Elucidating the molecular determinants in the process of gastrin C-terminal pentapeptide amide end activating cholecystokinin 2 receptor by Gaussian accelerated molecular dynamics simulations.

Gastrin plays important role in stimulating the initiation and development of many gastrointestinal diseases through interacting with the cholecystokinin 2 receptor (CCK2R). The smallest bioactive unit of gastrin activating CCK2R is the C-terminal tetrapeptide capped with an indispensable amide end. Understanding the mechanism of this smallest bioactive unit interacting with CCK2R on a molecular basis could provide significant insights for designing CCK2R antagonists, which can be used to treat gastrin-related diseases. To this end, we performed extensive Gaussian accelerated molecular dynamics simulations to investigate the interaction between gastrin C-terminal pentapeptide capped with/without amide end and CCK2R. The amide cap influences the binding modes of the pentapeptide with CCK2R by weakening the electrostatic attractions between the C-terminus of the pentapeptide and basic residues near the extracellular domain in CCK2R. The C-terminus with the amide cap penetrates into the transmembrane domain of CCK2R while floating at the extracellular domain without the amide cap. Different binding modes induced different conformational dynamics of CCK2R. Residue pairs in CCK2R had stronger correlated motions when binding with the amidated pentapeptide. Key residues and interactions important for CCK2R binding with the amidated pentagastrin were also identified. Our results provide molecular insights into the determinants of the bioactive unit of gastrin activating CCK2R, which would be of great help for the design of CCK2R antagonists.

One-step implementation of Toffoli gate for neutral atoms based on unconventional Rydberg pumping.

Compared with the idea of universal quantum computation, a direct synthesis of a multiqubit logic gate can greatly improve the efficiency of quantum information processing tasks. Here we propose an efficient scheme to implement a three-qubit controlled-not (Toffoli) gate of neutral atoms based on unconventional Rydberg pumping. By adjusting the strengths of Rabi frequencies of driving fields, the Toffoli gate can be achieved within one step, which is also insensitive to the fluctuation of the Rydberg-Rydberg interaction. Considering different atom alignments, we can obtain a high-fidelity Toffoli gate at the same operation time ∼7 µs. In addition, our scheme can be further extended to the four-qubit case without altering the operating time.

Surgical outcomes and survival for T4 gastric cancer extending to the transverse colon.

BACKGROUND: For the treatment of locally advanced (T4) gastric cancer, extended multi-organ resection remains controversial. This study aimed to evaluate the surgical outcomes and survival of patients with T4 gastric cancer extending to the transverse colon. METHODS: A total of 2,652 gastric cancer patients underwent surgery between December 2011 and December 2015. Data from 40 of these patients who underwent curative resection for T4 gastric cancer extending to the transverse colon were obtained. Patient characteristics, related complications, long-term survival, and prognostic factors for T4 gastric cancer were analyzed. RESULTS: Postoperative morbidity occurred in 5 (12.5%) patients. All of the patients were cured with conservative treatment. No procedure-related mortality occurred. The 1-, 3-, and 5-year overall survival (OS) rates were 75.0%, 49.2%, and 36.9%, respectively, with a median survival time of 24 months. Univariate analysis revealed tumor size (P=0.049), advanced T stage (P=0.013), and lymph node metastasis (P=0.006) to be poor prognostic factors of OS. Advanced T stage and lymph node metastasis were identified by multivariate analysis as being independent prognostic factors. Further, it was observed that lymph node metastasis grade was associated with poorer OS. CONCLUSIONS: Patients with T4 gastric cancer extending to the transverse colon might benefit from curative resection with acceptable morbidity and mortality.

Recombinant adenovirus expressing a dendritic cell-targeted melanoma surface antigen for tumor-specific immunotherapy in melanoma mice model.

Viral vectors represent a potential strategy for the treatment of human malignant tumors. Currently, recombinant adenovirus vectors are commonly used as gene therapy vehicles, as it possesses a proven safety profile in normal human cells. The recombinant adenovirus system has an ability to highly express exogenous genes and increase the stability of the carrier, which is only transiently expressed in the host cell genome, without integrating. Malignant melanoma cells are produced by the skin, and melanocyte tumors that exhibit higher malignant degrees lead to earlier transfer and higher mortality. In the present study, a recombinant adenovirus (rAd) was generated to express Anti-programmed death-1 (rAd-Anti-PD-1) and used to investigate the efficacy in melanoma cells and tumors. The results demonstrated that B16-F10 cell growth was significantly inhibited and the apoptosis incidence rate was markedly promoted following rAd-PD-1 treatment. The present study demonstrated that the production of α and ß interferon was increased, which led to the induction of dendritic cell (DCs) maturation in rAd-anti-PD-1-treated mice. The present study indicated that rAd-anti-PD-1 exhibited the ability to generate more cluster of differentiation (CD)4+CD8+ T cells and induce a PD-1-specific cytotoxic T lymphocyte through DC-targeted surface antigens in mice. This resulted in a further enhanced recognition of melanoma cells due to DCs being targeted by the rAd-anti-PD-1-encoded PD-1. Notably, mice treated with the rAd-anti-PD-1-targeted PD-1 demonstrated an improved protection compared with tumor-bearing mice from the challenge group treated with a recombinant gutless adenovirus and Anti-PD-1. In conclusion, the present study demonstrated that targeting the melanoma surface antigens via the rAd-anti-PD-1-infected tumor cells enhanced the ability of recombinant adenovirus to induce a potent tumor-inhibitory effect and antigen-specific immune response.

Association of long non-coding RNA HOTTIP with progression and prognosis in colorectal cancer.

Long non-coding RNA (lncRNA) has an important role in carcinoma progression and prognosis. However, little is known about the pathological role of lncRNA HOTTIP (HOXA transcript at the distal tip) in colorectal cancer (CRC) patients. This study attempted to investigate the association of lncRNA HOTTIP expression with progression and prognosis in CRC patients. LncRNA HOTTIP expression was measured in 156 CRC tissues and 21 adjacent non-malignant tissues using qRT-PCR. In present study, our results indicated that lncRNA HOTTIP was highly expressed in CRC compared with adjacent non-malignant tissues (P<0.001), and positively correlated with T stage (T1-2 vs. T3-4, P = 0.001), clinical stage (I-II stages vs. III-IV stages, P = 0.003), and distant metastasis (absent vs. present, P = 0.014) in CRC patients. Furthermore, we also observed that increased lncRNA HOTTIP expression was an unfavorable prognostic factor in CRC patients (P = 0.001), regardless of T stage, distant metastasis and clinical stage. Finally, overexpression of lncRNA HOTTIP was supposed to be an independent poor prognostic factor for CRC patients through multivariate analysis (P = 0.017). In conclusion, lncRNA HOTTIP overexpression maybe serves as an unfavorable prognosis predictor for CRC patients. However, a further larger sample size investigation is needed to support our results.

[Efficacy observation of paralleled clipping of rectal ligament in resection of rectal cancer in obese male patients].

OBJECTIVE: To investigate the approach and efficacy of dealing the rectal ligament in resection of rectal cancer in obese male patients. METHODS: A total of 92 patients (BMI>25 kg/m(2)) undergoing resection of rectal cancer from December 2008 to December 2010 in Henan Tumor hospital were assigned into 2 groups according to the surgical technique, the modified group (paralleled clipping of rectal ligament, 48 patients) and traditional group (44 patients). Operative time, intra-operational bleeding, rectal ulceration, ureteral injury, mesorectal integrity, and positive rate of lateral margin of pelvic wall were compared between two groups. RESULTS: The operative time was (66.9±99.8) min in modified group, which was significantly shorter than that in traditional group [(125.4±12.2) min, P=0.000]. Intra-operative bleeding was (160.3±27.2) ml in modified group and (150.5±28.5) ml in traditional group (P=0.093). Rectal ulceration rated were 0 and 18.2% (8/44), mesorectal disintegrity rates were 6.2% and 22.7%, pelvic infection rates were 2.1% (1/48) and 20.4 (9/44) in modified and traditional groups respectively, whose differences were all significant (all P<0.05). No ureteral injury and positive margin were found in both two groups. CONCLUSION: The approach of paralleled clipping of rectal ligament around the rectum meets the principle of TME, which is simple, safe and effective.

[The clinical application of compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx in controlling presacral venous plexus hemorrhage during rectectomy].

OBJECTIVE: To evaluate the effect of compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx in controlling presacral venous plexus hemorrhage during rectectomy. METHODS: From October 2002 to October 2012, 52 patients with rectal cancer received neoadjuvant radiotherapy and developed presacral venous plexus hemorrhage during rectectomy, included 36 male and 26 female cases. Their age were 36-65 years. The hemostasis time and blood loss were analyzed. RESULTS: All 52 patients achieved R0 resection. Of which 13 patients achieved suture hemostasis within 15 minutes, whereas 22 patients unsuccessfully treated within 15 minutes received compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx. The median blood loss was (196 ± 44)ml and hospitalization time was (15.2 ± 1.7)days in this group. Additionally, 7 patients achieved suture hemostasis within 20 minutes except 4 patients who received compression hemostasis, with a median blood loss of (1016 ± 86)ml and hospitalization time of (21.7 ± 6.3)days. Other 6 patients achieved suture hemostasis within 30 minutes except 3 patients who received compression hemostasis, with a median blood loss of (2508 ± 73)ml and the hospitalization time was (28.8 ± 3.3)days. There was statistically significant difference of bleeding (F = 4289.562) and hospitalization time (F = 50.121) in 3 groups of patients (P = 0.000). CONCLUSIONS: Once intraoperative presacral venous plexus hemorrhage can't be stopped timely, compression hemostasis with an arc-shaped transperineal incision in front of the apex of coccyx is an effective alternative for the patients with rectal cancer who received neoadjuvant radiotherapy.

[Common types of massive intraoperative haemorrhage, treatment philosophy and operating skills in pelvic cancer surgery].

OBJECTIVE: To explore the common types of massive intraoperative bleeding, clinical characteristics, treatment philosophy and operating skills in pelvic cancer surgery. METHODS: We treated massive intraoperative bleeding in 19 patients with pelvic cancer in our department from January 2003 to March 2012. Their clinical data were retrospectively analyzed. The clinical features of massive intraoperative bleeding were analyzed, the treatment experience and lessons were summed up, and the operating skills to manage this serious issue were analyzed. RESULTS: In this group of 19 patients, 7 cases were of presacral venous plexus bleeding, 5 cases of internal iliac vein bleeding, 6 cases of anterior sacral venous plexus and internal iliac vein bleeding, and one cases of internal and external iliac vein bleeding. Six cases of anterior sacral plexus bleeding and 4 cases of internal iliac vein bleeding were treated with suture ligation to stop the bleeding. Six cases of anterior sacral and internal iliac vein bleeding, one cases of anterior sacral vein bleeding, and one case of internal iliac vein bleeding were managed with transabdominal perineal incision or transabdominal cotton pad compression hemostasis. One case of internal and external iliac vein bleeding was treated with direct ligation of the external iliac vein and compression hemostasis of the internal iliac vein. Among the 19 patients, 18 cases had effective hemostasis. Their blood loss was 400-1500 ml, and they had a fair postoperative recovery. One patient died due to massive intraoperative bleeding of ca. 4500 ml. CONCLUSIONS: Most of the massive intraoperative bleeding during pelvic cancer surgery is from the presacral venous plexus and internal iliac vein. The operator should go along with the treatment philosophy to save the life of the patient above all, and to properly perform suture ligation or compression hemostasis according to the actual situation, and with mastered crucial operating hemostatic skills.

[Application of trans-abdominal-mediastinal drainage tube in patients with high risk of esophagogastric or esophago-jejunal anastomotic leakage].

OBJECTIVE: To evaluate the therapeutic effects of trans-abdominal-mediastinal drainage tube on the prevention of esophagogastric or esophago-jejunal anastomotic leakage. METHODS: A total of 79 patients underwent thoraco-abdominal radical resection for gastric cardia cancer, with high risk of leakage of the anatsomosis, from Aug. 2007 to Aug. 2011 were included in this study. They were assigned into 2 groups. Forty one patients had trans-abdominal-mediastinal drainage tube (improvement group) and 38 patients were without the mediastinal drainage tube (control group). The clinical data of all the 79 patients were reviewed and the therapeutic effects of the two treatment approaches were compared. RESULTS: There was anastomotic leakage in four patients of the improvement group. They were with stable vital signs and the median hospital stay was 29.3 days. There was anastomotic leakage in five cases of the contol group and all of them had high fever and chest tightness. One among those five patients had transdermal placement of thoracic drainage tube and was cured, and four among those five patients had second debridement operation, with 3 cured and one death case. Except the one death case, the median hospital stay of the control group was 53.4 days, significantly longer than that of the improvement group (P < 0.05). CONCLUSIONS: Although putting trans-abdominal-mediastinal drainage tube can not prevent the leakage of esophagogastric or esophago-jejunnal anastomosis, it can reduce the systemic inflammatory responses, death and painful suffering of the patients caused by anastomotic leakage.

[Application of an arc-shaped transperineal incision in front of the apex of coccyx during the resection of pelvic retroperitoneal tumors].

OBJECTIVE: To explore a better operative approach to resect complicated pelvic retroperitoneal tumors. METHODS: A total of 28 patients with complicated pelvic retroperitoneal tumors who received surgical resection in our hospital from 2006 to 2010 were included in this study. The surgical operation was assisted with an arc-shaped transperineal incision in front of the apex of coccyx. The operation time, intraoperative blood loss, death toll and length of hospital stay of the patients were retrospectively analyzed. RESULTS: The median operation time was 122.5 minutes. The median blood loss was 420 ml, and the median length of hospital stay of the patients was 17.5 days. There was no postoperative death in this group of patients. CONCLUSION: With the assistance of this arc-shaped transperineal incision in front of the apex of coccyx, the resection of pelvic retroperitoneal tumors can be effectively improved and the surgery risk is reduced.

[Association of early diarrhea after the low anterior resection of rectal cancer and anastomotic leakage].

OBJECTIVE: To evaluate the association of early diarrhea(postoperative day 1 to 7) and anastomotic leakage after low anterior resection for rectal cancer. METHODS: Clinical data of 192 cases (group A, tumor from the anal verge 4-7 cm) from May 2004 to May 2007 and 236 cases(group B) from July 2007 to May 2010 in our hospital who received low anterior resection of rectal cancer were analyzed retrospectively. RESULTS: In group A, the incidence of early postoperative diarrhea was 19.3%(37/192), of which 9 cases were treated with anti-diarrhea drugs. The morbidity of anastomotic leakage in patients with diarrhea was significantly higher than those without early diarrhea(16.2% vs. 5.2%, P<0.05). In group B, the incidence of early postoperative diarrhea was 16.5%(39/236). All the patients were treated with anti-diarrhea drugs. There was no difference in the morbidity of anastomotic leakage between patients with diarrhea and those without early diarrhea(16.2% vs. 5.2%, P<0.05). There was no difference in early diarrhea between groups A and B(P>0.05). However, the incidence of anastomotic leakage in patients with early diarrhea was lower in group B(P<0.05). CONCLUSIONS: Early diarrhea after the low anterior resection of rectal cancer may indicate anastomotic leakage. Treatment of early postoperative diarrhea may reduce the risk of anastomotic leakage.