Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Downregulated calmodulin expression contributes to endothelial cell impairment in diabetes.

Endothelial dysfunction, a central hallmark of cardiovascular pathogenesis in diabetes mellitus, is characterized by impaired endothelial nitric oxide synthase (eNOS) and NO bioavailability. However, the underlying mechanisms remain unclear. Here in this study, we aimed to identify the role of calmodulin (CaM) in diabetic eNOS dysfunction. Human umbilical vein endothelial cells and murine endothelial progenitor cells (EPCs) treated with high glucose (HG) exhibited downregulated CaM mRNA/protein and vascular endothelial growth factor (VEGF) expression with impeded eNOS phosphorylation and cell migration/tube formation. These perturbations were reduplicated in CALM1-knockdown cells but prevented in CALM1-overexpressing cells. EPCs from type 2 diabetes animals behaved similarly to HG-treated normal EPCs, which could be rescued by CALM1-gene transduction. Consistently, diabetic animals displayed impaired eNOS phosphorylation, endothelium-dependent dilation, and CaM expression in the aorta, as well as deficient physical interaction of CaM and eNOS in the gastrocnemius. Local CALM1 gene delivery into a diabetic mouse ischemic hindlimb improved the blunted limb blood perfusion and gastrocnemius angiogenesis, and foot injuries. Diabetic patients showed insufficient foot microvascular autoregulation, eNOS phosphorylation, and NO production with downregulated CaM expression in the arterial endothelium, and abnormal CALM1 transcription in genome-wide sequencing analysis. Therefore, our findings demonstrated that downregulated CaM expression is responsible for endothelium dysfunction and angiogenesis impairment in diabetes, and provided a novel mechanism and target to protect against diabetic endothelial injury.

Reversible Phase Transition with Ultralarge Dielectric Relaxation Behaviors in Succinimide Lithium(I) Hybrids.

Dielectric relaxations have widely applied on high permittivity capacitors, dielectric switches, ferroelectrics, pyroelectrics, and electrical insulating materials. However, few investigations of large dielectric relaxation behaviors on organic-inorganic hybrid materials have been documented before. Here we present a novel two-dimensional succinimide lithium(I) hybrid compound, [Li(PDD)2ClO4]n, 1, (PDD = 2,5-pyrrolidinedione = succinimide) which shows reversible phase transition behavior in the vicinity of 228 K accompanied by an unusual symmetry breaking from I41/amd to C2/c. X-ray single crystal diffractions analysis indicates the twist motion of pyrrolidine heterocycles, and order-disorder motion of ClO4- anions triggered the reversible phase transition. By means of an intuitive crystallographic model (rattling ion model), we further illustrated the mechanism of the interesting reversible phase transition. Particularly, 1 shows ultralarge dielectric relaxation behavior in the vicinity of the phase transition by its dielectric constant dependence on temperatures and frequencies as well as its Cole-Cole relation.

A new method of CT for the cardiac measurement: correlation of computed tomography measured cardiac parameters and pulmonary obstruction index to assess cardiac morphological changes in acute pulmonary embolism patients.

Acute pulmonary embolism (APE) is a serious disease which is life-threatening. Since it is crucial for APE patients to assess the changes of cardiac function safely and timely, the imaging research of cardiac morphology and function is becoming more and more important. The correlation of computed tomography (CT) measured cardiac parameters and pulmonary obstruction index (POI) was analyzed to discuss the morphological changes of the heart of APE patients in order to provide a new method to evaluate cardiac functions accurately and effectively. 118 APE patients confirmed with CT pulmonary angiography (CTPA) were divided into high-risk group (47 cases, POI ≥ 20) and low-risk group (71 cases, POI < 20) according to the Qanadli Score. The left to right diameter (RL) and the anteroposterior diameter (AP) of the cardiac chambers were compared among the high-risk group, the low-risk group, and the normal group (60 cases). The correlation between CT measured cardiac parameters and the POI was analyzed. Except for left ventricular AP and right atrial AP, there were statistically significant differences (P < 0.05) in the RL and AP of the each cardiac cavity, these parameters meant that right hearts were enlarged and the left hearts were decreased in size. The ratio of right/left heart diameter was statistically significant among the three groups, a < b < c (P < 0.05). Moreover, the POI of 118 APE patients was 14.29 ± 9.53, and there was significant linear correlation between CT measured cardiac parameters and the POI (P < 0.05), excluding the left ventricular AP and right atrial AP. The correlation coefficient reached 0.5 or more in terms of the right atrial LR, the right ventricular LR, the ratio of right/left atrial diameter and the ratio of right/left ventricular diameter. With the increasing value of POI, the right atrium and right ventricular of APE patients were enlarged, and the left atrium and left ventricular were decreased in size. These heart changes can be observed by using CTPA, even non-enhanced chest CT.

P21, COX-2, and E-cadherin are potential prognostic factors for esophageal squamous cell carcinoma.

Much research effort has been devoted to identifying prognostic factors for esophageal squamous cell carcinoma (ESCC) by immunohistochemistry; however, no conclusive findings have been reached thus far. We hypothesized that certain molecules identified in previous studies might serve as useful prognostic markers for ESCC. Therefore, the aim of the current study was to validate the most relevant markers showing potential for ESCC prognosis in our prospective esophageal cancer database. A literature search was performed using the PubMed database for papers published between 1980 and 2015 using the following key words: 'esophageal cancer,' 'prognosis,' and 'immunohistochemistry.' Literature selection criteria were established to identify the most widely studied markers, and we further validated the selected markers in a cohort from our single-surgeon team, including 153 esophageal cancer patients treated from 2000 to 2010. A total of 1799 articles were identified, 82 of which met the selection criteria. Twelve markers were found to be the most widely studied, and the validation results indicated that only P21, COX-2, and E-cadherin were independent prognostic factors for ESCC patients in this series. The systemic review and cohort validation suggest that P21, COX-2, and E-cadherin are potential prognostic factors for ESCC, paving the way for more targeted prospective validation in the future.

Outcome of laparoscopic versus open resection for rectal cancer in elderly patients.

BACKGROUND: Laparoscopic colorectal resection has been gaining popularity over the past two decades. However, studies about laparoscopic rectal surgery in elderly patients with long-term oncologic outcomes are limited. In this study, we evaluated the short-term and long-term outcomes of laparoscopic and open resection in patients with rectal cancer aged ≥ 70 y. METHODS: From 2007-2012, a total of 294 consecutive patients with rectal cancer from a single institution were included, 112 patients undergoing laparoscopic rectal resection were compared with 182 patients undergoing open rectal resection. RESULTS: Seven (6.3%) patients in the laparoscopic group required conversion to open surgery. The two groups were well balanced in terms of age, gender, body mass index, American society of anesthesiologists scores, site, and stage of the tumors. Laparoscopic surgery was associated with significantly longer median operating time (220 versus 200 min; P = 0.005), less estimated blood loss (100 versus 150 mL; P < 0.001), a shorter postoperative hospital stay (8 versus 11 d), lower overall postoperative complication rate (15.2% versus 26.4%; P = 0.025), wound-related complication rate (7.14% versus 17.03%; P = 0.015), less need of blood transfusion (8.04% versus 16.5%; P = 0.038), and surgical intensive care unit after surgery (12.5% versus 22.0%; P = 0.042) when compared with open surgery. Mortality, quality of surgical specimen, lymph nodes harvested, positive distal, and circumferential margin rate were not significantly different between two groups. The estimated 3-y survival rates were similar between two groups. CONCLUSIONS: Laparoscopic rectal surgery is safe and feasible in patients >70 y and is associated with better short-term outcomes when compared with open surgery.

Clinical parameters predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer.

INTRODUCTION: Preoperative chemoradiotherapy (CRT), followed by total mesorectal excision, has become the standard of care for patients with clinical stages II and III rectal cancer. Patients with pathologic complete response (pCR) to preoperative CRT have been reported to have better outcomes than those without pCR. However, the factors that predict the response to neoadjuvant CRT have not been well defined. In this study, we aimed to investigate the impact of clinical parameters on the development of pCR after neoadjuvant chemoradiation for rectal cancer. METHODS: A total of 323 consecutive patients from a single institution who had clinical stage II or III rectal cancer and underwent a long-course neoadjuvant CRT, followed by curative surgery, between 2005 and 2013 were included. Patients were divided into two groups according to their responses to neoadjuvant therapy: the pCR and non-pCR groups. The clinical parameters were analyzed by univariate and multivariate analyses, with pCR as the dependent variable. RESULTS: Of the 323 patients, 75 (23.2%) achieved pCR. The two groups were comparable in terms of age, sex, body mass index, tumor stage, tumor location, tumor differentiation, radiation dose, and chemotherapy regimen. On multivariate analysis, a pretreatment carcinoembryonic antigen (CEA) level of ≤ 5 ng/mL [odds ratio (OR) = 2.170, 95% confidence interval (CI) = 1.195-3.939, P = 0.011] and an interval of >7 weeks between the completion of chemoradiation and surgical resection (OR = 2.588, 95% CI = 1.484-4.512, P = 0.001) were significantly associated with an increased rate of pCR. CONCLUSIONS: The pretreatment CEA level and neoadjuvant chemoradiotherapy-surgery interval were independent clinical predictors for achieving pCR. These results may help clinicians predict the prognosis of patients and develop adaptive treatment strategies.

Prognostic factors for desmoid tumor: a surgical series of 233 patients at a single institution.

Desmoid tumors are rare soft tissue tumors with limited data on their management and prognosis. We sought to determine the rates of recurrence after surgery for desmoid tumors and analyze factors predictive of recurrence-free survival (RFS). From February 1976 to October 2011, 233 consecutive patients with desmoid tumors who underwent macroscopically complete resection were included in this study. Clinicopathologic and treatment characteristics were evaluated to determine predictors of recurrence. Patterns of presentation included primary (n = 156, 67.0 %) and locally recurrent (n = 77, 33.0 %) disease initially treated elsewhere. Most patients had a R0 resection (n = 169, 72.5 %). In addition to surgery, 43 (18.5 %) patients received radiotherapy and 10 (4.3 %) patients received systemic therapy. Median follow-up was 54 months; recurrence disease was observed in 62 (26.6 %) patients. The estimated 5- and 10-year RFS was 74.2 % (95 % confidence interval (CI), 68.3-80.1) and 70.7 % (95 % CI, 64.2-77.2), respectively. Factors associated with worse RFS were tumor size larger than 5 cm (hazard ratio (HR) = 3.757; 95 % CI, 1.945-7.259; p < 0.001), extra-abdominal tumor location (abdominal wall referent; HR = 3.373; 95 % CI, 1.425-7.984; p = 0.006), and R1 resection status (HR = 1.901; 95 % CI, 1.140-3.171; p = 0.014). Patients were grouped according to the number of unfavorable prognostic factors; the 10-year RFS rates of patients with zero, one, two, and three prognostic factors were 100, 86.9, 48.5, and 34.4 %, respectively (p < 0.001). Regardless of primary or recurrent disease, surgical resection remains central to the management of patients with desmoid tumors. However, there are clearly different prognostic subgroups that could benefit from different therapeutic strategies, and a wait-and-see policy is a possible option for a subset of patients.

Short-term outcomes of laparoscopically assisted surgery for rectal cancer following neoadjuvant chemoradiotherapy: a single-center experience.

OBJECTIVE: The efficacy of laparoscopic treatment of rectal cancer remains unclear, and little is known about its effect on sphincter preservation. We compared short-term outcomes of laparoscopically assisted and open surgeries following neoadjuvant chemoradiotherapy (CRT) for mid and low rectal cancer. METHODS: This study enrolled 137 patients with mid-low rectal cancer who underwent curative resection, 51 by laparoscopically assisted (Lap group) and 86 by conventional open (Open group) surgeries, following neoadjuvant CRT from July 2007 to July 2012. The clinical and surgical findings of the two groups of patients were prospectively collected and analyzed. RESULTS: Three patients (5.9%) in the Lap group were converted to an open procedure. The mean operating times were similar in both groups. The Lap group had a significantly higher rate of sphincter preservation (62.7% versus 41.9%, P = 0.018) and significantly lower mean blood loss than the Open group. Mean times to first flatus, start of a normal diet, and overall postoperative hospitalization were longer for open surgery. The complication rate (11.8% versus 31.4%, P = 0.009) was significantly lower in the Lap group. Mean distal resection margin, involvement of the circumferential resection margin (2.0% versus 3.5%, P = 1.000), and mean lymph nodes harvested (12 versus 11; P = 0.242) were equivalent in the two groups. CONCLUSIONS: Laparoscopically assisted surgery following neoadjuvant CRT is safe for patients with rectal cancer and provides favorable short-term benefits but without compromising oncologic outcomes. This sphincter-preserving procedure may be a treatment of choice for patients with lower rectal cancer.

Impact of interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer on surgical and oncologic outcome.

BACKGROUND: The aim of this study was to evaluate the effect of a longer interval between long-course neoadjuvant chemoradiotherapy and surgery on surgical and oncologic outcome. METHODS: A total of 233 consecutive patients with clinical stage II and III rectal cancer were divided into 2 groups according to the neoadjuvant-surgery interval: short-interval group (≤ 7 weeks, n = 111), and long-interval group (>7 weeks, n = 122). Data on neoadjuvant-surgery interval, operative time, perioperative complications, final pathology, disease recurrence, and mortality were prospectively collected and analyzed. RESULTS: The two groups were comparable in terms of demographics, tumor, and treatment characteristics. Operative time and perioperative complications were not influenced by a longer interval. Patients in the long-interval group had a significantly higher pathologic complete response (pCR) rate (27.1% vs. 15.3%, P = 0.029), and a decreased rate of circumferential resection margin involvement (1.6% vs. 8.1%, P = 0.020). After a median follow-up of 42 months (range 6-90 months), the 3-year local recurrence rate was 12.9% in the short-interval group versus 4.8% in the long-interval group (P = 0.025). CONCLUSIONS: A neoadjuvant-surgery interval >7 weeks is safe and is associated with a higher rate of pCR and R0 resection, and decreased local recurrence.

[Higher procalcitonin level in diabetic nephropathy patients compared with healthy volunteers].

OBJECTIVE: To investigate the difference of procalcitonin (PCT) level between uninfected diabetic nephropathy patients and healthy volunteers. METHODS: This study enrolled 76 patients with diabetes only [DM group, 24 h urinary micro albumin (mALB) < 30 mg/24 h], 81 patients with early DN (EDN group, mALB 30-300 mg/24 h), 87 DN patients (DN group, mALB > or = 300 mg/24 h), and 82 age- and sex-matched healthy volunteers. All the patients were free of systemic infection. PCT levels and various laboratory parameters including metabolic and kidney functions as well as inflammatory element profiles were assessed. RESULTS: The PCT level of DN group was significantly higher than that of healthy control group, DM group and EDN group (P < 0.001 or P < 0.05). Spearman's test showed a significant positive correlation between PCT and serum lactate dehydrogenase (LDH, r = 0.541, P < 0.01), Urine acid (UA) (r = 0. 320, P < 0.01), Urea (r = 0.324, P < 0.01), creatinine (Cr) (r= 0.403, P < 0.01), alpha-hydroxybutyrate dehydrogenase (alpha-HBD) (r = 0.791, P < 0.01) and C-reactive protein (CRP) (r = 0.694, P < 0.001) in diabetic nephropathy patients respectively. CONCLUSION: Serum PCT level of patients with diabetic nephropathy is higher than that of healthy volunteers, which may be associated with minimal inflammation and kidney function damage.

Optical diode made from a moving photonic crystal.

Optical diodes controlling the flow of light are of principal significance for optical information processing. They transmit light from an input to an output, but not in the reverse direction. This breaking of time reversal symmetry is conventionally achieved via Faraday or nonlinear effects. For applications in a quantum network, features such as the abilities of all-optical control, on-chip integration, and single-photon operation are important. Here we propose an all-optical optical diode which requires neither magnetic fields nor strong input fields. It is based on a "moving" photonic crystal generated in a three-level electromagnetically induced transparency medium in which the refractive index of a weak probe is modulated by the moving periodic intensity of a strong standing coupling field with two detuned counterpropagating components. Because of the Doppler effect, the frequency range of the crystal's band gap for the probe copropagating with the moving crystal is shifted from that for the counterpropagating probe. This mechanism is experimentally demonstrated in a room temperature Cs vapor cell.

[Outcome analysis of simultaneous liver resection for synchronous liver metastases from colorectal cancer].

OBJECTIVE: To analyze the outcomes of simultaneous liver resection for patients who have primary colorectal cancer with synchronous hepatic metastases to see if there is any advantage for doing so. METHODS: We retrospectively analyzed the medical records (1999 - 2009) of 53 consecutive patients with synchronously recognized primary colorectal carcinoma and hepatic metastases who underwent simultaneous (40 patients) or two-stage (13 patients) colonic and hepatic resections performed at our hospital. RESULTS: There was no thirty-day mortality in both groups. The two groups had significant differences in mean operation duration [(212.9 ± 72.3) min vs. (326.5 ± 140.2) min, P = 0.014], mean blood loss [(337.5 ± 298.0) ml vs. (594.6 ± 430.5) ml, P = 0.020], post-operative hospital stay [(16.2 ± 8.1) day vs. (25.8 ± 8.5) day, P = 0.001]. The incidence rates of post-operative complications were 25.0% (10/40) and 53.8% (7/13), respectively, in the two groups (P = 0.053). The 1-, 3-, 5-year survival rates in the simultaneous resection group were 95.0%, 57.0% and 37.4%, respectively, with a median overall survival of 40.0 months and median disease-free survival of 14.0 months. The 1-, 3-, 5-year survival rates in the two-stage resection group were 92.3%, 58.7% and 36.7%, respectively, with a median overall survival of 38.0 months and median disease-free survival of 13.0 months. There were no significant differences between the two groups in respect of their survivals (P > 0.05). CONCLUSIONS: Simultaneous colectomy and hepatectomy are safe and efficient for colorectal cancer patients who have synchronous colorectal liver metastases, with less complications and blood loss, and shorter hospital stay compared with the two-stage resection.

[Analysis of 21 cases treated by total laparoscopic rectosigmoid cancer surgery with transanal natural orifice specimen extraction].

OBJECTIVE: To evaluate the feasibility, safety and short-term outcomes of total laparoscopic rectosigmoid cancer surgery with transanal natural orifice specimen extraction. METHODS: From July 2012 to February 2013, 21 patients underwent total laparoscopic surgery with transanal natural orifice specimen extraction. There were 12 males and 9 females with a median age of 53 (48-77) years.Rectal cancer (n = 11) and sigmoid cancer (n = 10) were diagnosed. The clinical data such as bowel function recovery time, number of lymph nodes harvested and an incidence of anastomotic leakage was collected and retrospectively analyzed to assess the value of this technique. RESULTS: Operation was successfully accomplished without conversion into open surgery or conventional laparoscopic-assisted surgery. The median operative duration was 105 (80-165) min, the median volume of blood loss 50 (20-300) ml, the median number of lymph nodes harvested 16(8-29) and the time of first bowl movement was 48 (24-72) h. The postoperative hospitalization stay was 9 (6-12) d. There were abdominal hemorrhage (n = 1) and anastomotic leakage (n = 1). CONCLUSION: Total laparoscopic rectosigmoid cancer surgery with transanal natural orifice specimen extraction appears to be feasible, and oncologically acceptable for selected patients.

A study on the impact of mental health problems on the academic buoyancy of medical students and the mechanisms.

Objective: To analyze the effects of different family environmental backgrounds and mental health problems on academic buoyancy and to explore the potential mechanisms of their effects, using a sample of 2085 medical students in Jiangsu province. Methods: Using the multiple linear regression to analyze the impact of mental health problems on academic buoyancy in different family environment contexts. Results: (1) Higher family income and parental literacy implied higher levels of academic buoyancy in children; (2) mental health problems and academic buoyancy were negatively related, and generalized anxiety and uncertainty stress negatively predicted academic buoyancy levels; (3) uncertainty stress may have an indirect effect on academic buoyancy levels through a partially mediating effect of generalized anxiety.

[Protective effects of Lycium ruthenicum Murr. juice on alcoholic liver injury in rats].

Objective: To study the protective effects of Lycium ruthenicum Murr. juice on alcoholic liver injury in rats and explore the regulatory mechanism of toll-like receptors 4 (TLR4)/p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in this process. Methods: Sixty male SD rats were randomly divided into control group (C), model group (M), low-dose Lycium ruthenicum Murr. juice group (LLM), medium-dose Lycium ruthenicum Murr. juice group (MLM) and high-dose Lycium ruthenicum Murr. juice group (HLM), 12 rats in each group. The group M, LLM, MLM and HLM were treated with 20 ml/kg (8 g/(kg·d)) ethanol (400 g/L) intragastrically and the gavage was divided into two sessions, group C was treated with an equal volume of distilled water at the same time point. Four hours before the first alcohol gavage session, rats in each dose group of Lycium ruthenicum Murr. juice were administered with 2.4, 4.8, 9.6 ml/(kg·d) Lycium ruthenicum Murr. juice respectively, and the other groups were given equal volume of distilled water at the corresponding time points. Four weeks later, the rats were sacrificed 24 hours after the end of the last experiment, blood and liver were collected. The liver index was calculated. The morphology of the liver was observed by HE staining. The expressions of hepatic TLR4, p38 MAPK and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were detected by immunohistochemistry. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by colorimetry. The levels of hepatic tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-10 (IL-10) and interleukin-18 (IL-18) were detected by enzyme linked immunosorbent assay. Results: Compared with group C, the alcoholic liver injury model was established successfully in Group M. Compared with group M, related indicators in each dose group of Lycium ruthenicum Murr. juice were improved, the improvement of hepatic morphology in group HLM was the most significant, the liver index, the levels of serum ALT, AST and hepatic TLR4, p38 MAPK/p-p38 MAPK ratio, TNF-α, IL-1ß, IL-18 were decreased (P＜ 0.05 or P＜0.01), while the level of hepatic IL-10 was increased (P＜0.01). Comparison among the dose groups of Lycium ruthenicum Murr. juice, the levels of liver index, serum AST and hepatic TLR4, p38 MAPK/p-p38 MAPK ratio, TNF-α, IL-18 in HLM were lower than those in LLM (P＜0.05 or P＜0.01); the level of hepatic IL-10 in HLM was higher than that in LLM and MLM (P＜0.05 or P＜0.01); the other indicators in each dose group had no statistical difference (P＞0.05). Conclusion: Lycium ruthenicum Murr. juice can improve the inflammatory stress by regulating TLR4/p38 MAPK signaling pathway, relieve alcoholic liver injury in rats, and the effect of high-dose group is better than the others.

Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR).

PURPOSE: To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy [TNT]) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine [chemoradiotherapy; CRT]). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS). RESULTS: Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11; P < .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5% v 75.1%; P = .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (P < .001). CONCLUSION: Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.

The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy for unresectable rectal cancer (SUNRISE): interim analysis of a randomized phase II trial.

PURPOSE: The safety of an MRI simulation-guided boost after short-course preoperative radiotherapy (SCPRT) for unresectable rectal cancer is assessed with a planned interim analysis. METHODS AND MATERIALS: Patients diagnosed with clinical stage T3-4 or regional lymph node-positive disease with positive mesorectal fascia or T4b disease evaluated by pelvic MRI were randomly assigned to the SCPRT-boost group (25 Gy in 5 fractions plus 4 Gy delivered to the gross tumor volume, followed by four cycles of chemotherapy) or preoperative chemoradiotherapy group (50 Gy in 25 fractions with concurrent chemotherapy). Then, patients received total mesorectal excision surgery after preoperative treatment. The primary endpoint was the R0 resection rate. The interim analysis was performed when 42 patients completed their assigned treatments. RESULTS: From October 2018 to November 2019, a total of 43 patients were enrolled, and 42 patients were included in the interim analysis. During preoperative therapy, grade 3 or above toxicities were observed in 10/21 (47.6%) patients in the experimental group, and 4/21 (19.0%) patients in the control group. A total of 17 (81.0%) and 13 (61.9%) patients in the experimental group and control group underwent surgery, respectively. Overall, 65.1% of the patients achieved R0 resection in the intention-to-treat analysis. Surgery-related adverse complications were observed in 2 patients (11.8%) in the experimental group and 1 patient (7.7%) in the control group. CONCLUSION: Our results show that the toxicity of an MRI simulation-guided boost after SCPRT for unresectable rectal cancer is acceptable. Thus, this clinical trial will be continued as planned.

Quantitative analysis of three-dimensional reconstruction data to guide the selection of methods for laparoscopic distal pancreatectomy.

BACKGROUND/PURPOSE: To explore the risk factors of splenic vessel preservation in laparoscopic distal pancreatectomy (LDP) and to guide with the appropriate selection of surgical methods through three-dimensional (3D) reconstruction. METHODS: Patients suffering from benign or low-grade malignant tumors of pancreatic body and tail having undergone LDP in Ningbo Medical Center Lihuili Hospital from January 2014 to September 2019 were selected for quantitative analysis of the anatomical data of patients' pancreas, tumors, splenic vessels and spleens by 3D reconstruction. According to the final surgical methods, the patients were divided into the laparoscopic spleen-preserving distal pancreatectomy with splenic vessel preservation (lap-SVP) group and the non-lap-SVP group. Clinical data of the two groups were compared to assess the risk factors for surgical failure of lap-SVP and logistic regression model was applied to predict the choice of surgical methods. RESULTS: A total of 218 patients were included in the study, including 144 in the lap-SVP group and 74 in the non-lap-SVP group. Multivariate analysis confirms that large tumor volume, large contact area between the pancreas to be resected and the splenic vein, and large maximum ratio of the circumference of the splenic vessel embedded in the pancreas to be resected to the circumference of the splenic vessel are independent risk factors for surgical failure of lap-SVP (OR > 1, P < .05). The prediction accuracy of lap-SVP operation by the logistic regression reaches up to 80.9%. CONCLUSIONS: 3D reconstruction can provide essential basis for the surgical method selection of laparoscopic distal pancreatectomy.

[Effects of astaxanthin combined with aerobic exercise on renal aging of rat induced by D-galactose and its mechanism].

Objective: To study the effects and mechanisms of astaxanthin combined with aerobic exercise on renal senescence of rat induced by D-galactose. Methods: Sixty 3-month-old SPF SD rats were divided into control group (C group), acute senescence group (S group), astaxanthin+acute senescence group (AS group), aerobic exercise+acute senescence group (ES group), astaxanthin+aerobic exercise+acute senescence group (AES group), by two-factor two-level 2×2 factorial design with 12 rats in each group. Acute senescence model of rat was establshed by intraperitoneal injection with 100 mg/(kg·d) D-galactose, and the intervention was conducted with 20 mg/(kg·d) astaxanthin and/or aerobic exercise with 60% VO2max for 6 weeks. The histopathological/ultrastructural changes of the kidney were observed by light microscope/electron microscope; the levels of SOD, γ-GCS and MDA were detected by ELISA, and LDF in kidney was determined by fluorescence colorimetry; the protein expression of Nrf2 signaling pathway was detected by immunohistochemistry. Results: Compared with AS and ES group, in AES group, the improvement of renal tissue morphology/ultrastructure was more significant; LDF was decreased significantly (P＜0.01); SOD activity was significantly increased (P＜0.01); γ-GCS was significantly higher than that of AS group, but not significantly different from that of ES group (P＞0.05); there was no significant difference in MDA between groups (P＞0.05); the levels of Nrf2 and p-Nrf2 were increased significantly (P＜0.05, P＜0.01); HO-1 was significantly higher than that of ES group(P＜0.05), but not significantly different compared with that of AS group(P＞0.05). Conclusion: Astaxanthin combined with aerobic exercise can delay aging process of kidney, its mechanism may be that the combination regulate the protein expression in Nrf2 signaling pathway, Ⅱ detoxifying enzymes and antioxidant enzyme activity, and improve oxidative stress in kidney of rat induced by D-galactose.