Dynamic structural insights into the molecular mechanism of DNA unwinding by the bacteriophage T7 helicase.

The hexametric T7 helicase (gp4) adopts a spiral lock-washer form and encircles a coil-like DNA (tracking) strand with two nucleotides bound to each subunit. However, the chemo-mechanical coupling mechanism in unwinding has yet to be elucidated. Here, we utilized nanotensioner-enhanced Förster resonance energy transfer with one nucleotide precision to investigate gp4-induced unwinding of DNA that contains an abasic lesion. We observed that the DNA unwinding activity of gp4 is hindered but not completely blocked by abasic lesions. Gp4 moves back and forth repeatedly when it encounters an abasic lesion, whereas it steps back only occasionally when it unwinds normal DNA. We further observed that gp4 translocates on the tracking strand in step sizes of one to four nucleotides. We propose that a hypothetical intermediate conformation of the gp4-DNA complex during DNA unwinding can help explain how gp4 molecules pass lesions, providing insights into the unwinding dynamics of gp4.

Individualized treatment of pediatric inguinal hernia reduces adolescent recurrence rate: an analysis of 3006 cases.

PURPOSE: We implemented the individualized treatment (IT) regimen for children with inguinal hernia and the Lichtenstein hernioplasty using an acellular tissue matrix patch (LHAP) for those with high risks. This retrospective study compares the complications of conventional laparoscopic high hernia sac ligation (LHSL) with those of the IT regimen for the management of pediatric inguinal hernia and investigates whether the recurrence rate of inguinal hernias in children treated by IT is lower than that of those treated by LHSL. METHODS: The subjects of this retrospective study were 3006 children who underwent LHSL or IT for inguinal hernia between February, 2008 and February, 2016 at the Beijing Chao-Yang Hospital (Beijing, China). They comprised 1516 (50.4%) children who underwent LHSL between February, 2008 and December, 2012, and 1490 (49.6%) who underwent IT between January, 2013 and June, 2016. We analyzed the patients' data, including clinical characteristics and postoperative complications. The mean follow-up was 85.31 months for the LHSL group and 43.34 months for the IT group (P < 0.01). Given the difference in the follow-up periods, the log-rank test was used to analyze the recurrence rate. RESULTS: The mean age, weight, and height of these children at the time of surgery were 6 years old, 24.17 kg, and 114.48 cm in the LHSL group and 6 years old, 24.57 kg, and 115.18 cm in the IT group, respectively (P = 0.647, P = 0.393, P = 0.505). The mean age, body weight, and height for adolescents at the time of surgery were 14.7 years old, 57.19 kg, and 168.37 cm in the LHSL group and 14.9 years old, 57.96 kg and 169.21 cm in the IT group, respectively (P = 0.099, P = 0.061, P = 0.059). The male/female ratio was 5.1:1 (1268/248) in the LHSL group and 4.9:1 (1241/249) in the IT group (P = 0.795). The side ratio of inguinal hernia (right/left/bilateral) was about 10:7:8 (602/430/484) in the LHSL group and 3.8:2.8:3.4 (567/422/501) in the IT group (P = 0.551). The comorbidities of the male patients included hydrocele (206), cryptorchidism (15), umbilical hernia (12), congenital heart disease (16), and other congenital diseases (25). The comorbidities in the female patients included round ligament cysts (11). There was no significant difference between the groups in postoperative complications including hydrocele (P = 0.687), hematoma (P = 0.061), surgical site infection (P = 0.742), testicular atrophy (not found), and umbilical trocar hernia (P = 0.585). There were two cases of recurrence in the IT group and eight in the LHSL group (P = 0.07). The frequency of postoperative recurrence of adolescent inguinal hernia was 3.16% (7/221) in the LHSL group, 0 (0/223) in the IT group (P = 0.008), and 0 (0/128) in the LHSL subgroup in the IT group (P = 0.045). CONCLUSION: The favorable outcomes of IT, which had a lower recurrence rate than LHSL for adolescent inguinal hernia, demonstrate that this is a reasonable treatment regimen for pediatric inguinal hernia.

Primary thyroid leiomyosarcoma: A case report and literature review.

Primary thyroid leiomyosarcoma (LMS) is an extremely rare soft tissue cancer; only 22 cases have been reported in the literature to date. In the current study, the case of an 83-year-old male patient who presented with a neck mass that had grown rapidly over the previous 3 months is reported. The patient underwent thyroid lobectomy twice and two cycles of immunotherapy for the treatment of primary thyroid LMS; however, he succumbed to the disease 5 months after the second surgery. An accurate diagnosis of primary thyroid LMS is difficult, as the disease is often misdiagnosed as anaplastic carcinoma, and requires the combined assessment of clinical, imaging and pathological data. Diagnosis of the current patient with primary thyroid LMS and a comprehensive review of the relevant literature are presented herein.

Clinical significance of pre-operative neutrophil lymphocyte ratio and platelet lymphocyte ratio as prognostic factors for patients with colorectal cancer.

The present study aimed to investigate the independent prognostic values of the pre-operative neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in patients with colorectal cancer (CRC). The present study retrospectively analyzed the data of 216 patients with CRC from a single hospital. The clinicopathological characteristics of the patients were compared and prognostic factors were evaluated. NLR and PLR were associated with tumor differentiation status and the tumor diameter, respectively, and PLR was also associated with the primary tumor classification (T classification). Furthermore, NLR and PLR were positively associated with each other (R2=0.5368; P<0.0001). Univariate analyses indicated that stage II and III patients with a high NLR (≥4.98; P<0.001) or PLR (≥246.36; P<0.001) possessed a significantly poorer 5-year OS rate compared with those with a low NLR or PLR. Post-operative adjuvant chemotherapy improved the 5-year OS rate in patients with a high NLR or PLR. Multivariate analyses indicated that NLR and PLR were independent prognostic factors [NLR, relative risk (RR)=4.074 and P<0.001; PLR, RR=2.029 and P=0.029] in patients with CRC, and were associated with the T classification, lymph node metastasis and post-operative adjuvant chemotherapy response of patients. Additionally, the area under the curve (AUC) was 0.748 for NLR (95% CI, 0.684-0.804; P<0.0001) and 0.690 for PLR (95% CI, 0.623-0.751; P<0.0001). The RR and AUC indicated that NLR was the superior predictive factor in patients with CRC. In conclusion, the pre-operative NLR and PLR were significant independent prognostic factors in patients with CRC, and NLR was more effective as a prognostic marker compared with PLR. Adjuvant chemotherapy appeared to be more effective in CRC patients with a higher NLR or PLR.

Clinical significance of immunotherapy with combined three kinds of cells for operable colorectal cancer.

Surgery, chemotherapy, and radiotherapy have presented with the ability of killing tumor cells, as well as damaging the immune function, which can be corrected by the immunotherapy. The purpose of this perspective cohort study was to evaluate the efficacy of postoperative immunotherapies of tumor lysate-loaded dendritic cells (DC), in vitro DC-activated T (DC-AT), and activated T cells (ATC) combined with chemotherapy on the survival of patients with operable colorectal cancer. A total of 253 patients with primary colorectal cancer resection including 181 patients receiving postoperative simple chemotherapy (control group) and 72 patients receiving immunotherapies of DC, DC-AT, and ATC combined with chemotherapy during the corresponding period (immunotherapy group) were enrolled in this perspective cohort study. The survival of these patients was analyzed. The immunotherapy group presented a higher 5-year overall survival rate than the control group (75.63 vs 67.81 %, P = 0.035), as well as 3-year overall survival rate (87.07 vs 74.80 %, P = 0.045). For patients with advanced cancer (TNM stages III and IV), immunotherapy significantly promotes mean survival than control subjects (59.74 ± 3.21 vs 49.99 ± 2.54 years, P = 0.034). Patients who received more than three cycles of immunotherapies had a higher 5-year overall survival rate than those with less than three cycles (82.10 vs 69.90 %, P = 0.035). No serious adverse effect was observed in the immunotherapy group. Postoperative immunotherapies with DC, DC-AT, and ATC combination can promote the survival of patients with operable colorectal cancer (Clinical Trials, ChiCTR-OCH-12002610).

Advances and disputes of posterior malleolus fracture.

OBJECTIVE: The objective of this article is to summarize the development of evaluation and treatment of posterior malleolus fracture (PMF). DATA SOURCES: Data used in this review were mainly from English literature of PubMed data base. Study selection Articles were included in this review if they were related to the PMF or trimalleolar fracture. RESULTS: No consensus was found regarding what sizes of posterior malleolus fragments would lead to ankle instability thus affecting prognosis and should be fixed. X-ray measurement is unreliable, while CT scan is widely recommended and it can recognize the occult posterior malleolus fractures associated with tibia shaft fractures, which are always undetected previously. Direct posterior malleolus fixation is suitable to stabilize syndesmotic injury. The basic and clinical researches support direct reduction and buttress plate fixation of posterior malleolus fracture through the posterolateral approach. Operative indications and timing of weight bearing are still in discussion. CONCLUSIONS: Knowing whether ankle instability occurs and the proper methods to diagnose, evaluate, and operate can help manage the fracture. Further biomechanical research on ankle stability and clinical study to compare various treatment methods are required.

[Assessment value of preoperative neutrophil-lymphocyte ratio for the prognosis of patients with colorectal cancer after radical operation].

OBJECTIVE: To assess the value of preoperative neutrophil-lymphocyte ratio (NLR) for prognosis in patients with colorectal cancer after radical operation. METHODS: Clinical data of 140 patients with colorectal cancer undergoing radical operation in the Department of General Surgery of General Hospital of PLA from July 2005 to July 2011 were analyzed retrospectively. According to preoperative NLR, patients were divided into the low NLR group (NLR<5, n=105) and the high NLR group (NLR≥5, n=35). The overall 5-year survival rates of two groups were compared and the independent risk factors were examined by univariate analysis and Cox model. RESULTS: The overall 5-year survival rates of the low and high NLR groups were 74.8% and 54.7% respectively with significant difference (P=0.03). Univariate analysis revealed depth of tumor, lymph nodes metastasis, TMN stage and NLR were associated with survival (P<0.05, P<0.01). Cox model showed that NLR was independent risk factor of prognosis (RR=1.068, 95%CI:1.009-1.129, P=0.02). CONCLUSION: Preoperative NLR≥5 predicts poorer prognosis of colorectal cancer patients.

[Analysis of treatment and prognosis in 34 patients with anorectal malignant melanoma].

OBJECTIVE: To explore the prognostic factors of anorectal malignant melanoma (ARMM). METHODS: Medical records and follow-up data of 34 patients with ARMM treated in the Chinese PLA General Hospital from March 1993 to November 2011 were analyzed retrospectively. RESULTS: There were 26 abdominoperineal resections(APR) and 8 wide local excisions (WLE). Twenty patients underwent postoperative adjuvant therapy, including chemotherapy in 14 cases, radiotherapy in 2 cases, traditional Chinese medicine therapy in 4 cases and immunotherapy in 16 cases. Postoperative follow-up was carried out in all the patients and the mean follow-up period was 27 months. The 1-, 3- and 5-year overall survival rates were 76.3%, 39.6% and 20.6% respectively, while the 1-, 3- and 5-year disease-free survival rates were 60.6%, 30.8% and 12.8% respectively. APR and postoperative immunotherapy could significantly reduce the local recurrence rate. According to the Kaplan-Meier method, gross type of tumor, mural involvement, lymph metastasis, and clinical staging had significant effects on overall survival, while lymph metastasis and postoperative immunotherapy on disease-free survival. Cox proportional hazards model indicated that the clinical staging and postoperative immunotherapy were significant predictive factors. CONCLUSIONS: Early diagnosis and correct choice of surgical method are the keys to the treatment. Postoperative immunotherapy can prolong disease-free survival.

Robotic anterior resection of rectal cancer: technique and early outcome.

BACKGROUND: The Da Vinci system is a newly developed device for colorectal surgery. With advanced stereoscopic vision, lack of tremor, and the ability to rotate the instruments surgeons find that robotic systems are ideal laparoscopic tools. Since conventional laparoscopic total mesorectal excision is a challenging procedure, we have sought to assess the utility of the Da Vinci robotic system in anterior resections for rectal cancer. METHODS: Between November 2010 and December 2011, a total of 22 patients affected by rectal cancer were operated on with robotic technique, using the Da Vinci robot. Data regarding the outcome and pathology reports were prospectively collected in a dedicated database. RESULTS: There were no conversions to open surgery and no postoperative mortality of any patient. Mean operative time was (220 ± 46) minutes (range, 152 - 286 minutes). The median number of lymph nodes harvested was (14.6 ± 6.5) (range, 8 - 32), and the circumferential margin was negative in all cases. The distal margin was (2.6 ± 1.2) cm (range, 1.0 - 5.5 cm). The mean length of hospital stay was (7.8 ± 2.6) days (range, 7.0 - 13.0 days). Macroscopic grading of the specimen was complete in 19 cases and nearly complete in three patients. CONCLUSIONS: Robotic anterior resection for rectal surgery is safe and feasible in experienced hands. Outcome and pathology findings are comparable with those observed in open and laparoscopy procedures. This technique may facilitate minimally invasive radical rectal surgery.