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.

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.

[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.

[Regulatory effect of curcumin on splenic inflammation in overtraining rats and its mechanism].

Objective: To study the alleviating effects of curcumin on splenic inflammation in overtraining rats by regulating toll-like receptor 4 (TLR4)-p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. Methods: Male Wistar rats of 7-week old were divided into control group (C group, 12), overtraining model group (OM group, 11), curcumin + overtraining model group (COM group, 14). C Group did not undergo any exercise intervention. OM and COM group underwent 8-week incremental load swimming training. During the training, rats in the COM group were treated with 200 mg/ (kg·d) curcumin in the volume as 5 ml/kg, and the other groups were treated with an equal volume of 0.5 % sodium carboxymethylcellulose. 24 hours after the last training, the spleen index was calculated by weighing, the pathological changes of the spleen were observed by light microscopy, and the biochemical indicators of blood and spleen were detected. Results: After 8-week incremental load swimming training, the splenic structure in C group was normal under light microscope; the spleen index of OM group was significantly lower than that of C group (P＜0.01) and pathological changes of inflammation were obvious; the spleen index of COM group was significantly higher than that of OM group (P＜0.05) and pathological changes of inflammation were alleviated. Compared with C group, in OM group, the serum levels of corticosterone (Cor), NF-κB, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and TLR4 expression rate on splenic monocytes surface, splenic TNF-α, IL-6 were increased (P＜0.05 or P＜0.01), the expressions of p38 MAPK, phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and NF-κB in spleen were increased (P＜0.05 or P＜ 0.01); serum testosterone (T), serum and splenic interleukin-10 (IL-10) were decreased (P＜0.01). Compared with OM group, in COM group, serum levels of Cor, NF-κB, TNF-α, IL-6 and TLR4 expression rate on splenic monocytes surface, splenic TNF-α, IL-6 were decreased (P＜0.05 or P＜0.01), the expressions of p38 MAPK, p-p38 MAPK and NF-κB in spleen were decreased (P＜ 0.05); serum T, serum and splenic IL-10 were increased (P＜0.05). The trend of T/Cor ratio between groups was consistent with testosterone change. Conclusion: The 8-week incremental load swimming training aggravated inflammation of spleen in rats, led to pathological inflammatory changes. Curcumin supplementation during training can down-regulate expressions of TLR4-p38 MAPK/NF-κB signaling pathway-related proteins, thereby maintaining a dynamic equilibrium between pro-inflammatory/anti-inflammatory cytokines, protecting the spleen.

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.

Safety and efficacy of preoperative chemoradiotherapy in fit older patients with intermediate or locally advanced rectal cancer evaluated by comprehensive geriatric assessment: A planned interim analysis of a multicenter, phase II trial.

BACKGROUND AND PURPOSE: Comprehensive geriatric assessment (CGA) is a diagnostic method to assess the physical and mental health status of older patients. The purpose of this study was to assess the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for intermediate or locally advanced rectal cancer in older people who were classified as "fit" by CGA. The interim analysis focusing on safety was reported here as the first part of this trial. METHODS AND MATERIALS: This is a single arm, multicenter, phase II trial. The eligible patients for this study were aged 70 years or above that fulfilled the standard of intermediate or locally advanced risk category, and met the standard of fit (SIOG1) evaluated by CGA. All patients received preCRT (50 Gy) with Raltitrexed (3 mg/m2 on d1 and d22). Qualitative and quantitative variables were described using descriptive statistics. The surgery adherence predicting was analyzed by multivariate logistic regression. RESULTS: Thirty-nine fit patients were enrolled. All patients except one finished radiotherapy without dose reduction. Thirty-two patients finished the prescribed Raltitrexed therapy as scheduled. A serious toxicity was observed in 12 patients (30.8%), and only six patients (15.4%) experienced non-hematological side effects. CONCLUSION: Overall, our results showed that preCRT was feasible and safe in older patients with rectal cancer who were evaluated as fit based on CGA, supporting the use of CGA to tailor oncological treatment and predict the tolerance of a specific therapy. Completing this trial as planned would provide further valuable insights.

[Effects of aerobic exercise combined with Lycium ruthenicum on some indicators of myocardial lipid metabolism in rats with high-fat diet].

OBJECTIVE: To study the effects of aerobic exercise combined with Lycium ruthenicumon on some indicators of myocardial lipid metabolism in rats with high-fat diet. METHODS: Fifty-five male Wistar rats were subjected to adaptive feeding for 4 days and weight-free swimming training for 3 days, 20 min/d. After eliminating 5 rats that were not suitable for swimming training, the others were randomly divided into 5 groups according to their weight: regular diet + quiet control group (RDC), high fat diet + quiet control group (HDC), high-fat diet + Lycium ruthenicum quiet control group (HDLC), high fat diet + aerobic exercise group (HDM), high fat diet + Lycium ruthenicum + aerobic exercise group (HDLM), 10 in each group. Group HDM and HDLM did 60 min/d swimming training for 6 weeks with no-bearing. Group C were fed regular diet; The other groups were fed with high-fat diet; Group HDLC and HDLM were intragastrically treated with Lycium ruthenicum at the dose of 4.48 g/(kg·d), and the volume was 5 mL/kg, and the other groups were given equivalent distilled water. The Lee's index, serum and myocardial biochemical indexes were measured after 6 weeks. RESULTS: Compared with group RDC, Lee's index, serum free fatty acids (FFA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), myocardial FFA and intercellular adhesion molecule-1 (ICAM-1) increased significantly (P＜0.01), serum level of high-density lipoprotein cholesterol (HDL-C) decreased significantly (P＜0.01) in group HDC. Compared with group HDC, Lee's index, serum FFA, IL-6, TNF-α, TC, TG, LDL-C, myocardial FFA and ICAM-1 decreased significantly (P＜0.05 or P＜0.01), serum HDL-C levels increased significantly (P＜0.05 or P＜0.01) in group HDLC, HDM and HDLM. Compared with group HDLC and HDM, Lee's index, serum FFA, IL-6, TNF-α, TC, TG, LDL-C, myocardial FFA and ICAM-1 decreased significantly (P＜0.05), serum HDL-C level increased significantly (P＜0.05) in group HDLM. CONCLUSION: Aerobic exercise and/or Lycium ruthenicum can improve lipid metabolism in rats with high-fat diet, reduce lipotoxicity caused by obesity. Combined intervention is more effective.

Designing and Constructing a High-Temperature Molecular Ferroelectric by Anion and Cation Replacement in a Simple Crown Ether Clathrate.

Molecular ferroelectrics have displayed a promising future since they are light-weight, flexible, environmentally friendly and easily synthesized, compared to traditional inorganic ferroelectrics. However, how to precisely design a molecular ferroelectric from a non-ferroelectric phase transition molecular system is still a great challenge. Here we designed and constructed a molecular ferroelectric by double regulation of the anion and cation in a simple crown ether clathrate, 4, [K(18-crown-6)]+ [PF6 ]- . By replacing K+ and PF6 - with H3 O+ and [FeCl4 ]- respectively, we obtained a new molecular ferroelectric [H3 O(18-crown-6)]+ [FeCl4 ]- , 1. Compound 1 undergoes a para-ferroelectric phase transition near 350 K with symmetry change from P21/n to the Pmc21 space group. X-ray single-crystal diffraction analysis suggests that the phase transition was mainly triggered by the displacement motion of H3 O+ and [FeCl4 ]- ions and twist motion of 18-crown-6 molecule. Strikingly, compound 1 shows high a Curie temperature (350 K), ultra-strong second harmonic generation signals (nearly 8 times of KDP), remarkable dielectric switching effect and large spontaneous polarization. We believe that this research will pave the way to design and build high-quality molecular ferroelectrics as well as their application in smart materials.

Application of indocyanine green-enhanced near-infrared fluorescence-guided imaging in laparoscopic lateral pelvic lymph node dissection for middle-low rectal cancer.

BACKGROUND: As one effective treatment for lateral pelvic lymph node (LPLN) metastasis (LPNM), laparoscopic LPLN dissection (LPND) is limited due to the complicated anatomy of the pelvic sidewall and various complications after surgery. With regard to improving the accuracy and completeness of LPND as well as safety, we tried an innovative method using indocyanine green (ICG) visualized with a near-infrared (NIR) camera system to guide the detection of LPLNs in patients with middle-low rectal cancer. AIM: To investigate whether ICG-enhanced NIR fluorescence-guided imaging is a better technique for LPND in patients with rectal cancer. METHODS: A total of 42 middle-low rectal cancer patients with clinical LPNM who underwent total mesorectal excision (TME) and LPND between October 2017 and March 2019 at our institution were assessed and divided into an ICG group and a non-ICG group. Clinical characteristics, operative outcomes, pathological outcomes, and postoperative complication information were compared and analysed between the two groups. RESULTS: Compared to the non-ICG group, the ICG group had significantly lower intraoperative blood loss (55.8 ± 37.5 mL vs 108.0 ± 52.7 mL, P = 0.003) and a significantly larger number of LPLNs harvested (11.5 ± 5.9 vs 7.1 ± 4.8, P = 0.017). The LPLNs of two patients in the non-IVG group were residual during LPND. In addition, no significant difference was found in terms of LPND, LPNM, operative time, conversion to laparotomy, preoperative complication, or hospital stay (P > 0.05). CONCLUSION: ICG-enhanced NIR fluorescence-guided imaging could be a feasible and convenient technique to guide LPND because it could bring specific advantages regarding the accuracy and completeness of surgery as well as safety.

Intra-corporeal delta-shaped anastomosis in laparoscopic right hemicolectomy for right colon cancer: a safe and effective technique.

BACKGROUND AND OBJECTIVE: Intra-corporeal delta-shaped anastomosis (IDA) is an important development in laparoscopic digestive-tract reconstruction. We applied it in laparoscopic right hemicolectomy for right colon cancer and compared the short-term outcomes between the patients treated with IDA and conventional extracorporeal anastomosis (EA). METHODS: Between 1 January 2016 and 1 October 2017, 36 and 50 patients who underwent IDA and EA, respectively, were included. Data on clinicopathological characteristics, surgical outcomes, post-operative recovery and complications were collected and compared between the two groups. RESULTS: Surgical outcomes and clinicopathological characteristics were similar between the two groups except the length of incision, which was significantly shorter in the IDA group than in the EA group (4.6 ± 0.6 vs 5.6 ± 0.7 cm, P < 0.001). The time to ground activities, fluid diet intake and post-operative hospitalization did not differ between the groups; however, the time to first flatus was significantly shorter in the IDA group than in the EA group (2.8 ± 0.5 vs 3.2 ± 0.8 days, P = 0.004). The post-operative visual analogue scale for pain was lower in the IDA group than in the EA group on post-operative Day 1 (4.0 ± 0.7 vs 4.5 ± 1.0, P = 0.002) and post-operative Day 3 (2.7 ± 0.6 vs 3.4 ± 0.6, P < 0.001). The surgical complication rates were 8.3 and 16.0% in the IDA and EA groups (P = 0.470), respectively. No complications such as anastomotic bleeding, stenosis and leakage occurred in any patient. CONCLUSIONS: IDA is safe and feasible and shows more satisfactory short-term outcomes than EA.

The short-term effect analysis of intraoperative intraperitoneal perfusion chemotherapy with lobaplatin for colorectal cancer.

PURPOSE: To explore the safety and feasibility of intraoperative, intraperitoneal perfusion chemotherapy with lobaplatin for colorectal cancer (CRC). METHODS: From November 1, 2016 to January 15, 2017, a total of 100 patients with CRC in Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, who had undergone radical surgery, were randomized into two groups as follows: the lobaplatin group (50 patients) and the control group (50 patients). The time of recovery of postoperative intestinal functions, hematotoxicity, hepatic-renal toxicity, and postoperative complications were observed and analyzed, with the goal of exploring the safety and feasibility of the drug administration. RESULTS: The time to first gas exhaust in lobaplatin and the control group was 3.08 days and 3.20 days, respectively (p=0.392). The time of defecation in lobaplatin and the control group was 4.38 days and 4.50 days, respectively (p=0.524). There was no statistically significant difference between them in terms of the time of gas exhaust and defecation. One case with intra-abdominal hemorrhage, 1 case with anastomotic leakage, 3 cases with incision complication, 1 case with adhesive intestinal obstruction, and 1 case with pulmonary infection occurred in lobaplatin group compared to 1 case with anastomotic bleeding, 1 case with anastomotic leakage, 2 cases with incision complication, 2 cases with adhesive intestinal obstruction, 2 cases with pulmonary infection, and 1 case with lymphatic fistulas occurred in control group. There was no statistically significant difference between the groups in terms of the total incidence of postoperative complications (p=0.790). No statistically significant difference was observed between the groups in terms of leukocyte and platelet levels on the first, third, and fifth postoperative day. There was also no statistically significant difference in terms of platelet level 2 weeks after surgery. Both the lobaplatin and control group had 2 cases with postoperative abnormal hepatic-renal function. A total of 6 cases in the lobaplatin group and 7 cases in the control group developed gastrointestinal reactions, showing no statistically significant difference (p=0.766). CONCLUSION: Intraoperative intraperitoneal perfusion chemotherapy with lobaplatin showed no effect on short-term recovery in patients with CRC.

International consensus on natural orifice specimen extraction surgery (NOSES) for colorectal cancer.

In recent years, natural orifice specimen extraction surgery (NOSES) in the treatment of colorectal cancer has attracted widespread attention. The potential benefits of NOSES including reduction in postoperative pain and wound complications, less use of postoperative analgesic, faster recovery of bowel function, shorter length of hospital stay, better cosmetic and psychological effect have been described in colorectal surgery. Despite significant decrease in surgical trauma of NOSES have been observed, the potential pitfalls of this technique have been demonstrated. Particularly, several issues including bacteriological concerns, oncological outcomes and patient selection are raised with this new technique. Therefore, it is urgent and necessary to reach a consensus as an industry guideline to standardize the implementation of NOSES in colorectal surgery. After three rounds of discussion by all members of the International Alliance of NOSES, the consensus is finally completed, which is also of great significance to the long-term progress of NOSES worldwide.

Recipient-Derived Allo-iTregs Induced by Donor DCs Effectively Inhibit the Proliferation of Donor T Cells and Reduce GVHD.

To compare the potency of recipient-derived, antigen-specific regulatory T cells induced by different dendritic cells (DCs; iTregs) and freshly isolated natural regulatory T cells (nTregs) in preventing mouse graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT). CD4+ T cells from recipient BALB/c mice were stimulated with DCs from recipient BALB/c (syn-DCs), donor B6 (allo-DCs), and third-party C3H (third-party-DCs) mice to induce different iTregs. In parallel, nTregs were isolated from spleen cells of recipient BALB/c (syn-nTregs) and donor B6 (allo-nTregs) mice using magnetic-activated cell sorting. Mixed lymphocyte reaction (MLR) assays were performed to evaluate the suppressive ability of these various regulatory T cells (Tregs). Both the iTregs and nTregs were transfused to GVHD mice on Days 0, 1, 3, and 5. Body weight, GVHD score, and survival time were monitored. Peripheral Tregs were subsequently examined on Days 7, 14, 21, and 28 after BMT, while chimerism was evaluated on Days 14 and 60. Histopathology of colon, liver, and spleen were also performed. DCs markedly induced CD25+ and Foxp3+ expression on CD4+ T cells. The allo-DC-induced Tregs (allo-iTregs) suppressed the proliferation of alloreactive T cells better than the other iTregs/nTregs in MLR assays (P < 0.05). Meanwhile, transfusion of the allo-iTregs reduced the severity of GVHD (P < 0.05), increased survival time compared with the GVHD group (P < 0.05), and enhanced the chimerism proportion. On Day 28 after BMT, the allo-iTregs group had the highest frequency of peripheral Tregs (P < 0.05). Recipient-derived allo-iTregs induced by donor DCs included predominant clones that specifically recognized donor antigens. These allo-iTregs not only prevented GVHD by suppressing the proliferation of donor-alloreactive T cells, but also promoted engraftment, and prolonged the survival of GVHD mice. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 302:825-836, 2019. © 2018 Wiley Periodicals, Inc.

[Regulatory effects of curcumin on spleen apoptosis in overtraining rats and its mechanism].

OBJECTIVE: To study the mechanisms of curcumin alleviating oxidative stress and spleen apoptosis induced by overtraining in rats by regulating Kelch-like ECH-associated protein-1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway. METHODS: Male Wistar rats of 7 weeks old were divided into control group (C group, 12), overtraining group (OM group, 11), curcumin + overtraining group (COM group, 14). The C Group did not undergo any exercise intervention. The OM and COM group underwent 8-week incremental load swimming training. During the training, rats in the COM group were treated with curcumin at the dose of 200 mg/(kg·d) in the volume of 5 ml/kg by gavage, and rats in the other groups were given an equal volume of solvent, 0.5% sodium carboxymethylcellulose. Twenty-four hours after the last training, the spleen index was calculated by weighing, the pathological changes of the spleen were observed by light microscopy, and the biochemical indicators of blood and spleen were detected. RESULTS: The spleen structure of C group was normal under light microscope; the spleen index of OM group was significantly lower than that of C group (P＜0.01) and pathological changes were obvious; the spleen index of COM group was significantly higher than that of OM group (P＜0.05) and histomorphological changes were relieved. Compared with C group, in OM group, serum corticosterone (Cor) level, spleen apoptosis level, malondialdehyde (MDA) concentration and the expression of proapoptotic Bcl-2 associated X protein (Bax) in spleen were increased (P＜0.05 or P＜0.01); the body weight, serum testosterone (T), superoxide dismutase (SOD) activity, the expressions of heme oxygenase-1 (HO-1) and anti-apoptotic B cell lymphoma-2 protein (Bcl-2) in spleen were decreased (P＜0.05 or P＜0.01); the expression of Nrf2 was not changed significantly (P＞ 0.05). Compared with OM group, in COM group, there were no significant changes in body weight (P＞0.05), serum T level, SOD activity, the expressions of Bcl-2, Nrf2 and HO-1 in spleen were increased (P＜0.05 or P＜0.01); serum Cor level, spleen apoptosis level, MDA concentration and the expression of Bax were decreased (P＜0.05 or P＜0.01). The change trend of T/Cor ratio between groups was consistent with the change of testosterone, and the change trend of Bcl-2/Bax ratio was consistent with the change of Bcl-2. CONCLUSION: The 8-week incremental load excessive swimming training aggravated spleen apoptosis, led to pathological changes and dysfunction of spleen. Curcumin can up-regulate expression of Nrf2 and HO-1, alleviate oxidative stress induced by overtraining, enhance Bcl-2 expression and attenuate Bax expression, thereby inhibiting excessive spleen apoptosis of rats, protecting the structure and function of spleen.

Primary mucinous carcinoma of thyroid gland with prominent signet-ring-cell differentiation: a case report and review of the literature.

PURPOSE: This study reports a case of primary mucinous carcinoma of the thyroid gland with signet-ring-cell differentiation, and reviews the literature to evaluate its real incidence and the prognosis of these patients. PATIENTS AND METHODS: A 74-year-old Chinese woman, presenting with a mass in the right lobe of thyroid gland, came to the hospital. Computed tomography revealed a mass in the right lobe of the thyroid gland, accompanied with right neck lymphadenectasis and airway deviation caused by tumor compression. Thyroid imaging suggested a thyroid malignant tumor and suspicious lymph node metastasis. Histologically, the tumor was characterized by the tumor cells arranged in small nests or trabeculae with an abundant extracellular mucoid matrix. The tumor cells formed diffuse invasion among thyroid follicles. In the peripheral regions, prominent signet-ring-cells formed a sheet-like structure and extended into the extrathyroidal fat tissue. The tumor cells were diffusely positive for thyroid transcription factor-1 (TTF-1) and PAX8, while they were focally positive for pan-cytokeratin (AE1/AE3) and weakly expressed thyroglobulin. RESULTS: Based on the histological features and immunohistochemical profile, a diagnosis of primary mucinous carcinoma of the thyroid gland with signet-ring-cell differentiation was rendered. CONCLUSION: Using a panel of immunohistochemical markers may be helpful for differential diagnosis and for determining whether the tumor is primary or not.

Surgical specimen extraction via a prophylactic ileostomy procedure: A minimally invasive technique for laparoscopic rectal cancer surgery.

AIM: To retrospectively evaluate the safety and feasibility of surgical specimen extraction via a prophylactic ileostomy procedure in patient with rectal cancer. METHODS: We systematically reviewed 331 consecutive patients who underwent laparoscopic anterior resection for rectal cancer and prophylactic ileostomy in our institution from June 2010 to October 2016, including 155 patients who underwent specimen extraction via a prophylactic ileostomy procedure (experimental group), and 176 patients who underwent specimen extraction via a small lower abdominal incision (control group). Clinical data were collected from both groups and statistically analyzed. RESULTS: The two groups were matched in clinical characteristics and pathological outcomes. However, mean operative time was significantly shorter in the experimental group compared to the control group (161.3 ± 21.5 min vs 168.8 ± 20.5 min; P = 0.001). Mean estimated blood loss was significantly less in the experimental group (77.4 ± 30.7 mL vs 85.9 ± 35.5 mL; P = 0.020). The pain reported by patients during the first two days after surgery was significantly less in the experimental group than in the control group. No wound infections occurred in the experimental group, but 4.0% of the controls developed wound infections (P = 0.016). The estimated 5-year disease-free survival and overall survival rate were similar between the two groups. CONCLUSION: Surgical specimen extraction via a prophylactic ileostomy procedure represents a secure and feasible approach to laparoscopic rectal cancer surgery, and embodies the principle of minimally invasive surgery.