Objective:To investigate the expression and clinical significance of PD-L1 in colorectal cancer (CRC). Methods:A total of 210 CRC patients who accepted radical surgery in our hospital from January 2015 to January 2016 were divided into three groups, namely, high-frequency microsatellite instability (MSI-H), low-frequency microsatellite instability (MSI-L), and microsatellite stable (MSS). The expression of PD-L1 was detected by immunohistochemistry, and the expression characteristics of PD-L1 in different types of CRC were analyzed. Results:CRC cases with low differentiation had a higher expression of PD-L1 than CRC patients with high differ-entiation (P<0.05). PD-L1 had a positive rate of 75.8%in the MSI-H group and a rate of 9.3%in the MSI-L and MSS groups, wherein the difference between the two groups was statistically significant (P<0.05). Conclusion:PD-L1 was positively expressed in some CRC tu-mor tissues, and its positive rate was significantly higher in MSI-H than in MSI-L and MSS. The therapeutic effect of a PD-L1 blocker for patients with MSI-H CRC might be preferable.

Objective To investigate the therapeutic effect of the fourth ventricle tumors through lateral wall type of the transcerebellomedullary fissure approach under endoscope.Methods Clinical data of 14 cases with the fourth ventricle lesions were analyzed retrospectively.All the patients were treated by lateral wall type of the transcerebellomedullary fissure approach surgery.The endoscope was used if the lesions develop to the aqueduct and hard to be exposed.Both neurophysiological monitoring and intraoperative ultrasound were used regularly.Results Tumors were totally removed in 12 cases,subtotally in 1,and partially in 1.All the patients were diagnosed in postoperative histopathology,including 4 medulloblastoma,three epidermoid cyst,two ependymoma,two hemangioblastoma,one meningioma,one cavernous hemangioma and 1 astrocytoma.Hypopnea occurred immediate after operation in 1 patient.Ventilatory support was performed by Ventilator,and the respiration was restored 1 day later.Normal cerebrospinal fluid circulation was return in all cases.Neither aggravation of preoperative symptoms nor nuclei injury related complication had been found.The follow-up interval between 3 months to 28 months,one patient was dead with unexplained,and 1 medulloblastoma patient was relapse.Conclusion Lateral wall type of the transeerebellomedullary fissure approach,under endoscope,combined with the usage of neurophysiological monitoring and intraoperative ultrasound,can degrade the surgical related complications such as facial palsy and amblyacousia.

Objective To investigate the clinical efficacy and safety of flexible ureteroscopic lithotripsy ( FURL) using holmium laser for medullary sponge kidney stones. Methods A flexible ureteroscope was placed into renal calyx via a ureteral access sheath ( UAS) . The stones underlying the mucosa were found,and then broken by holmium laser following incision of renal papillary mucosa. The stone fragments were washed or clamped out. The remission of clinical symptoms and incidence of perioperative complications were observed,and a KUB plain film was rechecked postoperatively. Results Stones underlying mucosa were found and broken successfully in all 14 patients and there was no serious bleeding. Back pain symptoms of patients were relieved in 3 to 7 days postoperatively or after the removal of double J stent. The stone fragments were mainly discharged spontaneously. The rechecking KUB showed the amount of stones of most patients was significantly re-duced three months after operation. Conclusion FURL using holmium laser is effective for the treatment of medullary sponge kidney stones as it can significantly reduce the loads of stones without serious complications. It’ s a minimally invasive,effective,safe and suitable way which is suitable for further spread of clinical application.

Objective To investigate the feasibility of using anti-sense RNA against classⅡmajor histocompatibility complex(MHCⅡ)transactivator(CⅡTA),which might regulate MHCⅡexpression,to suppress the relative immune response.Methods Stable transfectants of dermal fibroblasts with pDarⅡ(pDarⅡ-D)were tested for the expression of classic MHCⅡ(HLA-DR,-DP,-DQ)antigens induced with recombinant human interferon-gamma(IFN-?).mRNA abundance of CⅡTA,and classic MHCⅡwas mea-sured by RT-PCR.IL-2mRNA expressed in T cells,stimulated by transfected dermal fibroblasts,was de-termined by mixed lymphocyte reaction.Results When induced with IFN-?,the expression of HLA-DR and-DP antigens on pDarⅡ-D was reduced by95.63%and87.89%,respectively.Meanwhile,the mRNA contents of CⅡTA and classic MHCⅡwere decreased significantly(P

Objective: To investigate the level of interleukin-6 (IL-6) and the effect of valproic acid(VPA) administration on IL-6 promoter methylation, further to explore the epigenetic mechanism in febrile seizures. Methods: Sprague-Dawley (SD) rats (21 day) were randomly divided into control group (n=12) and febrile seizure (FS) group (n=12), and seizures were generated using hot bath methods and evaluated by racine score and electroencephalogram (EEG). The IL-6 protein and mRNA levels were detected using ELISA and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively.Rat C6 cell line was cultured and randomly divided into control, VPA(0.2 mol/L), hyperthermia(43.5 ℃, 1 h), hyperthermia (43.5 ℃, 1 h)+VPA (0.2 mol/L) groups.The methylation status of IL-6 promoter in FS rats and the effect of VPA on IL-6 methylation in C6 cell line were examined by bisulfite sequencing polymerase chain reaction (BSP) to determine the epigenetic regulation of IL-6 level in FS. Results: Racine score and EEG results showed that the frequency and amplitude of neuronal discharge increased after hot water bath in rats, and the latency of convulsion was shorter.The expression levels of IL-6 mRNA and protein were significantly increased in Fs group compared with those in control group(mRNA: Control: 0.98±0.34; FS: 2.85±0.39, P<0.05; Protein: Control: (2 824.33±169.20)pg/ml; FS: (3 514.58±86.4)pg/ml, P<0.01). The methylation of IL-6 promoter in FS group (84% (21/25)) was lower than that in control group (100% (25/25)) (P<0.05). A significant increase in methylation of IL-6 promoter was observed in C6 cell line from VPA combined with hyperthermia (96% (24/25)) but no change was showed in that from VPA alone (100% (25/25)) compared with that from control(100% (25/25)). Conclusion IL-6 level is up-regulated in FS rats, and the hypomethylation or demethylation of the IL-6 promoter region might increase the IL-6 level.VPA administration can elevate its methylation level, which provides a strong experimental basis for the future study of the epigenetic mechanism in FS.

Hydrogen peroxide (H2O2) plays a significant role in regulating a variety of biological processes. Dys-regulation of H2O2 can lead to various diseases. Although numerous fluorescent imaging probes for H2O2 have been reported, the development of H2O2 ratiometric fluorescent probe with large Stokes shift re-mains rather limited. Such probes have shown distinct advantages, such as minimized interference from environment and improved signal-to noise ratio. In this work, we reported a new pyrene-based com-pound Py-VPB as H2O2 fluorescent probe in vitro. The probe demonstrated ratiometric detection behavior, large Stokes shift and large emission shift. In addition, the probe showed high sensitivity and selectivity towards H2O2 in vitro. Based on these excellent properties, we successfully applied Py-VPB to the visualization of exogenous and endogenous H2O2 in living cells. Cell imaging study also showed that our probe was localized in the mitochondria. We envision that the probe can provide a useful tool for unmasking the biological roles of mitochondrial H2O2 in living systems.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.