Two novel polymorphisms in PLCE1 are associated with the susceptibility to esophageal squamous cell carcinoma in Chinese population.

Esophageal cancer is the sixth leading cause of cancer-associated death worldwide. Phospholipase C epsilon 1 (PLCE1) gene was found to be associated with the risk of esophageal squamous cell carcinoma (ESCC) by three large-scale genome-wide association studies (GWAS) in Chinese populations. To evaluate the association between the single nucleotide polymorphisms (SNPs) in PLCE1 gene and ESCC risk, a case-control study including 550 patients with ESCC and 550 age, gender-matched controls was carried out to investigate the genetic susceptibility of three SNPs (rs3765524 C/T and two unreported potentially functional SNPs rs10882379 G/A and rs829232 G/A) as well as the interactions of gene-gene and gene-environment in the development of ESCC. And the results showed that GA genotype of rs10882379 was significantly associated with reduced ESCC risk compared with GG genotype (adjusted OR [95% CI]: 0.66 [0.51, 0.86]), while AA genotype of rs829232 was significantly associated with increased ESCC risk compared with GG genotype (adjusted OR [95% CI]: 1.37 [1.12, 1.67]). The haplotype analysis showed increased ESCC risk in Grs10882379Crs3765524Ars829232 and Grs10882379Trs3765524Ars829232 haplotypes with OR (95% CI) of 1.40 (1.13, 1.73) and 1.66 (1.18, 2.34), respectively and inversely reduced ESCC risk in Ars10882379Crs3765524Grs829232 haplotype with OR (95% CI) of 0.74 (0.61, 0.91). The gene-environment interaction analysis emerged a best model consisted of four factors (rs10882379, rs3765524, rs829232 and family history of ESCC) that could increase the ESCC risk in the 'high risk group' with 4.45-fold (OR [95% CI]: 5.45 [4.13, 7.19]), compared to the 'low risk group.' Our results further validate that the SNPs in PLCE1 gene may contribute to the ESCC susceptibility in Chinese Han population. Also the gene-gene and gene-environment interactions play a certain crucial role in the ESCC progression.

Solid freeform-fabricated scaffolds designed to carry multicellular mesenchymal stem cell spheroids for cartilage regeneration.

Three-dimensional (3D) cellular spheroids have recently emerged as a new trend to replace suspended single cells in modern cell-based therapies because of their greater regeneration capacities in vitro. They may lose the 3D structure during a change of microenvironment, which poses challenges to their translation in vivo. Besides, the conventional microporous scaffolds may have difficulty in accommodating these relatively large spheroids. Here we revealed a novel design of microenvironment for delivering and sustaining the 3D spheroids. Biodegradable scaffolds with macroporosity to accommodate mesenchymal stem cell (MSC) spheroids were made by solid freeform fabrication (SFF) from the solution of poly(D,L-lactide-co-glycolide). Their internal surface was modified with chitosan following air plasma treatment in order to preserve the morphology of the spheroids. It was demonstrated that human MSC spheroids loaded in SFF scaffolds produced a significantly larger amount of cartilage-associated extracellular matrix in vitro and in NOD/SCID mice compared to single cells in the same scaffolds. Implantation of MSC spheroid-loaded scaffolds into the chondral defects of rabbit knees showed superior cartilage regeneration. This study establishes new perspectives in designing the spheroid-sustaining microenvironment within a tissue engineering scaffold for in vivo applications.

Regulation of epidermal growth factor receptor signaling by plasmid-based microRNA-7 inhibits human malignant gliomas growth and metastasis in vivo.

MicroRNAs are endogenous, non-coding RNAs of approximately 20-22 nucleotides that regulate genes expression by binding to the 3' untranslated region (UTR) of targets mRNAs and play critical roles in cancer pathways. Malignant glioma is the most common and highly lethal central nervous system tumor for which little effective treatment is available over several decades. The purpose of this study was to explore the therapeutic potential of plasmid-based microRNA-7 (miR-7) for gliomas in vivo. Enhancing miR-7 levels in vitro could significantly induce cell apoptosis, and inhibit cell proliferation, cell migration and invasion. Western blotting analysis was performed, which indicated that miR-7 directly inhibited epidermal growth factor receptor (EGFR) and further antagonized the downstream protein kinases including ERK, Akt and Stat3. Furthermore, systemic administration of miR-7 encapsulated in cationic liposome resulted in glioma xenografts growth arrest and the metastatic nodules decrease effectively in a sequence-specific manner. In this study, miR-7 was applied in glioma treatment for the first time in vivo. Our findings suggested that the plasmid-mediated gene therapy with miR-7 appeared to be a promising candidate for the development of new antitumor and anti-metastasis treatment for human glioma.

[Accurate localization and successful treatment of 23 cases of migrating pharynx and cervical esophageal foreign bodies].

Objective: To explore clinical features, diagnosis, localization, and therapeutic strategy of migratory pharyngeal and cervical esophageal foreign bodies. Methods: A total 23 cases of pharyngeal and cervical esophageal migratory foreign bodies were admitted between January 2015 and December 2021. There were 14 females and 9 males with the age ranged from 35 to 82 (55.0±12.7)years. In all the cases, esophageal CT was taken to confirm the esophageal foreign body. Multiplanar reconstruction (MPR) was performed to locate the foreign body from the horizontal, coronal and sagittal dimensions as well as the corrected reconstructed MPR. According to the location of the foreign body, appropriate surgical method was selected.The symptoms, complications, types of foreign body, positioning, surgical methods, and relevant information were recorded.Data were analyzed using the descriptive method and SPSS 25.0 software. Results: The clinical symptoms of 23 migrating esophageal foreign bodies included pharyngodynia (20/23), foreign body sensation (6/23), hoarsenss (1/23), difficulty in turning neck(1/23), difficulty in opening mouth (1/23), fever (7/23), poor appetite (1/23), and abdominal pain (1/23). The foreign bodies included 19 fish bones, 2 wires, 1 embroidery needle and 1 chicken bone. There were 9 cases (39.1%) of foreign bodies located in extraluminal cervical esophagus, 2 cases (8.7%) of foreign bodies located in the muscular layer of the cervical esophagus and 12 cases (52.2%) of foreign bodies located in pharynx. Twenty-one cases of foreign bodies were removed by cervical lateral incision, in which 11 were removed by cervical lateral incision directly, 10 by the second lateral cervical incision after the foreign bodies were accurately located by MPR and/or corrected MPR, 1 foreign body was removed by incision of the pharyngeal mucosa under suspension laryngoscope, 1 foreign body was removed by tracheoscopy. Compared with patients with intraluminal foreign bodies (n=308) treated in the same period, intake of fishbone [19 (19/23) vs. 133 (82.6% (43.2%, 133/308), OR=7.31] and first visit was more than 24 hours [20(87.0%, 20/23) vs. 77(25.0%, 77/308),OR=17.2] were the significant risk factors of migratory esophageal foreign bodies. Conclusions: MPR and the corrected MPR can accurately locate the migrating pharyngeal and cervical esophageal foreign bodies, by providing more intuitive imaging evidence for doctors, which provide imaging basis for formulation of surgical programs. Foreign bodies in pharyngeal and cervical esophagus need to be treated as soon as possible, otherwise they are easy to migrate, leading lead to serious complications.

Os odontoideum: etiology, diagnosis, and management.

BACKGROUND: There have been few reports of os odontoideum since the initial description. METHODS: Forty-four patients with os odontoideum treated during the period 1980 through 1996 were reviewed. There were 33 males and 11 females. Their ages ranged from 7 to 56 years, with an average of 24.6 years. Five patients with no symptoms were treated conservatively. Thirty-nine patients underwent operative treatment including nine posterior atlantoaxial fusions and 33 occipitocervical fusions. RESULTS: The patients were followed up for one to 16 years, with an average of 6.5 years. Five patients treated conservatively have remained stable. All 39 treated patients achieved solid arthrodesis. The results were satisfactory. CONCLUSIONS: We conclude that fusion is indicated if atlantoaxial instability or clinical symptoms are significant, and that occipitocervical fusion should be considered in the operative management of os odontoideum if atlantoaxial arthrodesis is impossible.

Imaging diagnosis of cervical spine and spinal cord injuries in children.

OBJECTIVE: To provide the experience in imaging diagnosis of cervical spine and spinal cord injuries in children. METHODS: Imaging data of cervical spine and spinal cord injuries in 62 children were retrospectively reviewed. The routine radiography including the lateral, anteroposterior and open-mouth odontoid views were performed in all the patients. Tomography was available for 25 patients, and flexion-extension lateral views for 28 patients, CT scanning for 21 patients, MRI for 26 patients. RESULTS: Of these patients, 46 patients were identified with in juries of upper cervical spine (9 with atlantal arch fracture, seven with axial fracture, 21 with odontoid fracture, 1 with atlantal arch fracture combining with odontoid fracture, and 1 with atlantal transverse ligament disruption); 7 patients sustained injuries of lower cervical spine (3 fractures of vertebral body, 2 dislocations and 6 fracture-dislocations); 2 patients had multiple noncontiguous cervical injuries; and 3 had cervical spinal cord injury without radiographic abnormalities (SCIWORA). CONCLUSIONS: Imaging assessment is of great importance in the diagnosis of cervical spine and spinal cord injuries in children. Whenever cervical spine and spinal cord injuries are suspected for children patients, and the three-views should be routinely indicated. MRI should be routinely performed in all children with cervical SCIWORA.

[Os odontoideum].

Seventeen patients who had os odontoideum were reviewed. Among them occipito-cervical fusion was performed upon 12 patients with atlanto-axial instability. All of them achieved fusion. The patients were followed up for 2 to 16 years and satisfactory results were demonstrated. We consider that surgical treatment is indicated when os odontoideum is combined with atlanto-axial instability.

Targeting liposomal nanomedicine to cancer therapy.

Drug delivery systems (DDS) are designed to improve the pharmacological and therapeutic effect. In the past few decades, there are some problems that impeded applications of particulate DDS have been resolved, with several DDS formulations of anticancer now approved for clinical use. Liposomal nanoparticles (LNs) encapsulating therapeutic agents have been recognized as one of the most advanced classes of DDS. Liposomal nanoparticles (LNs) could encapsulate both conventional anticancer drugs and the new genetic drugs with several properties such as high drug-to-lipid ratio, excellent retention of drug and a long circulation lifetime. These excellent properties of LNs have the potentials to offer new treatments in area of cancer therapy. Here, we will discuss recent advances in this field involving conventional anticancer drugs as well as the new genetic drugs.

IL15 combined with Caspy2 provides enhanced therapeutic efficiency against murine malignant neoplasm growth and metastasis.

Interleukin-15 (IL15) is a potential immunotherapeutic treatment for cancer. Caspy2 is an active zebra caspase for inducing apoptosis and immune response in murine tumors. In this study, we aim to evaluate the potential of gene therapy using IL15 and Caspy2 against the murine tumors. Plasmid expressing both Caspy2 and IL15 genes was constructed, encapsulated in DOTAP/cholesterol cationic liposome and injected intratumorally into the mice bearing CT26, B16-F10 and 4T1 carcinoma. We found that coexpression of IL15 and Caspy2 could significant inhibit tumor growth and prolong survival of the mice bearing CT26 or B16F10 tumor. A significant reduction in spontaneous lung metastasis was observed in the 4T1 tumor model. In CT26 model, the mice treated with IL15 and Caspy2 acquired a long-time protective immunity against the parental tumor cell rechallenge. Cytotoxic T lymphocytes and terminal deoxynucleotidyltransferase-mediated nick end labelling assays showed that the combination of capsy2 and IL15 could enhance both the apoptosis and immune response induction, which may account for its extraordinary antitumor effect. Furthermore, we showed that the observed tumor suppression by IL15 and Caspy2 concurred with the Caspy2-mediated downregulation of IL10 and upregulation of interferon-γ and tumor necrosis factor-α. Our results therefore suggested that the combination regimen might be a novel and effective strategy for cancer treatment.

Effect of biomimetic remineralization on the dynamic nanomechanical properties of dentin hybrid layers.

The mineral and organic phases of mineralized dentin contribute co-operatively to its strength and toughness. This study tested the null hypothesis that there is no difference in nano-dynamic mechanical behavior (complex modulus-E*; loss modulus-E''; storage modulus-E'; in GPa) of dentin hybrid layers (baseline: E*, 3.86 ± 0.24; E'', 0.23 ± 0.05; E', 3.85 ± 0.24) created by an etch-and-rinse adhesive in the presence or absence of biomimetic remineralization after in vitro aging. Using scanning probe microscopy and nano-dynamic mechanical analysis, we demonstrated that biomimetic remineralization restored the nano-dynamic mechanical behavior of heavily remineralized, resin-sparse regions of dentin hybrid layers (E*, 19.73 ± 3.85; E'', 8.75 ± 3.97; E', 16.02 ± 2.58) to those of the mineralized dentin base (E*, 19.20 ± 2.42; E'', 6.57 ± 1.96; E', 17.39 ± 2.0) [p > 0.05]. Conversely, those resin-sparse, water-rich regions degraded in the absence of biomimetic remineralization, with significant decline [p < 0.05] in their complex and storage moduli (E*, 0.83 ± 0.35; E'', 0.88 ± 0.24; E', 0.62 ± 0.32). Intrafibrillar apatite deposition preserves the integrity of resin-sparse regions of hybrid layers by restoring their nanomechanical properties to those exhibited by mineralized dentin.

Biomimetic analogs for collagen biomineralization.

Inability of chemical phosphorylation of sodium trimetaphosphate to induce intrafibrillar mineralization of type I collagen may be due to the failure to incorporate a biomimetic analog to stabilize amorphous calcium phosphates (ACP) as nanoprecursors. This study investigated adsorption/desorption characteristics of hydrolyzed and pH-adjusted sodium trimetaphosphate (HPA-Na(3)P(3)O(9)) to collagen. Based on those results, a 5-minute treatment time with 2.8 wt% HPA-Na(3)P(3)O(9) was used in a single-layer reconstituted collagen model to confirm that both the ACP-stabilization analog and matrix phosphoprotein analog must be present for intrafibrillar mineralization. The results of that model were further validated by complete remineralization of phosphoric-acid-etched dentin treated with the matrix phosphoprotein analog and lined with a remineralizing lining composite, and with the ACP-stabilization analog supplied in simulated body fluid. An understanding of the basic processes involved in intrafibrillar mineralization of reconstituted collagen fibrils facilitates the design of novel tissue engineering materials for hard tissue repair and regeneration.

Surgical treatment of nonunited fractures of the odontoid process, with special reference to occipitocervical fusion for unreducible atlantoaxial subluxation or instability.

Fifty-seven consecutive patients treated surgically for nonunited fractures of the odontoid process were reviewed. All patients presented late, exhibiting neurological deficits subsequent to nonunion. Delay in presentation was between 6 and 120 months (mean 32 months) after the original injury, due to missed diagnosis or inappropriate management. Seven patients who were reduced in traction underwent a Gallie atlantoaxial fusion. In the remaining 50 patients who were unreducible, an occipitocervical arthrodesis was performed. They were followed up for a minimum of 2 years, except one who died from postoperative respiratory failure. All patients obtained a solid bony union, including two in whom nonunion occurred following atlantoaxial fusion, and occipitocervical fusion was added as a rescue. Thirty-eight patients achieved excellent neurological recovery, nine still had some disability, five retained their neurological deficits and two reported a deterioration. In two patients, a recurrence in a traumatic episode was experienced long after a resolution. Our findings demonstrate that occipitocervical arthrodesis is preferable for unreducible subluxation or instability of atlantoaxial articulation in nonunion of odontoid fractures.