This research study focuses on addressing the limitations of current neuropathic pain (NP) treatments by developing a novel dual-target modulator, E0199, targeting both Na_V1.7, Na_V1.8, and Na_V1.9 and K_V7 channels, a crucial regulator in controlling NP symptoms. The objective of the study was to synthesize a compound capable of modulating these channels to alleviate NP. Through an experimental design involving both in vitro and in vivo methods, E0199 was tested for its efficacy on ion channels and its therapeutic potential in a chronic constriction injury (CCI) mouse model. The results demonstrated that E0199 significantly inhibited Na_V1.7, Na_V1.8, and Na_V1.9 channels with a particularly low half maximal inhibitory concentration (IC₅₀) for Na_V1.9 by promoting sodium channel inactivation, and also effectively increased K_V7.2/7.3, K_V7.2, and K_V7.5 channels, excluding K_V7.1 by promoting potassium channel activation. This dual action significantly reduced the excitability of dorsal root ganglion neurons and alleviated pain hypersensitivity in mice at low doses, indicating a potent analgesic effect without affecting heart and skeletal muscle ion channels critically. The safety of E0199 was supported by neurobehavioral evaluations. Conclusively, E0199 represents a ground-breaking approach in NP treatment, showcasing the potential of dual-target small-molecule compounds in providing a more effective and safe therapeutic option for NP. This study introduces a promising direction for the future development of NP therapeutics.

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

OBJECTIVES: To analyze the differentially expressed genes (DEGs) with radiation-induced rat lung injury, and to reveal the protective mechanism for mild hypothermia in the radiation-induced lung injury in rats at the transcriptome level. METHODS: A total of 10 male SD rats aged 6-8 weeks were randomly divided into 2 groups to establish a rat model of radiation-induced lung injury, and one group was treated with mild hypothermia. RNA was extracted from left lung tissue of each group, and sequenced by BGISEQ-500 platform. Significance analysis of DEGs was carried out by edgeR software. Gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to analyze the gene function. Then 5 key DEGs were verified by real-time reverse transcription PCR (real-time RT-PCR). RESULTS: There were 2 790 DEGs (false discovery rate<0.001, |log CONCLUSIONS The DEGs and pathways related to mild hypothermia protection against radiation-induced lung injury in rats are obtained, which provides an experimental basis for the protection of mild hypothermia against radiation-induced lung injury.
Animals ; Gene Expression Profiling ; Hypothermia ; Lung Injury ; Male ; RNA-Seq ; Rats ; Rats, Sprague-Dawley ; Transcriptome

【Objective】 To investigate the clinical application of self-developed magnetic anchoring device for assisting thoracoscopic pulmonary resection. 【Methods】 Eleven patients underwent thoracoscopic pulmonary assisted with resection magnetic anchoring technique at the Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, from March to May 2019. Their clinical data were retrospectively analyzed. The operation time, blood loss, blood transfusion volume, postoperative hospital stay, and postoperative complications were recorded. 【Results】 There were seven male and four female patients, with the average age of (51.6±13.9) years (range from 22 to 69 years). Three single-port and eight single-utility-port thoracoscopic surgeries were performed. Magnetic instruments provided good surgical field exposure in all operations. Among 11 surgeries, one was converted to thoracotomy and one to three-hole surgery due to enlargement and adhesion of hilar lymph nodes. The operation time was (107.8±63.1) minutes (range of 27-182 minutes). The blood loss was 50 (10-50)mL (range of 5-1 000 mL). No blood transfusion was needed during the operation. The postoperative hospital stay was (5.0±1.8) days (range of 3-9 days). No postoperative complications occurred in all the patients. 【Conclusion】 Magnetic anchor technique can effectively alleviate the "chopstick effect" in thoracoscopic surgery. Magnetic anchor technique is safe and feasible in assisting thoracoscopic pulmonary resection.

Objective To evaluate the predicting value of circulating miRNAs for sepsis secondary to pneumonia in elderly patients.Methods From April 2016 to January 2017,44 cases with sepsis secondary to pneumonia,52 elderly patients with pneumonia and 21 healthy older adults as control were involved in this study.The expression levels of MiRNA-150 5p,miRNA-25-3p,miRNA-122 5p and miRNA-223-3p in plasma were evaluated by fluorescence quantitative PCR.The demographic characteristics,sequential organ failure assessment (SOFA)scores,prognosis and days stayed in ICU were recorded.The area under the receiver operating charaeteristic(ROC)curve was used to calculated the specificity and sensitivity of miRNA in identifying sepsis-associated pneumonia.Results There were significantly differences among levels of circulating miRNA-223-3p in pneumonia,sepsis and healthy control groups(F =36.441,P =0.000),△CT values were 2.39 ± 1.36,1.44± 1.43,and 4.58 ± 0.91,respectively.The relative expression levels of miRNA-223-3p in the three groups were significantly different (P =0.000),which were 0.189 (0.107,0.367),0.361 (0.221,0.735),and 0.044 (0.022,0.061),respectively.The AUC of miRNA-223-3p for predicting sepsis from pneumonia was 0.964(95 ％CI =0.925 1.000).At a cutoff value of 2.759,miRNA-223-3p yielded a sensitivity of 82.9％ and a specificity of 100.0％.Conclusions MiRNA-223-3p expression is up-regulated in patients with sepsis secondary to pneumonia compared to that of patients with pneumonia,and it could be used to predict sepsis associated pneumonia.

Objective To evaluate the value of hysterosalpingo-contrast-sonography in assessment the patency of fallopian tube after tubal interventional recanalization. Methods A total of 56 cases of fallopian tube recanalization were performed in Shanghai Putuo Hospital from January 2015 to September 2016. Seventy-eight fallopian tubes in 40 cases were treated with hysterosalpingo-contrast-sonography and hysterosalpingography before recanalization. Totally 106 fallopian tubes in 56 cases were performed hysterosalpingography before and after recanalization. Seventy-eight fallopian tubes in 40 cases were evaluated with hysterosalpingo-contrast-sonography before recanalization. The patency of the tubal was assessed by hysterosalpingo-contrast-sonography 3 months after recanalization, and the re-occlusion rate was calculated. Chi square test was used to compare the results of hysterosalpingo-contrast-sonography and hysterosalpingography before and after recanalization, and the patency of fallopian tube at just after operation and 3 months after recanalization. Results Before recanalization, the results of hysterosalpingo-contrast-sonography showed 40 obstructed and 38 partially obstructed. The results of hysterosalpingography showed 44 obstructed and 34 partially obstructed. There was no significant difference between the results of hysterosalpingo-contrast-sonography and hysterosalpingography. Before recanalization, 106 fallopian tubes in 56 cases showed 53 obstructed and 53 partially obstructed. After recanalization, 72 unobstructed, 34 partially obstructed, and no obstruction. However, 22 fallopian tubes were re-obstructed 3 months after recanalization, and the rate of re-occlusion was 20.7% (22/106). The re-occlusion rate of unobstructed fallopian tubes was 19.4% (14/73) and the re-occlusion rate of partially obstructed fallopian tubes was 23.5% (8/34). There was no statistically significant difference between them. Conclusions Re-obstruction may be present in some cases 3 months after tubal recanalization. Hysterosalpingo-contrast-sonography can provide an objective and effective basis for guiding pregnancy plan after tubal recanalization.

Objective To evaluate the relationship between endothelin-1 (ET-1) and p38 mitogenactivated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways during mechanical stretch-induced enhancement of adhesion of rat pulmonary microvascular endothelial cells (PMVECs).Methods Rat PMVECs were seeded in the culture plate at a density of 0.5×105 cells/ml (2 ml/well) and divided into 5 groups (n=24 each) using a random number table:control group (group C),mechanical stretch group (group MS),mechanical stretch plus specific PI3K inhibitor LY294002 group (LY group),mechanical stretch plus specific p38 MAPK inhibitor SB203580 group (SB group),and mechanical stretch plus selective ETA receptor blocker BQ123 group (BQ group).Cells were exposed to 20％ cyclic stretch at 0.3 Hz for 4 h using a sine wave.In LY,SB and BQ groups,LY294002,SB203580 and BQ123 at the final concentration of 10 μmol/L were added,respectively,after mechanical stretch,cells were incubated for 10 min,and then extracted and purified rat polymorphonuclear neutrophil leukocytes (PMNs,5× 105 cells/well) were added and co-incubated with PMVECs for 30 min and then washed out.The concentrations of ET-1 and interleukin-6 (IL-6) in the culture medium were determined using enzyme-linked immunosorbent assay.The expression of phosphorylated p38 MAPK (p-p38 MAPK) and phosphorylated Akt (p-Akt) was detected by Western blot.Adhesion of PMNs was measured by immuno-histochemistry,and the adhesion rate was calculated.The expression of P-selectin mRNA was detected using real-time polymerase chain reaction.Results Compared with group C,the concentrations of IL-6 and ET-1 in the culture medium were significantly increased,the expression of p-p38 MAPK,p-Akt and P-selectin mRNA was up-regulated,and the adhesion rate of PMNs was increased in the other four groups (P＜0.05).Compared with group MS,the concentration of IL-6 in the culture medium was significantly decreased,the expression of p-Akt and P-selectin mRNA was down-regulated,and the adhesion rate of PMNs was decreased in LY,SB and BQ groups,the concentration of ET-1 in the culture medium was significantly decreased in group BQ,and the expression of p-p38 MAPK was significantly down-regulated in SB and BQ groups (P＜0.05).Conclusion The signaling mechanism underlying ET-1-mediated enhancement of rat PMVEC adhesion may be related to activating p38 MAPK and PI3K/Akt signaling pathways.

Objective To observe the effects of mild hypothermia induced by pentobarbital sodium on hematology in male BALB/C mice.Method Healthy male BALB/C mice were divided randomly into two groups:control group ( C) and mild hypothermia group(M).The body temperature of the mild hypothermia group was maintained between 28℃ to 30℃( anal temperature ) for 4 hours induced by pentobarbital sodium injected intraperitoneally , then recover unaffected . Anal temperature, coagulation, electrolytes, and blood cell indexes were examined in 2, 24, 72 hours after treated by mild hypothermia;Control group was given equal volume of saline volume at constant temperature .Results The body temperature and coagulation in mild hypothermia group showed no significant difference compared with the control group ( P﹥0.05),but the concentration of K +and Na +in mild hypothermia group were higher than control group (P﹤0.01), the number of WBC in mild hypothermia group was lower than control group ( P﹤0.01或P﹤0.05 ) , and the RBC、HGB、MCH、MCHC in mild hypothermia group were lower than control group transiently (P﹤0.01或P﹤0.05).Conclusion Mild hypothermia induced by pentobarbital sodium affects some of hematological values in mice considerably .

BACKGROUNDLittle is known about asthma control and perception of asthma among asthmatic patients in China. This study marked the first survey conducted on a national scale that aimed at obtaining baseline information on asthma control and patients' perception of asthma and providing a point of reference for future studies.

METHODSThis face-to-face, questionnaire-based survey was conducted from April 2007 to March 2008 with 3 069 asthmatic patients from the respiratory outpatient clinics of 36 general hospitals located in 10 geographically dispersed cities.

RESULTSConsistent with the Global Initiative for Asthma (GINA) guidelines, 28.7% and 45.0% of our patients achieved control and partial control, respectively. Of the patients in the study, only 21.8% had used a peak flow meter (PFM), and 6.6% of these patients used it daily. Inhaled corticosteroids (ICS) plus a long-acting β2 agonist (LABA) and ICS were the two most common medication regimens and were used in 45.6% and 30.4% of patients, respectively. Asthma had a significant effect on the patients' life and work. A considerable number of hospitalizations, emergency department visits, and sick days were observed.

CONCLUSIONDespite improvements in asthma control and ICS and PFM compliance compared with past literature, the current level of asthma control countrywide continues to fall short of the goals set in the GINA.

Adolescent ; Adrenal Cortex Hormones ; therapeutic use ; Adrenergic beta-Agonists ; therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; epidemiology ; China ; epidemiology ; Data Collection ; Female ; Humans ; Male ; Middle Aged ; Surveys and Questionnaires ; Young Adult