Objective To evaluate the effects of dexmedetomidine on the activity of cAMP response element binding protein (CREB) and c-fos in the spinal dorsal horn in a rat model of neuropathic pain.Methods Fifty-four adult male Wistar rats,aged 6-8 weeks,weighing 180-220 g,were randomly divided into 3 groups (n =18 each):sham operation group (group S),chronic neuropathic pain group (group C) and dexmedetomidine group (group D).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The sciatic nerve was exposed and 4 ligatures were placed on the right sciatic nerve at 1 mm intervals with 4-0 silk thread in C and D groups.In group D,dexmedetomidine 50 μg/kg was injected intraperitoneally once a day starting from the end of operation until 1 day before the animals were sacrificed,while the equal volme of normal saline was injected instead of dexmedetomidine in S and C groups.Paw withdrawal threshold to mechanical stimulation with yon Frey filament (MWT) and paw withdrawal latency to thermal stimulation (TWL) were measured on 1 day before operation and 3,7 and 14 days after operation.The animals were sacrificed after measurement of MWT and TWL.Their lumbar segments (L4-6) of the spinal cord were removed for measurement of the expression of phosphorylated CREB (pCREB) and c-fos by immunohistochemistry.Results Compared with group S,MWT was significantly decreased,TWL was shortened,and the expression of pCREB and c-fos was up-regulated on 3,7 and 14 days after operation in C and D groups (P ＜ 0.05).Compared with group C,MWT was significantly increased,TWL was prolonged,and the expression of pCREB and c-fos was down-regulated on 3,7 and 14 days after operation in group D (P ＜ 0.05).MWT was significantly lower,and TWL was shorter on 3,7 and 14 days after operation than on 1 day before operation in C and D groups (P ＜ 0.05).MWT was significantly lower,TWL was shorter,and the expression of pCREB and c-fos was higher on 7 and 14 days after operation than on 3 days after operation in C and D groups (P ＜ 0.05).MWT was significantly higher,TWL was longer,and the expression of pCREB and c-fos was lower on 14 days after operation than on 7 days after operation in C and D groups (P ＜ 0.05).Conclusion The mechanism by which dexmedetomidine reduces neuropathic pain is related to inhibition of the activity of CREB and c-fos in the spinal dorsal horn of rats.

Objective To investigate the effects of Sulfotanshinone Sodium Injection (SSI) on neuropathic pain in rats.Methods One hundred and eight adult male Wistar rats,aged 6-8 weeks,weighing 180-220 g,were randomly divided into 3 groups (n =36 each):sham operation group (group S) ; chronic constrictive injury (CCI)group; group SSI.The animals were anesthetized with intraperitoneal 10% chloral hydrate 350 mg/kg.In groups CCI and SSI,4 ligatures were placed on the right sciatic nerve at 1 mm intervals with 4-0 silk thread according to the method described by Bennett et al.In group S,the right sciatic nerves were exposed,but not ligated.In group SSI,SSI 25 mg/kg was injected intraperitoneally once a day starting from the end of operation until one day before the animals were sacrificed,while the rats received the equal volume of normal saline (5 ml/kg) instead of SSI in groups S and CCI.Twelve animals in each group were chosen at 1 day before operation and 3,7 and 14 days after CCI (T1-4) to measure mechanical paw withdrawal threshold to yon Frey stimuli (MWT) and paw withdrawal latency to thermal nociceptive stimulus (TWL).Six rats in each group were sacrificed at T2-4 after measurement of pain threshold,and their lumbar segnents (L4-6) of the spinal cord were immediately removed for determination of Bcl2 and caspase-3 expression in spinal dorsal horn (by immune-histochemistry),and MDA content and SOD activity (by spectrophotometry) in spinal cord.Results Compared with group S,PWT was significantly decreased,PWL was shortened,the expression of Bcl-2 and caspase-3 was up-regulated,MDA content was increased and SOD activity was decreased at T2-4 in groups CCI and SSI (P ＜ 0.05).Compared with group CNP,PWT was significantly increased,PWL was prolonged,the expression of Bcl-2 was up-regulated,the expression of caspase-3 was downregulated,MDA content was decreased and SOD activity was increased at T2-4 in group SSI (P ＜ 0.05).Conclusion SSI can mitigate neuropathic pain in rats and inhibition of oxidative stress in spinal cord tissues and reduction of apoptosis in spinal dorsal horn neurons are involved in the mechanism.

Objective To evaluate the effect of dexmedetornidine on the expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) in the spinal cord in rats with neuropathic pain (NP).Methods One hundred and eight male Wistar rats,aged 6-8 weeks,weighing 180-220 g,were randomly assigned into 3 groups (n =36 each):sham operation group (group S),NP group and dexmedetomidine group (group D).NP was induced by chronic constrictive injury in anesthetized rats.Sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread.In group S,the right sciatic nerves were exposed,but not ligated.Dexmedetomidine 50 μg/kg was injected intraperitoneally once a day from the onset of operation to one day before the rats were sacrificed in group D,while the equal volume of normal saline was injected in groups S and NP.Mechanical withdrawal threshold (MWT) and thermal pain threshold (TPT) were measured on the day before operation (T0) and 3,7,and 14 days after operation (T1-3).After measurement of pain threshold at T1,T2 and T3 after operation,the L4-6 segments of the spinal cord were removed for determination of the expres-sion of TLR4 and NF-κB mRNA (by RT-PCR) and the expression of TLR4 and NF-κB in spinal dorsal horn (by immuno-histochemistry).Results Compared with group S,MWT and TPT were significantly decreased and the expression of TLR4,NF-κB and TLR4 and NF-κB mRNA was up-regulated after operation in groups NP and D (P ＜ 0.05).Compared with group NP,TPT and MWT were significantly increased and the expression of TLR4,NF-κB,TLR4 mRNA and NF-κB mRNA was significantly down-regulated after operation in group D (P ＜ 0.05).Conclusion The mechanism by which dexmedetomidine attenuates NP in rats is related to inhibition of the expression of TLR4 and NF-κB in rat spinal cord.

Objective To evaluate the effect of dexmedetomidine and small dose of ketamine on the expression of P2X4 receptor (P2X4 R) mRNA and P2X7 receptor (P2X7R) mRNA in the dorsal root ganglion of rats with neuropathic pain.Methods Ninety male Sprague-Dawley rats,aged 6-9 weeks,weighing 180-220 g,were randomly divided into 5 groups (n =18 each):sham group (group S),chronic constrictive injury group (group CCI),dexmedetomidine group (group D),ketamine group (group K) and dexmedetomidine + ketamine group (group DK).The animals were anesthetized with intraperitoneal 10％ chloral hydrate 400 mg/kg.Neuropathic pain was induced by CCI in CCI,D,K and DK groups.The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1mmintervals with 4-0 silk thread.In group S,the sciatic nerves were only exposed but not ligated.In D,K and DK groups,dexmedetomidine 50μg/kg,ketamine 10 mg/kg and dexmedetomidine 25μg/kg + ketamine 5 mg/kg were injected intraperitoneally,respectively,while the equal volume of normal saline was injected in S and CCI groups,once a day for 14 consecutive days after CCI.Mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CCI,and 3,7 and 14 days after CCI.Six animals were sacrificed after measurement of pain threshold at 3,7 and 14 days after CCI and the lumbar segments (L4-6) of the dorsal root ganglion were removed for determination of P2X4 R mRNA and P2X7 R mRNA expression by RT-PCR.Results Compared with group S,MWT and TWL were significantly decreased at 3,7 and 14 days after CCI in groups CCI,D,K and DK,the expression of P2X4R mRNA and P2X7R mRNA was up-regulated at 3,7 and 14 days after CCI in groups CCI,D and K,and the expression of P2X4 R mRNA and P2X7 R mRNA was up-regulated at 3 and 7 days after CCI in group DK (P ＜ 0.05).Compared with group CCI,TWL and MWT were significantly increased and the expression of P2X4 R mRNA and P2X7 R mRNA was down-regulated at 3,7 and 14 days after CCI in groups D,K and DK (P ＜ 0.05).Compared with D and K groups,TWL and MWT were significantly increased and the expression of P2X4 R mRNA and P2X7 R mRNA was down-regulated at 3,7 and 14 days after CCI in group DK (P ＜ 0.05).Conclusion The mechanism by which the combination of dexmedetomidine and small dose of ketamine produces a synergistic antinociception in rats with neuropathic pain may be related to down-regulation of the expression of P2X4 R mRNA and P2X7 R mRNA.

OBJECTIVE:To provide reference for avoiding the recurrence of medical safety(adverse)events or inducing more severe medical accident. METHODS:The medical safety(adverse)events reported by a class A grade 3 hospital from July 2013 to March 2016 were studied retrospectively,and excluded purely adverse drug reactions and transfusion reactions to analyze the rea-son and characteristics. RESULTS:Of 747 events,there were 578 medical,nursing and drug-related medical safety (adverse) events,accounting for 77.38%;among 175 medical related medical safety(adverse)events,top 3 reasons were basic skills defi-ciencies,defects in the system processes,inadequate communication and education, accounting for 32.00%,24.00%,19.43%. The occurrence of medical safety (adverse) events were closely related to working life and qualifications;among 578 medical, nursing and drug-related medical safety (adverse) events,the incidence of adverse events was 71.11% in 5-year working life group,and that was 73.18% in junior titles group. CONCLUSIONS:Various professionals should strictly implement procedure and regulations,strengthen communication and education in daily work,and improve professional knowledge and skills so as to prevent the occurrence of adverse event completely.

? With the acceleration of the aging process, the problem of aged frailty has become prominent, which has aroused widespread concern. Actively and accurately assessing, identifying and intervening the weakened elderly are of great significance for improving the quality of life of the elderly, reducing adverse outcomes and predicting disability. The development and application of various frailty assessment tools in the world are getting matured gradually. Domestic enterprises have begun to use or sinicize foreign tools, and build local assessment tools. This paper reviews the application and adaptation of various assessment tools for frailty in China, and the research progress and prospects of localized assessment tools. The purpose is to provide reference for the assessment of frailty in China, hence to guide the follow-up intervention research.

Objective:To investigate the association between metabolically healthy obesity(MHO) and atherosclerosis risk among Chinese community population aged 40 or older.Methods:A total of 9 525 participants without cardiovascular diseases (3 621 men and 5 904 women) from Jiading community in Shanghai were enrolled to complete questionnaires, undergo extensive physical examination including brachial-ankle pulse wave velocity (baPWV) and blood pressure (BP) assessment, and laboratory screening. According to body mass index (BMI) and metabolic status, these participants were categorized into 4 groups including metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), MHO, and metabolically unhealthy obese (MUO). High baPWV was defined as baPWV>1 400 mm/s, and high pulse pressure (PP) was defined as PP above fourth quartile of the population. Multivariate logistic regression model was conducted to explore the relationship between MHO and high baPWV as well as high PP after adjusting for confounders. Results:After multivariable adjustment, such as sex, age, current smoking, current drinking, and education, logistic regression analysis showed that MHO was significantly correlated with high baPWV ( OR=1.18, 95% CI 1.02-1.37) and high PP ( OR=1.72, 95% CI 1.43-2.08) in comparison with MHNO. Otherwise, both MUNO and MUO subjects were at higher risk for suffering from high baPWV (MUNO: OR=3.02, 95% CI 2.60-3.50; MUO: OR=3.26, 95% CI 2.87-3.70) and high PP (MUNO: OR=2.56, 95% CI 2.17-3.02; MUO: OR=3.49, 95% CI 3.01-4.06). Conclusion:On the basis of Chinese community population, there was a pronounced correlation between the MHO phenotype and the increased risk of developing atherosclerosis.

Objective:To investigate and summarize the chest CT imaging features of patients with novel coronavirus pneumonia (COVID-19), bacterial pneumonia and other viral pneumonia.Methods:Chest CT data of 102 patients with pulmonary infection due to different etiologies were retrospectively analyzed, including 36 patients with COVID-19 admitted to Hainan Provincial People's Hospital and the Second Affiliated Hospital of Hainan Medical University from December 2019 to March 2020, 16 patients with other viral pneumonia admitted to Hainan Provincial People's Hospital from January 2018 to February 2020, and 50 patients with bacterial pneumonia admitted to Haikou Affiliated Hospital of Central South University Xiangya School of Medicine from April 2018 to May 2020. Two senior radiologists and two senior intensive care physicians were participated to evaluated the extent of lesions involvement and imaging features of the first chest CT after the onset of the disease.Results:Bilateral pulmonary lesions were more common in patients with COVID-19 and other viral pneumonia, and the incidence was significantly higher than that of bacterial pneumonia (91.6%, 75.0% vs. 26.0%, P < 0.05). Compared with other viral pneumonia and COVID-19, bacterial pneumonia was mainly characterized by single-lung and multi-lobed lesion (62.0% vs. 18.8%, 5.6%, P < 0.05), accompanied by pleural effusion and lymph node enlargement. The proportion of ground-glass opacity in the lung tissues of patients with COVID-19 was 97.2%, that of patients with other viral pneumonia was 56.2%, and that of patients with bacterial pneumonia was only 2.0% ( P < 0.05). The incidence rate of lung tissue consolidation (25.0%, 12.5%), air bronchial sign (13.9%, 6.2%) and pleural effusion (16.7%, 37.5%) in patients with COVID-19 and other viral pneumonia were significantly lower than those in patients with bacterial pneumonia (62.0%, 32.0%, 60.0%, all P < 0.05), paving stone sign (22.2%, 37.5%), fine mesh sign (38.9%, 31.2%), halo sign(11.1%, 25.0%), ground-glass opacity with interlobular septal thickening (30.6%, 37.5%), bilateral patchy pattern/rope shadow (80.6%, 50.0%) etc. were significantly higher than those of bacterial pneumonia (2.0%, 4.0%, 2.0%, 0%, 22.0%, all P < 0.05). The incidence of local patchy shadow in patients with COVID-19 was only 8.3%, significantly lower than that in patients with other viral pneumonia and bacterial pneumonia (8.3% vs. 68.8%, 50.0%, P < 0.05). There was no significant difference in the incidence of peripheral vascular shadow thickening in patients with COVID-19, other viral pneumonia and bacterial pneumonia (27.8%, 12.5%, 30.0%, P > 0.05). Conclusions:The probability of ground-glass opacity, paving stone and grid shadow in chest CT of patients with COVID-19 was significantly higher than those of bacterial pneumonia, and it was more common in the lower lungs and lateral dorsal segment. In other patients with viral pneumonia, ground-glass opacity was distributed in both upper and lower lungs. Bacterial pneumonia is usually characterized by single lung consolidation, distributed in lobules or large lobes and accompanied by pleural effusion.

BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

Objective:To investigate the correlation between exposure to famine in early life and later risk of type 2 diabetes in adulthood.Methods:A cluster sampling method was used to include 8 868 residents who were lived in the Jiading community of Shanghai during the Great Famine from 1959 to 1962 in China. Subjects were divided into non-exposed group, fetal exposure group, childhood exposure group, and adolescent exposure group. Logistic regression model was used to analyze the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood. Results:Famine exposure during childhood and adolescent both increased the risk of developing type 2 diabetes in adulthood in women. No significant correlation was observed in men. In subjects with less physical activity and lower education level, the risk of developing type 2 diabetes mellitus in adulthood was significantly higher in the famine-exposed group than that of non-exposed groupand the interactions were statistically significant.Conclusion:Early life famine exposure increases the risk of developing type 2 diabetes in adults, especially in women.