Crop grey water footprints in China: The impact of pesticides on water pollution.

Agricultural water pollution is a significant challenge in China, a rapidly growing economy with a large agricultural sector. The grey water footprint (WF) is a tool for evaluating freshwater pollution. It expresses pollution in volumetric units identifying the pollutant that theoretically needs most water to be diluted to accepted water quality standards. Previous agricultural grey WF studies focused on nitrogen (N) and phosphorus (P), some studies included pesticides. This study assesses grey WFs based on N, P and 1513 pesticide combinations for twelve main crops and two crop categories in 31 Chinese provinces. Grey WFs, including the pesticide component, are far larger than estimated before, dominating total agricultural WFs (green, blue, and grey). The total grey WF of Chinese agriculture (4,900 109 m3 year-1) is determined by pesticides, while grey WFs related to N and P are 450 and 1,500 109 m3 year-1, differences of a factor of eleven and three respectively. The provinces Heilongjiang, Inner Mongolia, Hebei, Henan, and Shandong are hotspots contributing 37 % to the total grey WF. A limited number of pesticides used for maize, vegetables, fruits and potato (Mancozeb a fungicide, Acetochlor a herbicide and Cypermethrin an insecticide) dominate total grey WFs, contributing 80 % to the total grey WF. Eliminating the most polluting pesticides per category and redistributing the remaining ones with a similar function but lower grey WFs reduces national water pollution from agriculture by 64 %. Only five crops, i.e. maize, potato, soybean, rice and wheat, and the two crop categories, vegetables and fruits, contribute 94 % to this reduction. Probably grey WFs could reduce even further with a second elimination and redistribution effort. This study is the first national grey WF assessment related to pesticides in agriculture. It offers valuable insights to farmers and policymakers to enhance water quality in China and beyond.

Surgical treatment of nasopharyngeal cancer - a consensus recommendation from two Chinese associations.

BACKGROUND: Surgical treatment is playing an increasingly important role in the management of nasopharyngeal carcinoma (NPC). This consensus focuses on the indications for optimal surgery, and surgical methods in the whole process of treatment for NPC to provide a useful reference to assist these difficult clinical decisions. METHODOLOGY: A thorough review of available literature on NPC and surgery was conducted by the Association for the prevention and treatment of nasopharyngeal carcinoma in China, international exchange and promotion Association for medicine and healthcare, and the Committee on nasopharyngeal cancer of Guangdong provincial anticancer association. A set of questions and a preliminary draft guideline was circulated to a panel of 1096 experienced specialists on this disease for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the experts in two authoritative medical science and technology academic groups in the prevention and treatment of NPC in China for review and reconsideration. RESULTS: The initial round of questions showed variations in clinical practice even among similar specialists, reflecting the lack of high-quality supporting data and resulting difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of surgery, including indications and surgical approaches. CONCLUSION: By standardizing the surgical indications and practice, we hope not only to improve the surgical outcomes, but also to highlight the key directions of future clinical research in the surgical management of NPC.

[IL-8 Links NF-κB and Wnt/ß-Catenin Pathways in Persistent Inflammatory Response Induced by Chronic Helicobacter pylori Infection].

Helicobacter pylori (H. pylori) infection can cause persistent inflammatory response in human gastric mucosal epithelial cells, which may result in the occurrence of cancer. However, the underlying mechanism of carcinogenesis has not been elucidated yet. Herein, we established the models of chronic H. pylori infection in GES-1 cells and C57BL/6J mice. Interleukin 8 (IL-8) level was detected by ELISA. The expression of NF-κB p65, IL-8, Wnt2 and ß-catenin mRNA and proteins was evaluated by real-time PCR, Western blotting, immunofluorescence staining, and immunohistochemistry. The infection of H. pylori in mice was evaluated by rapid urease test, H&E staining and Warthin-Starry silver staining. The morphological changes of gastric mucosa were observed by electron microscopy. Our results showed that in H. pylori infected gastric mucosal cells along with activation of NF-κB signaling pathway and increase of IL-8 level, the expression of Wnt2 was also increased significantly, which preliminarily indicates that IL-8 can positively regulate the expression of Wnt2. Studies in chronic H. pylori infected C57BL/6J mice models showed that there was an increased incidence of premalignant lesions in the gastric mucosa tissue. Through comparing changes of gastric mucosal cell ultrastructure and analyzing the relationship between NF-κB signaling pathway and Wnt2 expression, we found that H. pylori infection activated NF-κB signal pathways, and the massive release of IL-8 was positively correlated with the high expression of Wnt2 protein. Subsequently, the activated Wnt/ß-catenin signal pathways may be involved in the malignant transformation of gastric mucosal cells. Collectively, H. pylori chronic infection may continuously lead to persistent inflammatory response: activate NF-κB pathway, promote IL-8 release and thereby activate Wnt/ß-catenin pathway. IL-8 probably plays an important role of a linker in coupling these two signal pathways.

[Long-term outcomes and failure patterns of definitive radiotherapy for cervical esophageal carcinoma].

Objective: To evaluate the long-term outcomes, failure patterns and prognostic factors of definitive radiotherapy in patients with cervical esophageal carcinoma (CEC). Methods: We retrospectively reviewed the clinical data of 148 CEC patients who treated with definitive radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2001 to December 2017. The median radiation dose was 66 Gy (59.4-70 Gy) and 33.1% of patients received concurrent chemotherapy. The Kaplan-Meier method was used to calculate survival rates. The log rank test was used for survival comparison and univariate prognostic analysis. The Cox model was used for multivariate prognostic analysis. Results: The median follow-up time was 102.6 months. The median survival time, 2- and 5-year overall survival (OS) were 22.7 months, 49.9% and 28.3%. The median, 2- and 5-year progression-free survival were 12.6 months, 35.8% and 25.8%. The 2- and 5-year locoregional recurrence-free survival were 59.1% and 50.8%. The 2- and 5-year distant metastases-free survival were 74.6% and 65.9%. Multivariate analysis showed that EQD(2)>66 Gy was the only independent prognostic indicator for OS (P=0.040). The median survival time and 5-year OS rate significantly improved in patients who received EQD(2)>66 Gy than those who received≤66 Gy (31.2 months vs. 19.2 months, 40.1% vs. 19.1%, P=0.027). A total of 87 patients (58.8%) developed tumor progression. There were 50 (33.8%), 23 (15.5%) and 39 (26.4%) patients developed local, regional recurrence and distant metastases, respectively. Eleven patients (7.4%) underwent salvage surgery, and the laryngeal preservation rate for entire group was 93.9%. Conclusions: Definitive radiotherapy is an effective treatment for cervical esophageal carcinoma with the advantage of larynx preservation. Local recurrence is the major failure pattern. EQD(2)>66 Gy is associated with the improved overall survival.

[Effects and mechanism of human umbilical vein endothelial cells-derived exosomes on wound healing in diabetic rabbits].

Objective: The investigate the effects and mechanism of exosomes derived from human umbilical vein endothelial cells (HUVECs) on wound healing in diabetes rabbits. Methods: The experimental research methods were used. The primary vascular endothelial cells (VECs) and human skin fibroblasts (HSFs) were extracted from skin tissue around ulcer by surgical excision of two patients with diabetic ulcer (the male aged 49 years and the female aged 58 years) admitted to Xiangya Third Hospital of Central South University in June 2019. The cells were successfully identified through morphological observation and flow cytometry. The HUVEC exosomes were extracted by ultracentrifugation and identified successfully by morphological observation, particle size detection, and Western blotting detection. Twenty female 3-month-old New Zealand rabbits were taken to create one type 2 diabetic full-thickness skin defect wound respectively on both sides of the back. The wounds were divided into exosomes group and phosphate buffer solution (PBS) group and treated accordingly, with 20 wounds in each group, the time of complete tissue coverage of wound was recorded. On PID 14, hematoxylin-eosin staining or Masson staining was performed to observe angiogenesis or collagen fiber hyperplasia (n=20). The VECs and HSFs were co-cultured with HUVEC exosomes for 24 h to observe the uptake of HUVEC exosomes by the two kinds of cells. The VECs and HSFs were divided to exosome group treated with HUVEC exosomes and PBS group treated with PBS to detect the cell proliferation on 4 d of culture with cell count kit 8, to detect and calculate the cell migration rate at 24 and 48 h after scratch by scratch test, to detect the cell migration number at 24 h of culture with Transwell test, and to detect the mRNA expressions of nuclear factor-erythroid 2-related factor 2 (NRF2) and transcription activating factor 3 (ATF3) by real time fluorescence quantitative reverse transcription polymerase chain reaction. Besides, the number of vascular branches and vascular length were observed in the tube forming experiment after 12 h of culture of VECs (n=3). The VECs and HSFs were taken and divided into PBS group and exosome group treated as before, and NRF2 interference group, ATF3 interference group, and no-load interference group with corresponding gene interference. The proliferation and migration of the two kinds of cells, and angiogenesis of VECs were detected as before (n=3). Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, independent sample t test, and least significant difference test. Results: The time of complete tissue coverage of wound in exosome group was (17.9±1.9) d, which was significantly shorter than (25.2±2.3) d in PBS group (t=4.54, P<0.05). On PID14, the vascular density of wound in PBS group was significantly lower than that in exosome group (t=10.12, P<0.01), and the collagen fiber hyperplasia was less than that in exosome group. After 24 h of culture, HUVEC exosomes were successfully absorbed by VECs and HSFs. The proliferative activity of HSFs and VECs in exosome group was significantly higher than that in PBS group after 4 d of culture (with t values of 54.73 and 7.05, respectively, P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs (with t values of 3.42 and 11.87, respectively, P<0.05 or P<0.01) and VECs (with t values of 21.42 and 5.49, respectively, P<0.05 or P<0.01) in exosome group were significantly higher than those in PBS group. After 24 h of culture, the migration numbers of VECs and HSFs in exosome group were significantly higher than those in PBS group (with t values of 12.31 and 16.78, respectively, P<0.01). After 12 h of culture, the mRNA expressions of NRF2 in HSFs and VECs in exosome group were significantly higher than those in PBS group (with t values of 7.52 and 5.78, respectively, P<0.05 or P<0.01), and the mRNA expressions of ATF3 were significantly lower than those in PBS group (with t values of 13.44 and 8.99, respectively, P<0.01). After 12 h of culture, the number of vascular branches of VECs in exosome group was significantly more than that in PBS group (t=17.60, P<0.01), and the vascular length was significantly longer than that in PBS group (t=77.30, P<0.01). After 4 d of culture, the proliferation activity of HSFs and VECs in NRF2 interference group was significantly lower than that in PBS group and exosome group (P<0.05 or P<0.01); the proliferation activity of HSFs and VECs in ATF3 interference group was significantly higher than that in PBS group (P<0.05 or P<0.01) and significantly lower than that in exosome group (P<0.05 or P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs and VECs in ATF3 interference group were significantly higher than those in PBS group (P<0.05 or P<0.01) and significantly lower than those in exosome group (P<0.05 or P<0.01). At 24 and 48 h after scratch, the migration rates of HSFs and VECs in NRF2 interference group were significantly lower than those in PBS group and exosome group (P<0.05 or P<0.01). After 24 h of culture, the migration numbers of VECs and HSFs in ATF3 interference group were significantly more than those in PBS group (P<0.05) and significantly less than those in exosome group (P<0.05 or P<0.01); the migration numbers of VECs and HSFs in NRF2 interference group were significantly less than those in PBS group and exosome group (P<0.01). After 12 h of culture, the vascular length and number of branches of VECs in NRF2 interference group were significantly decreased compared with those in PBS group and exosome group (P<0.01); the vascular length and number of branches of VECs in ATF3 interference group were significantly increased compared with those in PBS group (P<0.01) and were significantly decreased compared with those in exosome group (P<0.01). Conclusions: HUVEC exosomes can promote the wound healing of diabetic rabbits by promoting the proliferation and migration of VECs and HSFs, and NRF2 and ATF3 are obviously affected by exosomes in this process, which are the possible targets of exosome action.

A model for pregnancy rates after IVF-ET in patients with infertility and endometriosis.

OBJECTIVE: The objective of the present study was to examine the clinical factors influencing the pregnancy rate of infertile patients with endometriosis and establish a predictive model. PATIENTS AND METHODS: This study included 158 patients (158 cycles) with infertility and endometriosis who underwent laparoscopic surgery, and in vitro fertilization and embryo transfer (IVF-ET) were evaluated retrospectively between January 2019 and December 2020. The clinical factors in the pregnant and non-pregnant group were analyzed by univariate analysis. Statistically significant variables were subsequently used for multivariate logistic regression to establish the prediction model. RESULTS: Multivariate logistic regression analyses showed that GnRH-a treatment after operation (OR, 6.562; 95% CI: 2.782-15.477; p<0.01), ASRM stage (OR, 0.218; 95% CI: 0.093-0.509; p<0.05), the number of high-quality transferred embryos (OR, 3.155; 95% CI: 1.647-6.047; p<0.05) were independently associated with successful pregnancy. The area under the curve (AUC) of the prediction model was 0.774 (95% CI: 0.700-0.847). According to Hosmer-Lemeshow, the model was well fitted (p>0.05). We applied the bootstrapping method to internal validation, and the result showed that the pregnancy rate predicted by the model and the real data were consistent. CONCLUSIONS: The models for predicting pregnancy rates after IVF-ET in infertility and endometriosis patients showed high accuracy. The effective methods to increase the number of high-quality embryos need further study.

[Introduction and implications of WHO position paper: vaccines against influenza, May 2022].

On May 13, 2022, World Health Organization(WHO) Position Paper on Influenza Vaccine (2022 edition) was published. This position paper updates information on influenza epidemiology, high risk population, the impact of immunization on disease, influenza vaccines and effectiveness and safety, and propose WHO's position and recommendation that all countries should consider implementing seasonal influenza vaccine immunization programmes to prepare for an influenza pandemic. In addition, it proposes that the influenza surveillance platform can be integrated with the surveillance of other respiratory viruses, such as SARS-CoV-2 and Respiratory Syncytial Virus. This position paper has some implications for the prevention and control of influenza and other respiratory infectious diseases in China: (1) Optimize influenza vaccine policies to facilitate the implementation of immunization services; (2) Influenza prevention and control should from the perspective of Population Medicine focus on the individual and community to integrate with "Promotion, Prevention, Diagnosis, Control, Treatment, Rehabilitation"; (3) Incorporate prevention and control of other respiratory infectious diseases such as influenza, COVID-19, respiratory syncytial virus and adenovirus, and intelligently monitor by integrating multi-channel data to achieve the goal of co-prevention and control of multiple diseases.

Design, Synthesis, and Optimization of Macrocyclic Peptides as Species-Selective Antimalaria Proteasome Inhibitors.

With over 200 million cases and close to half a million deaths each year, malaria is a threat to global health, particularly in developing countries. Plasmodium falciparum, the parasite that causes the most severe form of the disease, has developed resistance to all antimalarial drugs. Resistance to the first-line antimalarial artemisinin and to artemisinin combination therapies is widespread in Southeast Asia and is emerging in sub-Saharan Africa. The P. falciparum proteasome is an attractive antimalarial target because its inhibition kills the parasite at multiple stages of its life cycle and restores artemisinin sensitivity in parasites that have become resistant through mutation in Kelch K13. Here, we detail our efforts to develop noncovalent, macrocyclic peptide malaria proteasome inhibitors, guided by structural analysis and pharmacokinetic properties, leading to a potent, species-selective, metabolically stable inhibitor.

Single port robotic assisted sacrocolpopexy: technique and tips.

INTRODUCTION AND HYPOTHESIS: Sacrocolpopexy is the most durable surgical procedure for the treatment of symptomatic pelvic organ prolapse (Maher et al. Cochrane Database Syst Rev. 2013;(4):CD004014). The single port robotic platform has recently been approved in the USA for use in urological surgery. Innovation in robotic surgery continues to evolve, minimizing abdominal wall trauma while improving instrumentation and technical feasibility. Identifying the appropriate procedures to utilize novel technology is important to understand the role of new surgical tools. Sacrocolpopexy procedure, when performed with supracervical hysterectomy, requires extension of an incision for specimen retrieval, making it ideal for single port surgery. The technique and adaptation to new instrumentation is demonstrated in this video. METHOD: A surgical demonstration of single port robotic sacrocolpopexy is shown. RESULTS: Sacrocolpopexy was successfully completed using the single port robotic platform. CONCLUSIONS: Sacrocolpopexy is technically feasible with use of the single port robotic platform.

[Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma].

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

[Current status and research advances on the use of assisted traction technique in endoscopic full-thickness resection].

Endoscopic full-thickness resection (EFTR) allows completely resecting deep submucosal tumors (SMTs) in the gastrointestinal wall, which has a broad application prospect in clinic. However, its application and promotion are limited by complex surgical procedures and high surgical risk. Various auxiliary traction techniques are expected to reduce the operation difficulty and risk of EFTR and improve its operative success rate. To provide a reference for clinicians, we summarize various auxiliary traction techniques in EFTR in this article. The clip-with-line method is simple to operate and widely used, whereas its traction is limited and there is a risk of clip falling off. The snare traction method and the clip-snare traction method has advantage of large traction force, but its thrust is affected by the hardness of snare. The traction point of the grasping forceps traction method is flexible and easy to adjust. Nevertheless, it requires the use of a dual-channel upper endoscope, which is difficult to operate. The transparent cap traction method and the full-thickness resection device traction method takes a short time and is easy to promote, whereas the resectable lesion is limited, and the size of the lesion may affect the success rate. In contrast, the suture loop needle-T-tag tissue anchors assisted method has a large resection range, but the operation is complicated and the feasibility has not been verified. The robot-assisted method has flexible operation and excellent visualization, whereas it is expensive and difficult to operate. There is no report of the application of magnetic anchor technology in EFTR, but it may have good application prospects in the auxiliary traction of EFTR.

Development, verification, and comparison of a risk stratification model integrating residual cancer burden to predict individual prognosis in early-stage breast cancer treated with neoadjuvant therapy.

BACKGROUND: A favorable model for predicting disease-free survival (DFS) and stratifying prognostic risk in breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) is lacking. The aim of the current study was to formulate an excellent model specially for predicting prognosis in these patients. PATIENTS AND METHODS: Between January 2012 and December 2015, 749 early-stage BC patients who received NAC in Xijing hospital were included. Patients were randomly assigned to a training cohort (n = 563) and an independent cohort (n = 186). A prognostic model was created and subsequently validated. Predictive performance and discrimination were further measured and compared with other models. RESULTS: Clinical American Joint Committee on Cancer stage, grade, estrogen receptor expression, human epidermal growth factor receptor 2 (HER2) status and treatment, Ki-67 expression, lymphovascular invasion, and residual cancer burden were identified as independent prognostic variables for BC treated with NAC. The C-index of the model consistently outperformed other available models as well as single independent factors with 0.78, 0.80, 0.75, 0.82, and 0.77 in the training cohort, independent cohort, luminal BC, HER2-positive BC, and triple-negative BC, respectively. With the optimal cut-off values (280 and 360) selected by X-tile, patients were categorized as low-risk (total points ≤280), moderate-risk (280 < total points ≤ 360), and high-risk (total points >360) groups presenting significantly different 5-year DFS of 89.9%, 56.9%, and 27.7%, respectively. CONCLUSIONS: In patients with BC, the first model including residual cancer burden index was demonstrated to predict the survival of individuals with favorable performance and discrimination. Furthermore, the risk stratification generated by it could determine the risk level of recurrence in whole early-stage BC cohort and subtype-specific cohorts, help tailor personalized intensive treatment, and select comparable study cohort in clinical trials.

[Risk factors of permanent stoma in rectal cancer patients undergoing transabdominal anterior resection with temporary stoma].

Objective: To investigate the risk factors of turning temporary stoma into permanent stoma in rectal cancer patients undergoing transabdominal anterior resection with temporary stoma. Methods: A case-control study was carried out. Data of rectal cancer patients who underwent transabdominal anterior resection with temporary stoma and completed follow-up in Department of General Surgery of Xiangya Hospital of Central South University from June 2008 to June 2018 were collected and analyzed. In this study, temporary stoma included defunctioning stoma (ostomy was made during operation) and salvage stoma (ostomy was made within one month after operation due to anastomotic leakage or severe complications). Cases of multiple intestinal tumors were excluded. A total of 308 rectal cancer patients were enrolled in the study, including 198 males and 110 females with a median age of 56 (48-65) years. Ninety-four patients received intraperitoneal chemotherapy during operation. Among 308 patients, upper rectal cancer was observed in 64 cases, middle rectal cancer in 89 cases and low rectal cancer in 155 cases. Twenty patients underwent transverse colostomy and 288 underwent ileostomy. Phone call following-up was conducted from August to September 2019 to investigate whether stoma was reversed, causes of reversal failure, and tumor relapsed or not in detail. Permanent stoma was defined as that the stoma was still not reversed by the latest follow-up. The univariate analysis was performed with chi-square test or Fisher's exact test, and variables with P value < 0.10 were included in the non-conditional logistic regression model for multivariate analysis. Results: The median follow-up time was 54.3 (32.4-73.8) months. During follow-up, 8 cases had local recurrence and 37 cases had distant metastasis. Among the 308 patients with temporary ostomy, 247 (80.2%) patients had stomas reversed and the median interval time was 4.5 (3.5-6.1) months. The median interval time in 65 patients with salvage stoma was significantly longer that in 182 patients with defunctioning stoma [5.5 (4.3-7.5) vs. 4.2 (3.4-5.5) months; Z=-4.387, P<0.001]. The temporary ostomy was confirmed to become permanent stoma in 61 patients (19.8%), including 45 cases of defunctioning stoma and 16 cases of salvage stoma. Univariate analysis showed that preoperative anemia, intraperitoneal chemotherapy during operation, middle rectal cancer, transverse colostomy, pathological stage, postoperative local recurrence and distant metastasis were associated with permanent stoma (all P<0.10). Multivariate analysis revealed that the intraperitoneal chemotherapy during operation (OR=1.961, 95% CI: 1.029-3.738, P=0.041), middle rectal cancer (OR=2.401, 95% CI: 1.195-4.826, P=0.014), transverse colostomy (OR=3.433, 95% CI: 1.234-9.553, P=0.018), and distant metastasis (OR=8.282, 95% CI:3.820-17.954, P<0.001) were independent risk factors of permanent stoma. Conclusions: There is high risk of turning temporary stoma into permanent stoma among rectal cancer patients undergoing transabdominal anterior resection who receive intraperitoneal chemotherapy during operation, present as the middle rectal cancer, undergo transverse colostomy or develop distant metastasis. Surgeons need to evaluate and balance the risks and benefits thoroughly, and then inform the patients in order to avoid potential conflicts.

Interferon-independent STING signaling promotes resistance to HSV-1 in vivo.

The Stimulator of Interferon Genes (STING) pathway initiates potent immune responses upon recognition of DNA. To initiate signaling, serine 365 (S365) in the C-terminal tail (CTT) of STING is phosphorylated, leading to induction of type I interferons (IFNs). Additionally, evolutionary conserved responses such as autophagy also occur downstream of STING, but their relative importance during in vivo infections remains unclear. Here we report that mice harboring a serine 365-to-alanine (S365A) mutation in STING are unexpectedly resistant to Herpes Simplex Virus (HSV)-1, despite lacking STING-induced type I IFN responses. By contrast, resistance to HSV-1 is abolished in mice lacking the STING CTT, suggesting that the STING CTT initiates protective responses against HSV-1, independently of type I IFNs. Interestingly, we find that STING-induced autophagy is a CTT- and TBK1-dependent but IRF3-independent process that is conserved in the STING S365A mice. Thus, interferon-independent functions of STING mediate STING-dependent antiviral responses in vivo.

Knockdown of HMGB2 inhibits proliferation and invasion of renal tumor cells via the p-38MAPK pathway.

OBJECTIVE: To investigate the function of HMGB2 in renal tumor ACHN cells in vitro and in vivo and to study the underlying molecular mechanisms. PATIENTS AND METHODS: Kaplan-Meier analysis was used to study the relationship between expression of HMGB2 and prognosis of renal tumor. MTT assay was employed to examine cell proliferation and flow cytometry analysis was used to study the role of HMGB2 in cell apoptosis in ACHN cells. Transwell assays were used to explore the migration and invasion of ACHN cells. The effect of HMGB2 on tumor growth was investigated in vivo. Western blot was performed to evaluate the expression levels of p-JNK, p-ERK and p-p38MAPK. RESULTS: HMGB2 was upregulated in renal tumor and correlated with worse overall survival in renal tumor patients. Down-regulation of HMGB2 suppressed ACHN cells proliferation, invasion and migration in vitro. Moreover, down-regulation of HMGB2 inhibited tumor growth in vivo and HMGB2 exerts the oncogene function partly via the inhibition of p-p38MAPK activation. CONCLUSIONS: Our results provide novel insights into neuropathic pain and help to explore therapeutic targets in the treatment.

Evaluation of the efficacy of postoperative antibiotic treatment in transoral endoscopic thyroidectomy: a prospective randomised controlled trial.

Transoral endoscopic thyroid surgery (TOET) is a new, minimally-invasive approach that does not result in a scar in the anterior neck. To prevent infection of the surgical site from oral cavity flora into the thyroidectomy area, postoperative antibiotics are generally given orally for 3-7 days. However, there is no clinical evidence to support this approach. This study was an open-label, randomised, controlled trial to evaluate the clinical usefulness of postoperative antibiotics given orally to patients having TOET. Patients were randomly assigned to receive amoxicillin-clavulanate 625mg orally three times a day for a week after operation (treated group) or no antibiotics (untreated group). Fifty patients - 25 treated and 25 untreated - were enrolled. Maximum body temperature, pulse rate, white blood cell count, and C-reactive protein concentrations did not differ between the two groups. Evaluation of the surgical site showed no significant differences between them. Seven patients in the treated group developed nausea, vomiting, and diarrhoea compared with none in the untreated group. The results suggest that postoperative oral antibiotics are not essential after TOET. Large-scale prospective series are required to confirm this finding.

Patterns of Symptom Management Medication Receipt at End-of-Life Among Medicare Beneficiaries With Lung Cancer.

CONTEXT: Older adults with advanced lung cancer experience high symptom burden at end of life (EOL), yet hospice enrollment often happens late or not at all. Receipt of medications to manage symptoms in the outpatient setting, outside the Medicare hospice benefit, has not been described. OBJECTIVES: We examined patterns of symptom management medication receipt at EOL for older adults who died of lung cancer. METHODS: This retrospective cohort used the Surveillance, Epidemiology, and End Results-Medicare database to identify decedents diagnosed with lung cancer at age 67 years and older between January 2008 and December 2013 who survived six months and greater after diagnosis. Using Medicare Part B and D claims, we identified monthly receipt of outpatient medications for symptomatic management of pain, emotional distress, fatigue, dyspnea, anorexia, and nausea/vomiting. Multivariable logistic regression estimated associations between medication receipt and patient demographic characteristics, comorbidity, and concurrent therapy. RESULTS: Of the 16,246 included patients, large proportions received medications for dyspnea (70.7%), pain (62.5%), and emotional distress (49.4%), with lower prevalence for other symptoms. Medication receipt increased from six months to one month before death. Women and dual Medicaid enrolled were more likely to receive medications for pain, emotional distress, dyspnea, and nausea/vomiting. Receipt of symptom management medications decreased with increasing age and racial/ethnical minorities. CONCLUSION: Symptom management medication receipt was common and increasing toward EOL. Lower use by males, older adults, and nonwhites may reflect poor access or poor patient-provider communication. Further research is needed to understand these patterns and assess adequacy of symptom management in the outpatient setting.

PPEF2 Opposes PINK1-Mediated Mitochondrial Quality Control by Dephosphorylating Ubiquitin.

Dysregulation of mitophagy, whereby damaged mitochondria are labeled for degradation by the mitochondrial kinase PINK1 and E3 ubiquitin ligase Parkin with phosphorylated ubiquitin chains (p-S65 ubiquitin), may contribute to neurodegeneration in Parkinson's disease. Here, we identify a phosphatase antagonistic to PINK1, protein phosphatase with EF-hand domain 2 (PPEF2), that can dephosphorylate ubiquitin and suppress PINK1-dependent mitophagy. Knockdown of PPEF2 amplifies the accumulation of p-S65 ubiquitin in cells and enhances baseline mitophagy in dissociated cortical cultures. Overexpressing enzymatically active PPEF2 reduces the p-S65 ubiquitin signal in cells, and partially purified PPEF2 can dephosphorylate recombinant p-S65 ubiquitin chains in vitro. Using a mass spectrometry approach, we have identified several p-S65-ubiquitinated proteins following mitochondrial damage that are inversely regulated by PPEF2 and PINK1. Interestingly, many of these proteins are involved in nuclear processes such as DNA repair. Collectively, PPEF2 functions to suppress mitochondrial quality control on a cellular level through dephosphorylation of p-S65 ubiquitin.