A Versatile Hydrogel with Antibacterial and Sequential Drug-Releasing Capability for the Programmable Healing of Infectious Keratitis.

Hydrogels have attracted tremendous attention as favorable corneal substitutes for treating severe infectious keratitis (IK). However, current hydrogel-based corneal substitutes were majorly designed to promote the single stage of corneal regeneration, which falls short in meeting the clinical management needs of severe IK including the multiple phases of corneal wound healing. Herein, we introduce a versatile hybrid hydrogel (SQPV) composed of silk fibroin and chitosan, which exhibits spatiotemporal properties for drug release. The SQPV is fabricated by incorporating verteporfin-loaded poly(lactic-co-glycolic)-polyethylene glycol-o-nitrobenzene micelles into a hydrogel network, which is formed from methacrylate silk fibroin and glycidyl methacrylate functionalized quaternized chitosan containing polydeoxyribonucleotide. This double network approach results in a material with exceptional anti-inflammatory, antibacterial, and proliferative stimulation and tissue remodeling regulation capabilities. Furthermore, SQPV showcases mechanical strength and transparency akin to those of native cornea. Extensive in vitro and in vivo studies validate SQPV's ability to effectively eliminate residual bacteria, mitigate inflammation, foster regeneration of corneal epithelium and stroma, prevent corneal scarring, and ultimately expedite wound healing. In summary, the SF/CS-based hybrid hydrogel may represent a promising substitute for comprehensive corneal repair and regeneration in severe IK.

Correction to: Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalance.

An amendment to this paper has been published and can be accessed via the original article.

Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalance.

BACKGROUND: Guizhi-Shaoyao-Zhimu decoction (GSZD) has been extensively used for rheumatoid arthritis (RA) therapy. Marked therapeutic efficacy of GSZD acting on RA has been demonstrated in several long-term clinical trials without any significant side effects. However, its pharmacological mechanisms remain unclear due to a lack of appropriate scientific methodology. METHODS: GSZD's mechanisms of action were investigated using an integrative approach that combined drug target prediction, network analysis, and experimental validation. RESULTS: A total of 77 putative targets were identified for 165 assessed chemical components of GSZD. After calculating the topological features of the nodes and edges in the created drug-target network, we identified a candidate GSZD-targeted signal axis that contained interactions between two putative GSZD targets [histone deacetylase 1 (HDAC1) and heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1)] and three known RA-related targets [NFKB2; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKBKB); and tumor necrosis factor-alpha (TNF-α)]. This signal axis could connect different functional modules that are significantly associated with various RA-related signaling pathways, including T/B cell receptor, Toll-like receptor, NF-kappa B and TNF pathways, as well as osteoclast differentiation. Furthermore, the therapeutic effects and putative molecular mechanisms of GSZD's actions on RA were experimentally validated in vitro and in vivo. CONCLUSIONS: GSZD may partially attenuate RA by reversing inflammation-immune system imbalance and regulating the HDAC1-HSP90AA1-NFKB2-IKBKB-TNF-α signaling axis.

[Small cell malignant tumors of bone: comparison between diagnosis using core needle biopsies and surgical specimens].

OBJECTIVE: To compare the pathologic diagnosis and immunohistochemistry of small cell malignant tumors (SCMT) of bone using both core needle biopsy and surgical specimen. METHODS: Seventy-seven cases of SCMT with core needle biopsies and surgical specimens available were respectively analyzed by histologic examination and immunohistochemical study, with literature review. RESULTS: The male-to-female ratio was 48:29. The age of the patients ranged from 6 to 73 years. The tumors studied included Ewing sarcoma/PNET (n = 38), myeloma (n = 23), lymphoma (n = 10), small cell osteosarcoma (n = 2), small cell carcinoma (n = 2) and mesenchymal chondrosarcoma (n = 2). The tumors involved limbs, axial skeleton and flat bones. Microscopically, the tumors shared similar histology, with small round cells and spindly cells arranged in diffuse sheets. The pathologic diagnosis by core needle biopsies correlated with that by surgical specimens in 84.4% (65/77) of the cases. CONCLUSIONS: SCMT represents a heterogeneous group of malignancy. Correlations with clinicoradiologic findings and application of ancillary investigations including immunohistochemistry and molecular study are important for definitive diagnosis. Pathologic diagnosis using core needle biopsies shows good results and provides useful information for surgical planning.

[Clinicopathologic features of primary osteosarcoma in elderly patients].

OBJECTIVE: To study the clinical manifestations, radiologic findings, pathologic diagnosis and differential diagnosis of primary osteosarcoma in elderly patients. METHODS: Twelve cases of primary osteosarcoma occurring in patients older than 60 years were encountered during the period from 1985 to 2010. The clinical manifestations, radiologic features and pathologic findings were studied and the follow-up data were analyzed. RESULTS: The sites of involvement included long bones (number = 7), ilium (number = 1), craniofacial bones (number = 2) and soft tissue (number = 2). Radiologic examination showed a mixture of osteosclerotic and osteolytic lesions in 10 patients, soft tissue lesions with high-density areas in 2 patients and soft tissue lesions with periosteal reaction in 8 patients. Histologically, most cases showed features of conventional osteosarcoma. There were 2 cases of malignant fibrous histiocytoma-like osteosarcoma, 2 cases of chondroblastic osteosarcoma and 1 case of well-differentiated intraosseous osteosarcoma. Immunohistochemical study played little role in pathologic diagnosis. Ten patients had undergone amputation, including one patient who had received adjuvant chemotherapy beforehand. Nine patients had follow-up information available. Three of them died of lung metastasis and 1 died of cardiovascular disease. CONCLUSIONS: Primary osteosarcoma rarely occurs in elderly patients and can easily be missed. Correlation with clinical, radiologic and histologic features is important for arriving at a correct diagnosis.

[Giant cell tumor of bone and malignancies in giant cell tumor: a clinicopathologic analysis].

OBJECTIVE: To study the clinicopathologic features, diagnosis and differential diagnosis of malignancies in giant cell tumor (MGCT). METHODS: The clinicopathologic features of 13 cases of MGCT were retrospectively reviewed. RESULTS: Thirteen cases of MGCT were found amongst a total of 603 cases of giant cell tumor encountered. Six of the 13 cases represented concurrent malignancy in giant cell tumor while the remaining 7 cases was malignant transformation in recurrent giant cell tumor. The age of the patients ranged from 21 to 71 years (mean age = 39.5 years) in the first group and from 27 to 52 years (mean age = 36.7 years) in the second group. In concurrent MGCT, a high-grade sarcoma component was present in conjunction with the giant cell tumor component. In malignant transformation of recurrent giant cell tumor, the original tumor was giant cell tumor and the recurrence showed features reminiscent of malignant fibrous histiocytoma. CONCLUSIONS: The diagnosis of malignancies in giant cell tumor requires correlation of clinical, radiologic and pathologic features. The entities need to be distinguished from other giant cell-rich tumors including primary malignant fibrous histiocytoma and giant cell osteosarcoma.

[Myositis ossificans: a clinicopathologic analysis of 15 cases].

OBJECTIVE: To study the clinicopathologic features, diagnosis and differential diagnosis of myositis ossificans (MO). METHODS: The clinical features, radiologic results and pathologic findings of 15 cases of MO (including biopsy and surgical specimens) were analyzed. The hematoxylin and eosin sections were reviewed under light microscope. Immunohistochemical staining for S-100 protein, vimentin, desmin, actin and osteonectin was performed. RESULTS: The age of the patients ranged from 12 to 46 years. The male-to-female ratio was 11:4. Thirteen cases were located in the parosteum of long bone or subperiosteal soft tissue. The remaining two cases occurred in iliac region and palm, respectively. Five patients had history of injury, while 2 patients had operation before. Four patients had no history of trauma and the remaining one had unknown clinical history. Histologically, zonation pattern was not conspicuous in 10 biopsy cases and 8 corresponding surgical specimens. On the other hand, zonation pattern was observed in 5 biopsy cases and 7 corresponding surgical specimens. Follow up revealed relapses in two patients. Immunohistochemical study showed various degree of positivity for vimentin, desmin, actin and osteonectin. S-100 protein was focally positive in 2 of the cases. The Ki-67 index varied from 1% to 10%. CONCLUSION: Correct diagnosis of MO relies on correlation of clinical features, radiologic examination and pathologic findings.