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 relationship between CCL21 and triggering receptor expressed on myeloid cells 2 (TREM2)/DNAX-activating protein of 12 kDa (DAP12) signaling pathways in the spinal dorsal horn in remifentanil-induced hyperalgesia in mice with incisional pain.Methods:Thirty-two SPF healthy male C57BL/6J mice, weighing 18-22 g, aged 8-10 weeks, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), CCL21 neutralizing antibody group (group anti-CCL21), remifentanil + incisional pain group (group R+ I), and CCL21 neutralizing antibody + remifentanil + incisional pain group (group anti-CCL21+ R+ I).A CCL21 neutralizing antibody 0.3 μg (diluted to 10 μl in normal saline) was intrathecally injected in anti-CCL21 and anti-CCL21+ R+ I groups twice a day.Normal saline 10 μl was intrathecally injected at the same time point twice a day in C and R+ I groups.Fifteen min after intrathecal injection, normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at an interval of 15 min in C and anti-CCL21 groups, and remifentanil 10 μg/kg (diluted to 0.1 ml in normal saline) was injected via the caudal vein for 4 consecutive times at an interval of 15 min in R+ I and anti-CCL21+ R+ I groups.The tail-flick latency (TFL) and mechanical paw withdrawal threshold (MWT) were measured at 24 h before remifentanil or normal saline injection (T 0) and 3, 6, 24 and 48 h after stopping injection of remifentanil or normal saline (T 1-4).The mice were sacrificed after the last measurement of pain threshold, and L 4-6 segments of the spinal cord were removed for determination of the expression of TREM2 and DAP12 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction). Results:Compared with group C, TFL was significantly shortened and MWT was decreased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was up-regulated in group R+ I and R+ I+ anti-CCL21 ( P<0.05), and no significant change was found in the parameters mentioned above in group anti-CCL21 ( P>0.05).Compared with group R+ I, TFL was significantly prolonged and MWT was increased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was down-regulated in group anti-CCL21+ R+ I ( P<0.05). Conclusions:CCL21 is involved in remifentanil-induced hyperalgesia by activating TREM2/DAP12 signaling pathways in the spinal dorsal horn of mice with incisional pain.

Objective:To evaluate the effect of sleep fragmentation on postoperative cognitive dysfunction (POCD) and hippocampal glutaminergic metabolism in aged mice anesthetized with isoflurane.Methods:Forty healthy SPF-grade male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 4 groups ( n= 10 each) by the random number table method: normal control group (group C), sleep fragmentation group (group SF), isoflurane anesthesia/surgery group (group I/S), and sleep fragmentation plus isoflurane anesthesia/surgery group (group SF+ I/S). Group C did not received any treatment. Group SF received sleep fragmentation for 24 h. The right carotid artery exposure was performed under isoflurane anesthesia in group I/S. Group SF+ I/S received isoflurane anesthesia/right carotid artery exposure at 24 h after sleep fragmentation. The metabolic levels of glutamate (Glu), glutamine (Gln), Glu/Gln complex (Glx), and N-acetylaspartate (NAA) and their ratio to creatine (Cr) were measured by in vivo 9.4T hydrogen proton magnetic resonance spectroscopy at 2 h after anaesthesia. Y maze and Morris water maze tests were used to evaluate the cognitive function at 1-7 days after surgery. The mice were sacrificed after the behavioral testing, brain tissues were immediately obtained, and the number of Nissl bodies and density of dendritic spines in the hippocampal CA1 region were measured by Nissl staining and Golgi staining, respectively. Results:Compared with group C, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr, Gln/Cr and Glx/Cr in the hippocampal CA1 region were increased, and the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in SF, I/S and SF+ I/S groups ( P<0.05). Compared with group SF and group I/S, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr and Glx/Cr in hippocampal CA1 region was increased, the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in group SF+ I/S ( P<0.05). Conclusions:Sleep fragmentation exacerbates POCD in aged mice anesthetized with isoflurane, and the mechanism is related to nerve injury induced by abnormality in hippocampal glutaminergic metabolism excitability.

Objective To investigate the changes in the expression of Ca2+/calmodulin-dependent protein kinase Ⅱ α (CaMK Ⅱ α) in the spinal cord and dorsal root ganglia (DRG) during remifentanil-induced hyperalgesia in a rat model of incisional pain (IP).Methods Thirty-two male Sprague-Dawley rats in which caudal vein catheter was successfully placed,aged 260-280 g,were divided into 4 groups (n=8 each) using a random number table method:control group (group C),IP group,remifentanil group (group R) and remifentanil plus IP group (group RIP).Normal saline was infused via the caudal vein for 60 min at a rate of 0.1 ml · kg-1 · min-1 in group C.Normal saline was infused via the caudal vein for 60 min at a rate of 0.1 ml · kg-1 · min-1,and the model of IP was simultaneously established in group IP.Remifentanil was infused via the caudal vein for 60 min at a rate of 1.0 μg · kg-1 · min-1 in group R.Remifentanil was infused via the caudal vein for 60 min at a rate of 1.0 μg · kg-1 · min-1,and the model of IP was simultaneously established in group RIP.Mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before infusion and 2,6,24 and 48 h after infusion (T0-4).The rats were sacrificed after the last behavioral test,and L4-6 segment of the spinal cord and DRGs were removed for determination of the expression of total and phosphorylated CaMK Ⅱ α (tCaMK Ⅱ α,pCaMK Ⅱ α) by Western blot.The ratio of pCaMK Ⅱ /tCaMK Ⅱ α was calculated.Results Compared with group C,MWT was significantly decreased,TWL was shortened,the expression of tCaMK Ⅱ α and pCaMK Ⅱ α in the spinal cord and DRGs was up-regulated,and the ratio of pCaMK Ⅱ α/tCaMK Ⅱ α was increased in I,R and RIP groups (P＜0.05 or 0.01).Compared with group IP and group R,MWT was significantly decreased,TWL was shortened,the expression of tCaMK Ⅱ α and pCaMK Ⅱ α in the spinal cord and DRGs was up-regulated,and the ratio of pCaMK Ⅱ α/tCaMK Ⅱ α was increased in group RIP (P＜0.05 or 0.01).Conclusion The mechanism by which remifentanil induces hyperalgesia may be related to upregulated expression of CaMK Ⅱ α in the spinal cord and DRGs in a rat model of IP.

Myocardial strain is a dimensionless parameter reflecting the degree of deformation of the whole or local myocardium under stress,which can quantitatively detect myocardial injury and guide the early diagnosis,intervention and prognostic assessment of cardiac diseases.Cardiac ultrasound,cardiac CT and cardiac magnetic resonance can all be used for strain imaging and analysis,with two-dimensional speckle-tracking echocardiography being the most widely used means of myocardial strain detection today.However,due to inter-observer variations in manual analysis of myocardial strain and differences in the imaging systems and analysis software,the consistency and reproducibility of measured strain values among vendors are poor,limiting the clinical application of myocardial strain.Artificial intelligence(AI)can overcome the defects of strain measurement to a certain extent through automatic strain calculation and image quality assessment,which has a broad developmental prospect.This review focuses on the progress of AI-assisted measurement of myocardial strain in ultrasound,magnetic resonance,and other imaging modalities,as well as its application to disease diagnosis and patient prognosis assessment.This will improve the efficiency and consistency of strain measurement and promote the routine application of myocardial strain to clinical practice,which will play an incremental role in assessing myocardial injury and cardiac function.However,most of the current studies involve small sample sizes and lack external validation,and the reliability of their results needs to be further verified.

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 explore the measurement method and its diagnostic performance based on MRI and CT measurement of vertebral bone density in patients to predict proximal junctional kyphosis after degenerative scoliosis surgery.Methods:Retrospectively included patients who underwent long-segment fixation and fusion surgery at the Department of Orthopedics, West China Hospital of Sichuan University from January 2010 to December 2020 and had complete preoperative whole-spine X-rays, CT, MRI and other imaging examination results, and were followed up on schedule. 68 cases of adult degenerative scoliosis, 16 male, 52 women, aged 66.87±6.65 years (range, 54-80 years). The patients were measured based on preoperative lumbar spine MRI T 1WI bone quality score (vertebral bone quality score, VBQ) and CT-based Hounsfield (HU) value, and the patients were divided into postoperative proximal junction kyphosis group or non-proximal junction kyphosis group based on the results of postoperative imaging examinations. The age, gender, BMI, comorbidities, lumbar spine VBQ score, L 1 CT HU value and various imaging parameters before and after surgery were compared between the two groups of patients, including pelvic incident, lumbar lordosis, sagittal vertical axis, pelvic tilt, sacral slope, pelvic incidence-lumbar lordosis, T 1 pelvic angle, Upper instrumented vertebrae screw angle, etc. The receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic efficacy, sensitivity and specificity of VBQ score, HU value and their combined indicators. Results:Seventeen cases were included in the PJK group and 51 cases in the non-PJK group. The preoperative VBQ and HU values of the PJK group were 3.10±0.43 and 99.76±16.34 respectively, while those of the non-PJK group were 2.62±0.37 and 115.27±13.46 respectively. The differences were statistically significant ( t=3.896, P<0.001; t=4.482, P<0.001). The area under curve (AUC) of VBQ was 0.773 [95% CI(0.633, 0.914)], the sensitivity and specificity are 82.4% and 70.6% respectively, the AUC of HU value was 0.814 [95% CI(0.680, 0.949)], the sensitivity and specificity are 76.5% and 76.5% respectively. The AUC of the two combined indicators was 0.895 [95% CI(0.795, 0.995)], and the sensitivity and specificity were 94.1% and 82.4% respectively. The maximum Youden index and the critical value were respectively, VBQ value 0.530, 2.895, HU value 0.530, 110.0, the combined index 0.765, 0.734. Conclusion:Both VBQ and L 1 HU value can accurately predict proximal junctional kyphosis after degenerative scoliosis surgery. The accuracy of HU value was slightly higher than that of VBQ value. The diagnosis accuracy of the combined index was the highest.

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.

Gouty arthritis （GA） is an inflammatory disorder caused by monosodium urate （MSU） crystal deposition， accompanied by elevated oxidative stress and aberrant release of inflammatory cytokines， resulting in joint tissue damage and intense pain. Nuclear factor E₂-related factor 2 （Nrf2）， a key transcription factor regulating the antioxidant defence system， exerts cytoprotective effects through dissociation from Kelch-like ECH-associated protein 1 （Keap1） and activates downstream antioxidant response element （ARE）-mediated pathways. It can upregulate the expression of heme oxygenase-1 （HO-1）， NADH quinone oxidoreductase 1 （NQO1）， superoxide dismutase （SOD）， and glutathione transferase （GST） to preserve redox homeostasis. Moreover， Nrf2 can suppress activation of NOD-like receptor protein 3 （NLRP3） inflammasomes， reduce pro-inflammatory cytokine production and release， modulate nuclear factor-κB （NF-κB） transcriptional activity， regulate gut microbiota balance， enhance mitophagy， and inhibit apoptosis， so as to reduce joint inflammation and pain and promote body recovery. This review systematically examined recent advancements in traditional Chinese medicine （TCM） for GA prevention and treatment via regulating the Nrf2 signaling pathway. It delineated Nrf2's molecular mechanisms and its role in GA pathogenesis and elucidated how TCM intervenes in multiple pathways including Keap1/Nrf2/ARE， Nrf2/HO-1（NQO1）， and Nrf2/NF-κB/NLRP3 to exert therapeutic effects. The study demonstrated that TCM monomers and compounds effectively counteract oxidative damage， attenuate inflammatory responses， promote autophagy， and inhibit apoptosis via regulating the Nrf2 signaling pathway. These findings not only clarify the scientific basis of TCM in GA treatment but also offer strategic insights for developing novel Nrf2-targeted anti-gout drugs.

Objective    To compare clinical effects of enlarged thymectomy for the treatment of myasthenia gravis (MG) complicated with thymoma via subxiphoid and subcostal arch thoracoscopic resection versus median sternotomy resection. Methods    We retrospectively analyzed the clinical data of patients with MG complicated with thymoma admitted in Tangdu Hospital of the Air Force Military Medical University between December 2011 and December 2021. Patients who underwent subxiphoid and subcostal arch thoracoscopic enlarged thymectomy were allocated to a SR group, and patients who underwent median sternotomy enlarged thymectomy were allocated to a MR group. Perioperative outcomes were compared between the two groups. Results    A total of 456 patients were collected. There were 51 patients in the MR group, including 30 males and 21 females aged 23-66 (49.5±11.8) years. There were 405 patients in the SR group, among whom 51 patients were matched to the MR group by propensity score matching, including 28 males and 23 females aged 26-70 (47.2±12.2) years. The operations were accomplished successfully in all patients, and no conversion to thoracotomy occurred in the SR group. The SR group had advantages in the operation time, intraoperative blood loss,  chest drainage duration, hospital stay time, patients’ satisfaction level, pain score and complications (all P<0.05). No statistical difference was found in the number of intraoperative lymph node dissection stations, number of intraoperative lymph nodes dissected or remission of MG between the two groups (P>0.05). Conclusion    Subxiphoid and subcostal arch thoracoscopic enlarged thymectomy and lymphadenectomy is a safe, effective and feasible minimally invasive procedure for the treatment of MG complicated with thymoma.