Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.

Objective To explore the effects of different phenotypes macrophages(Mφs)on the proliferation,mi-gration and osteogenic differentiation of periodontal ligament stem cells(PDLSCs).Methods PDLSCs were isola-ted and cultured by tissue block method.Tohoku Hospital Pediatrics-1(THP-1)cell line was stimulated to activate into unpolarized Mφs(M0),then induced to polarize into type Ⅰ Mφs(M1)and type Ⅱ Mφs(M2).Quantitative real-time PCR(qPCR)detected the inflammatory factors tumor necrosis factor α(TNF-α),interleukin(IL)-1 β,IL-6,IL-10 and transforming growth factor-β(TGF-β)mRNA expression level.After collecting culture superna-tants with different phenotypes,PDLSCs were stimulated,native control(NC)group did not receive the culture su-pernatant of Mφs.The effects of PDLSCs proliferation were assessed via Methylthiazolyldiphenyl-tetrazolium bro-mide(MTT)assay,while scratch assays were employed to evaluate their migration.Western blot was utilized to analyze the protein expression of Runt-related transcription factor 2(RUNX2)and alkaline phosphatase(ALP).Additionally,Alizarin Red staining was performed to investigate the deposition of calcified nodules in PDLSCs.Re-sults qPCR showed the relative expression of TNF-α,IL-1 β and IL-6 in M1 Mφs were higher than those in M0 and M2 Mφs(P＜0.05),and the relative expression of IL-10 and TGF-β in M2 Mφs were higher than those in M0 and M1 Mφs(P＜0.05);Western blot showed the expression of RUNX2 and ALP proteins in PDLSCs in M0 and M2 groups was higher than those in the NC group(P＜0.05),Alizarin Red staining showed increased calcified nodule deposition in PDLSCs in M0,M1 and M2 groups compared to the NC group;MTT assay showed the prolifer-ation of PDLSCs in the M0 and M1 groups was suppressed compared to the NC group(P＜0.05);and scratch ex-periment showed the migratory capacity of PDLSCs in the M1 and M2 groups was stronger than that in the NC group.Conclusion M0 and M1 Mφs inhibit PDLSCs proliferation,M1 and M2 Mφs promote PDLSCs migration,and all types of Mφs promote osteogenic differentiation of PDLSCs.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.

Objective: This study aimed to explore the role of SGK-1 in the occurrence of temporomandibular joint(TMJ) osteoarthritis(TMJ-OA). Methods: Sixteen rats were randomly divided into Control group(Control group) and TMJ-OA group(TMJ-OA group), and TMJ-OA group was injected with sodium iodoacetate(MIA) intra articular cavity while Control group was injected with 0.9% sodium chloride solution. Pain behavior was assessed by measuring the head withdrawal threshold(HWT) with a von-Frey apparatus. Hematoxylin-eosin(HE) and Safranin O-fast green stains were used to observe the histological structure changes of the condyle of TMJ-OA rats. Real-time PCR was performed to exam the expression levels of mRNA of SGK-1, MMP-13, IL-1β, COX-2 in mandibular condylar cartilage(MCC). HE stain was used to observe the histological structure changes of the trigeminal ganglion(TG) of TMJ-OA rats. Real-time PCR was performed to exam the expression levels of mRNA of SGK-1, COX-2 in TG. Results: MIA injection induced typical OA-like lesions in the TMJ within 28 days. Administration of MIA led to the significant decrease in HWT, disordered of the condyle cartilage and subchondral bone structure, demyelination aggravated of nerve fibers in TMJ rats. Compared with rats in Control groups, the expression levels of SGK-1 in MCC and TG of rats in TMJ-OA group were upregulated. Conclusion In the pathological process of TMJ-OA, SGK-1 may plays an important role not only in cartilage structural damage but also in pain transmission.

ObjectiveTo investigate the effect of proteasome subunit beta type 4 (PSMB4) on the proliferation and viability of human liver cancer SMMC7721 cells and its possible mechanisms. MethodsThe specific short-hairpin RNA (shRNA) technique was used to construct SMMC7721 cells with knockdown expression of PSMB4, and these cells were selected as experimental group. MTT assay and colony-forming assay were used to observe the change in cell proliferation, flow cytometry was used to measure the change in cell apoptosis rate, and Western blot was used to measure the change in the expression of related proteins. The independent samples t-test was used for comparison of continuous data between two groups. ResultsSMMC7721 cells with knockdown expression of PSMB4 were successfully constructed (shRNA1: t=22.67, P＜0.0001; shRNA2: t=30.88, P＜0.0001; shRNA3: t=67.82, P＜0.0001). The MTT assay showed that the experimental group had a significantly lower OD490 value than the control group on day 4 (0.4770±0.0135 vs 0.3237±0.0127, t=8286, P=0.0012) and day 5 (0.5893±0.0088 vs 0.3847±0.0090, t=16.220, P＜0.0001). The colony-forming assay showed a significant reduction in the number of cell colonies in the experimental group. Flow cytometry showed that compared with the control group, the experimental group had significantly higher early apoptosis rate (5.5570%±0.2589% vs 3.8870%±0.3324%, t=3.964, P=00166), late apoptosis rate (12.6300%±0.4198% vs 5.3100%±0.3062%, t=14.080, P=0.0001), and total apoptosis rate (181800%±0.6785% vs 9.1970%±0.6313%, t=9.967, P=0.0006), as well as a significant reduction in the protein expression of nuclear factor-kappa B p65 (0.8015±0.0120 vs 0.2841±0.0110, t=31.830, P＜0.0001) and a significant increase in the protein expression of nuclear factor-kappa B inhibitory protein α (0.4816±0.0112 vs 0.6583±0.0142, t=9.774, P=0.0006). ConclusionKnockdown of PSMB4 expression may reduce the proliferation and viability of liver cancer SMMC7721 cells by inhibiting the NF-κB signaling pathway.

Objective To investigate the expressions of metallothionein-2A (MT-2A), E-cadherin, interleukin-6 (IL-6), cyclin E, proliferating cell nuclear antigen (PCNA) and bcl-2 in prostate cancer tissues and their correlation with biochemical recurrence of prostate cancer. Methods Tissue specimens from 128 cases of prostate cancer who underwent radical prostatectomy in Shanxi Dayi Hospital from October 2012 to October 2017 were processed and transferred into tissue microarrays, the clinicopathological parameters of patients were also recorded. The expression levels of MT-2A, E-cadherin, IL-6, cyclin E, PCNA and bcl-2 were detected by immunohistochemical avidin-biotin complex (ABC) staining. The correlation between different molecular markers and biochemical recurrence of prostate cancer was analyzed. Results The biochemical recurrence rate of 128 patients with prostate cancer was 30.5％ (39/128). The biochemical recurrence rates of low-risk, intermediate-risk and high-risk prostate cancer patients were 14.8％(8/54), 38.7％(24/62) and 58.3％ (7/12), respectively. The risk classification and pathological T stage of patients with prostate cancer were associated with the expressions of MT-2A, cyclin E, IL-6 and E-cadherin (all P< 0.05). Multivariate Cox risk model showed that the high risk classification (HR= 1.81, 95％CI 1.56-2.19, P=0.042), MT-2A positive expression (HR= 2.01, 95％CI 1.08-3.15, P= 0.005), cyclin E positive expression (HR= 1.79, 95％CI 1.08-2.21, P= 0.042) and E-cadherin negative expression (HR= 1.92, 95％ CI 1.22-2.45, P= 0.020) were the independent risk factors for biochemical recurrence of prostate cancer. Conclusion The expression of MT-2A, cyclin E and E-cadherin may serve as independent predictors for biochemical recurrence of prostate cancer.

Objective: To evaluate the effects of sevoflurane on microglial polarization after traumatic brain injury (TBI) in rats. Methods: Seventy-two healthy adult male Sprague-Dawley rats, weighing 230-250 g, were divided into 3 groups (n=24 each) using a random number table method: sham operation group (group Sham), group TBI, and TBI plus sevoflurane anesthesia group (group TBI+ Sevo). TBI models were established by using Feeney′s method in TBI and TBI+ Sevo groups, 30 min later 2.4% sevoflurane was inhaled for 1 h once a day for 3 consecutive days in TBI+ Sevo group, while pure oxygen was inhaled instead in Sham and TBI groups.At 1, 3, 7 and 14 days after establishing the model, 6 rats were selected, the neurological function was evaluated with the modified neurologic severity score (mNSS), and tail venous blood samples were taken for determination of tumor necrosis factor-a (TNF-α), interleukin-1beta (IL-1β) and IL-6 concentrations by enzyme-linked immunosorbent assay.The rats were then sacrificed, the limbic cortical tissues of brain contusion lesion were taken for determination of cell apoptosis (by TUNEL) and expression of microglial marker Iba-1, microglial M1 phenotypic marker CD86 and microglial M2 phenotypic marker CD206 (by Western blot). Results: Compared with group Sham, the mNSS score, apoptosis rate of cortical cells, expression of Iba-1, CD86 and CD206, and concentrations of serum TNF-α, IL-1β and IL-6 were significantly increased in TBI and TBI+ Sevo groups (P<0.05). Compared with TBI group, the mNSS score, apoptosis rate of cortical cells, expression of Iba-1 and CD86 and concentrations of serum TNF-α, IL-1β and IL-6 were significantly decreased, and the expression of CD206 was up-regulated in TBI+ Sevo group (P<0.05). Conclusion The mechanism by which sevoflurane anesthesia reduces TBI may be related to promoting microglial polarization and inhibiting systemic inflammatory response in rats.

OBJECTIVETo summarize the application of staged ileostomy and closure operation combined with nutritional support therapy in the treatment of chronic radiation intestinal injury(CRII).

METHODSClinical data of patients with definite radiation history and pathological diagnosis of CRII receiving treatment at Department of General Surgery, Jinling Hospital from January 2012 to December 2016 were retrospectively analyzed. Patients who were diagnosed with tumor recurrence during operation or by postoperative pathology were excluded. Patients undergoing stageI( ileostomy and stageII( closure operation combined with nutrition support therapy were enrolled to the cohort. Detailed scheme of stage I( ileostomy and therapeutic time were determined by clinical symptoms and nutritional status. While performing ileostomy, the removal of intestinal lesions depended on range and degree of intestinal injury. Nutritional support therapy and other symptom-relieving therapy were offered after surgery. Timing for stageII( closure operation was decided according to nutritional status of patients. Lesions of remaining intestine were determined during operation, then necessary intestinal resection and closure operation were performed. Adhesion classification of radiation intestinal injury (total five levels) proposed by our center was adopted to evaluate the level and range of intestinal lesions. Level 0 indicated no adhesion between injured intestinal loop and surrounding organs; level 1 indicated that the adhesion and fibrosis were limited to right pelvis; level 2 indicated that the adhesion included all pelvis and the adhesion was severe and difficult to divide; level 3 was the forward extension of level 2 adhesion, which was between injured intestinal loop and anterior pelvic wall; level 4 was the upward extension of level 3 adhesion, which was between injured intestinal loop and anterior abdominal wall. Clavien-Dindo classification (lower level means milder symptom) and complication comprehensive index(CCI, lower CCI means milder symptom) calculated by on-line program (http:∕∕www.assessurgery. com) were applied to estimate postoperative complications. Resected intestinal length, adhesion classification of radiation intestinal injury, postoperative complications and time to total enteral nutritional (TEN) of both surgeries and nutritional status (body mass index and serum albumin) were compared between stageI( ileostomy and stageII( closure operation.

RESULTSTwenty-one patients were enrolled in the research with 2 males and 19 females. Primary tumor included 14 cervical cancers, 3 rectal cancers, 1 endometrial cancer, 1 ovarian carcinoma, 1 seminoma and 1 mixed germ cell tumor. Median interval between the end of radiation and radiation intestinal injury was 7(2 to 91) months and median interval between the incidence of radiation intestinal injury and ileostomy was 5(<1 to 75) months. Operative indications for ileostomy were obstruction in 14 cases (66.7%), intestinal internal fistula in 1 case (4.8%), intestinal outer fistula in 2 cases (9.5%), radiation proctitis in 3 cases (14.3%) and acute intestinal perforation in 1 case (4.8%). Average age of patients undergoing stageI( ileostomy was 48 (18 to 60) years with BMI (17.0±2.7) kg/m and serum albumin (36.8±5.2) g/L. Patients undergoing stageII( closure operation had significantly higher BMI [(18.4±2.0) kg/m, t=-2.747, P=0.013] and higher serum albumin [(40.8±3.6) g/L, t=-3.505, P=0.002]. Average interval between stageI( ileostomy and stageII( closure surgery was (197±77) days. Resected intestinal length of stageI( ileostomy was which was significantly longer than that of stageII( closure surgery [(74.0±56.1) cm vs. (15.5±10.4) cm, t=4.547, P= 0.000]. Abdominal adhesion classification of stageII( ileostomy plus closure operation was significantly better as compared to stage I( ileostomy(Z=-3.347, P=0.001). Morbidity of postoperative complications in stageI( ileostomy was 52.4% (11/21), which decreased to 19.0% (4/21) in stageII( operation with significant difference (χ²=5.081, P=0.024). Postoperative complication Clavien-Dindo classification and CCI scores in stageII( operation were significantly lower than those in stageI( operation (P=0.006 and P=0.002). Till June 2017, 17 of 21 patients(81.0%) were followed-up for (28±18) months. Except for 2 cases of relapse, 15 patients recovered to normal diet.

CONCLUSIONSApplication of staged ileostomy and closure operation combined with nutritional support therapy to CRII is in accordance with the principle of injury control surgery. Furthermore, this staged approach is safe and effective, can reduce the morbidity and the severity of complications, and can also be helpful to decide the margin for intestinal resection.

Adolescent ; Adult ; Anastomosis, Surgical ; Female ; Humans ; Ileostomy ; Intestinal Diseases ; etiology ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasms ; radiotherapy ; Nutritional Support ; Postoperative Complications ; Radiation Injuries ; surgery ; Retrospective Studies ; Young Adult

Objective To evaluated the clinical efficacy of transurethral en bloc resection of bladder tumor with 2 μm laser in the high-risk elderly patients with bladder cancer under local anesthesia. Methods All of 64 high-risk elderly patients having underwent surgical treatment from April 2015 to October 2016 were divided into 2 groups,2 μm laser group(30 patients)and transurethral resection of bladder tumor(TURBT)group(34 group)according to surgical methods.The area and degree of pain was observed and recorded using visual analogue scales(VAS)during the 2 μm laser operation. The operation time,bladder irrigation time,catheter indwelling time,hospital stay,complications and 1-year cumulative recurrence rate were compared between 2 groups. Results The ASA grade in 2 μm laser group was higher than that in TURBT group and there was significant difference(P<0.05).During the 2 μm laser operation,the urethra pain was 53.33%(16/30),bladder pain was 20.00%(6/30), both urethra and bladder pain was 26.67%(8/30).The VAS scores were(2.50 ± 1.38)points,all the patients tolerated the pain in the 2 μm laser group.There was no significant difference in operation time between 2 groups(P>0.05).The bladder irrigation time,catheter indwelling time and hospital stay were shorter in 2 μm laser group than those in TURBT group:(40.00 ± 19.06)h vs.(56.47 ± 14.55)h,(4.33 ± 1.40)d vs. (5.65 ± 0.93) d,(4.13 ± 1.51) d vs. (6.24 ± 0.75) d,P<0.05 or<0.01. The overall incidence of complications was lower in 2 μm laser group than that in TURBT group:13.33%(4/30) vs. 64.71% (22/34),χ2=8.719,P=0.003.Compared with that of pre-treatment,the quality of life was higher after treatment in two groups,but there were no significant differences between the two groups.There were no significant differences in 1-year cumulative recurrence rate between the two groups after treatment (χ2= 0.496,P = 0.481). Conclusions Transurethral 2 μm laser treatment in bladder cancer under urethral surface anesthesia is safe and reliable for the high-risk elderly patients and complications are fewer than TURBT.The recent curative effect is satisfied.

OBJECTIVETo compare the outcomes of early oral feeding (EOF) and the traditional oral feeding (TOF) in postoperative patients with colorectal cancer using Meta-analysis.

METHODSThe databases of PubMed, SCI, Ovid, The Cochrane Library, CNKI, CBM, VIP and Wanfang Data were searched to collect randomized controlled trial (RCT) about EOF versus TOF in patients undergoing elective colorectal surgery. The retrieval time span was from inception to June 1, 2016. The studies were screened according to the inclusion and exclusion criteria. The data were extracted and the quality was evaluated by 2 reviewers independently. The Meta-analysis was conducted using RevMan 5.2 software.

RESULTSA total of 14 studies with 1 807 patients (906 cases in EOF group and 901 cases in TOF group) were included. The time to first passage of flatus (MD=-16.11 h, 95%CI:-18.27 to -13.94 h, P=0.00), postoperative hospital stay (MD=-1.92 d, 95%CI:-2.83 to -1.01 d, P=0.00), hospitalization cost (ten thousand yuan) (MD=-0.58, 95%CI:-0.71 to -0.46, P=0.00) were less in EOF group compared to TOF group. EOF patients had lower total complication rate (OR=0.68, 95%CI:0.48 to 0.95, P=0.03), in which the pulmonary infection (OR=0.27, 95%CI:0.13 to 0.53, P=0.00), pharyngolaryngitis (OR=0.06, 95%CI:0.04 to 0.11, P=0.00) were lower than those in TOF group, while the tube reinsertion (OR=2.34, 95%CI:1.08 to 5.07, P=0.03) was higher. The incidence of anastomotic leakage, nausea, vomiting, abdominal distension, diarrhea, and wound infection between two groups was not significantly different(all P>0.05). There was no significant difference between two groups in IgM (P>0.05), while the IgA (MD=0.3, 95%CI:0.12 to 0.48, P=0.00), IgG (MD=2.13 ,95%CI:0.82 to 3.44, P=0.001), CD4+ (MD=3.80, 95%CI:2.55 to 5.04, P=0.00), CD4+/CD8+ (MD=0.22, 95%CI:0.04 to 0.41, P=0.02) in EOF group were higher than those in TOF group. Postoperative CRP decreased rapidly in EOF group (MD=-30.10, 95%CI:-48.07 to -12.13, P=0.00), and IL-6 was not significantly different (P>0.05). EOF patients had higher serum albumin level 5 days after operation (MD=3.27, 95%CI: 2.48 to 4.07, P=0.00).

CONCLUSIONSEOF can promote gas passage and defecation, reduce postoperative hospital stay and treatment costs. Also, it can decrease the incidence of complications and postoperative inflammation, and maintain immune function.