Poor Curative Effect Research Articles

Research progress in the role of microRNA-155 in regulation of autophagy and diagnosis and treatment for gastric cancer

China is one of the regions with a high incidence of gastric cancer worldwide. Low detection rate and poor curative effect lead to unsatisfied prognosis and low five-year survival rate. Surgery combined with radiotherapy and chemotherapy is the mainstream comprehensive treatment scheme, however, multi-drug resistance may gradually prevail in the chemotherapy process. Chemotherapy, miRNA and autophagy interact with each other, but the mechanism is complex. MiR-155 is abnormally expressed in gastric cancer, which could promote autophagy, inhibit apoptosis, and interact with Helicobacter pylori to induce gastric cancer. Through its regulatory effect on autophagy, miR-155 can be used to treat gastric cancer, improve chemotherapy sensitivity and reverse drug resistance. The high expression of miR-155 in gastric cancer tissues suggests poor prognosis.

Stereoelectroencephalography-guided three-dimensional radiofrequency thermocoagulation for the treatment of drug-resistant epilepsy

Objective To investigate the safety and efficacy of stereoelectroencephalography (SEEG)-guided radiofrequency thermocoagulation (RF-TC) with three-dimensional lesioning in the treatment of drug-resistant epilepsy. Methods Forty-eight patients with drug-resistant epilepsy who underwent SEEG-guided RF-TC with three-dimensional ablation at Neurosurgery Department of Xuanwu Hospital Capital Medical University from July 2015 to December 2017 were retrospectively enrolled into this study. There were 22 cases of mesial temporal lobe epilepsy (MTLE), 9 cases of hypothalamic hamartoma, 5 cases of frontal lobe epilepsy, 4 cases of insular lobe epilepsy, 1 case of periventricular nodular heterotopia, 1 case of tuberous sclerosis and 6 cases of multi-focal epilepsy. The clinical efficacy was evaluated based on the Engel grading system and the relevant complications were documented. Results The follow-up duration was 5-35 months, with an average of 16.3±7.3 months. The overall outcome was Engel Ⅰ in 23 (47.9%) cases, Engel Ⅱ in 12 (25.0%), Engel Ⅲ in 11 (22.9%) and Engel Ⅳ in 2 (4.2%). There were 71.9% (23/32) of patients who were seizure free at 1 year follow-up. The outcome was better in MTLE and hypothalamic hamartoma epilepsies, with Engel grade Ⅰ ratio of 59.1% (13/22) and 5/9 respectively. Multi-focal epilepsies (Engel grade Ⅲ: 4 out of 6 cases), frontal lobe epilepsies (Engel grade Ⅲ: 1 out of 5), Engel grade Ⅳ: 2 out of 5) had relatively poor curative effect. Transient complications following thermocoagulation occurred in 7 (14.6%) cases and permanent complications in 1 (2.1%). Conclusions SEEG-guided RF-TC with three-dimensional lesioning is minimally invasive, safe and effective in the treatment of drug-refractory epilepsy. Compared with other types of epilepsies, MTLE and hypothalamic hamartoma epilepsies have relatively better efficacy and RF-TC can be a complementary treatment for resective surgery. Key words: Epilepsy; Stereoelectroencephalography; Radiofrequency thermocoagulation; Three-dimensional

Bone remodeling in patients with juvenile condylar resorption after stabilization splint treatment

Objective: To investigate bone remodeling in patients with different types of juvenile condylar resorption after stabilization splint treatment using cone-beam CT (CBCT). Methods: Fifty-nine juvenile condylar resorption patients (114 sides of condyle) treated with stabilization splint from January 2012 to May 2018 in Department of Temporomandibular Joint, Stomatological Hospital of Chongqing Medical University were selected as splint group, while twenty-four patients (48 sides of condyle) who underwent natural remodeling without stabilization splint treatment after 6-12 months were severed as control group. Pre-and post-treatment CBCT was taken for all patients. There were three types of condyles (including type Ⅰ, type Ⅱ and type Ⅲ) before treatment and four types of condyles (including progression, no changes, stable without new bone and remodeled with new bone) after treatment. Progression and no change were considered as poor curative effect, and stable without new bone and remodeled with new bone were considered to be effective. The vertical distance of the condylar height was measured and compared before and after treatment in the two groups. Results: Significant difference in treatment outcome was found in types Ⅰ and Ⅱ between the splint group and the control group (Z=-2.874, P=0.004; Z=-3.874, P=0.000), and no significant difference was found in type Ⅲ between the two groups (Z=-0.617, P=0.537). The difference of condylar progression percentage [splint group: 43% (15/35), control group: 80% (16/20)] was statistically significant between the two groups in type Ⅱ (χ(2)=7.139, P=0.011), and no significant difference was found in types Ⅰ and Ⅲ between the two groups (χ(2)=0.103, P=0.748; χ(2)=1.249, P=0.540). In two groups, the condylar height difference before and after treatment in type Ⅱ condylar resorption was statistically significant (P<0.05). Conclusions: Stabilization splint treatment was effective in patients with different types of juvenile condylar resorption, especially in type Ⅰ. However, it was difficult to reverse the height reduction of the condylar bone regardless of treatment.

Encapsulation of chloroquine and doxorubicin by MPEG-PLA to enhance anticancer effects by lysosomes inhibition in ovarian cancer.

PurposeAs the deadliest gynecological malignancy, ovarian cancer ranks as a major cause of disease-related deaths to women worldwide and is treated with transurethral resection or systemic chemotherapy. However, traditional chemotherapeutic drug in antitumor therapy has shown unavoidable limitations, such as poor curative effects, systemic toxicity and development of drug resistance, leading to failure of tumor inhibition and recurrence. This study aims to explore an innovative method to enhance the clinical efficiency of ovarian cancer.Materials and methodsUsing MTT assay, the cell viability was detected under different culture systems. Western blot was used to examine the expression of P-gp in doxorubicin-resistant and wild-type A2780/SKOV3 cells. We used confocal to examine the drug concentration under different culture conditions. Also, flow cytometry was used to detect the drug absorption at the determined time points under different culture systems. Using nude mice model, we evaluated the killing efficacy of chemotherapeutic drugs with or without nanoparticle encapsulation. ELISA was used to examine the levels of creatinine, alanine aminotransferase and aspartate aminotransferase in plasma.ResultsWe found that pretreatment of chloroquine (CQ) as chemosensitizer markedly enhanced the anticancer effects in ovarian cancer. We also provided evidence that CQ efficiently increase the pH value of lysosomes in tumor cells, leading to the reverse of drug sequestration induced by lysosomes. To further improve the pharmacokinetics profiles and avoid the systemic toxicity caused by chemotherapeutic agents, we encapsulated CQ and chemotherapeutic drugs by polymeric nanoparticles methoxy poly(ethylene glycol)-poly(l-lactic acid). Codelivery of CQ and chemotherapeutic agents by nanocarrier revealed enhanced anticancer effects compared with the free drug delivery by tail vein injection. More importantly, accumulated drugs, prolonged drug circulation and reduced organic damages were observed in nanoparticles delivery.ConclusionCodelivery of CQ and chemotherapeutic drugs by methoxy poly(ethylene glycol)-poly(l-lactic acid) could significantly improve the anticancer effects and might have important potency in clinical applications for ovarian cancer therapy.

Radiosensitizing effects of miR-18a-5p on lung cancer stem-like cells via downregulating both ATM and HIF-1α.

Lung cancer is one of the main causes of cancer mortality globally. Most patients received radiotherapy during the course of disease. However, radioresistance generally occurs in the majority of these patients, leading to poor curative effect, and the underlying mechanism remains unclear. In the present study, miR‐18a‐5p expression was downregulated in irradiated lung cancer cells. Overexpression of miR‐18a‐5p increased the radiosensitivity of lung cancer cells and inhibited the growth of A549 xenografts after radiation exposure. Dual luciferase report system and miR‐18a‐5p overexpression identified ataxia telangiectasia mutated (ATM) and hypoxia inducible factor 1 alpha (HIF‐1α) as the targets of miR‐18a‐5p. The mRNA and protein expressions of ATM and HIF‐1α were dramatically downregulated by miR‐18a‐5p in vitro and in vivo. Clinically, plasma miR‐18a‐5p expression was significantly higher in radiosensitive than in radioresistant group (P < .001). The cutoff value of miR‐18a‐5p >2.28 was obtained from receiver operating characteristic (ROC) curve. The objective response rate (ORR) was significantly higher in miR‐18a‐5p‐high group than in miR‐18a‐5p‐low group (P < .001). A tendency demonstrated that the median local progression‐free survival (PFS) from radiotherapy was longer in miR‐18a‐5p‐high than in miR‐18a‐5p‐low group (P = .082). The median overall survival (OS) from radiotherapy was numerically longer in miR‐18a‐5p‐high than in miR‐18a‐5p‐low group (P = .281). The sensitivity and specificity of plasma miR‐18a‐5p to predict radiosensitivity was 87% and 95%, respectively. Collectively, these results indicate that miR‐18a‐5p increases the radiosensitivity in lung cancer cells and CD133+ stem‐like cells via downregulating ATM and HIF‐1α expressions. Plasma miR‐18a‐5p would be an available indicator of radiosensitivity in lung cancer patients.

Progress of pancreatic tumor researches in the Pancreas 2018 of Johns Hopkins Hospital

Pancreatic malignant tumor with more complex diagnosis and treatment is one of digestive system tumors, especially pancreatic cancer (PC) continues to have high malignancy and poor curative effect and prognosis. conference is currently held every two years, and it is acknowledged as a distinguished gathering of the pancreatic tumor field through showing abundant leading-edge achievements. Authors summarized contents and features of the Pancreas 2018 conference sponsored by Johns Hopkins Hospital, and made some analyses based on translational medicine, evidence-based medicine, multidisciplinary team, new surgical technology and domestic teams′ harvests, meanwhile, they also will disseminate and share leading-edge information with domestic doctors, and provide new ideas for diagnosis and treatment of PC and basic and clinical researches. Key words: Pancreatic neoplasms; Translational medicine; Precision medicine; Immunotherapy; Multidisciplinary team; Diagnosis

Stem-Like Tumor Cells Involved in Heterogeneous Vasculogenesis in Breast Cancer: A Possible Reason for the Poor Curative Effects of Antiangiogenic Therapy

Background: Potent angiogenesis inhibitor Sorafenib has been proved invalid in breast cancer clinical trial due to its limited effects on heterogeneous vasculatures, but the mechanism remains unclear. Methods: Here we isolated ALDH1 and ALDH1- MDA-MB-231 cells by a FACS sorter and cultured them in a 3D matrix to examined tube formation ability. Triple-negative breast cancer (TNBC) tissues and xenograft animal model tissue paraffin sections were pretreated as for IHC. We also applied various molecular biological methods combining with cell model, animal model and patients’ tissue to approach to this question. Findings: We found that breast cancer stem-like cells (BCSLCs, ALDH1 cells) are involved in vascular mimicry and mosaic vessels in triple-negative breast cancer tissues. Further, only ALDH1 BCSLCs sorted from MDA-MB-231 could exhibit the tube formation and angiogenesis ability. Sorafenib could inhibit vascularization from endothelial cells rather than that from ALDH1 cells. α-SMA was identified as a key molecule in vascular formation of BCSLCs. Mechanistically, HIF-1α enhanced the mRNA and protein levels of α-SMA by binding to the HRE element in the promoter directly and meanwhile increased the BCSLCs population. Interestingly, Pigment Epithelium-Derived Factor (PEDF), could inhibit both endothelial cell-derived and tumor cell-derived angiogenesis by down-regulating HIF-1α in breast cancer. Interpretation: Our finding clarified the possible reason for the poor outcome of anti-angiogenesis therapy and PEDF may have the therapeutic potential. Funding Statement: This study was supported by National Nature Science Foundation of China, Grant Number: 81872165, 81572342, 81770808, 81471033, 81600641, 81370945, 81570871, 81570764,81701414,81871211,81502507; National Key Sci-Tech Special Project of China, Grant Number:2013ZX09102-053, 2015GKS-355; Key Project of Nature Science Foundation of Guangdong Province, China, Grant Number: 2015A030311043, 2016A030311035. Guangdong Natural Science Fund, Grant Number: 2014A020212023, 2014A030313073, 2015A030313029, 2015A030313103; Guangdong Science Technology Project, Grant Number: 2017A020215075; Initiate Research Funds for the Central Universities of China (Youth Program), Grant Number: 13ykpy06, 14ykpy05, 16ykpy24. Key Sci-tech Research Project of Guangzhou Municipality, China, Grant Number: 201508020033, 201510010052, 201707010084, 201803010017; Pearl River Nova Program of Guangzhou Municipality, China, Grant number: 201610010186; 2017 Milstein Medical Asian American Partnership Foundation Research Project Award in Translational Medicine. Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: This study was approved by the medical ethics committee of Sun Yat-sen University for Medical Sciences, Guangzhou.

Effect of treatment of infant parotid hemangioma with no response to oral propranolol

Hemangioma is the most common vascular tumor in infantile period, and propranolol is the first choice, but there are still a few patients with poor curative effect. Seven cases of infant parotid hemangioma with no response to oral propranolol were treated with transcatheter arterial sclerosing embolization combined with cortisol and satisfactory results achievod. The treatment and efficacy are disccused in this paper.

Clinical effect of montelukast sodium combined with inhaled corticosteroids in the treatment of OSAS children.

This study was designed to investigate the clinical effect of montelukast sodium combined with inhaled corticosteroids in the treatment of children with obstructive sleep apnea syndrome (OSAS).One hundred ninety-five children were enrolled and divided into 3 groups: groups A, B, and C; the group A (oral use of montelukast sodium), group B (nasal spray of mometasone furoate), and group C (oral use of montelukast sodium + nasal spray of mometasone furoate). Telephone questionnaire surveys were carried out. Polysomnography monitoring was performed and lateral x-ray radiographs of the cervical spine were taken before treatment and at 12 weeks after treatment. The improvement of clinical symptoms after treatment and its effective rate were analyzed. The difference in clinical characteristics between groups C1 and C2 was analyzed.In the 3 groups, clinical symptoms improved at 12 weeks after treatment compared with before (P < .05 or P < .01). Apnea-hypopnea index value decreased (P < .05) and minimal SaO2 increased (P < .05), while adenoidal/nasopharyngeal ratio was reduced (P < .05). Compared with groups A and B, group C had a shortened response duration of snoring, apnea, and restless sleep (P < .05). Differences in the response duration of buccal respiration and hyperhidrosis were not statistically significant (P > .05). The total effective rate was higher in group C than in A and B (P < .05), while the differences in all indices between groups A and B were not statistically significant (P > .05). The difference in the grade of the size of the tonsil between groups C1 and C2 was statistically significant (P < .05).The total effective rate of the combined treatment was higher than that of the single use of any of the 2 drugs, which allowed the rapid relief of symptoms. Drug treatment may have a poor curative effect in the treatment of OSAS patients with ≥ grade 3 tonsil hypertrophy.

Multivariate analysis of risk factors for patients with stage 4 neuroblastoma who were older than 18 months at diagnosis: a report from a single institute in Shanghai, China.

This retrospective study evaluated the long-term outcomes and prognostic indicators of patients with stage 4 neuroblastoma who were older than 18 months at diagnosis. The medical records of 118 such children who were treated at Shanghai Children's Medical Center, China, from June 1998-December 2013 were reviewed. Event-free survival (EFS) and overall survival (OS) were analyzed by log-rank tests. Of the 118 patients, 14 improving patients did not complete treatment because of parental decisions, and 1 patient died during surgery. Of the 103 patients who completed the comprehensive protocols, 60 (58.3%) achieved very good partial remission (VGPR), 26 (25.2%) achieved partial remission (PR) after four courses of chemotherapy, and 17 (16.5%) progressed during treatment. The response to induction (including VGPR + PR) was 83.5%. After a median follow-up of 105 months (range 36-160 months), the 5- and 10-year OS were 21 and 18%, and the EFS was 19 and 13%, respectively. EFS was significantly better for patients with normal levels of urinary vanillylmandelic acid (VMA) at diagnosis, who had complete resection of the primary tumor, who were minimal residual disease- (MRD-) negative in their bone marrow after four courses of chemotherapy, and who achieved VGPR at the end of treatment (P < 0.05). The prognosis remains poor for patients with stage 4 neuroblastoma who are older than 18 months at diagnosis. Elevated VMA level, incomplete tumor resection, persistent MRD in bone marrow, and poor curative effect are associated with worse prognosis.

Chronic fungal rhinosinusitis:clinical and pathologic characteristics of 40 case

Objective:To further improve diagnosis and treatment for chronic fungal rhinosinusitis(CFRS). Method:Forty patients with CFRS were treated with nasal endoscopic surgrey(ESS). The key-points of surgery were as follows: ①for single fungal sphenoid sinusitis, fracturing middle turbinate ourward or resecting one-third of posterior middle turbinate, enlarging the osseous ostium of sinus, removing sinus fungal ball and polypoid nucosa, and flipping mucosa of ostium inside sphenoid sinus to avoid narrow of ostium;②for fungal maxillary sinusitis, retaining uncinate process or resecting tail of uncinate process, enlarging ostium of maxillary sinus according to surgical field, and resecting lesion tissue;③for frontal-ethmoidal sinus lesion, routine treatment was performed; ④iodoform gauze packing the surgical cavity after soaking it with diluted iodine solution(1∶1) for 5 min. Result:Pathological examination indicated that 39 cases were infected with fungus(38 cases with aspergillus and 1 case with mucor, respectively), including 4 cases in which lesion mucosa was invaded by fungus. Of these 39 cases,34 cured after receiving one operation, 4 cases relapsed and finally cured after receiving re-operation or outpatient treatment, 1 case had concomitant sphenoid sinus fibroblastoma with skull base invaded and was remitted after radiation therapy. In addition,1 case was diagnosed clinically as allergic fungal sinusitis although no fungus was found by culture and pathological examination, and the disease was not still controlled completely after several times of recurrence. No complication was observed for all of the cases. Conclusion:ESS is an effective treatment for CFRS, and intraoperative multi-point biopsy may be ignored easily.Confirming whether mucosa of sinus is invaded by fungus as well as pathogenic fungi types will have an important value for postoperative further treatment and reduction of recurrence. Concomitant disease should be considered for the cases with poor curative effect.

Intrathecal Injection of Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorates Neuropathic Pain in Rats.

Neuropathic pain (NP) is a clinically incurable disease with miscellaneous causes, complicated mechanisms and available therapies show poor curative effect. Some recent studies have indicated that neuroinflammation plays a vital role in the occurrence and promotion of NP and anti-inflammatory therapy has the potential to relieve the pain. During the past decades, mesenchymal stem cells (MSCs) with properties of multipotentiality, low immunogenicity and anti-inflammatory activity have showed excellent therapeutic effects in cell therapy from animal models to clinical application, thus aroused great attention. However there are no reports about the effect of intrathecal human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on NP which is induced by peripheral nerve injury. Therefore, in this study, intrathecally transplanted HUC-MSCs were utilized to examine the effect on neuropathic pain induced by a rat model with spinal nerve ligation (SNL), so as to explore the possible mechanism of those effects. As shown in the results, the HUC-MSCs transplantation obviously ameliorated SNL-induced mechanical allodynia and thermal hyperalgesia, which was related to the inhibiting process of neuroinflammation, including the suppression of activated astrocytes and microglia, as well as the significant reduction of pro-inflammatory cytokines Interleukin-1β (IL-1β) and Interleukin -17A (IL-17A) and the up-regulation of anti-inflammatory cytokine Interleukin -10 (IL-10). Therefore, through the effect on glial cells, pro-inflammatory and anti-inflammatory cytokine, the targeting intrathecal HUC-MSCs may offer a novel treatment strategy for NP.

Prognosis of clinical treatment for fungal keratitis and its influence factors

Background Fungal keratitis has poor prognosis and high blinding rate, so it is vital to identify the risk factors that affect the treating outcome and prognosis of fungal keratitis. Objective This study was to evaluate the clinical outcome of fungal keratitis and identify the affecting factors. Methods This was a series cases-observational study.A total of 267 eyes of 267 patients with fungal keratitis were included in Henan Eye Institute during January 2013 to January 2014.Eye examinations were performed including slit-lamp microscope examination, corneal smears, confocal microscopy, fungal culture and identification.Combined anti-fungal drugs were topically used in all eyes for the initial treatment then the treating regimen were selected based on the susceptibility testing.corneal lesion resection combined with conjunctival flap transplantation, lamellar corneal transplantation or penetrating corneal transplantation was performed respectively on the patients with poor curative effect after drug treatment.The clinical prognosis of the patients was graded and the affecting factors for clinical outcome were evaluated.This study protocol complied with Helsinki Declaration and was approved by Ethic Committee of Henan Eye Hospital.Written informed consent was obtained from patients or guardians. Results One hundred and eighty-five eyes were cured by anti-fungal eye drops with the effective rate of 69.29%, and the inflammation was controlled in 60 eyes who received combination procedure of anti-fungal drugs with different surgeries, while 22 eyes lost visual function because of refractory glaucoma and final evisceration.The total clinical effective rate was 91.76%.Aspergillus and Fusarium spp. appeared to be the most common pathogenic fungi by drug sensitivity test.The keratitis caused by Aspergillus had lowest cure rate among different fungi (χ2=11.350, P=0.002) and the most poor clinical prognosis (H=31.285, P=0.013). The medication curative rate was 71.8% in the patients with positive culture outcome, which was higher than 62.5% in the patients with negative culture outcome (χ2=8.75, P<0.01). A significant difference was found in the medication curative rate and prognosis between the patients with ≥2 kinds of sensitive anti-fungal drugs and the patients with <2 kinds of sensitive anti-fungal drugs (77.5% versus 52.3%, χ2=9.63, P<0.01; H=24.281, P=0.021). Size of infiltration area, with or without hypopyon, number of sensitive drugs, and pathogenic fungi were significantly correlated with clinical outcome(all at P<0.05). Conclusions In vitro susceptibility testing can guide clinical drug treatment of fungal keratitis.Infiltration area >16 mm2, hypopyon >2 mm, resistance to those drugs in vitro and infection of Fusarium.spp or Aspergillus.spp are predictors of a poor outcome. Key words: Eye infections, fungal/therapy; Keratitis, fungal, Treatment outcome; Risk factors; Human

Association of endothelial progenitor cells and peptic ulcer treatment in patients with type 2 diabetes mellitus.

The present study aimed to investigate the association between endothelial progenitor cells (EPCs) and peptic ulcers in patients with or without type 2 diabetes mellitus (T2DM), in association with the efficiency of peptic ulcer treatment. The study recruited healthy subjects and peptic ulcer patients with or without T2DM. All the ulcer patients, including those with and without T2DM, were administered omeprazole for 8 weeks. Peptic ulcer patients with T2DM were additionally treated with glipizide and novolin. Blood samples were then obtained from the three groups following ulcer treatment. CD133+ cells were isolated from the blood samples using magnetic bead selection, and cultured in complete medium 199. Morphological and quantity changes in EPCs were observed by light and fluorescence microscopy. In addition, flow cytometric analysis was used to quantify the number of vascular endothelial cells. The treatment was partially effective in 7 of the 32 peptic ulcer patients without T2DM and 12 of the 32 peptic ulcer patients with T2DM. However, this treatment was ineffective in 20 of the 32 peptic ulcer patients with T2DM. Notably, 25 peptic ulcer patients without T2DM were defined as completely recovered following treatment. In addition, the number of circulating EPCs as well as their colony forming ability was significantly reduced (P<0.05) in the peptic ulcer patients with T2DM following ulcer treatment, compared with the other groups. Circulating EPC counts were significantly increased in peptic ulcer patients without T2DM, as compared with the healthy controls. With regards to colony formation, peptic ulcer patients without T2DM did not exhibit improved colony formation ability. In conclusion, the number of circulating EPCs and their colony-forming ability was significantly reduced in peptic ulcer patients with T2DM following ulcer treatment when compared with the other groups. This suggests that the poor curative effect of peptic ulcer treatment in these patients is associated with impairment of EPCs.

Research progress of diffusion-weighted magnetic resonance imaging in radiotherapy of pancreatic cancer

In recent years, the incidence of pancreatic cancer shows rising trend and higher mortality. Pancreatic cancer lacks early diagnostic methods with high sensitivity and specificity, and the surgical resection rate is 10 %-20 % with high operation mortality, poor long-term curative effect and less than 5 % survival rate within 5 years. At present, researchers indicate that radiotherapy can improve the quality of life, increase tumor local control rate and prolong the overall survival time of patients with pancreatic cancer in different levels. Diffusion weighted imaging (DWI), as a functional imaging technology of magnetic resonance imaging (MRI), is the only way to react cell levels. This paper will summarize the application of DWI in radiotherapy of pancreatic cancer. Key words: Pancreatic neoplasms; Diffusion magnetic resonance imaging; Apparent diffusion coefficient; Radiotherapy

CXCR4 Receptor Overexpression in Mesenchymal Stem Cells Facilitates Treatment of Acute Lung Injury in Rats

Novel therapeutic regimens for tissue renewal incorporate mesenchymal stem cells (MSCs) as they differentiate into a variety of cell types and are a stem cell type that is easy to harvest and to expand in vitro. However, surface chemokine receptors, such as CXCR4, which are involved in the mobilization of MSCs, are expressed only on the surface of a small proportion of MSCs, and the lack of CXCR4 expression may underlie the low efficiency of homing of MSCs toward tissue damage, which results in a poor curative effect. Here, a rat CXCR4 expressing lentiviral vector was constructed and introduced into MSCs freshly prepared from rat bone marrow. The influence of CXCR4 expression on migration, proliferation, differentiation, and paracrine effects of MSCs was examined in vitro. The in vivo properties of CXCR4-MSCs were also investigated in a model of acute lung injury in rats induced by lipopolysaccharide. Expression of CXCR4 in MSCs significantly enhanced the chemotactic and paracrine characteristics of the cells in vitro but did not affect self-renewal or differentiation into alveolar and vascular endothelial cells. In vivo, CXCR4 improved MSC homing and colonization of damaged lung tissue, and furthermore, the transplanted CXCR4-MSCs suppressed the development of acute lung injury in part by modulating levels of inflammatory molecules and the neutrophil count. These results indicated that efficient mobilization of MSCs to sites of tissue injury may be due to CXCR4, and therefore, increased expression of CXCR4 may improve their therapeutic potential in the treatment of diseases where tissue damage develops.

Long-term follow-ups of comprehensive therapies for stage 4 neuroblastoma

To evaluate the long-term outcomes of childhood stage 4 neuroblastoma (NB) and its correlative prognostic factors. Comprehensive protocols including tumor resection, intensive chemotherapy, radiotherapy, autologous bone marrow transplantation and 13-cis-retinoid were designed and implemented. A total of 112 newly diagnosed NB stage 4 patients at Shanghai Children's Medical Center collected from June 1998 to December 2010 were treated. Their clinical features, therapeutic efficacies, long-term outcomes and prognostic factors were analyzed. There were 69 males and 43 females with an age range of 4 months to 15 years. Among them, 12 improving patients didn't complete treatment because of parental decisions. Among those completing the comprehensive protocols, 62 cases (62.0%) achieved very good partial remission (VGPR), 20 (20.0%) achieved partial remission (PR) while another 18 (18.0%) progressed during treatment. The efficiency rate (including VGPR+PR) of treatment was 82.0 % (n = 82). The median follow-up period was 78 (56, 120) months. And 13 cases were lost after a median follow-up of 16 months. The 2, 3, 5-year event-free survival (EFS) was 56.2% (59/105) , 40.8% (40/98) and 21.1% (19/90) respectively. Age (>18 months), poor curative effect (achieving no VGPR at the end of treatment), elevated level of lactate dehydrogenase (LDH) (> 5 times normal value), bone marrow involvement and brain metastasis were poor prognostic factors (χ(2) = 12.01, 13.66, 6.29, 5.44, 16.18, all P < 0.05) . According to the multivariate estimates of hazards, age, high levels of LDH, poor curative effect and brain metastasis were associated with a worse survival (OR = 3.54, 1.89, 3.08, 3.45, all P < 0.05) . Brain metastasis predicted a worse outcome with 100% mortality rate (n = 6). Compared to traditional chemotherapy, topotecan-based chemotherapy could not improved the efficiency (52.6% (10/19) vs 63.2% (36/57) , P > 0.05) and long-term outcome (2 ys-EFS 42.1% (8/19) vs 56.4% (31/55) , P > 0.05). The prognosis remains poor for neuroblastoma of stage 4. Age (>18 months), poor curative effect (achieving no VGPR at the end of treatment), elevated LDH level (>5 times normal value) and bone marrow infiltration are associated with worse prognosis. Brain metastasis predicts the worst with 100% death rate. Topotecan included chemotherapy can not be proved more effective in this study.

A novel drug delivery gel of terbinafine hydrochloride with high penetration for external use

Context: Terbinafine hydrochloride is an antifungal drug for onychomycosis. Poor permeability of its external preparation leads to poor curative effect. Transfersomes, also known as flexible liposome, could improve transmission of drug for local external use. Terbinafine hydrochloride-loaded liposome is expected to become a breakthrough on the treatment of onychomycosis.Objective: This study is aimed to prepare high skin penetration terbinafine hydrochloride transfersomes with high encapsulation efficiency, appropriate drug loading and good stability.Materials and methods: Taking entrapment efficiency as the main indicator, the formulations and the processes of preparation were investigated. Transfersomes with different surfactants were prepared in the optimization processes, and the formulations were optimized through the transdermal test in vitro. As a result, a gel contained transfersomes was obtained with a brief evaluation. Its pharmacokinetic properties of going through the skin were studied by using the micro dialysis technology and liquid chromatography-mass spectrometry to assay the penetration behavior of terbinafine.Results: Mean particle size of the terbinafine hydrochloride transfersomes was 69.6 ± 1.23 nm, and the entrapment efficiency was 95.4% ± 0.51. The content of the gel was 4.45 ± 0.15 mg/g. The accumulated permeation of the transfersomes gel in 12 h was 88.52 ± 4.06 µg cm−2 and the intracutaneous drug detention was 94.38 ± 5.26 µg cm–2. The results of pharmacokinetic studies showed the Cmax and area under the curve (AUC) were apparently higher than the commercial cream.Discussion and conclusion: The terbinafine hydrochloride transfersomes was highly absorbed by the skin. The absorption rate was significantly higher than that of the commercial cream either in the transdermal test in vitro or in the pharmacokinetic studies in vivo.

Standardization and promotion of surgical treatment for obesity and type 2 diabetes mellitus

The curative effect of surgical treatment for obesity and type 2 diabetes mellitus has been internationally recognized.In mainland China,the number of the minimally invasive gastric volume reduction surgery has been increased from 110 cases in 2008 to 2000 cases in 2012.While some of the patients suffered from poor curative effects or severe postoperative complications due to lack of unified standard treatment guidelines.Authoritative statistical agencies and the Chinese clinical database has not been formed till now,therefore the specification and promotion of Chinese surgical treatment standards for obesity and type 2 diabetes mellitus is imperative. Key words: Obesity; Diabetes mellitus, type 2; Surgical procedures, operative ; Standards

Clinical observation on radiant shock wave in the treatment of postherpetic neuralgia

Objective To evaluate the effect of radiant shock wave therapy (RSWT) on postherpetic neuralgia. Methods Twenty-six cases of postherpetic neuralgia were treated with RSWT around the pain point. Before and after the treatment, Visual Analogue Scale (VAS) and Neuropathic Pain Scale (NPS) were used to assess the therapeutic efficacy. Results Twenty-two cases completed RSWT. Two patients who were inconvenient to the clinic and another 2 patients attributed to poor curative effect were transfered to other treatments. After one course of treatment, 22 patients all presented obvious pain relief. The VAS and NPS scores reduced from 8.41 ± 1.11 and 1.88 ± 0.59 to 6.15 ± 1.23 and 1.38 ± 0.60 respectively, and the differences were statistically significant (P = 0.000, for all). After completing two courses of treatment, VAS score reduced to 3.57 ± 1.30 and NPS score reduced to 1.04 ± 0.31 in comparison with pre⁃treatment, and both of the differences were statistically significant (P = 0.000, for all). Conclusion Radiant shock wave therapy may alleviate the pain of patients with postherpetic neuralgia, which is a valuable method for conservative treatment of postherpetic neuralgia.