CXCL5 inhibits tumor immune of lung cancer via modulating PD1/PD-L1 signaling / 中华肿瘤杂志

Objective: To investigate the role of CXCL5 in tumor immune of lung cancer and to explore the potential molecular mechanisms. Methods: A total of 62 cases of patients with lung cancer admitted in the First Affiliated Hospital of Henan University from May 2018 to December 2019 were recruited as study object. Another 20 cases of patients with pulmonary infectious diseases and 20 cases of healthy control were selected as control. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of CXCL5 in patients with lung cancer, pulmonary infectious diseases and healthy control. Immunohistochemical staining (IHC) was used to detect the expressions of CXCL5 and PD-1/PD-L1 in tumor and paracarcinoma tissues of patients with lung cancer. Pearson correlation analysis was used to evaluate the correlation between CXCL5 and PD-1 in tumor and paracarcinoma tissues of patients with lung cancer. Lewis cells either expressing CXCL5 or vector plasmids were used to establish C57BL/6J mice model of lung cancer, and all mice were then divided into vehicle and PD-1 antibody treatment groups, 10 mice for each group. The mice survival and tumor growth curves were recorded. IHC was used to evaluate the expressions of CXCL5, PD-1 as well as the proportions of CD8(+) T and Treg cells in xenograft tumor tissues. Results: In patients with lung cancer, the serum level of CXCL5 [(351.7±51.5) ng/L] was significant higher than that in patients with pulmonary infectious diseases and healthy control [(124.7±23.4) ng/L, P<0.001]. The expression levels of CXCL5 (0.136±0.034), CXCR2 (0.255±0.050), PD-1 (0.054±0.012) and PD-L1 (0.350±0.084) in tumor were significant higher than those in paracarcinoma normal tissues [(0.074±0.022), (0.112±0.023), (0.041±0.007) and (0.270±0.043) respectively, P<0.001]. CXCL5 was significant positively correlated with PD-1 in tumor tissues of lung cancer (r=0.643, P<0.001), but not correlated with PD-1 in paracarcinoma tissues(r=0.088, P=0.496). The vector control group, CXCL5 overexpression group, vector control + anti-PD-1 antibody treatment group and CXCL5 overexpression + anti-PD-1 antibody treatment group all successfully formed tumors in mice, while CXCL5 overexpression increased the tumor growth significantly (P<0.01), which was abrogated by the treatment of anti-PD-1 antibody. CXCL5 overexpression decreased the mice survival time significantly (P<0.01), this effect was also abrogated by the treatment of anti-PD-1 antibody. The proportion of CD8(+) T cells in CXCL5 overexpression group [(10.40±2.00)%] was significant lower than that in vector control group [(21.20±3.30)%, P=0.002]. The proportion of CD4(+) Foxp3(+) Treg cells in CXCL5 overexpression group [(38.40±3.70)%] was significant higher than that in vector control group [(23.30±2.25)%, P<0.001]. After the treatment of anti-PD-1 antibody, no significant difference were observed for the proportion of CD8(+) T cells [(34.10±5.00)% and (33.40±4.00)% respectively] and Treg cells [(14.70±3.50)% and (14.50±3.30)% respectively] in xenograft tumor tissues between CXCL5 overexpression+ anti-PD-1 antibody treatment group and vector control + anti-PD-1 antibody treatment group (P>0.05). Conclusion: The expressions of CXCL5 and PD-1/PD-L1 are all increased significantly in the tumor tissues of patients with lung cancer, CXCL5 may inhibit tumor immune of lung cancer via modulating PD-1/PD-L1 signaling.

Curcumin inhibits apoptosis of HK-2 cell line induced by cisplatin / 基础医学与临床

Objective To investigate whether curcumin could inhibit cisplatin-induced apoptosis of HK-2 cells. Methods Using MTT methods to observe inhibitory effects of curcumin and cisplatin on the proliferation of HK-2 cell. Detecting caspases expression after curcumin and cisplatin treatment by Western blot. Results Cisplatin induced cell apoptosis, and the effect was dose-dependent(P＜0.05).Under the synergistic effect of curcumin and cisplatin on HK-2 cell, the number of apoptosis decreased(P＜0.05). In the same time the expression of Bcl-2 protein increased (P < 0.05) and the expression of Bcl-2 protein decreased (P < 0.05). Conclusions Cisplatin enhances the apoptosis of HK-2 cell in a dose-dependent manner, and is inhibited by curcumin. Curcumin can antagonize cisplatin-induced apoptosis in HK-2 by regulating the expressions of Bax and Bcl-2 protein.

Effect of transversus abdominis plane block on postoperative pain after colorectal surgery: a meta-analysis of randomized controlled trials

Objectives: To assess the analgesic efficacy of transversus abdominis plane [TAP] block in patients undergoing colorectal surgery [CRS]

Materials and Methods: The databases of PubMed, ISI Web of Science, and Embase were searched, and randomized controlled studies [RCTs] that compared TAP block to control for relief of postoperative pain in patients who underwent CRS were included. Outcomes, including postoperative pain at rest and with movement, morphine use, postoperative nausea and vomiting, and the length of hospital stay, were analyzed using STATA software. The weighted mean differences [WMDs] with 95% confidence intervals [95% CIs] or relative risk with 95% CI were used to present the strength of associations

Results: A total of 7 RCTs with 511 patients were included. The results of this study suggested that TAP block significantly relieved postoperative pain during postanesthetic recovery after CRS at rest and during movement [WMDs were -0.98 [95% CI -1.57 to -0.38] and -0.68 [-1.07 to -0.30], respectively], and also decreased pain intensity during movement 24 h after CRS [WMD: -0.57 [95% CI -1.06 to -0.08]]. TAP block significantly reduced opioid consumption within 24 h when compared to controls, with a WMD of 15.66 [95% CI -23.93 to -7.39]. However, TAP block did not shorten the length of hospital stay

Conclusions: TAP block was an effective approach for relief of postoperative pain and reduced postoperative consumption of morphine. More RCTs with large sample sizes are required to confirm these findings

Fresh and old tibial intercondylar eminence fracture by arthroscopic wire fixation / 中国组织工程研究

BACKGROUND:Arthroscopic treatment of tibial eminence fracture requires tiny wire,induces less epiphyseal plate damage during operations,obtains strong fixations,alows early movement postoperatively,obviously attenuate the injuries,facilitate wound healing,and reduce complications.OBJECTIVE:To investigate the biocompatibility of arthroscopic reduction and wire fixation in treatment of fresh and old tibial eminence fractures.METHODS:Twenty-five patients with fresh and old tibial eminence fractures were treated with arthroscopic reduction and wire fixation from January 2010 to April 2012 in the Second People's Hospital of Yichang City.The postoperative fracture healing time and knee function improvement in the two groups were observed.RESULTS AND CONCLUSION: Compared with the fresh fracture patients,the fracture healing time was longer,Lachman test positive rate was higher in the old fracture patients than (P＜0.05),knee flexion and extension activity and Lysholm score were lower (P＜0.05).Experimental findings indicate that,arthroscopic reduction and wire fixation is a feasible clinical treatment of fresh and old tibial intercondylar eminence fractures.

Effect of electro-acupuncture stimulation of Ximen (PC4) and Neiguan (PC6) on remifentanil-induced breakthrough pain following thoracal esophagectomy / 华中科技大学学报（医学）（英德文版）

The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII) scheduled for elective radical esophagectomy were randomized into three groups: group A (control) receiving a general anesthesia only; group B (sham) given EA needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS) electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 μg, followed by a continuous infusion of 2.25 μg/h. The patient self-administration of sufentanil was 0.75 μg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine (5 mg) intravenously at the patient's request. Blood samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after operation to measure the plasma β-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups (P<0.05). The total dose of sufentanil was 115±6.0 μg in EAS group, significantly lower than that in control (134.3±5.9 μg) and sham (133.5±7.0 μg) groups. Similarly, the rescue dose of dezocine was the least in EAS group (P<0.05) among the three groups. Plasma β-EP levels in EAS group at T3 (176.90±45.73) and T4 (162.96±35.00 pg/mL) were significantly higher than those in control (132.33±36.75 and 128.79±41.24 pg/mL) and sham (136.56±45.80 and 129.85±36.14 pg/mL) groups, P<0.05 for all. EAS could decrease the release of PGE2. Plasma PGE2 levels in EAS group at T2 and T3 (41±5 and 40±5 pg/mL respectively) were significantly lower than those in control (64±5 and 62±7 pg/mL) and sham (66±6 and 62±6 pg/mL) groups. Plasma 5-HT levels in EAS group at T2 (133.66±40.85) and T3 (154.66±52.49 ng/mL) were significantly lower than those in control (168.33±56.94 and 225.28±82.03) and sham (164.54±47.53 and 217.74±76.45 ng/mL) groups. For intra-group comparison, plasma 5-HT and PGE2 levels in control and sham groups at T2 and T3, and β-EP in EAS group at T3 and T4 were significantly higher than those at T1 (P<0.05); PGE2 and 5-HT levels in EAS group showed no significant difference among the different time points (P>0.05). No apnea or severe hypotension was observed in any group. It was concluded that intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative analgesia for patients undergoing radical esophagectomy with remifentanil anesthesia and significantly decrease requirement for parental narcotics. The underlying mechanism may be related to stimulation of the release of endogenous β-EP and inhibition of inflammatory mediators (5-HT and PGE2).

Effect of electro-acupuncture stimulation of Ximen (PC4) and Neiguan (PC6) on remifentanil-induced breakthrough pain following thoracal esophagectomy / 华中科技大学学报（医学）（英德文版）

The clinical analgesic effect of electro-acupuncture (EA) stimulation (EAS) on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients (ASAIII) scheduled for elective radical esophagectomy were randomized into three groups: group A (control) receiving a general anesthesia only; group B (sham) given EA needles at PC4 (Ximen) and PC6 (Neiguan) but no stimulation; and group C (EAS) electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 μg, followed by a continuous infusion of 2.25 μg/h. The patient self-administration of sufentanil was 0.75 μg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine (5 mg) intravenously at the patient's request. Blood samples were collected before (T1), 2 h (T2), 24 h (T3), and 48 h (T4) after operation to measure the plasma β-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale (VAS) scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups (P0.05). No apnea or severe hypotension was observed in any group. It was concluded that intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative analgesia for patients undergoing radical esophagectomy with remifentanil anesthesia and significantly decrease requirement for parental narcotics. The underlying mechanism may be related to stimulation of the release of endogenous β-EP and inhibition of inflammatory mediators (5-HT and PGE2).

Analysis of clinical characteristics and prognosis of perineural invasion in patients with gastric carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the association between perineural invasion(PNI) and clinicopathological factors and the effect of PNI on overall survival in patients with gastric carcinoma.</p><p><b>METHODS</b>A total of 178 patients with gastric carcinoma from January 2004 to May 2008 were analyzed retrospectively. Paraffin sections of surgical specimens from all the patients who underwent gastric resection were stained with laminin. PNI-positive was defined as infiltration of carcinoma cells into the perineurium or neural fascicles. The association of PNI with clinicopathologic features and prognosis of gastric carcinoma was studied.</p><p><b>RESULTS</b>PNI was positive in 78 of 178 patients(43.8%). The proportions of T stage, lymph node metastasis and TNM stage were significantly higher in PNI-positive group than those in PNI-negative group(all P<0.01). The PNI positive rate was correlated with the depth of gastric mural invasion and clinical stage. The overall survival in PNI-positive group was significantly lower than that in PNI-negative group by univariate analysis(P<0.01). The mean survival of PNI-positive patients(28.6 months) was significantly shorter than that of PNI-negative patients (44.3 months, P<0.01), which was also influenced by pN stage, pT stage, and clinical stage(P<0.01). By multivariable Cox proportional hazards model of overall survival, the positivity of PNI appeared to be an independent prognostic factor (hazards ratio=2.257, 95% CI:1.268-4.019, P=0.006).</p><p><b>CONCLUSIONS</b>PNI is associated with the degree of malignancy in gastric cancer. PNI can be a candidate of new prognostic factor.</p>

Muscarinic receptors modulate the mRNA expression of NMDA receptors in brainstem and the release of glutamate in periaqueductal grey during morphine withdrawal in rats / 生理学报

The antisense approach and RT-PCR were used to study the effects of muscarinic receptors on the scores of morphine-withdrawal syndrome and the expression of NMDA receptor subtypes (NR(1A) and NR(2A)) mRNA in rat spinal cord and brainstem. The concentrations of glutamate in periaqueductal grey (PAG) of morphine-withdrawal rats were determined by capillary electrophoresis with laser-induced fluorescence detection. The data showed that the NR(1A) and NR(2A) mRNA levels were increased significantly in the spinal cord and brainstem 1 h after the injection of naloxone (4 mg/kg, i.p.) in morphine-dependent rats. Moreover, in morphine-dependent rats pretreated (i.p.) with scopolamine (0.5 mg/kg), or pirenzepine (10 mg/kg), MK801 (0.125 mg/kg), L-N-nitroarginine methylester (10 mg/kg) 30 min before naloxone injection, the NR(1A) and NR(2A) mRNA levels were significantly lower than those of 1 h morphine-withdrawal rats. Intrathecal injection of NR(1A) or M(2) receptor antisense oligonucleotides (A-oligo, 4 microg/per rat) 24 h prior to naloxone challenge could block the morphine withdrawal symptoms including wet dog shaking, irritability, salivation, diarrhea, chewing and weight loss. Meanwhile, in morphine-dependent rats the NR(1A) mRNA levels in the spinal cord and brainstem were down-regulated by intrathecal injection of M(2) receptor A-oligo. The glutamate concentrations in PAG microdialysis were increased to a maximal level 15 min after naloxone injection. The glutamate response was inhibited by pretreatment with M(2) receptor A-oligo but not by M(1) A-oligo. The results suggest that the expression of NMDA receptors and the release of glutamate in brainstem are involved in the processes of morphine withdrawal and that the NMDA receptor expression is possibly regulated by the muscarinic receptors during morphine withdrawal.

mRNA expression of muscarinic receptors in spinal cord and brainstem in morphine dependent rats / 药学学报

<p><b>AIM</b>To observe mRNA expression of muscarinic acetylcholine receptors in spinal cord and brainstem in morphine dependent or withdrawal rats.</p><p><b>METHODS</b>The mRNA expression level of m1, m2, m3, m4 and m5 were determined by RT-PCR, the beta-actin mRNA expression was used as internal control.</p><p><b>RESULTS</b>The mRNA level of m1, m2, m3, m4 and m5 in spinal cord and m1 and m2 in brainstem were increased significantly during morphine dependence, and the levels of m1, m2, m3 and m4 in spinal cord and m1 in brainstem were decreased 1 h after the injection of naloxone (4 mg.kg-1, i.p.) in morphine dependent rats. Either scopolamine (0.5 mg.kg-1) or pirenzepine (10 mg.kg-1) was shown to significantly decrease the morphine withdrawal symptoms in rats. The levels of m1, m2, m3 and m5 in spinal cord were increased by pretreatment with pirenzepine and the levels of m2, m3 and m4 in spinal cord were increased by pretreatment with scopolamine.</p><p><b>CONCLUSION</b>The adaptive expression of muscarinic receptors at spinal and supraspinal levels play important role in mediating morphine dependence and withdrawal in rats.</p>

The Quantiative CT Measurement and Analysis of the Density of the Lumbar Vertibra ofUygar and Han People in Xinjiang Uygar Autonomous Region / 实用放射学杂志

Objective To provide useful suggestion for the prevention and treatment of osteoporosis by analyzing the density of the lumbar vertibra of normal Uygar and Han people in Xinjiang.Methods Normal Uygar males were 104,Uygar females were 85, Han males were 230,Han females were 182,the age ranged from 20 to 69 and was divided into five groups.Cann-Genant method was adopted to make human skeleton model,by which the density of bone was worked out.Results (1)The bone density was obviously negatively interrelated to age (?

Expression of ? and ? opiate receptor in spinal cord andbrainstem during morphine withdrawal in rats / 中国临床药理学与治疗学

Aim To observe the gene expression of ? and ? opiate receptor in spinal cord and brainstem,and the effects of muscarinic receptor antagonist, NMDA receptor antagonists and inhibitor of nitric oxide synthase on the expression of these genes during morphine withdrawal in rats. Methods The mRNA levels of ? and ? opiate receptor mRNA were assayed by reverse transcription polymerase chain reaction (RT_PCR) with the beta_actin mRNA as an internal control. Results The ? opiate receptor mRNA levels were increased significantly in spinal cord and brainstem during morphine dependence, and decreased after injection of naloxone during morphine withdrawal in rats. The ? opiate receptor mRNA levels in spinal cord and brainstem were changed conversely compared with the ? opiate receptor mRNA levels during morphine dependence and withdrawal. The ? and ? opiate receptor mRNA levels in spinal cord and brainstem were decreased by administration of either Rp_cAMPs or calyculin A while these levels were not changed by Sp_cAMPs at half hour before injection of naloxone in morphine dependent rats. Administration of l_N_nitric arginine methylester(10 mg?kg-1) resulted in a decrease of ? opiate receptor and ? opiate receptor levels in spinal cord , and ? opiate receptor levels in spinal cord and ? opiate receptor levels in brainstem were dedcreased by pretreatment with methyl_scopolamine (0.5 mg?kg-1) during morphine withdrawal. However, the ? and ? opiate receptor levels in both spinal cord and brainstem were not different from those of morphine withdrawal rats pretreated with either MK801 (0.125 mg?kg-1) or pirezenpine(10 mg?kg-1). In adddition, ?_actin mRNA levels were not different in each group.Conclusion The expression of ? opiate receptor and ? opiate receptor mRNA plays an important role in mediating the process of morphine dependence and withdrawal, and the expression of ? opiate receptor and ? opiate receptor mRNA in spinal cord and brainstem could be inhibited by block of muscarinic receptor or inhibition of nitric oxide production.