Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

Humans ; Lymphoma, T-Cell, Cutaneous/complications* ; Neuroglia ; Pruritus/pathology* ; Skin Neoplasms/complications* ; Spinal Cord/pathology* ; Sympathetic Nervous System

Objective To analyze the management experience of Swedish medical research funding,and provide reference for further rationalization of medical research investment management in China.Methods Literature research method,descriptive statistics and other methods were used to systematically sort out the source of Swedish medical research funding,and specifically analyze the capital investment and distribution in medical fields in the past ten years.Results The Swedish government 's budget in the UO9 (health,medical and social care) field is steadily increasing.The annual average budget accounts for 7.14％ of the total government budget.There are scientific management methods for fund allocation.The appropriation projects are mainly divided into three main directions including public health categories,health care and social care.Conclusions Taking into account of the problems existing in the investment and distribution of medical research funds in China,this paper proposes to explore the capital investment mode suitable for China's national conditions,enhance the targeted investment of funds in medicine,and establish a scientific and efficient fund investment management mechanism.

Objective The paper aims to analyze the effectiveness and problems of health personnel construction in China since 2012,provide reference for promoting the construction of health professionals.Methods Using national data from China health statistics yearbook,adopted the methods of descriptive statistics and literature research and so forth.Results The construction of health personnel has been continuously strengthened in China,the structure and distribution of health personnel have been further optimized,the medical service capabilities have been improved.However,there are still inappropriate or imbalanced situations.Conclusions The construction of key personnel such as primary health personnel and urgently needed personnel need to be further strengthened;promote the construction of health service personnel to meet new health needs;continue to improve the construction of high-level and management personnel to play a leading role.

Objective To analyze the hot spots and frontiers in domestic and foreign precision medicine with CiteSpace. Methods The CNKI and WOS-covered papers on precision medicine were analyzed by bibliometrics combined with CiteSpace. Results Domestic precision medicine got off in 1992 and scholars became interested in it from 2010 . Foreign precision medicine started in 1985 and studies on it increased rapidly from 2006 . The node of precision medicine was the largest in China with a rather high value of gene mutation, US president Barack Obama ( precision medicine program) , personalized medicine, gene chip, genomics and pharmacogenomics whereas the node of personalized medicine, cancer and breast cancer was the largest with a rather high value of precision medi-cine, pharmacogenomics and pharmacogenetics. Conclusion The number of domestic and foreign papers on US president Barack Obama ( precision medicine program) is rapidly increased and pharmacogenomics is their common frontier. However, cancer is highly concerned in foreign countries.

In this cross-sectional study, consecutive Chinese Han ethnic inpatients in the Division of Cardiology, the First Affiliated Hospital of Soochow University from January 1, 2010 to December 31, 2013 were included. According to the exclusion criteria, 9 587 patients [1 604 with type 2 diabetes mellitus (T2DM) and 7 983 without T2DM]were obtained for final analysis. Logistic regression model was used to analyze the association of ApoB/A-1 ratio with T2DM and the possible interactions between ApoB/A-1 ratio and other risk factors. The results showed that the distribution of ApoB/A-1 ratio was positively skewed in Chinese Han ethic population. The median of ApoB/A-1 ratio of female was lower than that of male (0.68 vs 0.73,P<0.01). In all groups, the proportion of T2DM was increased with the raised ApoB/A-1 ratio. By the stratification analyses of sex, age, coronary artery disease, and the use of statins, ApoB/A-1 ratio was still correlated with T2DM. There existed significant interactions between ApoB/A-1 ratio and the smoking status or creatinine in T2DM.

Objective To study the effect of different grades of gastric mucosa epithelial neoplasia tissues of Helicobacter pylori (Hp ) infection and the relationship between chemokine CXCL12 and its receptor CXCR4 expression and significance. Methods Based on a total of 138 cases of endoscopic specimens, there were normal gastric mucosa (NGM) in 32 cases, low grade intraepithelial neoplasia (LGIEN) in 35 cases, high grade intraepithelial neoplasia (HGIEN) in 36 cases, and gastric adenocarcinoma (GCA) in 35 cases. Hp infection was determined by 13C breath test and serum Hp antibodies,the double positive for Hp infection. CXCL12 and its receptor CXCR4 were detected by immunohistochemical method. Results The positive rates of CXCL12 and CXCR4 in LGIEN,HGIEN and GCA were higher than those in NGM:71.43%(25/35), 86.11%(31/36), 91.43%(32/35) vs. 25.00%(8/32);71.43%(25/35), 86.11%(31/36), 91.43%(32/35)vs. 28.12%(9/32), P<0.05;the positive rates of CXCL12 and CXCR4 in HGIEN and GCA were higher than those in LGIEN (P<0.05);the positive rates of CXCL12 and CXCR4 in HGIEN and GCA had no significant difference (P>0.05). The positive expression of CXCL12 and CXCR4 had no correlation with Hp infection (P>0.05). Conclusions The positive rates of CXCL12 and CXCR4 in LGIEN,HGIEN and GCA are higher than those in NGM.The positive rates of CXCL12 and CXCR4 in HGIEN and GCA are higher than those in LGIEN. The positive rates of CXCL12 and CXCR4 in HGIEN and GCA are similar. The positive expression of CXCL12 and CXCR4 have no correlation with Hp infection, it suggests that Hp infection may not play oncogenic role by CXCL12 and CXCR4 receptor expression.

Objective Establish an objective and fair evaluation index system for the implementation effectiveness of the National Major New Drug Development Program of China.Methods Based on literature review and Delphi method,the framework of the evaluation index system was built and analytic hierarchy process was applied to determine the priority of each indicator of the system.The objectiveness and validness of the results were assured by determining expert activeness coefficient,authority coefficient,indicator rationality,and by applying consistency check.Results A targeted and systematic evaluation index system was constructed for the National Major New Drug Development Program,and through expert consultation and analytic hierarchy process,the factor of product result was considered of the highest weight of 39.03％,followed by technical result,theoretical result and organization and management result.The evaluation index system suggested that product result and technical result are two relatively more significant factors to be considered during evaluation.Conclu sion After consultation on expert opinions,the evaluation index system for the National Major New Drug Development Program was constructed with each factor been assigned with a scientific and rational weight,and this will provide a guideline for the decision making of program administrators and evaluation practice.

ObjectiveTo explore the influence of the CT scanning mode on the gross tumor volume (GTV) delineation of solitary pulmonary lesion (SPL),and to evaluate the feasibility of the spiral CT scan in CT simulation.Methods Sixteen patients with SPL underwent axial scan,spiral scan during free breathing.Compare the target position,volume between GTVS and GTVA (paired t-test).The matching index (MI) between GTVS and GTVA and correlations between MI and the tumor volume were calculated ( bivariate correlation analysis).ResultsGTVS and GTVA volume was 8.95 cm3 and 9.38 cm3 ( t =0.43,P =0.667),respectively.The centroid position for GTVS and GTVA in x,y and z axises were 6.80 cm and 6.81 cm (t =0.27,P =0.794),36.19 cm and 36.05 cm (t =0.37,P =0.717),and 4.99 cm and 4.96cm (t =0.65,P =0.526),respectively.There were also no statistically significant difference in the distance between the centroidal position and origin of coordinates for GTVS and GTVA (38.31 cm∶ 38.23 cm,t =0.47,P =0.646 ).MI between GTVS and GTVA was 0.36 ( range 0-0.77 ),correlated with the tumor volume (r =0.587,P =0.017).ConclusionsThere was no significant difference between the axial scan and spiral scan in the GTV volume and position for SPL,but MI between GTVS and GTVA were small.A correlation was found for the MI between GTVS and GTVA with the tumor volume.Spiral CT scan was more timesaving,and was feasible in CT simulation scan.