ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

Objective Based on the theory of"stomach disharmony leads to restlessness",the causal relationship between gastroesophageal reflux disease and insomnia was discussed by Mendel randomization method with two samples.Methods The data were collected from genome-wide association studies,the exposure factor was gastroesophageal reflux disease,and the outcome variable was insomnia.Mendel randomization analysis is realized by inverse variance weighted method,MR-Egger method,simple model method,weighted model method and weighted median method.Sensitivity analysis includes pleiotropic test,heterogeneity test and one-by-one elimination test,and is calculated by MR-Egger method,Cochran Q test and one-out-of-one method in turn.Results A total of 75 single nucleotide polymorphisms(SNPs)were screened.The inverse variance weighted method showed that gastroesophageal reflux disease increased the risk of insomnia(OR=1.255,95%CI:1.071-1.470,P<0.05).The weighted median method also confirmed that there was a positive causal relationship between gastroesophageal reflux disease and insomnia(OR=1.403,95%CI:1.117-1.762,P<0.05).Multiple sensitivity analysis indicated that there was no pleiotropy and heterogeneity in the results of Mendelian randomized analysis,which verified the stability of the research results.Conclusion There is a positive causal relationship between gastroesophageal reflux disease and insomnia,which enriches the theoretical connotation of"stomach disharmony leads to restlessness"from the genetic point of view and lays a foundation for further study.

Objective Based on the theory of"stomach disharmony leads to restlessness",the causal relationship between gastroesophageal reflux disease and insomnia was discussed by Mendel randomization method with two samples.Methods The data were collected from genome-wide association studies,the exposure factor was gastroesophageal reflux disease,and the outcome variable was insomnia.Mendel randomization analysis is realized by inverse variance weighted method,MR-Egger method,simple model method,weighted model method and weighted median method.Sensitivity analysis includes pleiotropic test,heterogeneity test and one-by-one elimination test,and is calculated by MR-Egger method,Cochran Q test and one-out-of-one method in turn.Results A total of 75 single nucleotide polymorphisms(SNPs)were screened.The inverse variance weighted method showed that gastroesophageal reflux disease increased the risk of insomnia(OR=1.255,95%CI:1.071-1.470,P<0.05).The weighted median method also confirmed that there was a positive causal relationship between gastroesophageal reflux disease and insomnia(OR=1.403,95%CI:1.117-1.762,P<0.05).Multiple sensitivity analysis indicated that there was no pleiotropy and heterogeneity in the results of Mendelian randomized analysis,which verified the stability of the research results.Conclusion There is a positive causal relationship between gastroesophageal reflux disease and insomnia,which enriches the theoretical connotation of"stomach disharmony leads to restlessness"from the genetic point of view and lays a foundation for further study.

Neuropathic pain is a chronic pain condition caused by damage or dysfunction of the nervous sys-tem.Symptoms of neuropathic pain include spontaneous pain,hyperalgesia,and sensory abnormalities.AMP-activated protein kinase(AMPK)is a key energy regulator that maintains cellular homeostasis by modulating carbohydrate and lipid metabolism.Recent studies have highlighted its role in synaptic plasticity and glial cell function,suggesting that AMPK signaling pathways contribute to the onset and progression of neurological disorders.Investigations using animal models of neuropathic pain as well as clinical research have illustrated aberrations in AMPK expression and activity at various sites along sensory conduction pathways.Treatment with AMPK agonists has been shown to alleviate pain symptoms,suggesting that dysregulation of AMPK expression/function contributes to the development and persistence of neuropathic pain.There-fore,the development of analgesics targeting AMPK has garnered considerable attention worldwide.This article provides a comprehensive review of the mechanisms by which AMPK participates in neuropathic pain,with the aim of guiding the de-velopment of related analgesic drugs.

Objective:To evaluate the effect of mixed reality (MR) in the standardized resident training on oral and maxillofacial-head and neck tumor surgery.Methods:Twenty resident doctors, who received standardized training in the department of maxillofacial oncology of our hospital, were randomly divided into experimental group and control group. The MR teaching method was used in the experimental group, while the traditional teaching method was used in the control group. The teaching effect was evaluated by theoretical and operational tests and a questionnaire survey. Statistical analysis was performed with the SPSS 24.0 software. Statistical comparisons were performed by the Students' t-test or the Wilcoxon rank correlation test. Results:The theoretical test results showed that the scores of the experimental group were significantly higher than those of the control group (85.30±3.59 vs. 80.20±5.63, t = 2.41, P = 0.027). The operational test results showed that the scores of the experimental group were significantly higher than those of the control group (89.20±5.07 vs. 82.30±6.36, t = 2.68, P = 0.015). The questionnaire survey results showed that the MR teaching helped to easily acquire the knowledge of head and neck anatomy and operation skills. Besides, the doctors in the experimental group were more active and glad to communicate with others than those in the control group. In addition, the MR teaching method improved the learning interest of doctors. The doctors in the experimental group were more satisfied with the teaching effect than those in the control group, and they recommended that the MR teaching method be used in clinical training and teaching on oral and maxillofacial-head and neck tumor surgery. Conclusion:MR teaching can help doctors understand and master the knowledge of head and neck anatomy and operation skills and improve their learning interest, achieving a good teaching effect, so it has important application value in the standardized resident training on oral and maxillofacial-head and neck tumor surgery.

Objective:To explore the effect of the application of mixed reality (MR) technology in clinical teaching of fibular flap preparation.Methods:Twenty residents from the Department of Oral and Maxillofacial Surgery in School of Stomatology, the Fourth Military Medical University in 2018 and 2019 participated in the present study. They were randomly divided into two groups according to the method of random drawing. The teaching content of the two groups was fibular flap preparation. The MR group was taught by using the new teaching mode which was mainly based on MR, while the conventional teaching group was educated by conventional teaching method. At the end of the training, the theoretical knowledge and operational skills of the residents were statistically analyzed to evaluate the learning effect. Questionnaire survey was also conducted. Each item in the questionnaire was scored between 0 and 5, representing poor to excellent.Results:The theoretical scores of MR group (91.4±4.4) were higher than that of the conventional teaching group (83.3±3.2) ( P<0.01). The durations of preoperative marking and simulated osteotomy in MR group [(5.7±1.2) and (20.9±2.28) min, respectively] were shorter than those in the conventional teaching group [(7.2±1.7) and (26.1±3.6) min, respectively] ( P<0.05). The results of the questionnaire showed that MR group had a significant improvement in the scores of classroom atmosphere, satisfaction, three-dimensional construction, theoretical knowledge and problem-solving ability ( P<0.01). However, there was no statistically significant difference in scores of learning concentration between the two groups ( P>0.05). Conclusions:The application of MR technology achieved a better teaching effect, which could help residents to deeply understand the methods of fibular flap preparation, and showed a broad application prospect.

Objective:To observe the effect of breastfeeding on the incidence of retinopathy of prematurity (ROP).Methods:A retrospective clinical study. From June 2017 to December 2019, 1256 eyes of 628 premature infants who were born in Ningbo Women and Children's Hospital and were screened for ROP were included in the study. Among them, there were in 325 males (650 eyes) and 303 females (606 eyes). According to the feeding situation, premature infants were divided into breastfeeding (research) group and formula feeding (control) group, with 390 cases of 780 eyes and 238 cases of 476 eyes, respectively. The changes in the retina of the fundus of the two groups of premature infants during the observation period were compared. The qualitative data comparison between groups was performed by the χ2 test; the quantitative data comparison was performed by the two independent sample t test. Results:The sex ratio of premature infants in the study group and control group ( χ2=0.217), birth weight ( t=0.728), gestational age at birth ( t=0.351), Apgar score at birth ( t=0.816), oxygen inhalation time ( t=0.427), were compared with the length of stay in the neonatal intensive care unit ( t=1.580), the difference was not statistically significant ( P>0.05). Among the 390 cases in the study group, 108 cases (27.7%, 108/390) and 282 cases (72.3%, 282/390) were with or without ROP, respectively; in the 238 cases in the control group, 86 (36.1%, 86/238) were with ROP, 152 (63.9%, 152/238) cases were without ROP. There was a statistically significant difference in the incidence of ROP between the two groups ( χ2=4.934, P=0.026). Among the 108 cases of ROP in the study group, 50 (12.8%, 50/108), 35 (9.0%, 35/108), 23 (5.9%, 23/108) cases were in stage 1, 2 and 3, respectively. Among the 86 ROP cases in the control group, stages 1, 2 and 3 were 25 (10.5%, 25/86), 40 (16.8%, 40/86), and 21 (8.8%, 21/86), respectively. In the comparison of ROP staging between the two groups, the difference in stage 1 was not statistically significant ( χ2=0.754, P>0.05), and the difference in stage 2 and above was statistically significant ( χ2=11.400, P<0.05). Conclusion:Breastfeeding may reduce the incidence and severity of ROP.

N-methyladenosine (mA), a ubiquitous RNA modification, is installed by METTL3-METTL14 complex. The structure of the heterodimeric complex between the methyltransferase domains (MTDs) of METTL3 and METTL14 has been previously determined. However, the MTDs alone possess no enzymatic activity. Here we present the solution structure for the zinc finger domain (ZFD) of METTL3, the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14. We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3' consensus sequence, but does not to one without. The ZFD thus serves as the target recognition domain, a structural feature previously shown for DNA methyltransferases, and cooperates with the MTDs of METTL3-METTL14 for catalysis. However, the interaction between the ZFD and the specific RNA is extremely weak, with the binding affinity at several hundred micromolar under physiological conditions. The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel β-sheet. Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface. As a division of labor, the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues from β-sheet and zinc finger 2. Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded, which may permit the cooperation between the two domains during catalysis. Together, the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA mA modification.

Objective: To analyze the reasons for failure of Meek micro-skin grafting in children with severe burns and to observe the clinical effects of the treatment measures. Methods: Thirty children with severe burns hospitalized in the First Affiliated Hospital of Anhui Medical University (hereinafter referred to as the author′s affiliation) from January 2012 to January 2018, conforming to the inclusion criteria were included to failed skin graft group. Children in failed skin graft group were performed with Meek micro-skin grafting operation and the operation failed, including 17 males and 13 females aged 1 to 12 year(s). Thirty children with severe burns hospitalized in the author′s affiliation during the same period of time, conforming to the inclusion criteria, were included to successful skin graft group. Children in successful skin graft group were performed with Meek micro-skin grafting operation and the operation succeeded, including 16 males and 14 females aged 1 to 12 year(s). Main treatment measures and effects before operation, area and survival rate of Meek micro-skin graft, infected pathogens status, selection status of sensitive antibiotics, preoperative nutrition status, and wound infection status in plum rain season of children in the two groups, and nutritional status before and after strengthening nutritional support of postoperative surviving children in failed skin graft group were analyzed retrospectively. Data were processed with chi-square test and t test. Results: (1) The numbers of children in the two groups performed with main treatment measures of dilatation and anti-shock, tracheotomy intubation, ventilator-assisted respiration, and limb incision decompression after admission were close (χ²=0, 0.016, 0.025, 0.009, P>0.05). After taking the above-mentioned main treatment measures, effects of correcting shock, preventing asphyxia, correcting breathing difficulty, and improving peripheral circulation of limb were achieved. (2) The area of Meek micro-skin grafting of children in successful skin graft group was (20.6±2.5)% total body surface area (TBSA), close to (21.2±2.2)% TBSA in failed skin graft group (t=0.534, P>0.05). The survival rate of Meek micro-skin graft of children in successful skin graft group was (79±5)%, significantly higher than (26±3)% in failed skin graft group (t=2.956, P<0.01). (3) The microbial culture of wound secretion of 5 (16.67%) children in 30 patients in successful skin graft group was positive, with Pseudomonas aeruginosa of 2 children, and Escherichia coli, Staphylococcus aureus, and Aspergillus of one patient respectively. As children in successful skin graft group were with no symptom of systemic infection, no blood microbial culture was done. The microbial culture of wound secretion of 30 (100.00%) children in 30 patients in failed skin graft group was positive, and blood microbial culture of 8 (26.67%) children was positive. The main pathogen was Pseudomonas aeruginosa of 11 (36.67%) children in 8 pathogens caused infection with gram-negative bacteria of 22 (73.33%), gram-positive bacteria of 11 (36.67%) children, and fungi of 6 (20.00%) children. (4) Ten kinds of sensitive antibiotics such as cephalosporins, glycopeptides, carbapenems, and tetracyclines antibiotics were used in children in failed skin graft group, of which the use rate of imipenem of 9 (30.00%) was the highest. Only 4 kinds of sensitive antibiotics such as ceftazidime were used in 30 children in successful skin graft group. (5) The preoperative levels of albumin and prealbumin of children in successful skin graft group were (32±4) g/L and (133±41) mg/L respectively, significantly higher than (27±4) g/L and (93±35) mg/L in failed skin graft group (t=5.090, 4.064, P<0.01). The albumin and prealbumin levels of postoperative surviving children in failed skin graft group after nutritional support treatment were (35±4) g/L and (168±49) mg/L, significantly higher than (27±4) g/L and (94±38) mg/L before nutritional support treatment (t=6.911, 6.315, P<0.01). (6) Wound infection of 9 children in 30 children with wound infection in failed skin graft group happened in the plum rain season, and fungi infection of 3 children in 6 children with fungi infection happened in the plum rain season. Wound infection of 2 children in 5 children with wound infection in successful skin graft group happened in the plum rain season, and the only one children with fungi infection happened in the plum rain season. Conclusions The main reasons for the failure of Meek micro-skin grafting in children with severe burns include infection, nutrition, and season factors, etc. Measures of strengthening wound dressing change, reasonable use of sensitive antibiotics to control infection, internal and external intestinal nutritional support, and reducing disturbance of the plum rain season by enhancing ventilation are effective and worthy of clinical promotion.

Objective: To explore the influence of three-level collaboration network of pediatric burns in Anhui province on treatment effects of burn children. Methods: The data of medical records of pediatric burn children transferred from Lu′an People′s Hospital and Fuyang People′s Hospital to the First Affiliated Hospital of Anhui Medical University from January 2014 to December 2015 and January 2016 to September 2017 (before and after establishing three-level collaboration network of pediatric burns treatment) were analyzed: percentage of transferred burn children to hospitalized burn children in corresponding period, gender, age, burn degree, treatment method, treatment result, occurrence and treatment result of shock, and operative and non-operative treatment time and cost. Rehabilitation result of burn children transferred back to local hospitals in 2016 and 2017. Data were processed with t test, chi-square test, Mann-Whitney U test, and Fisher′s exact test. Results: (1) Percentage of burn children transferred from January 2014 to December 2015 was 34.3% (291/848) of the total number of hospitalized burn children in the same period of time, which was close to 30.4% (210/691) of burn children transferred from January 2016 to September 2017 (χ²=2.672, P>0.05). (2) Gender, age, burn degree, and treatment method of burn children transferred from the two periods of time were close (χ²=3.382, Z=-1.917, -1.911, χ²=3.133, P>0.05). (3) Cure rates of children with mild, moderate, and severe burns transferred from January 2016 to September 2017 were significantly higher than those of burn children transferred from January 2014 to December 2015 (χ²=11.777, 6.948, 4.310, P<0.05). Cure rates of children with extremely severe burns transferred from the two periods of time were close (χ²=1.181, P>0.05). (4) Children with mild and moderate burns transferred from the two periods of time were with no shock. The incidence of shock of children with severe burns transferred from January 2014 to December 2015 was 6.0% (4/67), and 3 children among them were cured. The incidence of shock of children with severe burns transferred from January 2016 to September 2017 was 3.9% (2/51), and both children were cured. The incidences and cures of shock of children with severe burns transferred from the two periods of time were close (χ²=0.006, P>0.05). Incidence of shock of children with extremely severe burns transferred from January 2014 to December 2015 was 57.1% (32/56), significantly higher than that of burn children transferred from January 2016 to September 2017 [34.5% (10/29), χ²=3.925, P<0.05]. Shock of 25 children with extremely severe burns transferred from January 2014 to December 2015 were cured, and shock of 9 children with extremely severe burns transferred from January 2016 to September 2017 were cured. The cures of shock of children with extremely severe burns transferred from the two periods of time were close ( χ²=0.139, P>0.05). (5) Time of operative treatment of children with moderate, severe, and extremely severe burns transferred from January 2014 to December 2015 was obviously longer than that of burn children transferred from January 2016 to September 2017 (t=2.335, 2.065, 2.310, P<0.05). Time of operative treatment of children with mild burns transferred from the two periods of time was close (Z=-0.417, P>0.05). Costs of operative treatment of children with moderate and severe burns transferred from January 2014 to December 2015 were significantly more than those of burn children transferred from January 2016 to September 2017 (Z=-3.324, t=2.167, P<0.05). Costs of operative treatment of children with mild and extremely severe burns transferred from the two periods of time were close (t=0.627, 0.808, P>0.05). (6)Time of non-operative treatment of children with mild, moderate, and severe burns transferred from January 2014 to December 2015 was obviously longer than that of burn children transferred from January 2016 to September 2017 (t=2.335, Z=-2.095, t=2.152, P<0.05). Time of non-operative treatment of children with extremely severe burns transferred from the two periods of time was close (t=0.450, P>0.05). Costs of non-operative treatment of children with moderate and severe burns transferred from January 2014 to December 2015 were obviously higher than those of burn children transferred from January 2016 to September 2017 (Z=-2.164, t=2.040, P<0.05). Costs of non-operative treatment of children with mild and extremely severe burns transferred from the two periods of time were close (t=0.146, 1.235, P>0.05). (7) Sixty-seven burn children transferred from January 2016 to September 2017 were transferred back to local hospitals for rehabilitation under the guidance of experts of the First Affiliated Hospital of Anhui Medical University, with 25 patients in 2016 and 42 patients in 2017. Effective rehabilitation rates of burn children transferred back to local hospitals for rehabilitation in 2016 and 2017 were both 100%. Conclusions The three-level collaboration network of pediatric burns treatment in Anhui province can effectively increase cure rate of children with mild, moderate, and severe burns, reduce incidence of shock of children with extremely severe burns, shorten time of operative treatment of burn children with moderate, severe, and extremely severe burns, and time of non-operative treatment of children with mild, moderate, and severe burns, reduce treatment costs of children with moderate and severe burns, and improve rehabilitation effectiveness of children transferred from Lu′an People′s Hospital and Fuyang People′s Hospital to the the First Affiliated Hospital of Anhui Medical University.