ObjectiveTo investigate the role of δ-opioid receptor in remifentanil-induced N-methyl-D-aspartate (NMDA) receptor miniature excitatory postsynaptic currents (mEPSCs) in rat spinal dorsal horn neurons.MethodsMale 14-18 d old Wistar rats weighing 50-60 g were used in this study.The animals were anesthetized with intraperitoneal choral hydrate 400 mg/kg and sacrificed.Their lumbar segments of spinal cord (L1-S1 ) were immediately removed and sliced.Twenty-four slices were randomly divided into 4 groups ( n =6 each): control group (group C) ; glycine group (group G) ; remifentanil group (group R) and remifentanil + naltrindole(a δ receptor antagon) (group RN).Slices were cultured in artificial cerebrospinal fluid (ACSF) (group C) or incubated in ACSF containing glycine 0.24 μmol/L (group G) or remifentanil 4 nmol/L (group R) or remifentanil 4 nmol/L+ naltrindole 1 nmol/L (group RN) for 60 min.Whole cell patch clamp technique was used to measure NMDA receptor mEPSCs.ResultsThe amplitude and frequency of mEPSCs were significantly higher in group R than in groups C and RN ( P ＜ 0.01).There were no significant differences in amplitude and frequency of mEPSCs among gorups C,G and RN ( P ＞ 0.05).ConclusionActivation of δ-receptor can enhance NMDA receptor function in spinal dorsal horn neurons in rats which may be the mechanism of remifentanil-induced hyperalgesia.

Objective To evaluate the efficacy of transarterial chemoembolization (TACE) and percutaneous cryosurgery sequential therapy for unresectable hepatocellular carcinoma (HCC).Methods Four hundred and twenty patients with unresectable HCC were divided into sequential TACE-cryosurgery sequential (sequential) group (n=290) and cryosurgery alone (cryoalone) group (n = 130). TACE was performed with the routine operation; the percutaneous cryosurgery was conducted 2 to 4 weeks after TACE. The patients were followed up at the first month and once every 2 to 3 month later. Liver ultrasound or both computer tomography and alpha fetal protein were examined during follow-up. Results During a mean follow-up of (42±17) months (range from 24 to 70 months), the local recurrence rate of ablated lesion was 17% for all the patients, 11% and 24% for patients in sequential group and cryoalone groups respectively (P=0. 001). The overall 1-, 2-, 3-, 4-and 5-year survival rate was 72%, 57%, 47%, 39% and 31%, respectively. The 1- and 2-year survival rates (71% and 61 % ) in sequential group were similar to those (73 % and 54 % ) in cryo-alone group (P=0.69 and 0. 147), while the 4- and 5-year survival rates were higher in sequential group (49 % and 39 % ) than those (29 % and 23 % ) in cryo-alone group (P= 0.001). Eighteen patients with large HCC (＞5 cm in diameter) in sequential group survived for more than 5 years while no one in cryo-alone group. Complication rate was 24% in all patients, 21% and 26% for the sequential and cryo-alone groups respectively (P=0. 06). The incidence of hepatic bleeding was higher in cryo-alone group than in sequential group (P=0. 02). Liver crack occurred in two patients of the cryoalone group. Conclusions Pre-cryosurgical TACE increased the cryoablation efficacy and decrease its complications, especially hepatic bleeding. TACE and cryosurgery sequential therapy may be a better treatment for unresectable HCC, especially for large HCC.

Objective To evaluate the changes in the expression of transient receptor potential vanilloid 1 (TRPV1) in dorsal root ganglions (DRGs) during remifentanil-induced hyperalgesia in the rats with incisional pain.Methods Thirty-two SPF healthy male Sprague-Dawley rats,weighing 240-260 g,aged 2-3 months,in which caudal catheters were successfully implanted,were divided into 4 groups (n=8 each) using a random number table:control group (group C),incisional pain group (group Ⅰ),remifentanil group (group R),and incisional pain + remifentanil group (group I+R).A 1 cm longitudinal incision was made through skin,fascia and muscle of the plantar aspect of the left hindpaw to establish the model of incisional pain.In group R,remifentanil was intravenously infused for 60 min at a rate of 1.2 μg · kg-1 · min-1.In group Ⅰ,the model of incisional pain was established,and the equal volume of normal saline was intravenously infused for 60 min at the same time.In group I+R,the model of incisional pain was established,and remifentanil was intravenously infused for 60 min at a rate of 1.2 μg · kg-1 · min-1 at the same time.In group C,the equal volume of normal saline was intravenously infused for 60 min.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawl latency (TWL) were measured at 24 h before normal saline or remifentanil infusion (To) and 2,6,24 and 48 h after the end of infusion (T1-4).The rats were sacrificed after the last measurement of pain threshold,and the DRGs of the lumbar segment (L4-6) were removed for determination of the expression of TRPV1 protein and mRNA by Western blot and real-time polymerase chain reaction,respectively.Results Compared with group C,the MWT was significantly decreased,and the TWL was shortened at T1-4,and the expression of TRPV1 protein and mRNA was up-regulated in R,I and I+R groups (P＜0.05).Compared with group R or group I,the MWT was significantly decreased,and the TWL was shortened at T1-4,and the expression of TRPV1 protein and mRNA was up-regulated in group I+R (P＜0.05) Conclusion Up-regulated expression of TRPV1 in DRGs may be involved in the mechanism underlying remifentanil-induced hyperalgesia in the rats with incisional pain.

Objective: To evaluate the role of neuroligin 1 (NL-1) in trafficking of GluR1-containing AMPA receptor to cell membrane in spinal cord dorsal horns during remifentanil-induced hyperalgesia in mice with incisional pain. Methods: Forty SPF healthy male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 5 groups (n=8 each) using a random number table method: control group (group C), NL1-shRNA plasmid group (group NL), incisional pain plus remifentanil group (group I+ R), incisional pain plus remifentanil plus blank vector group (group I+ R+ B), and incisional pain plus remifentanil plus NL-1-shRNA plasmid group (group I+ R+ NL). Negative lentivirus was intrathecally injected in group I+ R+ B.In NL and I+ R+ NL groups, 10 μl NL-1-shRNA lentivirus at 1×10⁸ IFU/ml was intrathecally injected once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected at the same time point in C and I+ R groups.After transfection was stable, normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at 15 min intervals in C and NL groups.In I+ R, I+ R+ B and I+ R+ NL groups, 0.1 ml remifentanil 10 μg/kg was injected via the caudal vein for 4 consecutive times at 15 min intervals, and the model of incisional pain was established after the first administration.The mechanical paw withdrawal threshold (MWT) and tail-flick latency (TFL) were measured at 24 h before normal saline or remifentanil administration (T₀) and at 3, 6, 24 and 48 h after the end of administration (T_1-4). The animals were sacrificed after measurement of pain threshold at T₄, and L_4-6 segments of the spinal dorsal horn were then collected for determination of the expression of NL-1 protein and mRNA and AMPA receptors, and the ratio of AMPA receptor expression in the membrane protein to that in the total protein (m/t ratio) was calculated. Results: Compared with group C, the MWT was significantly decreased, and TFL was shortened at T_1-4, the expression of NL-1 protein and mRNA and GluR1-containing AMPA receptors in membrane and total proteins was up-regulated, and m/t ratio was increased in I+ R and I+ R+ B groups (P<0.05). Compared with I+ R and I+ R+ B groups, the MWT was significantly increased and TFL was prolonged at T_1-4, the expression of NL-1 protein and mRNA and GluR1-containing AMPA receptors in membrane and total proteins was down-regulated, and m/t ratio was decreased in group I+ R+ NL (P<0.05). Conclusion NL-1 in spinal cord dorsal horns can promote the trafficking of GluR1-containing AMPA receptors to cell membrane, which is involved in the development and maintenance of remifentanil-induced hyperalgesia in mice with incisional pain.

Objective:To evaluate the role of secreted protein acidic and rich in cysteine like protein 1 (SPARCL1) in spinal dorsal horns in the development of remifentanil-induced hyperalgesia in mice with incisional pain.Methods:Forty-eight healthy male C57BL/6J mice, aged 8-10 weeks, weighing 18-22 g, were divided into 6 groups ( n=8 each) using a random number table method: control group (group C), incisional pain group (group I), remifentanil group (group R), incisional pain plus remifentanil group (group I+ R), incisional pain plus remifentanil plus negative control group (group I+ R+ N), and incisional pain plus remifentanil plus SPARCL1-siRNA group (group I+ R+ S). In I+ R+ N and I+ R+ S groups, 1×10 8 IFU/ml negative control siRNA and SPARCL1-siRNA 10 μl were intrathecally injected, respectively, once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected once a day for 3 consecutive days in C, I, R and I+ R groups.After transfection was stable, normal saline 0.1 ml was intravenously injected through the tail vein for 4 consecutive times at 15 min interval in C and I groups, and remifentanil 10 μg/kg (diluted to 0.1 ml in normal saline) was intravenously injected via the tail vein for 4 consecutive times at 15 min interval in R, I+ R, I+ R+ N and I+ R+ S groups.The incisional pain model was established after the first administration via the tail vein in R, I+ R, I+ R+ N and I+ R+ S groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before infusing normal saline or remifentanil (T 0) and 3, 6, 24 and 48 h after stopping infusion (T 1-4). Animals were sacrificed after measuring pain threshold at T 4, and L 4-6 segments of the spinal cord were removed for determination of the expression of SPARCL1 protein and mRNA by Western blot and quantitative real-time polymerase chain reaction, respectively. Results:Compared with group C, MWT was significantly decreased and TWL was shortened at T 1-4 in I+ R and I+ R+ N groups and at T 2-4 in I, R and I+ R+ S groups, and the expression of SPARCL1 protein and mRNA was significantly up-regulated in R, I+ R and I+ R+ C groups ( P<0.05 or 0.01). Compared with group I and group R, MWT was significantly decreased, TWL was shortened, and the expression of SPARCL1 protein and mRNA was up-regulated in group I+ R ( P<0.01). Compared with group I+ R, MWT was significantly increased and TWL was prolonged at T 1-4, and the expression of SPARCL1 protein and mRNA was down-regulated in group I+ R+ S ( P<0.05 or 0.01). Conclusion:Enhanced activity of SPARCL1 in the spinal dorsal horns is involved in the development of remifentanil-induced hyperalgesia in mice with incisional pain.

Objective To investigate the effects of emotions(subjective well-being,depressed effect,worry,and guilt)on cancer(colorectal cancer,hepatic cancer,thyroid cancer,lung cancer,and breast cancer).Methods Two-sample bi-directional Mendelian randomization(MR)method was adopted.All data were based on summary data from genome-wide association studies(GWAS).Inverse variance weighting(IVW)was used to generate the main results,and weighted median(WM)and MR-Egger methods were employed to calculate supplementary results.The outcome measure was odds ratio(OR),and sensitivity analysis was conducted.Results For depressed effect,a significant association with lung cancer(OR=1.005,95％CI:1.001-1.009,P=0.015)was found.For worry,a significant association with breast cancer(OR=1.199,95％CI:1.011-1.423,P=0.038)was observed.For guilt,a significant association with thyroid cancer(OR=2.083,95％CI:1.080-4.017,P=0.029)was identified.After removing all potentially pleiotropic SNPs detected by MR PRESSO,the association between worry and breast cancer showed no statistical difference(P=0.064),while the association between worry and colorectal cancer remained significant(OR=0.739,95％CI:0.571-0.956,P=0.021).No causal relationship was found between cancer and emotions.Conclusion There is a causal relationship between depression and increased lung cancer incidence,guilt and increased thyroid cancer incidence,as well as anxiety and decreased colorectal cancer incidence.

Objective To evaluate the relationship between NR2B subunit-containing N-methyl-D-aspartate (NMDA) receptors (NR2B receptors) and Ca2+/calmodulin-dependent protein kinase Ⅱ α (CaMK Ⅱ α) in the spinal cord during remifentanil-induced hyperalgesia in a rat model of incisional pain (IP).Methods Forty male Sprague-Dawley rats in which intrathecal and caudal catheters were successfully placed,weighing 260-280 g,aged 2-3 months,were divided into 4 groups (n=10 each) using a random number table method:control group (group C),remifentanil plus IP group (group RI),NR2B antagonist Ro 25-6981 group (group Ro) and remifentanil plus IP plus Ro 25-6981 group (group RI+Ro).In group C,normal saline 0.1 ml was intrathecally injected,and 10 min later normal saline was infused for 60 min via the tail vein at a rate of0.1 ml · kg-1 · min-1.In group RI,normal saline 0.1 ml was intrathecally injected,and 10 min later remifentanil was infused for 60 min via the tail vein at a rate of 1.0 μg · kg-1 · min-1,and IP was established immediately after onset of remifentanil infusion.In group Ro,Ro 25-6981 (0.1 ml) 10 μg was intrathecally injected,and 10 min later normal saline was infused for 60 min via the tail vein at a rate of 0.1 ml · kg-1 · min-1.In group RI+Ro,Ro 25-6981 (0.1 ml) 10 μg was intrathecally injected,and 10 min later remifentanil was infused for 60 min via the tail vein at a rate of 1.0 μg · kg-1 · min-1,and IP was established immediately after onset of remifentanil infusion.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intravenously infusing normal saline or remifentanil and at 2,6,24 and 48 h after the end of infusion (T0-4).The rats were sacrificed after the last behavioral test,and the L4-6 segment of the spinal cord was removed for determination of the expression of NR2B in total and membrane protein (tNR2B and mNR2B) and expression of CaMK Ⅱ α in total protein (tCaMK Ⅱ α) and phosphorylated CaMK Ⅱ α (pCaMKⅡα).The ratios of mNR2B/tNR2B and pCaMKⅡα/tCaMK Ⅱα were calculated.Results Compared with group C,the MWT was significantly decreased,TWL was shortened,the expression of tNR2B,mNR2B,tCaMKⅡα and pCaMKⅡα was up-regulated,and the ratios of mNR2B/tNR2B and pCaMK Ⅱ α/tCaMK Ⅱ α were increased in group RI (P＜0.05 or 0.01).Compared with group RI,the MWT was significantly increased,TWL was prolonged,the expression of tNR2B,mNR2B,tCaMKⅡα and pCaMKⅡα was down-regulated,and the ratios of mNR2B/tNR2B and pCaMK Ⅱ α/tCaMK Ⅱ α were decreased in group RI+ Ro (P＜0.05 or 0.01).Conclusion Enhanced function of NR2B can activate CaMKⅡα during remifentanil-induced hyperalgesia,which may be involved in the mechanism of remifentanil-induced hyperalgesia in a rat model of IP.

Objective:To identify the threshold of a health warning system based on the association of apparent temperature and years of life lost (YLL).Methods:Daily mortality records and meteorological data were collected from 364 Chinese counties for 2006-2017. Distributed lag nonlinear model and multivariate Meta-analyses were applied to estimate the association between the apparent temperature and YLL rate. A regression tree model was employed to estimate the warning thresholds of the apparent temperature. Stratified analyses were further conducted by age and cause of death.Results:The daily YLL rate was 23.6/10 5. The mean daily apparent temperature was 15.7 ℃. U-shaped nonlinear associations were observed between apparent temperature and YLL rate. The actual temperature-caused YLL rate for the elderly was higher than the young population. The daily excess deaths rate increased with the higher effect levels. Conclusions:Regression tree model was employed to define the warning threshold for meteorological health risk. The present study provides theoretical support for the weather-related health warning system.

[Objective] To analyze the correlation of the distribution and morphological characteristics of breast calcification with the risk of breast malignant tumors, so as to further reveal the important value of the calcification in diagnosis of breast malignant tumors. [Methods] A total of 108 patients who had received concurrent puncture biopsy and surgical treatment of breast calcification at The Second Affiliated Hospital of Xi’an Jiaotong University from January 1, 2019 to December 31, 2019 were recruited, and their imaging data and postoperative pathological results were analyzed. We divided the distribution of breast X calcification into two categories based on segmental/linear calcification and regional/diffuse calcification. We classified the morphology of breast X calcification into punctate, small branching, polymorphic, amorphous, and coarse ones. We then explored the distribution, morphology, and BI-RADS classification of tumor calcification under breast X-ray, and its correlation with the occurrence, age, menopausal status, hormone receptors, and molecular typing of breast malignant tumors. [Results] Among the 108 patients enrolled in the study, 21 cases were malignant and 87 cases were benign. The results showed that the distribution of calcification was segmental/linear (χ²=11.2, P=0.003) and the calcification morphology was of small branching calcification (χ²=9.3, P=0.046). The detection rate in malignant tumors was significantly higher than that in benign tumors. The distribution and morphology of calcification were not significantly correlated with ER, PR, HER2, Ki67, pathological type, or molecular typing (P>0.05). Logistic regression analysis showed that , calcification distribution was segmental/linear [OR=19.94(3.061-129.9), P=0.002], calcification morphology was small branching [OR=3.906(1.141-13.37), P=0.030], and B-RADS classification was 4 grade and above [OR=39.99(2.703-591.7), P=0.007], which were closely related to the occurrence of malignant tumors. [Conclusion] For patients with breast tumors in which calcification can be detected under mammography, their imaging characteristics are closely related to the occurrence of malignant tumors. The distribution of calcification is segmental/linear, and the morphology of calcification is small branching/amorphous, which is more likely to be a malignant tumor and closely related to the occurrence of breast cancer.

Objective: To investigate the association between sleep duration and frailty among people aged 50 years and over. Methods: Cross-sectional data was collected from the first wave of World Health Organization Study on global AGEing and adult health in China. Frailty index was constructed on the proportion of deficits, out of the 40 variables. A two-level (individual level and community level) linear model was performed to identify the related factors on frailty. All the models were stratified by age, gender, residence (urban/rural). Restricted cubic spline was performed to graphically evaluate the dose-response association between self-reported sleep duration and frailty. Results: A total of 13 175 individuals aged 50 years and over participated in this study. Without adjusting on any confounding factors, shorter or longer sleep duration significantly increased the risk of weakness compared with normal sleep time (OR=2.05, 95%CI: 1.71-2.44; OR=1.35, 95%CI: 1.12-1.63). After adjusting for confounding factors such as gender, age, residence, education, family assets, vegetable, smoking, drinking and physical activity, a positive association between short sleep duration and frailty was noticed compared with normal sleep time (aOR=1.60, 95%CI: 1.27-2.01). The results of stratified analysis on sex, age and urban and rural areas showed that, after adjusting for gender, age, residence, education level, family assets, intake of vegetables and fruits, smoking, drinking and physical activity, only shorter sleep duration was positively correlated with the risk of weakness. In addition, among people aged 65 years and over, adjusted for confounding factors, the risk of weakness increased by 91%, compared with normal sleep time (aOR=1.91, 95%CI: 1.46-2.49). The dose-response curve also showed that the sleep duration and frailty present an approximate "U" shaped relationship. Conclusion Short sleep duration might be associated with frailty.