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Pancreatic cancer is one of the common malignant tumors of the digestive system, and its clinical treatment is still very challenging. Most of the pancreatic cancer chemotherapeutic drugs have poor plasma stability, low cell uptake efficiency, and are prone to developing drug resistance and toxic side effects. Besides, pancreatic cancer often has a dense extracellular matrix, which consists of collagens, hyaluronic acid, and other proteoglycans. Among them, hyaluronic acid is a key component of the dense matrix, which results in vascular compression and insufficient perfusion, and hinders the delivery of chemotherapeutic drugs. In this study, we explore using hyaluronidase in tumor-bearing mice to eliminate the hyaluronic acid barrier, to reduce blood vessel compression and reshape the tumor microenvironment. In addition, we evaluate using doxorubicin-loaded nanoprobes to improve the stability and local tumor-killing effect of the drug. The nanoprobes have the characteristics of near-infrared optical imaging, which are used to monitor the tumor size in real-time during the treatment process, and dynamically observe the tumor inhibitory effect. The results show that elimination of the hyaluronic acid barrier combined with the doxorubicin-loaded nanoprobes can greatly increase drug penetration into tumor tissue and improve the effectiveness of chemotherapy drugs. This study provides a novel strategy for the treatment of pancreatic cancer.

Objective To assess the clinical and histological features of metabolic associated fatty liver disease (MAFLD) in non-lean population. Methods Current study enrolled consecutive non-lean (Body Mass Index (BMI) > 23 kg/m2) patients with MAFLD and available liver biopsy results. Patients were stratified by BMI into two groups for the comparison of their clinical and histological variables, which included the overweight (BMI 23 ~ 1) were also analysed through the logistic regression model. Results Among 184 non-lean patients with MALFD enrolled, 65 and 119 were overweight and obese, respectively. Patients in the obesity group had a significantly lower level of gamma-Glutamyl transpeptidase (GGT), higher levels of platelet (PLT), Glucose (Glu), prothrombin time (PT), and more common of moderate to severe inflammatory activity when compared to those in the overweight group. However, a significant low frequency of moderate to severe fibrosis was found in the obesity group vs the overweight group (19.33% vs 40.00%, P = 0.002). Multivariate logistic regression analysis of fibrosis found that aspartate transaminase (AST), BMI, alanine transaminase (ALT) and cholesterol (CHOL) were independent predictors for moderate to severe fibrosis in non-lean patients with MAFLD. Compared with the traditional FIB-4 (AUC = 0.77) and APRI (AUC = 0.79) indexes, the combined index based on AST, BMI, ALT and CHOL was more accurated in predicting moderate to severe fibrosis in non-lean patients with MAFLD (AUC = 0.87). Conclusions Clinical and histological features differed between obesity and overweight patients with MAFLD. When compared to the traditional serum markers, the combination index including AST, BMI, ALT and CHOL provides a better model to predictor moderate to severe fibrosis in non-lean patients with MAFLD.

Photoacoustic imaging (PAI) is a rapidly emerging modality in biomedical research with the advantages of noncontact operation, high optical resolution, and deep penetration. Great efforts and progress in the development of PAI agents with improved imaging resolution and sensitivity have been made over the past 2 decades. Among them, organic agents are the most promising candidates for preclinical/clinical applications due to their outstanding in vivo properties and facile biofunctionalities. Motivated by the unique properties of aggregation-induced emission (AIE) luminogens (AIEgens), various optical probes have been developed for bioanalyte detection, multimodal bioimaging, photodynamic/photothermal therapy, and imaging-guided therapeutics. In particular, AIE-active contrast agents have been demonstrated in PAI applications with excellent performance in imaging resolution and tissue permeability in vivo. This paper presents a brief overview of recent progress in AIE-based agents in the field of photoacoustic imaging. In particular, we focus on the basic concepts, data sorting and comparison, developing trends, and perspectives of photoacoustic imaging. Through numerous typical examples, the way each system realizes the desired photoacoustic performance in various biomedical applications is clearly illustrated. We believe that AIE-based PAI agents would be promising multifunctional theranostic platforms in clinical fields and will facilitate significant advancements in this research topic.

Colon cancer is a common cause of cancer-related death worldwide. However, the underlying mechanism of tumor progression of colon cancer remains far from being elucidated. In the present study, we report the role of UNBS5162 in colon cancer. UNBS5162 is a naphthalimide that can intercalate into DNA and suppress the expression level of CXCL chemokines. Here, we investigated its effect on cell proliferation, mobility and apoptosis in HCT116 cells, and explored the underlying mechanism. A CCK8 assay revealed that UNBS5162 can block the proliferation of colon cancer cells. Base on a Transwell assay, we showed that cell migration and invasion ability of HCT116 cells are inhibited by UNBS5162. In addition, Annexin V-FITC/PI assay and Western blot analysis were performed to detect whether UNBS5162 could induce cell apoptosis. The results indicated that UNBS5162 increases the number of apoptotic cells remarkably. Furthermore, Western blot analysis demonstrated that UNBS5162 down-regulates the expression level of Bcl2, and up-regulates that of Bax as well as the level of activated Caspase-3. Moreover, we examined the impact of UNBS5162 on PI3K/Akt signaling pathway. UNBS5162 substantially inhibited the phosphorylation of Akt and its downstream effector mTOR, and reduced the expression of p-70. Taken together, these results suggest that UNBS5162 should be considered as a potent therapeutic anticancer agent that targets the PI3K/AKT signaling pathway.

Nutrition and inflammation play a crucial role in the development of cancer. The prognostic value of the prognostic nutritional index (PNI) has been confirmed in some types of human cancers. This study analyzed the prognostic significance of the preoperative PNI in patients with stage III gastric cancer after curative surgery.In this retrospective study, we enrolled 274 patients who underwent curative operation for stage III gastric cancer. The correlation between the preoperative PNI and overall survival (OS) was analyzed using Kaplan-Meier curves and multivariate Cox regression analyses.The patients with a high PNI had a significantly higher median OS than did those with a low PNI (46.8 months vs 24.1 months, p=0.01). In the subgroup analysis, the survival benefit of the PNI was limited to the patients with poorly differentiated gastric cancer (high PNI, 46.8 months; low PNI, 21.8 months, p=0.004) and was not observed in those with well and moderately differentiated cancer (high PNI, 30.3 months; low PNI, 26.7 months, p=0.30). In the multivariate analysis, the PNI was an independent prognostic factor for OS.The PNI can be used as an independent prognostic biomarker for operable advanced gastric cancer.

Exposing the recurrent laryngeal nerve (RLN) during all types of thyroid surgery is essential to protect this nerve. Endoscopic thyroidectomy (ET) has gained acceptance from both patients and physicians, in part due to the cosmetic benefits. Therefore, the avoidance of intraoperative RLN impairment during ET is of critical significance. We have developed a standard approach to expose the RLN during ET that prevents RNL impairment.ET was performed in 120 consecutive patients with thyroid disease. In order to develop a standard procedure that protects the RLN, several steps that differed from the traditional open procedure were introduced. First, the thyroid gland was freed from the isthmus instead of the superior pole. Then, the inferior pole of the thyroid gland was meticulously freed, and the lateral side of the thyroid gland was freed followed by the superior pole. At this point, the RLN was easily visualized in the tracheoesophageal groove. The thyroidectomy was then performed simultaneously with exposure of the RLN from the inferior to superior aspects. All RLNs were exposed when hemithyroidectomies, subtotal thyroidectomies, or total thyroidectomies were performed. The operative time and parathyroid hormone (PTH) and calcium levels were recorded prospectively and analyzed.Using this method, all RLNs were easily exposed within 15 minutes. Only one case of transient RLN palsy occurred due to accidental contact of the harmonic scalpel to the nerve. Postoperative hypocalcemia occurred in 23 cases (19.2%), and the PTH level decreased significantly in 33 cases (27.5%). The PTH levels returned to normal within 3 months.Use of the described approach to expose and protect the RLN when performing ET is safe and feasible.

After more than half a century of development, obesity and metabolic surgery in western countries has become a complete surgical specialties, but the introduction of obesity and metabolic surgery was only 10 years old in China. The surgical treatment of obesity and related metabolic diseases, especially obesity of type 2 diabetes has been recognized and acknowledgd by the majority of surgical colleagues and patients as a new direction of development. The current trend of obesity and metabolic surgery is favorable, but there are many problems in the development of obesity and metabolic surgery in China, for example, the surgery nomenclature is not standardized, surgical indications are loosened, the surgical procedure is modified arbitrarily, the evaluation criteria is confusing, the postoperative follow-up protocol is not unified, etc. These problems require the majority of surgical colleagues to work together to make the standards scientifically a nd objectively in accordance with the actual situatioin of our country, so as to promote the healthy development of obesity and metabolic surgery in China.

To investigate the feasibility and efficacy of laparoscopic Roux-en-Y gastric bypass(LRYGB) for super obesity(BMI≥50 kg/m(2)).Clinical data of 42 patients undergoing LRYGB in the First Affiliated Hospital of Jinan University between 2004 and 2008 were analyzed retrospectively.All the LRYGB procedures were successfully performed with no conversion to open surgery. Average operation time was 145.1 minutes, volume of blood loss during the surgery was 25.0 ml, and length of postoperative hospital stay was 9.9 days. The cases were followed up for 1 month to 30 months. Body weight and BMI decreased significantly 1 month after the operation and reached a minimum level after 2 years then became stable while excess body weight loss rate(EWL) increased(P0.05). All the obese-related symptoms were relieved significantly. Four cases(9.5%) showed complications during perioperative period including 1 case of respiratory failure, 2 cases of gastrojejunal anastomotic bleeding, 1 case of umbilical wound infection, and 11 developed long-term complications. All of them were cured by conservative treatment.Treatment of super obesity by LRYGB is feasible with significant short-term results. But due to the difficulty of the operation and postoperative complications, comprehensive treatment from experienced bariatric surgical team is needed. The long-term outcome needs for further observation.

To compare short-term postoperative outcomes between antecolic and retrocolic laparoscopic Roux-en-Y gastric bypass(LRYGB).Forty obesity patients were admitted into The First Affiliated Hospital of Jinan University from March 2008 to July 2010. All patients were randomly assigned to undergo antecolic (group A, 20 cases) and retrocolic (group B, 20 cases) gastroenteric anastomosis. Short-term outcomes were compared.LRYGB procedures were successfully performed in all the 40 patients. There were no significant differences between the two groups in estimated blood loss during surgery, time to flatus passage, time to resumption of oral intake, or length of postoperative hospital stay. The operation time was longer in group B than that in group A [(163.4±28.1) min vs.(131.8±22.7) min, P0.05]. There were no patients developed internal hernia or anastomotic leakage in either group. Comparison of short-term gastrointestinal symptoms after surgery showed no statistical significance.Although retrocolic procedure may be closer to anatomical structure, antecolic and retrocolic anastomosis have comparable short-term outcomes after surgery. Further study is warranted to investigate long-term outcomes.

To investigate the efficacy of laparoscopic Roux-en-Y gastric bypass (LRYGB) in the treatment for obesity and type 2 diabetes mellitus (DM).Twenty-one cases of obesity and 9 cases of type 2 DM received the LRYGB. Weigh changes, excess body weight lose rate (EWL%) and blood glucose level were measured after surgery and occurrence of complications was observed postoperatively.LRYGB procedures in all the 30 cases were successfully performed with no conversion to open surgery. Average operation time was 168 minutes (110-270 mins), volume of blood loss during the surgery was 24.0 ml (10-75 ml). Twenty-one cases of simple obesity received follow-up from 2 months to 5 years. Body weight and BMI decreased significantly in one month [(85.1+/-10.1) kg vs (97.2+/-15.0) kg, 31.2+/-2.2 vs 35.3+/-3.5, both P0.01] and to a minimal level in 2 to 3 years [(66.8+/-9.2) kg, 24.3+/-1.1], and then maintained at this level. EWL% was correspondingly higher (all P0.05). Nine type 2 DM patients were followed up for 3 to 8 months, fasting blood glucose and blood glucose OGTT2 hours decreased significantly [(5.9+/-1.4) mmol/L vs (12.6+/-2.6) mmol/L, (7.8+/-1.4) mmol/L vs (17.8+/-4.1) mmol/L, both P0.05], of whom 4 patients with obesity decreased in BMI significantly (P0.05), and 5 patients without obesity had no significant changes in BMI (P0.05). Five cases (16.7%) had postoperative complications, including 1 case of death due to acute fulminant pancreatitis, 1 case of mesenteric hiatal hernia with obstruction in line for reoperation, and the other 3 cases of healing by conservative therapy.Treatment of obesity and type 2 DM by LRYGB surgery is feasible with significant short term result. Long term outcome needs further observation.

To investigate the surgical approach, feasibility and effectiveness of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery for treating type 2 diabetes mellitus.Seven obese patients with type 2 diabetes and 5 type 2 diabetic patients without obesity received LRYGB surgery. The changes of the body mass, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG), C peptide (C-P) and HbA1c% were observed postoperatively.LRYGB procedures were successfully performed in all the 12 patients with no conversion to open surgery. The resolution rate was 85.7% in the obese group and 80% in the non-obese diabetic group.LRYGB surgery is feasible for treatment of type 2 diabetes with good short-term result, but the long-term outcome awaits further observation.

To investigate the feasibility and safety of endoscopic thyroidectomy via the areola of breast approach.Between April 2005 to September 2008, endoscopic thyroidectomy via the areola of breast approach was performed in 28 female patients. Of the patients, 25 cases presented with nodular goiter, 2 cases with Grave's disease and 1 case with minimum papillary carcinoma. The average age was 22.5 years (range, 18-38 years). A 10 mm trocar was placed on the medial border of the areola of the right breast for the video-endoscopy and removing specimens, and a 5 mm trocar was placed on the lateral border of the areola of the same breast as the assisted operation hole. Another 5 mm trocar was placed on the medial border of the areola of left breast as the main operation hole. The operation data was recorded and analyzed.All the 28 operations were successful. The procedures included one lobe total thyroidectomy in 5 cases, one lobe subtotal thyroidectomy in 15 cases, subtotal thyroidectomy in 3 cases, one lobe near total thyroidectomy + the other lobe subtotal thyroidectomy in 4 cases, and one lobe total thyroidectomy + the central group lymph node resection + the other lobe subtotal thyroidectomy in 1 case. The average operation time was 60.7 minutes (range, 40-125 minutes), the average operation blood loss was 5.8 ml (range, 2-15 ml), the average length of post-operative hospital stay was 3.1 days (range, 2-5 days). No adverse effects was found after the operation, such as damage to the parathyroid gland and the laryngeal nerve. The patients were followed-up for 1 to 40 months with satisfactory results. All 28 patients were satisfied with the cosmetic effects of the operation.Endoscopic thyroidectomy via the areola of breast approach produces an outstanding cosmetic effect, it is safe and feasible.

To discuss the method, the safety, the advantages and disadvantages of endoscopic thyroidectomy via chest and breasts.From Mar. 2002 to Dec. 2006, endoscopic thyroidectomy via anterior chest and breast approach was performed in 500 patients, including 76 cases of Grave's disease (1 case had an opened operation history), 111 cases of thyroid adenoma, 291 cases of nodular goiter (10 cases have 1-2 opened thyroidectomy history, 2 cases secondary of hyperthyroidism), and 22 cases of thyroid carcinoma.The endoscopic thyroidectomy was successfully carried out in 492 cases, including tumor enucleation in 50 cases, partial lobectomy in 210 cases, subtotal thyroidectomy in 212 cases (including 73 cases of Graves' disease), and lobectomy in 16 cases of thyroid carcinoma. The operative time length ranged from 40 to 270 min (mean 74.5 min). Mean operative blood loss was 5.5 ml (3-250 ml), no cases underwent blood transfusion. The drainage was taken out in the second or third days postoperatively. Postoperative hospital stay ranged from 3 to 8 days (mean 4.2 days). There were some complications including subcutaneous bleeding (3 cases), burn of the epidermal (1 case), inflammation of the incision (2 cases), subcutaneous bruising (3 cases), subcutaneous effusion (6 cases), thyroid crisis (1 case), and temporarily hoarseness of 2 cases. There were no complications such as permanence damage to recurrent laryngeal nerve or parathyroid glands. The complication rate was 3.6% (18/492). The hospital charges ranged from 7600 to 13,500 RM yuan. The average cost of endoscopic thyroidectomy was 10,510 RM yuan, in contrast to 5700 RM yuan for the open thyroidectomy patients. The post-operative following-up was 3 to 57 months (mean 27 months). All the patients were satisfied with the cosmetic results and the same curative effects as conventional surgery were obtained. However, 3 cases of nodular goiter, 1 case of thyroid carcinoma, and 1 case of Grave's disease were recurrence. The operations were converted into open surgery in 8 cases. The 22 cases with carcinoma were survival until now.Endoscopic thyroidectomy is a safe and effective method of thyroid surgery. Since all the minimal incisions are on concealed parts of the body, the obvious cosmetic effect of this method is guaranteed. Some disadvantages such as complications and more costs are needed to be improve.

To evaluate the clinical practice of laparoscopic rectopexy in the treatment of severe rectal prolapse.From March 1998 to February 2007, 4 cases of complete rectal prolapse, including 1 male and 3 female,ranged 21-82 years old, were treated by laparoscopic rectopexy. In one case, the posterior wall of rectum was freed and elevated, and pre-rectal introcession was closed by silk suture, then the posterior wall was suspended and fixed on sacral promontory fascia, finally the sigmoid colon was fixed by sutures on the fascia of left psoas major. In other three cases, insertion of mesh was performed. Rectum was freed and elevated to the level of levalor ani. A sheet of T-shape polypropylene mesh was placed posterior to the rectum, whose lower margin was at the level of levator ani and wrapped around the rectum covering except the anterior wall. The free margin of the mesh was sutured on the muscular layer of rectum, then the mesh was put posterior to the rectum and fixed on the sacral promontory fascia by clipping to repair hernia. After that, the pelvic peritoneum was closed, and finally the sigmoid colon was fixed by sutures on the fascia of left psoas major.Four operation procedures were completed successfully. There was no conversion operation. The time was consumed 92.5 (80-100) min, and the bleeding amount was 6.5 (5-10) ml. No post-operative complications were found. Urine incontinence and encopresis were relieved. No recurrence and constipation was found after 2 months to 3 years follow up postoperatively.Laparoscopic rectopexy is a safe, workable and effective procedure, which can reduce operative trauma and shorten hospitalization time.

To discuss the method, the advantages and disadvantages of endoscopic thyroidectomy.Endoscopic thyroidectomy via areola of breasts approach was performed in 150 patients, including 41 cases of thyroid adenoma, 64 cases of nodular goiter, 40 cases of Graves' disease, and 5 cases of thyroid carcinoma.The endoscopic thyroidectomy was successfully carried out in 144 cases, including tumor dissection in 32 cases, one lobe partial thyroidectomy in 54 cases, two lobe partial thyroidectomy in 19 cases, subtotal thyroidectomy in 37 cases of Graves' disease, and radical thyroidectomy in 2 cases of thyroid carcinoma. The operative time length ranged from 50 to 270 min (mean 80 min). There were no complications such as damage to recurrent laryngeal nerve or parathyroid glands. Postoperative hospital stay ranged from 3 to 7 days (mean 4 days). The post-operative following-up for 1 approximately 13 months indicated that all the patients were satisfied with the cosmetic results and the same curative effects as conventional surgery were obtained. However, the operations were converted into open surgery in 6 cases.Endoscopic thyroidectomy is a safe and effective method of thyroid surgery. Since all the minimal incisions are on concealed parts of the body, the obvious cosmetic effect of this method is guaranteed.

To evaluate the clinical application of laparoscopic vertical banded gastroplasty (LVBG) for morbid obesity.Four patients undergoing LVBG were evaluated by comparison of the preoperative and postoperative morbidities and body weights.Laparoscopic surgery was successfully performed in all the 4 cases without laparotomy. The average operative time was 210 min without intraoperative or postoperative complications. In the 24-month follow-up, the body weight was reduced by over 50% of the excessive weight.LVBG is an effective and safe treatment for morbid obesity.

To investigate the role of the mitochondrial pathway in JTE-522-induced apoptosis and to investigate the relationship between cytochrome C release, caspase activity and loss of mitochondrial membrane potential (Deltapsim).Cell culture, cell counting, ELISA assay, TUNEL, flow cytometry, Western blot and fluorometric assay were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanism.JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Caspases 8 and 9 were activated during apoptosis as judged by the appearance of cleavage products from procaspase and the caspase activities to cleave specific fluorogenic substrates. To elucidate whether the activation of caspases 8 and 9 was required for the apoptosis induction, we examined the effect of caspase-specific inhibitors on apoptosis. The results showed that caspase inhibitors significantly inhibited the apoptosis induced by JTE-522. In addition, the membrane translocation of Bax and cytosolic release of cytochrome C accompanying with the decrease of the uptake of Rhodamin 123, were detected at an early stage of apoptosis. Furthermore, Bax translocation, cytochrome C release, and caspase 9 activation were blocked by Z-VAD.fmk and Z-IETD-CHO.The present data indicate a crucial association between activation of caspases 8, 9, cytochrome C release, membrane translocation of Bax, loss of Deltapsim and JTE-522-induced apoptosis in AGS cells.

AIM: To analyze the prognostic factors of 5-year survival and 10-year survival in hepatocellular carcinoma (HCC) patients, and to explore the reasons for long-term survival and provide choice of treatment modalities for HCC patients. METHODS: From January 1990 to October 2012, 8450 HCC patients were included in a prospective database compiled by the Information Center after hospital admission. Long-term surviving patients were included in a 10-year survival group (520 patients) and a 5-year survival group (1516 patients) for analysis.The long-term survival of HCC patients was defined as the survival of 5 years or longer. Clinical and biologic variables were assessed using univariate and multivariate analyses. The survival of patients was evaluated by follow-up data. RESULTS: The long-term survival of HCC patients was associated with the number of lesions, liver cirrhosis and Child-Pugh classification. It was not found to be associated with tumor diameter, histological stage, and pretreatment level of serum α-fetoprotein. The differences in clinical factors between the 5-year survival and the 10-year survival were found to be the number of lesions, liver cirrhosis, Child-Pugh classification, and time elapsed until first recurrence or metastasis. The survival period of different treatment modalities in the patients who survived for 5 years and 10 years showed significant differences: (in order of significance) surgery alone > surgery-transcatheter arterial chemoembolization (TACE) > TACE-radiofrequency ablation (RFA) > TACE alone > surgery-TACE-RFA. The 10-year survival of HCC patients was not associated with the choice of treatment modality. CONCLUSION: This retrospective study elucidated survival outcomes, prognostic factors affecting survival and treatment modalities in HCC patients.

JTE-522-induced apoptosis in human gastric adenocarinoma cell line AGS cells by caspase activation accompanying cytochrome C release, membrane translocation of Bax and loss of mitochondrial membrane potential