Deep reinforcement learning-aided autonomous navigation with landmark generators.

Mobile robots are playing an increasingly significant role in social life and industrial production, such as searching and rescuing robots, autonomous exploration of sweeping robots, and so on. Improving the accuracy of autonomous navigation of mobile robots is a hot issue to be solved. However, traditional navigation methods are unable to realize crash-free navigation in an environment with dynamic obstacles, more and more scholars are gradually using autonomous navigation based on deep reinforcement learning (DRL) to replace overly conservative traditional methods. But on the other hand, DRL's training time is too long, and the lack of long-term memory easily leads the robot to a dead end, which makes its application in the actual scene more difficult. To shorten training time and prevent mobile robots from getting stuck and spinning around, we design a new robot autonomous navigation framework which combines the traditional global planning and the local planning based on DRL. Therefore, the entire navigation process can be transformed into first using traditional navigation algorithms to find the global path, then searching for several high-value landmarks on the global path, and then using the DRL algorithm to move the mobile robot toward the designated landmarks to complete the final navigation, which makes the robot training difficulty greatly reduced. Furthermore, in order to improve the lack of long-term memory in deep reinforcement learning, we design a feature extraction network containing memory modules to preserve the long-term dependence of input features. Through comparing our methods with traditional navigation methods and reinforcement learning based on end-to-end depth navigation methods, it shows that while the number of dynamic obstacles is large and obstacles are rapidly moving, our proposed method is, on average, 20% better than the second ranked method in navigation efficiency (navigation time and navigation paths' length), 34% better than the second ranked method in safety (collision times), 26.6% higher than the second ranked method in success rate, and shows strong robustness.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

Comparison of the therapeutic efficacy between systemic chemotherapy with and without radiofrequency ablation for colorectal cancer liver metastases: A propensity score matching study.

OBJECTIVE: To compare therapeutic efficacy between systemic chemotherapy (SC) alone and preoperative SC followed by radiofrequency ablation (SC+RFA) in patients with colorectal cancer liver metastases (CRLM). METHODS: This study identified a cohort of patients with CRLM after treatment between 2010 and 2016. Patients who received SC+RFA were compared with SC patients by propensity score matching. Overall survival (OS) and intrahepatic progression-free survival (PFS) were compared using stratified log-rank test. The outcomes after SC and SC+RFA were also assessed in patient subgroups. RESULTS: This study identified 338 patients with CRLM who had underwent SC and had different response to chemotherapy, including non-progressive disease (non-PD) or progressive disease (PD). Of this cohort, 64 patients in SC+RFA group were matched by propensity score to 64 patients who received SC alone. Compared with SC cohort, the SC+RFA cohort yielded better OS (HR, 0.403; 95% CI, 0.271-0.601) and PFS (HR, 0.190; 95% CI, 0.113-0.320). The estimated OS rates at 1, 3 and 5 years were 93.8%, 51.6% and 15.6% for SC+RFA group and 81.3%, 26.6% and 10.9% for SC group (p＜0.001). The cumulative PFS rates at 1, 3, and 5 years were 43.8 %, 14.1% and 3.1% for the SC+RFA group and 1.6%, 0 and 0% for SC group (p＜0.0001). In subgroup analysis, compared with patients with PD response, patients with non-PD response could gain better PFS (HR, 0.207; 95% CI, 0.121-0.354) and OS (HR, 0.390; 95% CI, 0.246-0.617). CONCLUSIONS: RFA was associated with improved OS and intrahepatic PFS in CRLM patients with preoperative SC,especially in non-PD response subgroup after SC. ADVANCES IN KNOWLEDGE: The addition of RFA was advocated for CRLM patients with preoperative SC. This study will provide important reference and evidence to better perform the management of unresectable CRLM.

Sub-Tenon's bupivacaine injection is superior to placebo for pediatric strabismus surgery: A meta-analysis.

Background: The effect of post-operation sub-Tenon's bupivacaine injection for pediatric strabismus surgery is controversial. The objective of this meta-analysis is to compare the outcome of sub-Tenon injection of bupivacaine and placebo duringstrabismus surgery. Methods: We searched the databases (Pubmed, Cochrane library and EMBASE) and reference lists systematically. Randomized controlled trials (RCTs) comparing sub-Tenon's bupivacaine and placebo injection for pediatric strabismus surgery were included. The methodological quality was evaluated by the Cochrane risk of bias (ROB) tool. Outcome measurements were pain score, oculocardiac reflex (OCR), additional drug consumption and related complications. RevMan 5.4 was used for the statistical analysis and graph preparation. For the outcomes that are not suitable for statistical analysis, descriptive analysis was performed. Results: A total of 5 RCTs with 217 patients were finally identified and analyzed. Sub-Tenon's bupivacaine injection showed pain relief within 30 min after operation. But with the extension of time, the analgesic effect gradually disappeared at 1 h. It can reduce the incidence of OCR, vomiting and supplementary drug requirements. However, in terms of nausea, there is no difference between the two groups. Conclusion: Sub-Tenon's bupivacaine injection can relieve short-term postoperative pain, reduce the incidence of OCR and vomiting, and reduce the use of supplementary drugs in strabismus surgery.

The prevalence, awareness, management and influencing factors of diabetes in middle-aged and elderly in China, evidence from the CHARLS in 2015.

Diabetes seriously affects the health of middle-aged and elderly. What we can do is to suppress the progression and avoid complications of diabetes. The aim of this study was to evaluate the prevalence, management and influencing factors in middle-aged and elderly diabetics. The data used in our study came from the follow-up survey (2015) of China Health and Retirement Longitudinal Study. After all the questionnaire data of participants was acquired, the first screening step was conducted and the participants without blood glucose or glycosylated hemoglobin test results were excluded. In the second screening step, participants without self-reported diabetes, age <45 were excluded. After data screening, STATA 16.0 software (StataCorp, USA) was used to conduct statistical analysis. Multiple logistics regression was used to analyze the influencing factors of diabetes in middle-aged and elderly. After data screening, A total of 9738 participants were enrolled in the survey of the China Health and Retirement Longitudinal Study in 2015, including diabetes 1965 and control 7773. The prevalence of diabetes in age >60 (22.20%) was significantly higher than that in age 45 to 60 (16.60%). Age, residence, physical activity, drinking, smoking and body mass index were key influencing factors according to the results of logistics regression. 46.92% diabetics were diagnosed in hospital, 22.14% were diagnosed by community medical care. 1298 among 1965 diabetes patients had standardized medication to control blood glucose, the rate was only 66.01%. The awareness rate of diabetes was only 28.75%, and the monitoring, treatment and accepting medical advice rates were 68.32%, 66.01% and 56.99% separately. The follow-up rate of diabetes was only 14.16%. Diabetes is widely prevalent in the middle-aged and elderly with the prevalence of 16.60% in the participants with age 45 to 60. The rate of self-rated diabetics underestimated the true prevalence of diabetes. Age, residence, physical activity, drinking, smoking and body mass index are key influencing factors to diabetes. Although a national diabetes health management model has been established, the awareness of diabetes was only 28.75%. Standardized diabetes registration and regular follow up should also be strictly implemented.

Multiple Mechanistic Models Reveal the Neuroprotective Effects of Diterpene Ginkgolides against Astrocyte-Mediated Demyelination via the PAF-PAFR Pathway.

Currently, therapies for ischemic stroke are limited. Ginkgolides, unique Folium Ginkgo components, have potential benefits for ischemic stroke patients, but there is little evidence that ginkgolides improve neurological function in these patients. Clinical studies have confirmed the neurological improvement efficacy of diterpene ginkgolides meglumine injection (DGMI), an extract of Ginkgo biloba containing ginkgolides A (GA), B (GB), and K (GK), in ischemic stroke patients. In the present study, we performed transcriptome analyses using RNA-seq and explored the potential mechanism of ginkgolides in seven in vitro cell models that mimic pathological stroke processes. Transcriptome analyses revealed that the ginkgolides had potential antiplatelet properties and neuroprotective activities in the nervous system. Specifically, human umbilical vein endothelial cells (HUVEC-T1 cells) showed the strongest response to DGMI and U251 human glioma cells ranked next. The results of pathway enrichment analysis via gene set enrichment analysis (GSEA) showed that the neuroprotective activities of DGMI and its monomers in the U251 cell model were related to their regulation of the sphingolipid and neurotrophin signaling pathways. We next verified these in vitro findings in an in vivo cuprizone (CPZ, bis(cyclohexanone)oxaldihydrazone)-induced model. GB and GK protected against demyelination in the corpus callosum (CC) and promoted oligodendrocyte regeneration in CPZ-fed mice. Moreover, GB and GK antagonized platelet-activating factor (PAF) receptor (PAFR) expression in astrocytes, inhibited PAF-induced inflammatory responses, and promoted brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion, supporting remyelination. These findings are critical for developing therapies that promote remyelination and prevent stroke progression.

The self-rated health status and key influencing factors in middle-aged and elderly: Evidence from the CHARLS.

ABSTRACT: To evaluate the self-rate health (SRH) status and explore influence factors of middle-aged and elderly in China.China Health and Retirement Longitudinal Survey was conducted in 2011, 2013, 2015 and 2018. Data of the China Health and Retirement Longitudinal Survey in 2018 was used in our study and a total of 17898 participants were included. SRH status was graded as "very good, good, average, bad, very bad." Participants who answered "very good" and "good" were regarded as self-rated good health and who answered "average," "bad" and "very bad" were regarded as self-rated poor health. Odds ratio and 95% confidence interval of Logistics regression were calculated to evaluate the correlation between SRH and chronic diseases, demographic characteristics and lifestyle of middle-aged and elderly participants.A total of 4476 (25.01%) participants reported they had good health, and 13422 (74.99%) reported they had poor health. 9975 participants self-rated they had no chronic disease (55.73%), and 7923 (44.27%) participants self-rated they suffered from one and above chronic diseases. The prevalence of chronic diseases showed significant odds ratio and trend with SRH poor rate of participants. The more kinds of chronic diseases they suffered from, the poorer SRH was reported in middle-aged and elderly participants. Except for the chronic diseases, participants with higher age, living in rural, with high Center for Epidemiological Survey-Depression Scale score of depression and fewer time of physical activities also correlated with higher SRH (poor) rate.The SRH (good) rate was very low in middle-aged and elderly, participants who accompanied with more kinds of chronic diseases, fewer physical activities, higher age and living in the rural had a worse health status. A more comprehensive and integrated health framework should be strengthened to improve the health of middle-aged and elderly in China.

Delirium in Older Patients after Combined Epidural-General Anesthesia or General Anesthesia for Major Surgery: A Randomized Trial.

BACKGROUND: Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting stress response to surgery. This trial therefore tested the hypothesis that combined epidural-general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery. METHODS: Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days. RESULTS: Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural-general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural-general anesthesia group (15 [1.8%] of 857 patients) than in the general anesthesia group (43 [5.0%] of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 [49%] vs. 288 [33%]; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 [58%] vs. 387 [45%]; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001). CONCLUSIONS: Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension.

Long-term Survival after Combined Epidural-General Anesthesia or General Anesthesia Alone: Follow-up of a Randomized Trial.

BACKGROUND: Experimental and observational research suggests that combined epidural-general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural-general anesthesia improves long-term survival in elderly patients. METHODS: This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival. RESULTS: Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural-general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural-general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural-general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural-general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815. CONCLUSIONS: In elderly patients having major thoracic and abdominal surgery, combined epidural-general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference.

Tumor associated neutrophils promote the metastasis of pancreatic ductal adenocarcinoma.

The aim of this study was to investigate the role of tumor-associated neutrophils (TANs) in the metastasis of pancreatic ductal adenocarcinoma (PDAC), to explore the regulation of TANs, and to determine the mechanisms governing the metastasis of PDAC. The correlation between neutrophils and the patient's clinical pathological data was first evaluated. Then, the effects of neutrophils on the invasion of PDAC were analyzed using a combination of conditioned media, direct and indirect coculture of human peripheral blood neutrophils, and PDAC cell lines (Panc-1, MiaPaCa-2 and AsPC-1). The cytokines secreted by neutrophils were detected through ELISA. TAN density was significantly correlated with poor metastasis-free survival (P < .05). Through coculture, it was found that the effect of neutrophils on pancreatic cancer cells was dependent on concentration, and a high concentration of neutrophils showed a lethal effect, while a low concentration of neutrophils primarily promoted the migration ability of cancer cells. The results of the wound-healing assay, the Transwell invasion assay, and laser confocal microscopy confirmed the promoting effect and indicated that the effect of neutrophils toward cancer cells may function indirectly by releasing a series of cytokines. The results of ELISA show that this effect may be achieved through the secretion of a large amount of TNF-α and TGF-ß1 by neutrophils. Our study indicated that neutrophils may increase the metastasis of PDAC by releasing a series of cell cytokines, such as TNF-α and TGF-ß1.

Deep Brain Stimulation of Anterior Thalamic Nucleus for Treatment of Patient with Tuberous Sclerosis-Related Refractory Epilepsy.

BACKGROUND: Neuromodulation is recommended for patients with refractory tuberous sclerosis related epilepsy (TRE) who are unable to localize epileptogenic nodules after comprehensive preoperative evaluation or for patients and families who do not agree to resection. CASE DESCRIPTION: We report a patient with refractory TRE who received deep brain stimulation of anterior thalamic nucleus (ANT-DBS) and achieved a satisfactory response. To our knowledge, this is the first case of TRE being treated with ANT-DBS. A 22-year-old male was admitted to the hospital for refractory TRE seeking surgical treatment. Seizures were mainly manifested by deep temporal and frontal lobe epilepsy and suspected to originate in the limbic system. Magnetic resonance imaging revealed extensive potentially epileptogenic nodules in the brain lacking significant nodules. Scalp electroencephalogram showed a comprehensive, bilateral synchronous low-voltage rapid rhythm, unable to localize seizure origin. We performed bilateral ANT-DBS according to the preoperative evaluation, and the frequency and intensity of seizures were significantly reduced after the 15-month follow-up (P <0.05, Student's t-test). Our case extends the therapeutic indications of ANT-DBS to a certain extent, providing a neuromodulation alternative to vagus nerve stimulation for patients with TRE who are unsuitable candidates or refuse resection.

The predictive value and role of stromal tumor-infiltrating lymphocytes in pancreatic ductal adenocarcinoma (PDAC).

Recently, increasing evidence has indicated that the presence of tumor infiltrating immune cells has shown predictive significance for many solid tumors. Present study was performed to evaluate the predictive value of stromal tumor-infiltrating lymphocytes (TILs) for the presence of liver metastasis and overall survival in PDAC (pancreatic ductal adenocarcinoma) patients after complete resection and to explore the potential role of lymphocytes in PDAC. A total of 155 resectable patients with PDAC were enrolled in our study. Stromal TIL density was investigated in hematoxylin and eosin-stained sections of surgical specimens and scored. The effect and possible mechanism of lymphocytes on cancer cells was evaluated using co-culture techniques and ELISA test. Stromal TIL negative status (HR = 2.80, 95% CI 1.75-4.48, P < 0.01) was not only an independent predictor of worse OS (HR = 2.7, 95% CI 1.80-4.06, P = <0.01) but also a significant independent predictor of liver metastasis. Higher CEA (P = 0.01) or CA19-9 (P = 0.01) levels were associated with low stromal TIL density. Stromal TIL negative patients appeared to develop tumors with a higher CEA (P = 0.01), larger diameter (P = 0.05) and advanced stage (P = 0.02). The co-culture experiment suggests that lymphocytes can inhibit pancreatic cancer cell proliferation. Further ELISA and cell culture test indicate that lymphocytes may cause pancreatic cancer cells apoptosis through TNF-alpha secretion. Our data suggest a potential favorable role of stromal TILs in predicting liver metastasis and overall survival of patients with PDAC after complete resection. Lymphocytes may inhibit the growth of PDAC through TNF-alpha secretion, which suggest a potential therapeutic approach against PDAC.

Impact of inhalational versus intravenous anaesthesia on early delirium and long-term survival in elderly patients after cancer surgery: study protocol of a multicentre, open-label, and randomised controlled trial.

INTRODUCTION: Elderly patients who have solid organ cancer often receive surgery. Some of them may develop delirium after surgery and delirium development is associated with worse outcomes. Furthermore, despite all of the advances in medical care, the long-term survival in cancer patients is far from optimal. Evidences suggest that choice of anaesthetics during surgery, that is, either inhalational or intravenous anaesthetics, may influence outcomes. However, the impact of general anaesthesia type on the occurrence of postoperative delirium is inconclusive. Although retrospective studies suggest that propofol-based intravenous anaesthesia was associated with longer survival after cancer surgery when compared with inhalational anaesthesia, prospective studies as such are still lacking. The purposes of this randomised controlled trial are to test the hypotheses that when compared with sevoflurane-based inhalational anaesthesia, propofol-based intravenous anaesthesia may reduce the incidence of early delirium and prolong long-term survival in elderly patients after major cancer surgery. METHODS AND ANALYSIS: This is a multicentre, open-label, randomised controlled trial with two parallel arms. 1200 elderly patients (≥65 years but <90 years) who are scheduled to undergo major cancer surgery (with predicted duration ≥2 hours) are randomised to receive either sevoflurane-based inhalational anaesthesia or propofol-based intravenous anaesthesia. Other anaesthetics and supplemental drugs including sedatives, opioids and muscle relaxants are administered in both arms according to routine practice. The primary early outcome is the incidence of 7-day delirium after surgery and the primary long-term outcome is the duration of 3-year survival after surgery. ETHICS AND DISSEMINATION: The study protocol has been approved by the Clinical Research Ethics Committees of Peking University First Hospital (2015[869]) and all participating centres. The results of early and long-term outcomes will be analysed and reported separately. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-15006209; NCT02662257; NCT02660411.

Can we predict postoperative complications in elderly Chinese patients with hip fractures using the surgical risk calculator?

PURPOSE: Hip fractures are associated with poor prognosis in elderly patients partly due to the high rate of postoperative complications. This study was aimed to investigate whether the surgical risk calculator is suitable for predicting postoperative complications in elderly Chinese patients with hip fractures. METHODS: The incidence of postoperative complications among 410 elderly patients with hip fractures was predicted by the surgical risk calculator and then compared with the actual value. The risk calculator model was evaluated using the following three metrics: Hosmer-Lemeshow test for the goodness-of-fit of the model, receiver operating characteristic curve (ROC) (also referred as C-statistic) for the predictive specificity and sensitivity, and the Brier's score test for predictive accuracy. RESULTS: Preoperative risk factors including gender, age, preoperative functional status, American Society of Anesthesiologists grade, hypertension, dyspnea, dialysis, previous cardio-vascular history, and cerebrovascular disease were positively correlated with the incidence of postoperative complications in elderly patients with hip fractures. The predicted complication incidence rate was well matched with the actual complication rate by Hosmer-Lemeshow test. The model had high sensitivity and specificity for predicting the mortality rate of these patients with a C-statistic index of 0.931 (95% CI [0.883, 0.980]). The surgical calculator model had an accuracy of 90% for predicting the reoperation rate (Brier's score <0.01). CONCLUSIONS: The surgical risk calculator could be useful for predicting mortality and reoperation in elderly patients with hip fracture. Patients and surgeons may use this simple calculator to better manage the preoperative risks.

[A multi-center, double-blind, placebo-controlled, randomized trial for effect of Longxue Tongluo capsule in treatment of patients of atherosclerotic thrombotic cerebral infarction with blood-stasis syndrome in convalescence].

To evaluate the effectiveness and safety of Longxue Tongluo capsule on patients of atherosclerotic thrombotic cerebral infarction convalescence with blood-stasis syndrome, a double-blind, randomized controlled, multi-center clinical trial was conducted. A total of 160 eligible patients were randomly divided into treatment group and control group, with 80 patients in each group, and all of them were orally given Troxerutin pill(three pills each time, three times daily). Longxue Tongluo capsule was applied in the treatment group, while placebo was applied in the control group(two capsules each time, three times daily) for 4 weeks. Main outcomes were measured by ITT analysis. The neurological function deficits scale showed a decrease of 5.17±2.60 in the treatment group, while 4.31±2.31 in the control group, with significant differences between the two groups(P<0.05); the reduction rate in the treatment group (37.2±15.8)% was significantly higher than that in the control group (29.9±15.3)%(P<0.05). In terms of the comprehensive curative effect by ITT, the effective rates in the treatment and control group were 31.6% and 13.5%, respectively(P<0.05). With respect to the efficacy of traditional Chinese medicine syndrome by ITT, the total effective rate of the treatment group was significantly higher than the control group 88.2% vs 68.9%, P<0.05. Three cases of adverse events occurred in this study, including 1 case of diarrhea in treatment group and 2 cases of skin itch and upper respiratory infection in control group. In conclusion, Longxue Tongluo capsule is effective and safe in the treatment of patients of atherosclerotic thrombotic cerebral infarction convalescence with blood-stasis syndrome, and can effectively alleviate the patients' nerve function defect degree and invalidism, with a good effect on blood stasis syndrome.

Effects of two different anesthesia-analgesia methods on incidence of postoperative delirium in elderly patients undergoing major thoracic and abdominal surgery: study rationale and protocol for a multicenter randomized controlled trial.

BACKGROUND: Delirium is a common complication in elderly patients after surgery and associated with increased morbidity and mortality. Studies suggest that deep anesthesia and intense pain are important precipitating factors of postoperative delirium. Neuraxial block is frequently used in combination with general anesthesia for patients undergoing major thoracic and abdominal surgery. Compared with general anesthesia alone and postoperative intravenous analgesia, combined epidural-general anesthesia and postoperative epidural analgesia decreases the requirement of general anesthetics during surgery and provided better pain relief after surgery. However, whether combined epidural-general anesthesia plus epidural analgesia is superior to general anesthesia plus intravenous analgesia in decreasing the incidence of postoperative delirium remains unknown. METHODS/DESIGN: This is a multicenter, open-label, randomized, parallel-controlled clinical trial. One thousand eight hundred elderly patients (age range 60-90 years) who are scheduled to undergo major thoracic or abdominal surgery are randomized to receive either general anesthesia plus postoperative intravenous analgesia or combined epidural-general anesthesia plus postoperative epidural analgesia. The primary outcome is the 7-day incidence of postoperative delirium. Secondary outcomes include the duration of postoperative delirium, the intensity of pain during the first three days after surgery, the 30-day incidences of postoperative non-delirium complications, the length of stay in hospital after surgery and 30-day all-cause mortality. DISCUSSION: Results of the present study will provide information to guide clinical practice in choosing appropriate anesthesia-analgesia method for elderly patients undergoing major thoracic and abdominal surgery. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov NCT01661907 and Chinese Clinical Trial Registry ChiCTR-TRC-12002371 .

A 3D sphere culture system containing functional polymers for large-scale human pluripotent stem cell production.

Utilizing human pluripotent stem cells (hPSCs) in cell-based therapy and drug discovery requires large-scale cell production. However, scaling up conventional adherent cultures presents challenges of maintaining a uniform high quality at low cost. In this regard, suspension cultures are a viable alternative, because they are scalable and do not require adhesion surfaces. 3D culture systems such as bioreactors can be exploited for large-scale production. However, the limitations of current suspension culture methods include spontaneous fusion between cell aggregates and suboptimal passaging methods by dissociation and reaggregation. 3D culture systems that dynamically stir carrier beads or cell aggregates should be refined to reduce shearing forces that damage hPSCs. Here, we report a simple 3D sphere culture system that incorporates mechanical passaging and functional polymers. This setup resolves major problems associated with suspension culture methods and dynamic stirring systems and may be optimal for applications involving large-scale hPSC production.

Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of patients with mixed-lineage-leukemia-rearranged acute leukemia: Results from a prospective, multi-center study.

The purpose of this study is to define the role for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mixed-lineage-leukemia (MLL)-rearranged acute leukemia, which is now poorly understood. A prospective, multi-center cohort study to determine whether allo-HSCT could decrease relapse rates and improve long-term survival of MLL+ leukemia patients was performed. Fifty-six consecutive patients diagnosed with MLL-rearranged acute leukemia undergoing allo-HSCT from two transplant centers in China were enrolled between October 2007 and October 2012. The trial was registered at www.chictr.org as # ChiCTR-ONC-12002739. The incidences of grades II to IV acute graft versus host disease (aGVHD) and of grades III and IV aGVHD were 28.8% (CI, 16.87-40.8%), and 14.2% (CI, 5.4-23.0%), respectively. The cumulative incidences for chronic GVHD (cGVHD) at 2 years after HSCT were 35.2% (CI, 21.2-49.2%). Up to April 30, 2013, 12 patients had relapsed and 11 died from relapse, and 37 patients were still alive without disease recurrence. The relapse and NRM rates at 3 years were 25.3% (CI, 12.7-37.9%) and 18.0% (CI, 2.6-33.4%), respectively. The probalities of overall survival and leukemia free survival were 61.8% (CI, 46.0-77.6%) and 56.3% (CI, 38.1-74.5%) at 3 years, respectively. Patients transplanted during their hematological first complete remission (CR1) had a lower relapse rate (17.9% vs. 48.1%, P = 0.03) compared with patients transplanted beyond CR1. The median overall survival for the 29 patients not receiving allo-HSCT during the study period was 145 days from diagnosis. This study showed that allo-HSCT could be a valuable treatment choice for MLL+ acute leukemia.