PPIH acts as a potential predictive biomarker for patients with common solid tumors.

BACKGROUND: Our previous studies have indicated that mRNA and protein levels of PPIH are significantly upregulated in Hepatocellular Carcinoma (LIHC) and could act as predictive biomarkers for patients with LIHC. Nonetheless, the expression and implications of PPIH in the etiology and progression of common solid tumors have yet to be explored, including its potential as a serum tumor marker. METHODS: We employed bioinformatics analyses, augmented with clinical sample evaluations, to investigate the mRNA and protein expression and gene regulation networks of PPIH in various solid tumors. We also assessed the association between PPIH expression and overall survival (OS) in cancer patients using Kaplan-Meier analysis with TCGA database information. Furthermore, we evaluated the feasibility and diagnostic efficacy of PPIH as a serum marker by integrating serological studies with established clinical tumor markers. RESULTS: Through pan-cancer analysis, we found that the expression levels of PPIH mRNA in multiple tumors were significantly different from those in normal tissues. This study is the first to report that PPIH mRNA and protein levels are markedly elevated in LIHC, Colon adenocarcinoma (COAD), and Breast cancer (BC), and are associated with a worse prognosis in these cancer patients. Conversely, serum PPIH levels are decreased in patients with these tumors (LIHC, COAD, BC, gastric cancer), and when combined with traditional tumor markers, offer enhanced sensitivity and specificity for diagnosis. CONCLUSION: Our findings propose that PPIH may serve as a valuable predictive biomarker in tumor patients, and its secreted protein could be a potential serum marker, providing insights into the role of PPIH in cancer development and progression.

A preliminary metabolomics study of the database for biological samples of schizophrenia among Chinese ethnic minorities.

BACKGROUND: Schizophrenia (SCZ) is a profound mental disorder with a multifactorial etiology, including genetics, environmental factors, and demographic influences such as ethnicity and geography. Among these, the studies of SCZ also shows racial and regional differences. METHODS: We first established a database of biological samples for SCZ in China's ethnic minorities, followed by a serum metabolomic analysis of SCZ patients from various ethnic groups within the same region using the LC-HRMS platform. RESULTS: Analysis identified 47 metabolites associated with SCZ, with 46 showing significant differences between Miao and Han SCZ patients. These metabolites, primarily fatty acids, amino acids, benzene, and derivatives, are involved in fatty acid metabolism pathways. Notably, L-Carnitine, L-Cystine, Aspartylphenylalanine, and Methionine sulfoxide demonstrated greater diagnostic efficacy in Miao SCZ patients compared to Han SCZ patients. CONCLUSION: Preliminary findings suggest that there are differences in metabolic levels among SCZ patients of different ethnicities in the same region, offering insights for developing objective diagnostic or therapeutic monitoring strategies that incorporate ethnic considerations of SCZ.

A novel electrospun nanofiber system with PEGylated paclitaxel nanocrystals enhancing the transmucus permeability and in situ retention for an efficient cervicovaginal cancer therapy.

Overcoming the vaginal barrier to achieve sufficient drug penetration and retention is a huge obstacle for drug delivery in chemotherapeutics for cervical cancer. In this study, we investigate the feasibility of a novel composite nanocrystal/nanofiber system for improving the transmucus penetration and, thus, enhancing retention and drug delivery to the lesion of a cervicovaginal tumor. Herein, paclitaxel (PTX) was sequentially formulated in the form of nanocrystals, coated with polydopamine (PDA), and modified with PEG. The nanocrystals (NCs@PDA-PEG) were creatively fabricated to create a composite nanofibrous membrane (NCs@PDA-PEG NFs) by using an electrospinning technique. The morphology, size distribution, drug loading, encapsulation efficiency, X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectra, in vitro release, in vivo vaginal retention, apoptosis index, anti-tumor efficacy in a murine cervicovaginal tumor model, and local irritation were characterized. The NCs@PDA-PEG were formulated in a cube-like shape with an average size of 385.6 ± 35.47 nm; they were dispersed in electrospun nanofibers, and the drug loading was 7.94 %. The XRD curves indicated that the phase state of PTX changed after the creation of the nanocrystals. The FTIR spectra showed that the drug and the excipients were compatible with each other. In vitro delivery showed that the dissolution of PTX in the electrospun nanofibers was significantly faster than that when using bulk PTX. Compared with the PTX NC NFs, the NC@PDA-PEG NFs exhibited prolonged vaginal residence, superior transmucus penetration, minimal mucosal irritation, and significant tumor inhibition efficacy after the intravaginal administration of the NFs in tumor-bearing mice. In conclusion, by acting as novel pharmaceutical repositories, NCs@PDA-PEG NFs can be promising candidates for non-invasive local treatment, leading to efficient tumor inhibition in cervicovaginal cancer.

Fluorescence wavelength shifts combined with light scattering for ratiometric sensing of chloride in the serum based on CsPbBr3@SiO2 perovskite nanocrystal composite halide exchanges.

A traditional fluorescence-scattering intensity based ratiometric sensing system utilizes both inherent scattering and fluorescence intensity and has drawn extensive attention owing to its simplicity and self-calibration properties. In this work, we propose a novel ratiometric fluorescence sensing system that combines a fluorescence wavelength shift and scattering in a single window, using second-order scattering (SOS) as the representative scattering signal based on the halide exchange of CsPbBr3@SiO2 perovskite nanocrystal composites. We observe a fast halide exchange within 10 seconds, resulting in an identifiable fluorescence wavelength blue shift, while the scattering wavelength remains relatively constant for self-correction. This system could be applied for ratiometric sensing of Cl- in the serum without any sample treatment. The established wavelength-based ratiometric system demonstrates high reliability and reproducibility, paving a new way for fluorescence sensing.

[Corrigendum] HIF-1α contributes to tube malformation of human lymphatic endothelial cells by upregulating VEGFR-3.

Subsequently to the publication of the above article, the authors have realized that Fig. 4 on p. 145 (showing the results from the colony formation assay) was published containing erroneous images in Fig. 4C. Essentially, incorrect images were selected to represent the negative control (NC) experiments owing to an altered shooting angle and incorrect naming of the files. The corrected version of Fig. 4, now showing the correct data for the NC experiments in Fig. 4C, is shown on the next page. The authors confirm that the error made in the presentation of Fig. 4 did not adversely affect either the results or the conclusions reported in this paper, and they are grateful to the Editor of International Journal of Oncology for granting them this opportunity to publish a Corrigendum. They also apologise to the readership for any inconvenience caused. [International Journal of Oncology 54: 139-151, 2019; DOI: 10.3892/ijo.2018.4623].

Management of Macrocystic Lymphatic Malformation in the Cervicofacial Region: Ultrasound-Guided Iodine Tincture Cauterization Combined With Intralesional Negative Pressure.

PURPOSE: The purpose of our study was to evaluate the efficacy and safety of ultrasound-guided iodine tincture cauterization combined with postoperative intralesional negative pressure in the management of cervicofacial cystic lymphatic malformation (cLM). METHOD: From January 2019 to July 2021, indocyanine green lymphography was performed preoperatively to confirm the lymph inflow, and this treatment was administered in 71 patients with cervicofacial cLM in our center. All cases were evaluated by curative effects, treatment frequency, and adverse events. The duration of posttreatment follow-up was from 12 to 14 months. RESULTS: Indocyanine green lymphography indicated at least one lymphatic inflow in each cLM lesion. Excellent resolution was observed in 87.3% of cases, and good improvement of the treated cLM occurred in 9.9% of cases, and 2 cases with fair outcomes required subsequent treatment. It is noteworthy that no case was treated more than 3 times. Some minor adverse effects, including localized itch and scar, were managed by symptomatic treatment. CONCLUSIONS: Because of satisfactory outcomes and low treatment frequency, ultrasound-guided iodine tincture cauterization combined with intralesional negative pressure represents an efficacious, safe, and feasible method for the management of macro-cLM in the cervicofacial region.

Intermittent Administration Regimen of Sirolimus for Refractory Cervicofacial Lymphatic Malformation.

BACKGROUND: The cervicofacial lymphatic malformations (LMs) often have poor outcomes due to their microcystic component and diffuse infiltration. Mostly, traditional treatments are inadequate for these refractory cases. Recent researches have shown that sirolimus is effective in the treatment of complicated LMs, however, there is still no standard strategy. OBJECTIVE: To evaluate the efficacy and safety of intermittent oral sirolimus in treating refractory cervicofacial LMs as a second-line treatment. METHODS: Fifteen pediatric patients of refractory cervicofacial LMs were retrospectively analyzed in this study. All the cases had received traditional therapy before, but could not completely control the symptoms and eliminate lesions. As a remedy, sirolimus was then proceeded with an intermittent administration regimen, that is 3 continuous months as a course and started the next course after 1 month interval. The clinical characteristics, imaging data of patients, the changes in the signs and symptoms observed, and associated adverse effects were collected and analyzed. RESULTS: The patients initiated sirolimus therapy at the average age of 2.3 years (range 28 days-8 years 9 months). At the end point of the study, 2 patients remained on sirolimus in continuous courses of treatment. Of 13 patients who withdrawn therapy, 4 had restarted due to recurrence of symptoms and re-expansion of LMs. All patients demonstrated reduction in residual LMs and complete disappearance of symptoms during treatment, and 2 patients with complete resolution on imaging. Toxicity was tolerant in this series. There was no patient develop opportunistic or systemic bacterial infection. CONCLUSIONS: Sirolimus is commended as a second-line treatment to treat intractable cervicofacial LMs after failure of traditional therapy. The intermittent administration regimen is efficacious to completely control symptoms and partially reduce residual lesions with good tolerance and limited side effects.

Testing the circulation of expanded flaps-prevention of necrosis of expanded flaps (a clinic study).

Background: Expanded flaps are commonly used in plastic surgery. Although expanded flaps are more resistant to hypoxia than unexpanded flaps, flap necrosis can sometimes occur, particularly with skin incisions of regular proportion. Distal skin necrosis of the expansion flap can be avoided by careful design; however, the utilization rate of the expansion flap decreases. Consequently, successfully avoiding distal skin flap necrosis remains a challenge. In this study, we designed a device for testing the circulation of the expanded flap that can decrease the risk of expanded flap necrosis, thus maximizing the use of an expanded flap. Methods: A total of 128 patients who underwent surgical repair between 2011 and 2019 and were retrospectively examined with the device for testing the circulation of the expanded flap were included in the study. The procedure included (1) making a device for testing the circulation, (2) implanting a skin expander, (3) injecting normal saline into the skin expander, (4) testing the circulation of the expanded flap, and (5) transferring the expanded flap to repair the defect. Results: One hundred forty-eight expanded flaps were implanted in 128 patients. The expanded flap that was transferred to repair the defect had no necrosis or infection. None of the expanded flaps with separated blood supply, which could be observed during operations, revealed complications. The survival rates of the expanded flap were increased by testing the circulation of the expanded flap. Expanded flaps designed by this method showed no swelling or paleness and no obvious temperature changes. In addition, the length-to-width ratio could be extended to 3:1. Conclusions: Our proposed method resulted in an effective surgical procedure for the repair of tissue defects. This approach could effectively change the direction of the blood vessel of the expanded skin flap and prevent necrosis of the expanded flap, thus representing a practical way to increase the use of expanded flaps and the flap survival rate, making the whole expanded flap transfer procedure more convenient.

Sorafenib Nanomicelles Effectively Shrink Tumors by Vaginal Administration for Preoperative Chemotherapy of Cervical Cancer.

To investigate the potential of sorafenib (SF) in preoperative chemotherapy for cervical cancer to reduce tumor volume, sorafenib micelles (SF micelles) with good stability and high drug loading were designed. SF micelles were prepared by film hydration followed by the ultrasonic method. The results showed that the SF micelles were spherical with an average particle size of 67.18 ± 0.66 nm (PDI 0.17 ± 0.01), a considerable drug loading of 15.9 ± 0.46% (w/w%) and satisfactory stability in buffers containing plasma or not for at least 2 days. In vitro release showed that SF was gradually released from SF micelles and almost completely released on the third day. The results of in vitro cellular intake, cytotoxicity and proliferation of cervical cancer cell TC-1 showed that SF micelles were superior to sorafenib (Free SF). For intravaginal administration, SF micelles were dispersed in HPMC (SF micelles/HPMC), showed good viscosity sustained-release profiles in vitro and exhibited extended residence in intravaginal in vivo. Compared with SF micelles dispersed in N.S. (SF micelles/N.S.), SF micelles/HPMC significantly reduced tumor size with a tumor weight inhibition rate of 73%. The results suggested that SF micelles had good potential for preoperative tumor shrinkage and improving the quality life of patients.

Coaxial Electrospun PLLA Fibers Modified with Water-Soluble Materials for Oligodendrocyte Myelination.

Myelin sheaths are essential in maintaining the integrity of axons. Development of the platform for in vitro myelination would be especially useful for demyelinating disease modeling and drug screening. In this study, a fiber scaffold with a core-shell structure was prepared in one step by the coaxial electrospinning method. A high-molecular-weight polymer poly-L-lactic acid (PLLA) was used as the core, while the shell was a natural polymer material such as hyaluronic acid (HA), sodium alginate (SA), or chitosan (CS). The morphology, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), contact angle, viability assay, and in vitro myelination by oligodendrocytes were characterized. The results showed that such fibers are bead-free and continuous, with an average size from 294 ± 53 to 390 ± 54 nm. The DSC and FTIR curves indicated no changes in the phase state of coaxial brackets. Hyaluronic acid/PLLA coaxial fibers had the minimum contact angle (53.1° ± 0.24°). Myelin sheaths were wrapped around a coaxial electrospun scaffold modified with water-soluble materials after a 14-day incubation. All results suggest that such a scaffold prepared by coaxial electrospinning potentially provides a novel platform for oligodendrocyte myelination.

Sequential Release of Paclitaxel and Imatinib from Core-Shell Microparticles Prepared by Coaxial Electrospray for Vaginal Therapy of Cervical Cancer.

To optimize the anti-tumor efficacy of combination therapy with paclitaxel (PTX) and imatinib (IMN), we used coaxial electrospray to prepare sequential-release core-shell microparticles composed of a PTX-loaded sodium hyaluronate outer layer and an IMN-loaded PLGA core. The morphology, size distribution, drug loading, differential scanning calorimetry (DSC), Fourier transform infrared spectra (FTIR), in vitro release, PLGA degradation, cellular growth inhibition, in vivo vaginal retention, anti-tumor efficacy, and local irritation in a murine orthotopic cervicovaginal tumor model after vaginal administration were characterized. The results show that such core-shell microparticles were of spherical appearance, with an average size of 14.65 µm and a significant drug-loading ratio (2.36% for PTX, 19.5% for IMN, w/w), which might benefit cytotoxicity against cervical-cancer-related TC-1 cells. The DSC curves indicate changes in the phase state of PTX and IMN after encapsulation in microparticles. The FTIR spectra show that drug and excipients are compatible with each other. The release profiles show sequential characteristics in that PTX was almost completely released in 1 h and IMN was continuously released for 7 days. These core-shell microparticles showed synergistic inhibition in the growth of TC-1 cells. Such microparticles exhibited prolonged intravaginal residence, a >90% tumor inhibitory rate, and minimal mucosal irritation after intravaginal administration. All results suggest that such microparticles potentially provide a non-invasive local chemotherapeutic delivery system for the treatment of cervical cancer by the sequential release of PTX and IMN.

Enhanced mucosal penetration and efficient inhibition efficacy against cervical cancer of PEGylated docetaxel nanocrystals by TAT modification.

To investigate the potential of cell penetrating peptide (CPP) modification on nanomedicine for improving mucosal penetration and effective therapy of cervical cancer, docetaxel nanocrystals modified with trans-activator of transcription (TAT) peptide were designed for treatment of cervical cancer via vaginal administration. Docetaxel nanocrystals were coated by polymerization of dopamine to form polydopamine (PDA) coating which facilitated TAT modification and PEGylation for less mucus entrapment to get PEGylated nanocrystals modified with TAT (NC@PDA-PEG-TAT). Enhanced cellular drug uptake and cytotoxicity of NC@PDA-PEG-TAT was observed in cervical cancer-related TC-1 cells than that of PEGylated nanocrystals (NC@PDA-PEG). Intravaginally administered NC@PDA-PEG-TAT dispersed in poloxamer 407-based thermosensitive gel exhibited prolonged in vivo intravaginal retention, deeper mucosal penetration and more potent inhibition on the growth of murine orthotopic cervical cancer than NC@PDA-PEG, PDA-coated nanocrystals or unmodified nanocrystals. All data suggested the significance of CPP-modification on nanocrystals in the local treatment of vaginal mucosa-related diseases by vaginal administration.

Carnosine suppresses human glioma cells under normoxic and hypoxic conditions partly via inhibiting glutamine metabolism.

L-Carnosine (ß-alanyl-L-histidine) is a naturally occurring dipeptide, which has shown broad-spectrum anticancer activity. But the anticancer mechanisms and regulators remain unknown. In this study, we investigated the effects of carnosine on human glioma U87 and U251 cell lines under normoxia (21% O2) and hypoxia (1% O2). We showed that carnosine (25-75 mM) dose-dependently inhibited the proliferation of the glioma cells; carnosine (50 mM) inhibited their colony formation, migration, and invasion capacity. But there was no significant difference in the inhibitory effects of carnosine under normoxia and hypoxia. Treatment with carnosine (50 mM) significantly decreased the expression of glutamine synthetase (GS) at the translation level rather than the transcription level in U87 and U251 cells, both under normoxia and hypoxia. Furthermore, the silencing of GS gene with shRNA and glutamine (Gln) deprivation significantly suppressed the growth, migratory, and invasive potential of the glioma cells. The inhibitory effect of carnosine on U87 and U251 cells was partly achieved by inhibiting the Gln metabolism pathway. Carnosine reduced the expression of GS in U87 and U251 cells by promoting the degradation of GS through the proteasome pathway, shortening the protein half-life, and reducing its stability. Given that targeting tumor metabolism is a proven efficient therapeutic tactic, our results may present new treatment strategies and drugs for improving the prognosis of gliomas.

Synergistic Antitumor Effects on Drug-Resistant Breast Cancer of Paclitaxel/Lapatinib Composite Nanocrystals.

Drug resistance presents serious difficulties for cancer treatment. A combination of paclitaxel (PTX) and lapatinib (LAPA) shows potentials in multiple drug resistant cancers in the clinic, but it is almost impossible to deliver these two drugs to the tumor at the same time with the best proportion by simple co-administration of the respective current formualtions for their different pharmacokinetic profiles. Here composite nanocrystals of PTX and LAPA (cNC) were designed with a ratio of 2:1 (w/w), which was their intracellular ratio at the best synergistic efficacy on a drug-resistant cancer cell line (MCF-7/ADR). Such cNC were prepared using a bottom-up method to achieve a nearly spherical appearance and a narrow size distribution of 95.1 ± 2.1 nm. For nanocrystal stabilization, Polyethylene glycol (PEG) coating was introduced into the cNC via polydopamine (PDA) coating in order to get a PEGylated composite nanocrystal (cNC@PDA-PEG) with nanoscale size (170.5 ± 1.4 nm), considerable drug loading (PTX: 21.33 ± 1.48%, LAPA: 10.95 ± 1.24%) and good stability for at least 4 days in plasma-containing buffers. Differential scanning calorimeter (DSC) and XRD data both indicated the different crystalline states of the cNC as well as the cNC@PDA-PEG in comparison with bulk drugs. In vitro release data showed that PTX and LAPA were gradually and completely released from cNC@PDA-PEG in 3 days, while drug release from bulk drugs or cNC was only 30%. cNC@PDA-PEG also showed negligible hemolysis in vitro. Cellular uptake experiments in the MCF-7/ADR cell line showed that the nanocrystals entered the cells in a complete form through endocytosis and then released the drug in the cell. cNC@PDA-PEG inhibits the growth of this drug-resistant cell more effectively than the unmodified version (cNC). In summary, PEGylated PTX and LAPA composite nanocrystals showed the potential for treament of drug-resistant tumors by simultaneously delivering two drugs to tumor cells with the best proportion.

HIF-1α contributes to tube malformation of human lymphatic endothelial cells by upregulating VEGFR-3.

Hypoxia­inducible factor­1α (HIF­1α) is upregulated in various tumors and associated with lymphangiogenesis and angiogenesis during tumor development and metastasis. However, the role of HIF­1α in cystic lymphatic malformations (cLM) remains unclear. In the present study, expression of HIF­1α and vascular endothelial growth factor receptor 3 (VEGFR­3) was evaluated in 20 pairs of cLM specimens from patients who accepted curative surgery at Children's Hospital of Nanjing Medical University (Nanjing, China). Additionally, a stable HIF­1α­overexpressing human lymphatic endothelial cell (HLEC) line was established. Overexpression and silencing of HIF­1α were used to investigate the biological role in colony formation, migration and lymphatic tube formation. HIF­1α and VEGFR­3 were upregulated in cLM specimens compared with adjacent normal tissues. In addition, HIF­1α effectively induced HLEC colony formation and migration. Furthermore, lymphatic malformation of HLECs was promoted in vitro by overexpression of HIF­1α. HIF­1α overexpression upregulated VEGFR­3 during lymphangiogenesis. Additionally, expression of lymphatic endothelial markers prospero homeobox protein 1 and lymphatic vessel endothelial hyaluronan receptor 1 increased significantly during lymphatic tube malformation. The presented data demonstrated that HIF­1α overexpression in HLECs promoted colony formation, migration and tube malformation via upregulation of VEGFR­3. These findings may assist in the development of HIF­1α­targeted cLM therapeutics in the future.

The adipogenesis in infantile hemangioma and the expression of adipogenic-related genes.

Infantile hemangioma, a common benign tumor of infancy, grows quickly in six months to one year after birth, then slowly involutes into fibrofatty tissue childhood. In this study, we observed the adipogenesis in hemangioma and investigated the expression of adipogenic differentiation-related genes. 33 fresh resected hemangioma samples were collected, including 18 proliferating cases (less than one year old), 9 involuting cases (from one to five years old), and 6 involuted cases (more than five years old). The pathological evolution of hemangioma was observed by H-E staining. The expression of Perilipin A was showed by immunohistochemistry staining. The expression and location of PPAR-γ (a key transcription factor in adipogenesis) was displayed by Immunofluorescence staining, with the co-staining of α-SMA and CD31. The expression of adipose differentiation-related genes including PPAR-γ2, LPL, CEBPA, and Perilipin A was detected by Quantitative real time PCR. The results of H-E and Immunohistochemical staining showed the increase of adipose cells as hemangioma developed from the proliferative phase to involuting phase and later to involuted phase. Immunofluorescence staining showed that PPAR-γ wa expressed in the perivascular cells in hemangioma. Quantitative PCR analysis showed a significant increase of PPAR-γ2, LPL, CEBPA and Perilipin A genes' expression in the involuting and involuted heangioma. In conclusion, the PPAR-γ(+) perivascular cells (specific mesenchymal stem cells or pericytes) contribute to the adipogenesis in hemangioma. The siginificantly increased expression of adipogenic differentiation-related genes in the involuting and involuted phase suggested that they played a role in the adipogenesis in hemangioma.

[Management for lymphatic malformation in infants: a single center experience].

Objective: To assess the therapeutic effect of management for lymphatic malformation (LM) in infants. Methods: This retrospective study recruited clinical data of 996 patients with LM from June 2004 to July 2015 in our center. All patients were diagnosed as LM after ultrasound, CT or MR scan. All patients were divided into Group 1 (427 patients, treated by endoscopic LM partial resection combined with cautery and postoperative intratumoral negative pressure and absolute ethyl alcohol),Group 2 (239 patients, treated by combined pinyangmycin and dexamethasone injection),Group 3 (330 patients, treated by surgical resection only).The clinical effects were observed in three groups, and therapeutic effect differences in gender, age, maximum diameter, location, range, histological typing, lymph property and treatments were analysed in cervicofacial LM. Results: Group 1:333 patients were cured (78.0％),Group 2:165 patients were cured (69.0％),Group 3:238 patients were cured (72.1％).The difference in cure rate between Group 1 and Group 2 or between Group 1 and Group 3 was significant(P ＜0.05).The number of patients with ≥ 2 treatments in Group 3 was significantly less than that in other two groups. The cure rate of LM in cervicofacial area was significantly lower than that in other parts of body (P ＜ 0.05).In cervicofacial LM patients, the therapeutic effect differences in maximum diameter, range, histological typing, lymph property were statistically significant (P ＜ 0.05).At the multivariable logistic regression analysis, LM range as well as histological typing were independent factors influencing the therapeutic effect (P ＜ 0.05). Conclusions: Both treatment of endoscopic LM partial resection combined with cautery and postoperative intratumoral negative pressure and absolute ethyl alcohol, and surgical resection have good therapeutic effect on LM in infants. LM range as well as histological typing are important factors independently influencing the therapeutic effect of cervicofacial LM in infants.

Over-expression of PPAR-γ2 gene enhances the adipogenic differentiation of hemangioma-derived mesenchymal stem cells in vitro and in vivo.

BACKGROUND: Most of infantile hemangiomas involute into fibrofatty tissue in childhood, which indicates adipogenesis during this period. Mesenchymal stem cells (MSCs) contribute to the adipogenesis in IH. In this study, we investigated the effects of overexpression of PPAR-γ2 gene on the adipogenic differentiation of Hemangioma-derived MSCs (Hem-MSCs), and discussed the possibility of targeted therapy via PPAR-γ pathway. METHODS: MSCs were isolated from proliferating hemangioma by their selective adhesion to plastic culture dishes. Recombinant lentivirus with PPAR-γ2 gene were prepared, and used to transfect Hem-MSCs. Transfected cells were cultured in adipogenic medium to observe the differentiation in vitro. And the cells were mixed with Matrigel, then subcutaneously injected into the back of nude mice to observe the differentiation in vivo. RESULTS: In the in vitro tests, Hem-MSCs with overexpression of PPAR-γ2 gene showed enhanced adipogenic differentiation with increased expression of adipogenic-related genes, including PPAR-γ2, ADD1, LPL, and CEBPA genes. In the in vivo tests, Hem-MSCs/Matrigel plugs with overexpression of PPAR-γ2 gene also showed accelerated adipogenesis and time-phased changes of above genes. CONCLUSIONS: Overexpression of PPAR-γ2 gene enhances and accelerates the adipogenic differentiation of Hem-MSCs in vitro and in vivo. The results may provide the preliminary evidences for the targeted therapy of IH via PPAR-γ signal pathway.

[Clinical study of radiofrequency ablation combined with lauromacrogol for the treatment of parotid gland hemangioma in infants].

Objective: To investigate the clinical effect of radiofrequency ablation (RFA) combined with lauromacrogol for the treatment of parotid gland hemangioma in infants. Methods: From Sep.2005 to Dec.2014,a total of 117 patients with parotid gland hemangioma were divided into observation group (n =32),control group 1 (n =30),control group 2 (n =28) and control group 3 (n =27).The observation group was treated by RFA combined with lauromacrogol, while the control group 1 was treated by RFA only, the control group 2 was treated by pingyangmycin only, and the control group 3 received additional pingyangmycin based on RFA. All the patients were followed up for 6 to 24 months, and the clinical effects were observed in four groups. Results: Control group 1:16 patients were cured (53.3％),and the number of patients with ≥2 treatments was 9.There was 1 case with skin ulceration,1 with abdominal discomfort,1 with liver function damage and 1 with high fever.Control group 2:17 patients were cured(60.7％),and number of patients with ≥2 treatments was 12.There were 3 cases with skin ulceration,9 with abdominal discomfort,6 with liver function damage and 5 with high fever.Control group 3:21 patients were cured(77.8％),and number of patients with ≥2 treatments was 2.There were 2 cases with skin ulceration,6 with abdominal discomfort,4 with liver function damage and 4 with high fever.However,in observation group,25 patients were cured(78.1％) and number of patients with ≥ 2 treatments was 4,which were significantly different from that in control group 1 or control group 2 (P ＜0.05).And the difference in postoperative adverse reactions between observation group and control group 2 or control group 3 was also of significance (2 with skin ulceration,1 with abdominal discomfort,1 with liver function damage and 6 with high fever,P ＜ 0.05). Conclusions: Combined RFA and lauromacrogol has a good therapeutic effect on parotid gland hemangioma with relatively low adverse effect, so it deserves to be suggested and applied in clinical practice.

Piezosurgical Suturectomy and Sutural Distraction Osteogenesis for the Treatment of Unilateral Coronal Synostosis.

Different surgical procedures are used for the treatment of synostosis. Among them, suturectomy and sutural distraction osteogenesis (SDO) are suitable for young infant patients. In this report, we present the case of a young infant patient with a clear synostosis of the left coronal suture, which was treated by piezoelectric suturectomy combined with SDO and 2 internal distractors. One-year follow-up showed good results. Thirty-six months after surgery, normal skull growth and shape were observed by 3D computed tomographic examination. No infection, bleeding, fistula, and other complications were observed. The results suggested that the treatment of unilateral coronal synostosis in young infant patient by piezosurgical suturectomy and SDO is to be preferred because of its simplicity and relatively minimal invasiveness.