and highlights the importance of distinguishing exogenous pigment from melanocytic proliferation. Methods: A 64-year-old man presented with an asymptomatic 6-mm blue dermal nodule on the left fifth digit at the site of a penetrating pencil injury sustained during childhood. After remaining unchanged for decades, the lesion gradually enlarged over three years and produced mild nail plate deformity without periungual or subungual pigmentation. Cellular blue nevus, nodular melanoma, and graphite foreign-body granuloma were considered. A shave biopsy was performed, followed by histopathologic examination. Results: The biopsy revealed a well-demarcated intradermal lesion containing abundant dark amorphous pigment and sclerosis. Higher-power examination demonstrated coarse granular black pigment associated with multinucleated giant cells and surrounding fibrosis, without melanocytic proliferation. These findings established the diagnosis of graphite foreign-body granuloma. Conclusions: Retained graphite may produce a delayed foreign-body reaction and become clinically concerning many years after implantation. Because its clinical features may overlap with melanoma and other pigmented tumors, a history of remote trauma can refine the differential diagnosis but cannot replace tissue examination. Histopathologic evaluation remains essential for definitively distinguishing exogenous pigment from melanocytic proliferation.
Gene therapy offers a fundamental approach to treating genetic disorders, malignant tumors, and refractory chronic diseases by directly modifying or replacing defective genes at the molecular level. Driven by policy support, increased investment, and technological innovation, China has achieved remarkable progress in adenoviral and adeno-associated virus (AAV) vectors, gene editing, genetically engineered immune cells, oncolytic microorganisms, and small nucleic acid drugs. This review provides a comprehensive narrative overview of the technical principles, product pipelines, and clinical advances in these fields. Notable achievements include the approval of AAV-based gene therapy products in China, the entry of multiple in vivo and ex vivo gene editing therapies into clinical trials, a leading number of CAR-T trials worldwide with expansion into solid tumors and autoimmune diseases, encouraging efficacy of oncolytic virotherapy in liver cancer and melanoma, and positive clinical data of small interfering RNA/antisense oligonucleotide drugs for chronic hepatitis B and hypercholesterolemia. However, challenges remain including suboptimal tissue specificity, off-target risks, limited cargo capacity, high production costs, and poor accessibility. Future directions should focus on tissue-selective vectors, precise editing tools, off-the-shelf cell products, scalable manufacturing, and improved regulatory frameworks. With abundant clinical resources and strong manufacturing capabilities, China is poised to play a significant role in the global gene therapy landscape.
The eye is well suited to gene therapy because of its compartmentalized anatomy, accessibility for local delivery, and capacity for longitudinal assessment. In China, ocular gene therapy is undergoing rapid clinical translation, with expanding innovation in vector engineering, delivery technologies, genome editing, and therapeutic modalities. Clinical development has progressed from inherited optic neuropathies and retinal diseases to complex acquired ocular disorders, anterior-segment genome editing, and optogenetic vision restoration. This review summarizes the technological landscape and representative clinical advances of ocular gene therapy in China, highlighting the evolution from established gene-replacement approaches toward increasingly differentiated therapeutic strategies. We further discuss key challenges in interpreting clinical benefit and translating early clinical signals into durable, reproducible outcomes. Future progress will depend on clinically driven innovation, rigorous evidence of meaningful patient benefit, and standardized pathways for sustainable clinical translation.
