Objective: To investigate the effects of nicotine on the morphology, structure of offspring's dental germ, enamel organ and other dental tissues and the further potential epigenetic mechanisms by establishing prenatal nicotine exposure mouse model. Methods: Ten C57BL/6 pregnant mice were randomly divided into control group (physiological saline subcutaneous injection) and prenatal nicotine exposure (PNE) group (nicotine subcutaneous injection) by using a random number table. Postnatal day 0 (P0), postnatal day 14 (P14) and postnatal day 25 (P25) offspring mice were collected for subsequent experiments. The offspring mice were divided into offspring control group and offspring PNE group according to the maternal group respectively. Weights of P0 and P25 offspring mice were recorded. Micro-CT, scanning electron microscope (SEM) and Vickers hardness test were performed to analyze the related parameters of hard tissues including alveolar bones and mandibular incisors. Total RNAs were extracted from mandible tissues and the third generation of dental epithelial stem cells (DESC) in P25 mice. The relative expression levels of osteogenic and ameloblastic differentiation related genes were measured by real-time quantitative PCR (RT-qPCR). Immunohistochemical stainings of paraffin sections were then performed to observe the distribution and expression level of proliferating cell nuclear antigen (Pcna), amelogenin (Amelx), histone H3 trimethylated at lysine 27 (H3K27me3) and enhancer of zeste homolog 2 (Ezh2). Cell counting kit-8 (CCK-8) assays were used to detect the cell viabilities of DESCs after administrations of different concentrations of nicotine (0.01, 0.1, 1 mmol/L) and GSK126 (an inhibitor of histone methyltransferase Ezh2). Results: Compared with the control group, pregnant mice in PNE group were more likely to have adverse pregnancy outcomes, such as significantly lower offspring body weight [P0: offspring control (1.20±0.04) g, offspring PNE (0.99±0.02) g, P<0.001; P25: offspring control (15.26±1.70) g, offspring PNE (9.65±1.32) g, P<0.001] and increased stillbirths rate [offspring control (0), offspring PNE (46.40±9.30) %, P<0.001]. At P14 and P25, the distance parameters between the enamel mineralized deposits of mandibular incisors and the mesial surface of the first molar in offspring PNE group [P14: (-1 349±45) μm; P25: (-1 192±147) μm] was significantly decreased compared with the control group [P14: (-506±380) μm, P25: (504±198) μm] (P<0.05, P<0.001). The enamel column and enamel column stroma of incisors in offspring PNE group were blurred, arranged loosely and disorderly than those in the control group, while the microhardness of incisor enamel in offspring PNE group [(245.7±18.4) MPa] was significantly lower compared to the control group [(371.9±28.7) MPa] (P<0.001). HE staining showed disordered pre-ameloblast (Pre-Am) arrangement and delayed mineralization deposition point in offspring PNE group compared with the control group, while the length of transit-amplifying cell (TA) and Pre-Am region were prolonged as well. Immunohistochemical staining results displayed that the overall Pcna (P<0.05), H3K27me3 (P<0.01), Ezh2 (P<0.01) expression of labial cervical loop (LaCL) in PNE group were increased, while the positive signal of Amelx in ameloblast cytoplasm was impaired. In vitro, the addition of 1 mmol/L nicotine could significantly upregulate the expression level of Pcna (P<0.01) and downregulate the expression levels of B lymphoma Mo-MLV insertion region 1 (P<0.05), leucine rich repeats and immunoglobulin like domains 1 (P<0.05), Amelx (P<0.01). In addition, 1 mmol/L nicotine could also significantly enhance the proliferation activity of DESCs (P<0.001). Addition of 10 μmol/L GSK126, could rescue the proliferation activation effect of 1 mmol/L nicotine on DESCs. Conclusions: PNE may delay the process of enamel formation and lineage differentiation, leading to the abnormal proliferation of DESCs and changes of epigenetic modification state in H3K27me3, which affect the development of enamel in offspring mice,suggesting PNE might be one of risk environmental factor for tooth development.

Objective: To explore the effects of reduced parathyroid function in early growth and development on tooth eruption and enamel development by establishing an animal model of idiopathic hypoparathyroidism (IHP) and to explore the mechanism of IHP affecting tooth eruption with a view to provide experimental basis for early diagnosis and clinical treatment of IHP. Methods: Forty-eight SD rats at postnatal day 7 were randomly and equally divided into sham operation group and IHP group. The bilateral parathyroidectomy (PTX) was performed by using carbon nanoparticles technique to establish an IHP rat model, while no parathyroids were removed in the sham operation group using the same technique. Serum was extracted after surgery, serum calcium, serum phosphorus, and serum parathyroid hormone (PTH) concentrations were detected in order to verify the success of the modeling. At postnatal day 14, day 25 and day 38 (P14, P25 and P38) the rats were sacrificed to collect the mandible samples (six from each group) and to analyze the volume of enamel, the height of the tooth eruption and the bone microarchitecture parameters of the root-oriented alveolar bone of mandibular third molar quantitatively by micro-CT scanning. Histological sections were prepared. The distribution and expression levels of osteoblast differentiation markers runt-related transcription factor 2 (RUNX2) and osterix (OSX) in the alveolar bone around the third molar were detected by immunohistochemical staining and the osteoclast activity was detected by tartrate-resistant acid phosphatase (TRAP) staining. After each of the third molars was isolated, the microhardness of the enamel was measure by using a microhardness tester and the enamel microstructure was photographed by using scanning electron microscope. Primary dental follicle stem cells were isolated from other six mandibulars from each group at P14 and cultured in vitro. The cell proliferation activity was tested by cell colony forming units detection. After induction of dental follicle stem cells into osteogenic differentiation, the degree of mineralization was detected by using alkaline phosphatase staining and alizarin red staining. The mRNA of mandibular tissues and dental follicle cells were extracted, the expression of genes related to osteoblasts and osteoclast differentiations and parathyroid hormone receptor 1 (PTH1R) were detected by real-time quantitative PCR. Results: Bilateral parathyroidectomy was successfully performed on rats with the help of carbon nanoparticles under stereomicroscope. After surgery, the serum calcium concentration reduced, the serum phosphorus concentration increased and the serum PTH concentration distinctly reduced (P<0.01). The volume of enamel [(4.58±0.24) mm3] and the microhardness [(167.76±21.86) MPa] in IHP group were significantly lower than that in sham operation group [(5.22±0.46) mm3, P<0.05; (223.92±10.94) MPa, P<0.01, respectively]. The eruption height of the mandibular third molar in the IHP group was respectively lower than that in the sham operation group (P<0.05). The bone volume over total volume and trabecular number of the root-oriented alveolar bone of the mandibular third molars in the IHP group were respectively lower than that in sham operation group (P<0.05). The expression levels of RUNX2 and OSX proteins in the root-oriented alveolar bone of the mandibular third molars in the IHP group respectively reduced, compared to that in sham operation group (P<0.05). Furthermore, the number of osteoclasts (3.86±1.07) in crown-oriented alveolar bone in the IHP group was respectively lower than that in sham operation group (6.43±1.27) (P<0.01). The proliferative activity of dental follicle stem cells in the IHP group respectively decreased (P<0.01). After the induction of osteogenic differentiation, the mineralization ability of dental follicle stem cells in the IHP group was weakened. In the mandibular tissues of IHP group, the expression levels of osteogenesis related genes such as RUNX2 and OSX and the the expression of PTH1R significantly reduced (P<0.05). The receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) ratio reduced significantly (P<0.01) compared to those of sham operation group. Also in the dental follicle cells of IHP group, the expression levels of osteogenesis related genes such as RUNX2 and OSX, the RANKL/OPG ratio and the expression of PTH1R significantly decreased simultaneously compared to that in sham operation group (P<0.01). Conclusions: Under the condition of idiopathic hypoparathyroidism, the weakening of PTH/PTH1R signaling may reduce the proliferative activity of dental follicle stem cells, inhibit their regulation for osteoblast and osteoclast differentiations and functions, thereby interfere the bone remodeling of alveolar bone around the tooth germ during tooth eruption, which eventually leads to delayed tooth eruption.

Anastomotic leakage with abscess is a rare but severe complication of bariatric surgery. However, there is currently a lack of attention regarding this complication. This study aimed to investigate the risk factors for this complication and relevant treatment strategies to call attention to this severe complication. We retrospectively reviewed the patients who were rehospitalized for anastomotic leakage with abscess after bariatric surgeries in West China Hospital of Sichuan University from November 2017 to November 2018. The clinical profiles analyzed included body mass index, body weight before and after surgery, postoperative hospital stay, diet prescriptions, treatment strategies, and outcomes. A total of six patients (two men and four women) were included. The mean baseline body mass index was 37.52 (29.84-43.37), and the mean weight was 104.95 kg (74.5-127.5). The chief complaints leading to rehospitalization were fever and dull abdominal pain. The average postoperative hospital stay was 3.3 (3-4) days, and the onset time ranged from 7 to 15 days. Finally, revision surgeries were performed in two of the six patients (33%), and they were all cured by percutaneous drainage-based treatments. The postoperative fever and abdominal pain were the signs of leakage and abscess. Similar patients should be followed up once a week for 3 weeks after bariatric surgery to facilitate the early recognition of this complication. A longer hospital stay and sufficient parenteral nutrition plus a later implementation of diet should be helpful to minimize this severe complication. Percutaneous drainage played a significant role in the treatment of these patients.

INTRODUCTION: Presently, bariatric surgery is a widespread treatment for obesity and its co-morbidities. Comprehensive evidence from outcomes of bariatric surgery supported that the surgery is safe and effective. However, we should be aware of the multiple risks of bariatric surgery, especially the severe infection at the operation site. CASE PRESENTATION: A 30-year-old woman was hospitalized for anastomotic leakage with abscess after laparoscopic sleeve gastrectomy. After 53 days of percutaneous drainage, absolute diet fasting, parenteral nutrition and culture based antibiotics etc., she was discharged for recovery. DISCUSSION: Theoretically, malabsorption and early diet will increase the risk of anastomotic leakage, but this problem is seldom to be mentioned in related articles. Moreover, it seems to be common that people received bariatric surgery had a relatively short post-operative stay. CONCLUSION: Essential nutritional support, longer post-operative hospital stay and strict follow-up are necessary to minimize this complication. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.

目的 探讨核因子(NF-κB)在肝细胞癌组织中的表达与CT影像特点间的关系.方法 收集华西医院有完整临床资料和全肝CT扫描图像并经手术完整切除的肝癌组织标本患者80例,采用免疫组织化学方法染色定量分析癌组织中NF-κB表达情况和在不同的临床参数中表达的差异;再分别以肿瘤坏死、血供、瘤体直径和瘤周子灶的有无分四组,探讨NF-κB表达量在不同CT影像特征中有无差异.结果 CT检测80例患者中肝癌细胞核内NF-κB表达阳性有74例(92.5％).肝细胞癌NF-κB表达与临床参数,包括性别、肝炎病史无相关性,瘤体大小与NF-κB表达无统计学差异.CT检测肿瘤血供、坏死及瘤周子灶的有无与NF-κcB表达相关(P＜0.05),富血供肝细胞癌NF-κB表达较乏血供者明显增高,而瘤体有坏死者较未发生坏死者低,瘤周出现子灶的病例NF-κB表达也增高,且差异有统计学意义(P＜0.05).结论 肝癌血供、坏死及瘤周子灶CT影像特点与NF-κB水平密切相关.瘤体血供丰富、瘤内无坏死、瘤周伴有子灶的肝癌组织NF-κB表达水平明显增高,NF-κB表达水平量可能与肿瘤的生物学特性,疾病的转归和预后相关,CT检测可为肝癌的治疗及预防评估提供重要依据.

Hepatocellular carcinoma (HCC) is a lethal disease that kills hundreds of thousands of people each year worldwide. Transcatheter arterial chemoembolization (TACE) is a widely used approach in clinical practice to treat HCC. Many patients with unresectable HCC benefited from this technique. Now, TACE has evolved into the first choice among non-surgical HCC's for its minimally invasive nature and definite therapeutic effects. However, this technique was beset with relative high incidence of complications plus low cure rate. For optimal TACE's antitumor effect, many efforts have been made in varies aspects of TACE procedure including alterative contrast agent, combination therapies, newly developed embolizing agents and evaluation techniques et al. Therefore, this paper reviews recent advances in TACE for HCC, highlighting newly developed embolization agents and TACE-based integrated therapies in an attempts to improve local curability which may help to get closer to ultimate success of HCC treatment.

Surgery is the first choice of treatment for patients with non-small-cell lung cancer (NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies include radiotherapy and chemotherapy, as well as complementary and alternative therapies, usually with disappointing results. Bronchial artery infusion (BAI) is a manageable and effective method for treating advanced NSCLC. Outcome is good by BAI due to its repeatability and low toxicity. Icotinib hydrochloride is a newly developed and highly specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and has been safely and efficiently used to treat advanced NSCLC. We herein report a 73-year-old patient with chronic cough, who was diagnosed with advanced NSCLC with the EGFR mutation of L858R substitution in exon 21, and treated with the combination of oral icotinib and BAI chemotherapy as the first-line therapy, which resulted in a satisfactory clinical outcome. Complete remission of advanced NSCLC can be achieved using the combination of oral icotinib and BAI chemotherapy.

Hepatocellular carcinoma is a lethal disease that kills several hundred thousands of people every year across the globe.Transcatheter arterial chemoembolization(TACE) is a widely used approach in clinical practice to treat hepatocellular carcinoma(HCC).However,we are now facing many challenges in the field of improving the survival outcomes of TACE for the treatment of HCC.This paper reviews recent advances in TACE treatment of HCC with the highlights of newly developed embolization agents and combiantion use of TACE and other treatment methods to get im proved outcome of patients with HCC.

Natural medicine is a system of therapy that administrates natural agents and their derivatives to treat human diseases. This medicine has been used to treat many kinds of human diseases for thousands of years. The treatment protocols of natural medicine are integrative in nature, and are required to utilize the most appropriate therapies to address the needs of the individual patient. Because of the relative convenience, safety and efficacy, natural medicine is now increasing worldwide. Naturopathic doctors are licensed in many areas of the world and regulated partly by law in these areas, which is quite different from various other forms of complementary and alternative medicine. Liver diseases, such as hepatitis, liver cirrhosis and liver carcinoma, are serious health problems worldwide. Nearly half of the natural agents used in treatment of liver diseases today are natural products and their derivatives. Although natural medicine is beneficial and safe, physicians should pay close attention to the potential side-effects of the naturopathic agents, which lead to liver injury, interstitial pneumonia and acute respiratory failure. Therefore, when administrating naturopathic protocols to patients for the treatment of liver diseases, we should try our best to prevent and avoid as much as possible the negative impact of these medicines. This article highlights the current practice and recommended improvement of natural medicines in the treatment of liver diseases and gives some specific examples to emphasize the prevention and management of adverse reactions of the natural agents and suggests that natural medicine should be cautiously used to treat liver problems.

Natural medicine is a system of therapy that administrates natural agents and their derivatives to treat human diseases. This medicine has been used to treat many kinds of human diseases for thousands of years. The treatment protocols of natural medicine are integrative in nature, and are required to utilize the most appropriate therapies to address the needs of the individual patient. Because of the relative convenience, safety and efficacy, natural medicine is now increasing worldwide. Naturopathic doctors are licensed in many areas of the world and regulated partly by law in these areas, which is quite different from various other forms of complementary and alternative medicine. Liver diseases, such as hepatitis, liver cirrhosis and liver carcinoma, are serious health problems worldwide. Nearly half of the natural agents used in treatment of liver diseases today are natural products and their derivatives. Although natural medicine is beneficial and safe, physicians should pay close attention to the potential side-effects of the naturopathic agents, which lead to liver injury, interstitial pneumonia and acute respiratory failure. Therefore, when administrating naturopathic protocols to patients for the treatment of liver diseases, we should try our best to prevent and avoid as much as possible the negative impact of these medicines. This article highlights the current practice and recommended improvement of natural medicines in the treatment of liver diseases and gives some specific examples to emphasize the prevention and management of adverse reactions of the natural agents and suggests that natural medicine should be cautiously used to treat liver problems.

Background: Both interventional therapy and molecular targeted therapy are important methods of treatment for lung cancer, but the combined use of the two methods has been less commonly reported. We aimed to observe and evaluate the safety and clinical effectiveness of bronchial arterial infusion chemotherapy (BAI) combined with icotinib hydrochloride as first-line treatment for advanced lung cancer. Methods: 24 adult patients with advanced non-small-cell lung cancer (NSCLC) received BAI only (control group), while 22 adult patients received BAI plus icotinib (combined group). The study was done in the department of oncology, West China Hospital, Sichuan University, from January 2014 to January 2017. Icotinib was given to patients of the combination group until they had severe side effects or could not tolerate. The clinical effect and safety was compared and data analysed using statistical software SAS version 9.4. The study registration number is ChiCTR-OPN-15006795. Findings: In the combined group, the response rate (RR) was 86.36%, while the RR was 29.00% in the control group (p<0.0001). In the combined group, after 1 months of the treatment, the incidence of quality of life (QOL) improvement was 86.36%, which was higher than the 58.33% of the control group (p=0.0349). Both of the two groups had no severe complication. The number of BAI regimens for the combined group and control group were 1.5±0.74 and 3.71±1.46, respectively (p<0.0001). There was no significant difference in 1-year cumulative survival rate between the two groups (p=0.7524). Interpretation: Combined BAI plus icotinib treatment can lead to better short-term clinical efficacy and improved QOL, reduced BAI number, and does not increase the incidence of complication. However, the limitation of this trial was that it did not compare the clinical effect and safety of icotinib alone versus other regimens in the treatment advanced lung cancer. Funding: None. Conflicts of interest: We declare that we have no conflicts of interest.

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.

[ABSTRACT]Objective:To analyze the malignant degree of primary hepatocellular carcinoma after treatment of endostar combined with transcatheter arterial chemoembolization (TACE)treatment.Methods:A total of 68 patients with primary hep-atocellular carcinoma treated in the hospital were enrolled for study and divided into observation group and control group with 34 cases in each group according to different treatment methods.Control group received TACE treatment,while observation group received endostar combined with TACE treatment,and then differences in levels of serum amino acid,micro-RNA,&nbsp;GP73,GPC3,GS,etc.,as well as levels of ChE,TBA and AFP were compared between two groups after treatment.Results:Serum aspartic acid,leucine and arginine levels in observation group after treatment were higher than those in control group, and α-aminoadipic acid,methionine,β-alanine and 3-methylhistidine levels were lower than those in control group (P <0.05);relative values of serum miR-106b,miR-222 and miR-21 expression in observation group after treatment were lower than those in control group,and relative values of miR-1 99a and miR-122 expression were higher than those in control group (P <0.05);GP73,IL-1 7,IL-6,GPC3,GS and HSP70 levels in observation group after treatment were lower than those in control group, while endostatin level was higher than that in control group (P <0.05);ChE level in observation group after treatment was higher than that in control group,and TBA and AFP levels were lower than those in control group (P <0.05).Conclusions:Endostar combined with TACE treatment for patients with primary hepatocellular carcinoma can effectively inhibit tumor pro-liferation,invasion and other malignant processes and improve liver function,with a positive clinical significance.

CalliSpheres® embolic microspheres for embolization of the vasculature of liver cancer are designed, manufactured, and verified, in order to improve the effect of transcatheter arterial chemoembolization in the treatment of primary liver cancer.

Objectives Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Microwave ablation is regarded as a safe and effective therapy for the treatment of HCC and has gained considerable attention as a rapidly expanding curative ablation option. This study aims to review the current application of microwave ablation therapy (MAT) for HCC. Methods A literature search was conducted in the PubMed (MEDLINE) database from inception up to August 2016, with no limitations imposed on language or study type, about the application of MAT for HCC. Results MAT for HCC has been reported to be effectively delivered through open laparotomy, laparoscopy and a percutaneous approach for appropriate patients, with many different tools for imaging guidance, including ultrasound, X-ray fluoroscopy, CT, MRI, PET-CT and combined US/CT-MRI. MAT provides the advantages of short treatment duration, a controllable wound and large ablation areas, and may even have the potential to enhance host resistance to malignancies. It is recommended as a first-line therapy for patients with very early and early stage HCC, and is a palliative option for advanced HCC. For tumors larger than 3 cm in diameter with an incomplete capsule, or with visible satellite lesions, or tumors in difficult anatomic locations, combination therapy with other treatments, such as TACE, PEI, iodine-125 particles, immunotherapy, etc, should be considered. Conclusions MAT has gained recognition in the treatment of early or advanced HCC. With the development of image guidance, multiple innovative instruments and different combination therapy modalities, MAT is a promising therapy for development and clinical application in the future. Acknowledgments This research was financially supported by Sichuan University (Grant No. 2016SCU11033).

Objectives Liver disease, especially the chronic diseases, is a serious health problem worldwide. Natural medicines have been used for thousands of years to treat liver problems. Patients with liver problems sometimes try natural medicines, especially medicinal herbs, and some natural agents. This study aims to discuss several aspects of natural medicines for treating liver problems. Methods Electronic databases including Web of Science and PubMed were searched for in vitro, in vivo and clinical studies on the effects of natural medicines on liver problems. Results Nearly half of the natural medicines used in treatment of liver diseasestoday are natural products and their derivatives. Sho-saiko-to is effective on hepatitis, liver fibrosis, and HCC. But long-term consumption of this herb drug may lead to interstitial pneumonia and even acute respiratory failure. Silybum marianum is a hepatoprotective agent and long-term use of this herb was considered to be safe. Some other natural medication, such as long pepper, holy basil, coffee, apple, and citrus, for example, have hepatoprotective effect, but more in-depth studies are required to confirm the dosages of each agent to avoid side effects when using them to treat liver problems. Conclusions Naturopathy is becoming more popular worldwide and provides benefits to many patients with liver diseases such as hepatitis, liver cirrhosis and liver cancer. The integration of conventional and naturopathic medicine will produce a practice style that provides excellent medical care for the liver. Acknowledgements This research was financially supported by Sichuan University (Grant No. 2016SCU11033).