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Objective:To clarify peripheral Th17 level in SSc patients and its correlation with disease.Methods:Chinese databases CNKI, CBM, Wanfang and VIP, and English databases PubMed, EMBASE, Web of Science, Cochrane Library and Science Direct were searched to collect a case-control study on the content of Th17 cells in peripheral blood of patients with SSc. The papers published when the database was first developed in 25 February 2021. Meta-analysis was conducted using Stata 12.0 software, and I2 and Egger tests were used to evaluate the heterogeneity and publication bias between studies. Results:A total of 26 case-controls were included in the study, including 1 160 patients with SSc and 778 healthy controls. Overall, the percentage of Th17 cells in SSc patients was higher than in healthy controls [SMD(95% CI)=1.85 (1.33, 2.38), P<0.001], which was most significant in IL-17 +Th17 concentration [SMD(95% CI)=1.88 (1.28, 2.48), P<0.001]. As for disease activity, the proportion of Th17 cells in active SSc patients was much higher than those of patients in remission [SMD(95% CI)=1.92 (1.12, 2.71), P<0.001]. SSc patients had a reduced Th17 level after receiving DMARDs treatment [SMD(95% CI)=-0.74 (-1.05, -0.42), P=0.029]. Conclusion:The number of Th17 cells increase significantly in the peripheral blood of patients with SSc, and is related to disease activity. DMARDs can be used to treat this disease by downregulating Th17 levels.
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Neoadjuvant therapy has become the first choice for locally advanced esophageal carcinoma. Patients with post-neoadjuvant positive lymph node staging (ypN+) have poor prognosis, and there is no effective adjuvant therapy. Programmed death protein-1 (PD-1) antibody can obtain better clinical efficacy in the treatment of advanced esophageal cancer. The authors designed a multicenter, prospective, randomized controlled clinical trial of Toripalimab (PD-1 antibody) adjuvant therapy on esophageal squamous cell carcinoma patients with ypN+ after the treatment of neoadjuvant chemotherapy combined with surgical resection, in order to provide clinical practices for the adjuvant treatment of ypN+ patients.
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Objective@#To evaluate the role of extracellular signal-regulated kinase (ERK) signaling pathway in intrathecal dexmedetomidine-induced reduction of spinal cord ischemia-reperfusion (I/R) injury in rats.@*Methods@#Eighty clean-grade male Sprague-Dawley rats, aged 9-10 weeks, weighing 300-350 g, were divided into 4 groups (n=20 each) using a random number table method: sham operation group (group S), spinal cord I/R group (group I/R), dexmedetomidine group (group D), and dexmedetomidine plus ERK signaling pathway blocker PD98059 group (group P). Spinal cord ischemia was produced by cross-clamping of the abdominal aorta distal to the left renal artery for 25 min followed by reperfusion to establish the model of spinal cord I/R injury.Dexmedetomidine 1 μg/kg was intrathecally injected at 20 min before establishing the model in D and P groups, PD98059 2 mg/kg was given via the tail vein at the same time in group P, and the equal volume of normal saline was given instead in S and I/R groups.Five rats were selected at 6, 8, 10 and 12 h of reperfusion, and the modified Basso, Beattie, Bresnahan (BBB) scale was used to assess the hindlimb locomotor function.Five rats were sacrificed after assessing the locomotor function at 6 h of reperfusion, and the L3-5 segments of the spinal cord were taken for determination of cell apoptosis (by TUNEL) and expression of phosphorylated ERK (p-ERK) (by Western blot). The apoptosis index was calculated.@*Results@#Compared with group S, the BBB scores were significantly decreased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was up-regulated in the other three groups (P<0.05). Compared with I/R group, the BBB scores were significantly increased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was up-regulated in group D, and no significant change was found in the apoptosis index or p-ERK expression in group P (P>0.05). Compared with group D, the BBB scores were significantly decreased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was down-regulated in group P (P<0.05).@*Conclusion@#The mechanism by which intrathecal dexmedetomidine reduces spinal cord I/R injury is related to activating ERK signaling pathway in rats.
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Objective To evaluate the role of extracellular signal-regulated kinase (ERK) signaling pathway in intrathecal dexmedetomidine-induced reduction of spinal cord ischemia-reperfusion (I/R)injury in rats.Methods Eighty clean-grade male Sprague-Dawley rats,aged 9-10 weeks,weighing 300-350 g,were divided into 4 groups (n =20 each) using a random number table method:sham operation group (group S),spinal cord I/R group (group I/R),dexmedetomidine group (group D),and dexmedetomidine plus ERK signaling pathway blocker PD98059 group (group P).Spinal cord ischemia was produced by cross-clamping of the abdominal aorta distal to the left renal artery for 25 min followed by reperfusion to establish the model of spinal cord I/R injury.Dexmedetomidine 1 μg/kg was intrathecally injected at 20 min before establishing the model in D and P groups,PD98059 2 mg/kg was given via the tail vein at the same time in group P,and the equal volume of normal saline was given instead in S and I/R groups.Five rats were selected at 6,8,10 and 12 h of reperfusion,and the modified Basso,Beattie,Bresnahan (BBB) scale was used to assess the hindlimb locomotor function.Five rats were sacrificed after assessing the locomotor function at 6 h of reperfusion,and the L3-5 segments of the spinal cord were taken for determination of cell apoptosis (by TUNEL) and expression of phosphorylated ERK (p-ERK) (by Western blot).The apoptosis index was calculated.Results Compared with group S,the BBB scores were significantly decreased at each time point of reperfusion,the apoptosis index was increased,and the expression of pERK was up-regulated in the other three groups (P＜0.05).Compared with I/R group,the BBB scores were significantly increased at each time point of reperfusion,the apoptosis index was increased,and the expression of p-ERK was up-regulated in group D,and no significant change was found in the apoptosis index or p-ERK expression in group P (P＞0.05).Compared with group D,the BBB scores were significantly decreased at each time point of reperfusion,the apoptosis index was increased,and the expression of pERK was down-regulated in group P (P＜0.05).Conclusion The mechanism by which intrathecal dexmedetomidine reduces spinal cord I/R injury is related to activating ERK signaling pathway in rats.
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The concept that peri-operative treatment could improve long-term survival of esophageal cancer patients has been universally accepted, including radiation alone, chemotherapy alone, and chemoradiation. The most controversial therapy is perioperative chemotherapy. Here we review the published literatures for reference. The result shows that perioperative chemotherapy is effective for esophageal cancer patients, especially for the so-called chemo-sensitive patients, and the preferred delivering time is before surgery. According to the current data, it is still unclear whether the efficacy of neoadjuvant chemotherapy is inferior to that of neoadjuvant chemoradiation.
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Humans , Chemoradiotherapy , Esophageal Neoplasms , Drug Therapy , General Surgery , Neoadjuvant Therapy , Survival RateABSTRACT
Objective To investigate the changes in myocardial proteomics in the late phase of limb ischemic preconditioning (LIP) in rats.Methods Twelve pathogen-free adult male Sprague-Dawley rats,aged 8-9 weeks,weighing 260-280 g,were randomly assigned into LIP group (n=6) and control group (group C,n=6) using a random number table.Limb ischemia was preceded by 3 cycles of 5-min ischemia which was induced by ligation of the root of the right hindlimb with a rubber band followed by 5-min reperfusion in group LIP.At 24 h after LIP,the tissues were obtained from the left ventricle,and the isobaric tags for relative and absolute quantification technique and liquid chromatography-mass spectrometry were applied to detect the differences in protein expression profiles between the two groups (the difference in expression between the two groups＞ 1.2 times and P＜0.05).The identified differentially expressed proteins were analyzed using the bioinformatics,and some were further verified by Western blot.Results A total of 55 proteins were identified to be differentially expressed,and among the 55 proteins,the expression of 35 proteins was up-regulated,and the expression of 20 proteins was down-regulated.Bioinformatics analysis showed that most of the 55 proteins were organelles,cell membrane or macromolecular compounds,were involved in the process such as metabolism,biological regulation,stress response and signal transduction,and showed functions such as the binding affinity to molecules,catalytic activity,anti-oxidant activity,and modulation of the activity of enzyme.The results verified by Western blot were consistent with those shown by using the isobaric tags for relative and absolute quantification analysis.Conclusion The late phase of LIP can induce changes in the expression of the 55 proteins involving regulation of energy metabolism,anti-oxidant action,regulation of gene expression,and protein folding and degradation in the myocardium,which may be the mechanism of myocardial protection in rats.