Objective:To observe the protein and mRNA expressions of microtubule-associated protein 1 light chain 3 (LC3)B, P62 and Beclin1 in the liver of rats with chronic fluorosis, and to explore the role of autophagy in pathogenesis of liver injury induced by fluorosis.Methods:Using a group design, 54 SD rats were divided into 9 groups according to their weight (100 - 120 g) using a random number table method, each group with 6 rats, half male and half female. They were control group (NC group), low fluoride group (LF group), high fluoride group (HF group), NC + rapamycin (RAP) group, LF + RAP group, HF + RAP group, NC + chloroquine (CQ) group, LF + CQ group, and HF + CQ group. The NC group drank tap water (fluoride concentration was 0.5 mg/L), LF group drank fluoride water (fluoride concentration was 5.0 mg/L), HF group drank fluoride water (fluoride concentration was 50.0 mg/L); NC + RAP group, LF + RAP group and HF + RAP group were fed with corresponding drinking water, respectively, for 3 months, and then RAP (1.5 mg/kg) was intraperitoneally administered for 10 d; NC + CQ group, LF + CQ group and HF + CQ group were fed with corresponding drinking water, respectively, for 3 months, and then CQ (60 mg/kg) was intraperitoneally administered for 10 d. Bone and 24-hour urine samples of rats in each group were collected to detect the contents of bone fluoride and urine fluoride; liver histomorphological changes were observed through hematoxylineosin staining; protein and mRNA expressions of LC3B, P62 and Beclin1 in liver were detected by immunohistochemistry and real-time fluorescence quantitative PCR, respectively.Results:Compared with the NC group [(0.03 ± 0.00) mg/kg, (0.34 ± 0.08) mg/L], the contents of bone fluoride [(3.86 ± 0.08) mg/kg] and urine fluoride [(1.11 ± 0.16) mg/L] in HF group were higher ( P < 0.05). In the NC group, the lobule structure of liver tissue was clear, the hepatic cords were arranged in order, and the cell structure was normal. There were different degrees of hepatocyte edema in LF and HF groups. After intraperitoneal injection of RAP, compared with the corresponding fluoride group, the morphology of hepatocytes did not change significantly. After intraperitoneal injection of CQ, compared with the corresponding fluoride group, the liver cells showed obvious edema, and the degree of edema aggravated with the increase of fluoride concentration. Compared with the NC group, the protein expressions of LC3B and Beclin1 in HF group were higher ( P < 0.05), and the protein expression of P62 was lower ( P < 0.05). After intraperitoneal injection of RAP, the protein expressions of LC3B and P62 in LF + RAP group was lower than that in LF group ( P < 0.05); Compared with HF group, the protein expressions of LC3B and Beclin1 in HF + RAP group were lower ( P < 0.05). After intraperitoneal injection of CQ, protein expression of P62 in LF + CQ group was higher than that in LF group ( P < 0.05); Compared with HF group, protein expression of P62 in HF + CQ group was higher ( P < 0.05). Conclusions:Early (3 month) fluoride intake could promote autophagy and induce edema of hepatocytes in rats, and RAP had similar effects. CQ may induce liver injury by inhibiting autophagy of hepatocytes.

Objective To evaluate and analyse the efficacy and safety of endoscopic papillectomy for tumors of major duodenal papilla.Methods The clinical data of thirty-four patients with tumors of major duodenal papilla who were treated by endoscopic papillectomy were retrospectively reviewed,and the clinical outcome was summarized.Results The success rate of endoscopic papillectomy was 94.12％ (32/34),and the complete resection was 66.67％ (20/30).Short-term complications occurred in 10 cases,including postoperative gastrointestinal bleeding in 7cases and postoperative pancreatitis in 3 cases.Five cases need further surgical intervention for the reason that tumor was too deep in 2 cases,bile duct was invaded in 2 cases and conservational medication was unsuccessful in 1 case.Thirty-three cases were pathologically diagnosed as low grade intraepithelial neoplasia (LGIN),17 cases high grade intraepithelial neoplasia (HGIN),1 case carcinoid and 3 cases adenocarcinoma.The recurrence rate was 23.33 (7/33).tumor recurrence rate of HGIN was higher than that of LGIN(42.86％ VS10％,P =0.078).Conclusion Endoscopic papillectomy is an effective method for treating tumors of major duodenal papilla,however,hemorrhage is the main postoperative complication,the recurrence rate is higher in HGIN group.

Objective To evaluate the clinical value of preoperative mark with methylene blue for the submucosal tumor originating from the muscluaris propria around the cardia in submucosal tunnel.Meth-ods A total of 27 patients with cardiac tumors originating from muscularis propria diagnosed by endoscopy and endoscopic ultrasonography underwent endoscopic submucosal tunnel dissection from June 2011 to May 2014.Eighteen cases were marked by methylene blue,and 9 others were not.The operation time and the in-cidence of complications were compared between the two groups.Results All lesions were resected success-fully.The time of lesion location of non-mark group was 14.7 minutes(9-32 min),and that of mark group was 8.1 minutes(7-10 min).The incidence of subcutaneous emphysema of thorax and cervix of non-mark group was 2 /9(2 cases),and that of the mark group was 1 /18(1 case).The incidence of pneumoperitone-um of non-mark group was 1 /9(1 case),while that of the mark group was 2 /18(2 cases).There was no pneumothorax or mediastinal emphesema in all cases.Conclusion Marking with methylene blue before op-eration can shorten operation time effectively and lower incidence of complications.

OBJECTIVETo examine the feasibility and safety of gastric submucosal tunnel dissection of gastric submucosal tumors (SMTs) by double tunnel and double flex endoscope.

METHODSFifty patients with gastric SMTs detected by gastric endoscopy and endoscopic ultrasonography between January, 2012 and August, 2013 were enrolled in this study. Using carbon dioxide throughout the procedure, the mucous in the arc was incised along the margins of the lesion to separate the submucosa and create a tunnel. The exposed SMTs were resected completely and the mucosa was covered by endoscopic forceps followed by clipping of the incision. The complication, clinical outcomes, hospital stays and operation time were evaluated.

RESULTSOf the 50 lesions, 50 were located in the gastric fundus, 17 in the gastric antrum and 5 in the gastric body. The lesions were completely resected in all the patients. The diameter of the resected lesions ranged from 0.5 to 2.5 cm (mean 1.1 ± 0.6 cm), and the operation lasted for 35.3 ± 16.2 min (range 23-76 min). In 5 cases (10%), perforation occurred during the operation and was closed by clipping the incision with endoclips after the lesion resection; these patients were discharged after conservative management. Intraoperative bleeding occurred in 16 cases and was successfully managed through endoscopic methods. No delayed postoperative bleeding or perforation occurred in these patients. None of the 48 patients followed up showed tumor recurrence at one year after the operation, and 2 patients were lost for follow up.

CONCLUSIONEndoscopic submucosal dissection of gastric SMTs is effective and safe using double tunnel and double flex endoscope.

Dissection ; Endoscopes ; Endoscopy ; Endosonography ; Gastric Mucosa ; pathology ; surgery ; Humans ; Neoplasm Recurrence, Local ; Stomach Neoplasms ; surgery

Objective To investigate the safety and efficacy of ultrasound ablation in treatment of uterine fibroids. Methods Ninety-nine patients with 117 leiomyomas in total treated by Haifu JC focused ultrasound tumor therapeutic system were enrolled in prospective and non-randomized clinical trial in First Affiliated Hospital of Chongqing Medical University and Academy of Military Medical Sciences. Ultrasound ablation was performed guided by real-time ultrasonography under conscious sedation for single session. All patients were followed up at 6 months after treatment. On the day of treatment and after 1 month, patients were given by magnetic resonance imaging(MRI) exam to evaluate the effect of fibroids ablation. At 3 and 6months after treatment, the ratio of ablated area and volume reduction of fibroids more than 50% were evaluated by MRI exam again. The symptoms improvements were evaluated by uterine fibroid symptom (UFS) and complications were analyzed by guideline of society of international radiation (SIR). Results The average ablated area ratio of the target fibroid was (76 ± 24)%. The average reduction in fibroid volume determined by MRI at 3 and 6 months after treatment was (45 ± 21)% and (59 ± 26)%. Which were significantly decreased than those before treatment (P < 0. 05). At 6 months after treatment, 84. 6% (99/117) of patients showed more than 50% volume reduction, the rate of improved symptom score was 92%(66/72). All patients could resume normal daily activities at 2 hours after treatment. The adverse reactions of SIR C - D included delayed hospitalization, repeat treatment and increased level of nursing. E - F included permanent sequelae and death. In this study, no adverse reactions of C - F were recorded. Common complications (SIR A- B, only observation or simple management without sequelae) were 35% (35/99).Four cases with adverse reactions B of SIR were found, including 2 cases with skin burning of degree Ⅱ and 2 cases with febrile, they were administered by symptomatic therapy and changing dressing The other adverse reaction A of SIR included sorness of buttock, vaginal discharge, dysuria and painful urination, they were only suggested by follow-up. Conclusion It was efficacy and safe that ultrasound ablation as a single strategy were used in treatment of uterine fibroids.

Objective:To explore whether chronic fluorosis can cause liver fibrosis in rats by observing expression changes in type Ⅰcollagen (Col-Ⅰ), type Ⅲ collagen (Col-Ⅲ) and alpha smooth actin (α-SMA) in the liver tissue of chronic fluorosis rats.Methods:According to body weight (90 - 100 g), forty-eight SD rats were randomly divided into control group (drinking water fluoride ion concentration < 0.5 mg/L), low, medium and high concentration fluoride groups (drinking water fluoride ion concentration of 5.0, 50.0 and 100.0 mg/L), with 12 rats in each group (half male and half female), and fed for 6 months. Fluoride ion selective electrode method was used to detect bone fluoride and urinary fluoride levels; hematoxylin-eosin staining (HE staining) and Masson staining were used to observe the pathological and morphological changes and the collagen deposition of liver tissue; quantitative real-time polymerase chain reaction and immunohistochemical staining were used to observe Col-Ⅰ, Col-Ⅲ and α-SMA mRNA and protein expressions.Results:There was significant difference in bone fluoride and urine fluoride between the 4 groups [bone fluoride: (92.52 ± 5.64), (112.21 ± 11.86), (142.99 ± 7.87), (235.63 ± 11.55) mg/kg; urinary fluoride: (5.47 ± 0.88), (17.78 ± 1.48), (54.16 ± 5.96), (121.11 ± 6.32) mg/L, P < 0.001]. Under light microscope, with the increase of fluoride concentration, the degree of hepatic cell edema was aggravated, and the deposition of collagen fiber around the central vein and the portal area increased significantly. The mRNA expression level of Col-Ⅰ in low, medium and high concentration fluoride groups (1.20 ± 0.09, 1.80 ± 0.08, 1.58 ± 0.06) was significantly higher than that in control group (1.00 ± 0.00, P < 0.05); Col-Ⅲ and α-SMA mRNA expression levels in medium and high concentration fluoride groups (Col-Ⅲ: 1.15 ± 0.14, 1.64 ± 0.24; α-SMA: 1.69 ± 0.02, 2.34 ± 0.06) were significantly higher than those of low concentration fluoride group (Col-Ⅲ: 0.59 ± 0.17; α-SMA: 0.80 ± 0.13, P < 0.05). With the increase of fluoride concentration, the liver tissue Col-Ⅰ(0.00 ± 0.00, 0.03 ± 0.01, 0.08 ± 0.01, 0.13 ± 0.02), Col-Ⅲ (17 803.05 ± 3 221.16, 47 523.15 ± 3 490.10, 127 786.35 ± 13 008.86, 237 233.03 ± 47 614.63) and α-SMA (516.83 ± 181.18, 2 885.03 ± 864.92, 11 186.94 ± 2 394.08, 37 182.43 ± 12 390.59) protein levels were also increased significantly ( P < 0.05). Conclusion:Long-term excessive intake of fluorine may cause the production of collagen fibers around the central vein and the portal area of the liver in rats to increase, and then lead to the formation of liver fibrosis.

BACKGROUNDGastric varices (GV) are life-threatening for patients with portal hypertension. Endoscopic injection with butyl cyanoacrylate (BC), the mainstay of the therapy for GV, has been reported to be effective for hemostasis of bleeding varices, but its efficacy in the obliteration of GV and impact on the survival of patients still needs clarification. Here we summarized our experience of 10 years' practice to evaluate the efficacy and safety of endoscopic therapy using BC for GV patients.

METHODSFrom January 1997 to April 2006, GV cases treated with endoscopic injection using BC were collected. The "sandwich method" and the "modified sandwich method" were used to inject BC intravascularly. Retrograde analysis was made on the data of treatment and follow-up.

RESULTSA total of 635 GV cases treated with endoscopic injection using BC were collected, most of them (90.2%) suffered from post-hepatitis cirrhosis. Emergency hemostasis was achieved in 139 out of 146 sessions (95.2%). Complications occurred in 32 cases (5.2%), including hemorrhage due to early expulsion of tissue glue (3.1%), septicemia (1%) and ectopic thrombosis (0.5%), such as spleen infarction. Endoscopic follow-up in 503 patients showed complete disappearance (76.9%), collapse (17.3%) or remnants (5.8%) of gastric varices. A total of 550 patients were followed up clinically for 3 to 115 months. Of these patients, 44 had recurrent bleeding (8.0%) and 44 died from hepatic failure, recurrent bleeding, hepatic carcinoma or other causes. The longest survival was 115 months, with a median survival of 25 months. Survival rates at 1, 2, 3, 4 and 5 year were 95%, 92%, 90%, 83% and 81%, respectively.

CONCLUSIONSEndoscopic sclerotherapy with BC is effective for the hemostasis of bleeding GV, as well as obliteration of GV which contributes to less rebleeding and better survival. The modified sandwich method may be useful to minimize ectopic embolism, which we speculated to result from excess iodized oil.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Enbucrilate ; therapeutic use ; Endoscopy, Gastrointestinal ; methods ; Esophageal and Gastric Varices ; mortality ; therapy ; Female ; Humans ; Male ; Middle Aged ; Sclerotherapy ; adverse effects ; methods ; Tissue Adhesives ; therapeutic use

A proportion of patients experience acute or even prolonged cognitive impairment after surgery, a condition known as postoperative cognitive dysfunction (POCD). It is characterized by impairment in different cognitive domains and neuroinflammation has been implicated as one of the inciting factors as strategies targeting inflammation tend to improve cognitive performance. Siegesbeckia Orientails L. (S. Orientails) is a common Chinese medicinal herb used for managing chronic inflammatory diseases. We investigated if pretreatment with S. Orientails before surgery confers any neuroprotective effects in postoperative animals in terms of reducing inflammation and mitigating cognitive impairment. Three-month-old male C57BL/6N mice were fed different doses of S. Orientails extract for 14 days before they underwent a laparotomy. After cognitive testing they were sacrificed on postoperative day (POD) 3. Our results showed that animals with extract pretreatment demonstrated memory improvement in a dose-dependent manner compared with control. Further, evidence for the attenuation of systemic and neuroinflammation was found in the pretreated animals, along with the inhibition of inflammatory pathways and significantly reduced tau phosphorylation in the hippocampus. Taken together, these results demonstrated a neuroprotective effect of S. Orientails in postoperative animals, indicating a therapeutic potential of S. Orientails in minimizing POCD and the possibility of utilizing this traditional Chinese medicine perioperatively.
Animals ; Asian Continental Ancestry Group ; Cognition Disorders ; Hippocampus ; Humans ; Inflammation* ; Laparotomy ; Male ; Medicine, Chinese Traditional ; Memory ; Mice ; Neuroprotective Agents ; Phosphorylation ; Plants, Medicinal

Objective:To investigate the expression changes of Hedgehog related factors (Ihh, Shh and Smo) in bone of rats with chronic fluorosis, and the significance.Methods:Thirty-six healthy SD rats were divided to three groups with the method of random digits table by body weight (100 - 120 g), 12 rats in each group, half male and half female. The rats of control were fed with tap water (NaF < 1 mg/L), and the experimental rats were exposed to NaF (low dose fluoride group: 5 mg/L, high dose fluoride group: 50 mg/L) added to the drinking water to establish the chronic fluorosis model. After the rats were raised for six months, 24-hour urine samples were collected and the femoral metaphysis of the rats was taken. Urine fluoride and bone fluoride were detected by fluorin ion selective electrode method. Bone tissues were stained with hematoxylin-eosin and observed under light microscope. The content of bone alkalinephosphatase (BALP) in rats' serum was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Ihh, Shh and Smo mRNA and protein in bone were detected by Real-time PCR and immunohistochemistry (IHC).Results:The contents of urine fluoride, bone fluoride and serum BALP were increased gradually in the control, low and high doses fluoride groups [urine fluoride: (1.37 ± 0.44), (5.96 ± 0.56), (7.60 ± 0.61) mg/L; bone fluoride: (306.04 ± 12.58), (652.91 ± 51.83), (1 094.11 ± 126.34) mg/kg; BALP: (27.78 ± 4.09), (46.59 ± 5.75), (57.45 ± 3.99) U/L, P < 0.05]. It could observed that bone sclerosis by light microscope in low and high doses fluoride groups. The expressions of Ihh, Shh and Smo mRNA in high dose fluoride group (1.39 ± 0.36, 0.56 ± 0.23, 0.40 ± 0.15) were higher than those of the control and low dose fluoride groups (0.73 ± 0.19, 0.92 ± 0.34; 0.19 ± 0.04, 0.36 ± 0.16; 0.14 ± 0.04, 0.24 ± 0.13; P < 0.05). The expression of Shh mRNA in low dose fluoride group was higher than that of the control group ( P < 0.05). The expressions of Ihh and Smo protein in high dose fluoride group (138.89 ± 3.72, 149.29 ± 7.63) were higher than those of the control and the low dose fluoride groups (127.39 ± 2.69, 134.81 ± 3.53; 129.64 ± 12.62, 139.07 ± 9.30), and the low dose fluoride group were higher than those of the control group ( P < 0.05). The expression of Shh protein in high dose fluoride group (141.26 ± 7.49) was higher than that of the control group (130.96 ± 11.10, P < 0.05). Conclusion:The expression of Hedgehog signaling pathway related factors in bone of rats with chronic fluorosis is changed, which indicates that bone formation can be affected by activation of Hedgehog signaling pathway induced by fluoride.

Objective To analyze the clinical and magnetic resonance imaging(MRI)findings of solid pseudopapillary tumor(SPT)of the pancreas in male patients. Methods Clinical and MRI features of 51 patients with pathologically-proved SPT were retrospectively analyzed.The following MRI features of the lesions were analyzed:location,maximal diameter,shape,margin,capsule,solid and cystic components,signal intensity characteristics,and enhancement patterns.Results The average maximal diameter of the SPT in male patients was significantly smaller [(3.9±1.6)cm vs.(6.3±3.9)cm,P=0.035]than that of SPT in female patients.Pure solid tumors were signiciantly more common in male patients(8/14)than in female patients(9/37)(P=0.037).T-weighted images of SPT showed mainly homogenous hypo-intensity in male patients(11/14)and heterogeneous hypo-intensity in female patients(23/37)(P=0.001).Hemorrhage was more prevalent in female patients(22/37)than in male patients(2/14)(P=0.005).There were no significant differences between male and female patients regarding clinical features and other magnetic resonance features(P>0.05).Conclusions On MRI,SPT in male patients is small and shows mainly pure solid component with rare hemorrhage.The clinical and other MRI features of SPT are not different between males and females.