In recent years, immunotherapy, especially immune checkpoint inhibitors, has shown obvious advantages in prolonging the survival of patients with advanced tumors, and the tumor microenvironment is one of the important factors affecting the efficacy of immunity. Patients with microsatellite-stable colorectal cancer exhibit immune responses in combination with immune checkpoint inhibitor therapy. In-depth exploration of the tumor microenvironment characteristics of microsatellite-stable colorectal cancer and the application of combined immune checkpoint inhibitor therapy can provide new ideas and directions for colorectal cancer immunotherapy.

Objective: To evaluate the effect of hybrid operation suite in the treatment of cerebral and spinal vascular diseases and intracranial hypervascular tumors. Methods: A retrospective study was conducted on 132 patients with various cerebral and spinal vascular diseases and intracranial hypervascular tumors who were treated by hybrid surgery at Department of Neurosurgery, Huashan Hospital from October 2016 to December 2017.There were 70 male and 62 female patients with a mean age of 48.33 years (range: 14-78 years), including 64 cases of intracranial aneurysm (41 complicated aneurysm cases), 28 cases of brain arteriovenous malformation (BAVM), 12 cases of hypervascular tumor, 12 cases of dural arteriovenous fistula (DAVF), 6 cases of carotid artery stenosis, 5 cases of Moyamoya disease, 3 cases of intracranial aneurysm or BAVM combined with tumor, 1 case of scalp arteriovenous fistula and 1 case of critical brain trauma in which a foreign metal stick approached the basal vascular circuit.Abnormalities were found in 16 cases in intraoperative angiography. The clinical data of all patients was collected as a perspective cohort. The success rate of hybrid surgery, intra-operative and post-operative complications, morbidity, mortality, rate of infection, the length of hospital stay were all analyzed to illustrate the effect of hybrid operation mode to traditional surgical pattern. Results: For 64 cases with intracranial aneurysms, the immediate complete occlusion rate was 90.5%, with a mortality of 4.7% and a morbidity of 14.0%. For 28 cases of BAVM and 12 cases of DAVF, all patients achieved total obliteration and favorable social independent outcomes after hybrid surgery, with no complication.For 6 cases of carotid artery stenosis and 5 cases of Moyamoya, intra-operative confirmed good cerebral reperfusion without any new post-operative neurologic deficits. After tumor vessels embolization, 4 out of 12 cases of hypervascular tumor needed intra-operative blood transfusion, and all patients achieved total tumor resection in a single stage. Only one patient with medulla oblongata hemangioblastoma died 6 months after operation due to respiratory deficit related pneumonia. Compared to traditional surgeries, the hybrid operation pattern did not significantly increase the total infection rate, central nervous system infection rate, hospital stay days and post-operative hospital stay days (all P>0.05) while the in-patient cost increased mildly (119 332 yuan vs.98 215 yuan, t=2.38, P=0.02). Conclusions The operations of complex cerebral and spinal vascular diseases and intracranial hypervascular tumors can be performed in hybrid operation suite safely.This surgical mode can ensure the quality of operation and promote the development of innovative and complicated surgical procedures.

In the original publication Fig. 1D and supplementary material is incorrect. The correct figure and supplementary material is provided in this correction.

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research.

Recently we have established a new culture condition enabling the derivation of extended pluripotent stem (EPS) cells, which, compared to conventional pluripotent stem cells, possess superior developmental potential and germline competence. However, it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment. Here, we show that EPS cells can be robustly generated from non-permissive NOD-scid Il2rg mice through de novo derivation from blastocysts. Furthermore, these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-scid Il2rg fibroblasts. NOD-scid Il2rg EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting. Notably, these cells contribute to both embryonic and extraembryonic lineages in vivo. More importantly, they can produce chimeras and integrate into the E13.5 genital ridge. Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains, which could potentially be a general strategy for deriving mouse pluripotent cells. The generation of NOD-scid Il2rg EPS cell lines permits sophisticated genetic modification in NOD-scid Il2rg mice, which may greatly advance the optimization of humanized mouse models for biomedical applications.

Objective To observe the therapeutic efficacy of needling QIN's eight head acupoints in treating insomnia.Method Sixty patients were randomized into QIN's eight head acupoints group (30 cases) and a conventional acupuncture group (30 cases). The modified Spiegel sleep questionnaire was evaluated respectively after 4-week and 8-week treatment.Result After 4-week treatment, there was a significant difference in comparing the modified Spiegel sleep questionnaire between the two groups (P<0.05), and QIN's eight head acupoints group was superior to the conventional acupuncture group; after 8-week treatment, there was no significant difference between the two groups in comparing the modified Spiegel sleep questionnaire (P>0.05).Conclusion QIN's eight head acupoints group had a more significant therapeutic efficacy compared to conventional acupuncture group after 4-week treatment.

Objective To investigate the clinical features,pathogenesis and treatment of intracranial hemorrhage occurring after carotid artery stenting (CAS) angioplasty.Methods The clinical data and imaging materials of 5 patients with carotid artery stenosis,who were admitted to authors' hospital during the period from January 2008 to January 2017 to receive CAS and developed intracranial hemorrhage after CAS,were retrospectively analyzed.Results Of the 513 patients with carotid artery stenosis who received CAS angioplasty,5 patients (0.97％) developed intracranial hemorrhage,which was confirmed by postoperative cranial CT and/or DSA.The 5 patients included 3 males and 2 females,with an average age of (71.4±5.0) years.The stenosis rate of carotid artery ranged from 90％ to 99％.The intracranial hemorrhage occurred during CAS procedure or within 10 days after CAS.DSA examination demonstrated moyamoya vessels at ipsilateral basal ganglia region in one patient and perforating artery bleeding in another patient.Conservative medication was employed in 3 patients,one of them recovered well and the other two died.Two patients received hematoma puncture drainage and developed hemiplegia.Conclusion The incidence of intracranial hemorrhage after CAS is very low,but intracranial hemorrhage carries higher mortality and morbidity.Clinically,there are a lot of causes that can induce intracranial hemorrhage.Sufficient preoperative assessing and screening of the risk factors are helpful for reducing the occurrence of intracranial hemorrhage.Once intracranial hemorrhage after CAS occurs,active measures,including control of blood pressure,drug sedation,discontinuation of anticoagulant,reduction or discontinuation of antiplatelet drugs and surgical intervention,can improve the survival rate of patients.

Objective To compare the perioperative complications of prophylactic use of three antiplatelet strategies in unruptured intracranial aneurysms treated by stent assisted coiling. Methods A total of 203 consecutive patients were brought into this retrospective study including the following three groups:the loading group (n=54), with a loading dose of 300 mg to 600 mg clopidogrel at 2 h to 24h before the stenting; tirofiban group (n=50), a loading dosage of tirofiban (8 μg/kg/min over 3 min) followed by a 0.1μg/kg/min maintenance dosage; dual antiplatelet group (n=99), dual oral antiplatelet drugs (clopidogrel 75 mg + aspirin 100 mg) pretreated for 3-5 days before the operation. Events of hemorrhage and thromboembolism were recorded and the complications were compared to assess the safety and efficacy of various antiplatelet strategies. Chi-square or Fisher exact tests were used for categorical variables. Results The hemorrhagic rates were 11.1% in loading group, 2.0% in dual antiplatelet group, and 0% in tirofiban group, respectively, while the thromboembolic rates were 7.4% in loading group, 4.0% in dual antiplatelet group, and 0% in tirofiban group, respectively. For total complications, significant difference (P<0.05) existed among the three groups, and the complication rate in loading group was significantly higher than that of the dual group (P=0.016) and tirofiban group (P=0.001), while there was no significant difference between tirofiban group and dual antiplatelet group(P>0.05). The hemorrhagic rate in loading group was significantly higher than that of the dual group (P=0.023) and tirofiban group (P=0.027), while there was no significant difference between tirofiban group and dual antiplatelet group (P>0.05). In subgroup analysis of the loading group, the postoperative thromboembolic rate was significantly higher in those exposed to low molecular weight heparin than those not (P=0.039) with no increase of hemorrhagic events (P>0.05). Conclusions When compared with the dual antiplatelet strategy, tirofiban strategy may be used as a new prophylactic protocol in unruptured intracranial aneurysms treated by stent assisted coiling. Those treated by low molecular weight heparin postoperatively after receiving dual antiplatelet therapy may increase the hemorrhagic risk, although there was a significant decrease in thromboembolic events postoperatively.

Objective To explore the application value of L VIS stetu in interventional treatment of intracranial wide-necked small aneurysms,and evaluate its safety and effectiveness.Methods A total of 11 patients with intracranial wide-necked small aneurysms,admitted to and received LVIS stent-assisted coil embolization in our hospital trom November 2014 to June 2015,were chosen in our study.Their clinical data and treatment effects were retrospectively analyzed.Results All operations were successful in 11 patients;11 LVIS stents were deployed;Raymond classification right after the surgery hinted grade Ⅰ in 4 aneurysms,grade Ⅱ in 5 aneurysms,and grade in in 2 aneurysms.There were 2 patients enjoying suboptimal opening ofLVIS stents.Raymond classification 6 months after the surgery hinted grade Ⅰ in 8 aneurysms and grade Ⅱ in one aneurysm.Modified Rankin scale 6 months after the surgery indicated that 10 patients had 0 point and one patient had 2 points.Conclusion The LVIS stent is safe and effective for treatment of intracranial wide-necked small aneurysms;short-term effect is good;the technique requirements of stetu releases are relatively high and require more attention of clinicians.

Objective To study the clinical efficacy of treatment of atrophic scars of facial hemangioma after isotopes radiotherapy with micro-plasma.Methods A total of 52 patients with atrophic scars were selected under micro-plasma treatment for 4 times,one time every six weeks.And their efficacies were evaluated by compared with single standard of that before and after the treatment.Results By means of rate of clinical index,the total effective rate of atrophic scars was 82.7％.The degree of improvement was as follows:cured in 53.8％,marked effective in 28.9％,effective in 17.3％ and no case ineffective.The total effective rate of hyperpigmentation was 90.3％,including cured in 59.6％,marked effective in 30.8％,effective in 9.6％ and no ineffective cases.Conclusions Micro-plasma is an effective therapy for atrophic scars of facial hemangioma after isotopes radiotherapy,which can significantly improve the depression degree of scars,eliminate the hyperpigmentation and improve the color of scars,but it only has adverse reactions of wound pain and postoperative wound erythema.